literature review

516681 research-article2013 ANP0010.1177/0004867413516681ANZJP ArticlesWatson et al. Research Australian &

ORDER A PLAGIARISM FREE PAPER NOW

New Zealand Journal of Psychiatry 2014, Vol. 48(6) 564­–570 DOI: 10.1177/0004867413516681 Childhood trauma in bipolar disorder © The Royal Australian and New Zealand College of Psychiatrists 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav anp.sagepub.com Stuart Watson1, Peter Gallagher1, Dominic Dougall2, Richard Porter3, Joanna Moncrieff2, I Nicol Ferrier1 and Allan H Young4 Editor’s Choice Abstract Objective: There has been little investigation of early trauma in bipolar disorder despite evidence that stress impacts on the course of this illness. We aimed to compare the rates of childhood trauma in adults with bipolar disorder to a healthy control group, and to investigate the impact of childhood trauma on the clinical course of bipolar disorder. Methods: Retrospective assessment of childhood trauma was conducted using the Childhood Trauma Questionnaire (CTQ) in 60 outpatients with bipolar disorder being treated for a depressive episode and 55 control participants across two centres in north-east England and New Zealand. Results: Significantly higher rates of childhood trauma were observed in patients with bipolar I and bipolar II disorder compared to controls. Logistic regression, controlling for age and sex, identified emotional neglect to be the only significant CTQ subscale associated with a diagnosis of bipolar disorder. Childhood history of sexual abuse was not a significant predictor. Associations with clinical severity or course were less clear. Conclusions: Childhood emotional neglect appears to be significantly associated with bipolar disorder. Limitations include the relatively small sample size, which potentially increases the risk of type II errors. Replication of this study is required, with further investigation into the neurobiological consequences of childhood trauma, particularly emotional neglect. Keywords Bipolar disorder, childhood trauma, depression, emotional neglect Introduction The high prevalence and incidence (Merikangas et al., 2011), chronicity of symptoms (Judd et al., 2002, 2003), and psychosocial impairment (Judd et al., 2005) of bipolar disorder underlines the need to establish its aetiological and risk factors. Bipolar disorder is highly heritable (McGuffin et al., 2003); psychosocial stress also appears to increase the likelihood of first and possibly subsequent episodes (Etain et al., 2008; Post, 1992). Childhood trauma is a recognised indicator of poor prognosis in major depressive disorder (Douglas and Porter, 2012; Nanni et al., 2012) but, in bipolar disorder, whilst the impact of stressors in adulthood on the course of illness has been investigated (Cohen et al., 2004; Paykel, 2003), the impact of early trauma has been relatively neglected. One study has shown that early parental loss is more common (Agid et al., 1999), whilst others have shown that childhood stressful life events are less common (Horesh et al., 2011) or as common (Horesh Australian & New Zealand Journal of Psychiatry, 48(6) and Iancu, 2010) in bipolar disorder compared with healthy controls. Children and adolescents with bipolar disorder have been shown to be exposed to more negative life events and less positive events compared to controls (Romero et al., 2009), although interestingly, a recent paper suggested that the link between stressful events and bipolar disorder may be a consequence of the illness (Hosang et al., 1The Institute for Neuroscience, Newcastle University, Newcastle, UK of Brain Sciences, University College London, London, UK 3Department of Psychological Medicine, University of Otago, Christchurch, New Zealand 4Centre for Affective Disorders, Institute of Psychiatry, Kings College London, London, UK 2Faculty Corresponding author: Stuart Watson, The Wolfson Unit, Campus for Aging and Vitality, The Institute for Neuroscience, Newcastle University, Newcastle NE4 6BE, UK. Email: stuart.watson@newcastle.ac.uk 565 Watson et al. 2012). Studies using the Childhood Trauma Questionnaire (CTQ) (Bernstein et al., 2003) have reported a higher rate of childhood trauma (Fowke et al., 2012), particularly emotional abuse (Etain et al., 2010), in bipolar disorder. Retrospectively reported childhood abuse has been associated with an adverse illness course (Garno et al., 2005; Leverich et al., 2002), more depressive episodes (Garno et al., 2005), greater severity of mania (Garno et al., 2005; Leverich et al., 2002), with earlier onset (Carballo et al., 2008; Garno et al., 2005; Leverich et al., 2002), suicidal ideation (Carballo et al., 2008; Leverich et al., 2002), substance abuse (Brown et al., 2005; Carballo et al., 2008), and with impaired performance on tests of neuropsychological function (Savitz et al., 2008). However, interpretation of these findings is limited by the clinical and methodological heterogeneity of these studies (Daruy-Filho et al., 2011). In this study, childhood trauma, as measured by the CTQ, was compared in a sample of people with bipolar disorder recruited for a randomised trial (Watson et al., 2012) and in a healthy control group. It was predicted that higher CTQ scores would be associated with a diagnosis of bipolar disorder and secondly, that childhood trauma would be associated with measures of clinical severity. Methods Sample This analysis uses baseline assessment data from a randomised placebo-controlled trial of mifepristone treatment in bipolar depression (Watson et al., 2012). The study was carried out in two centres, Newcastle University in the north-east of England and Otago University in Christchurch, New Zealand. The main inclusion criterion was a diagnosis of bipolar disorder current episode depressed, confirmed with the Structured Clinical Interview for DSM-IV (SCID) (First et al., 1997). Additional inclusion criteria were: age between 18 and 65 years, stable medication for a minimum of 4 weeks, the ability to provide informed consent and the ability to adequately understand both written and verbal English. Both men and women were eligible. Potential participants were excluded if they fulfilled criteria for substance abuse or dependence (First et al., 1997), were pregnant, suffered significant medical illness which would render recruitment into the clinical trial unsafe (such as: suffered head trauma with persistent loss of consciousness, a neurological disorder or uncompensated endocrine disorder). A co-morbid axis II diagnosis was not an exclusion criterion. After a complete description of the study, written informed consent was obtained from all participants. The study received full approval from the local ethics committee. Participants were recruited from outpatient clinics allied to the respective centres. Sixty patients were randomized over a 5-year period from October 2004, of which 31 patients met SCID criteria for bipolar I and 25 the criteria for bipolar II. A cohort of 55 age- and sex-matched comparators, who were SCID confirmed as having no current or past history of an axis I disorder, was concurrently locally recruited. Assessment After an initial screening visit, baseline data was collected by trained psychiatrists with full history, case note and medication review. The data included demographic and clinical characteristics of sex, age, body mass index (BMI), pre-morbid IQ measured by the National Adult Reading Test (NART) (Nelson and Willison, 1991) and number of years of education. Measures which may indicate clinical severity included: the 17-item version of the Hamilton Depression Rating Scale (HDRS-17) (Hamilton, 1960); diagnosis of DSM-IV melancholia; length of the current depressive episode (weeks); number of previous hospitalisations; current alcohol intake (standard UK alcohol units per week); diagnosis of rapid cycling bipolar disorder; history of attempted suicide; any form of current suicidal ideation reported to the assessor. The childhood trauma questionnaire (CTQ) was also completed. The CTQ is a validated 28-item self-report questionnaire used to provide a retrospective measure of childhood trauma (Bernstein et al., 2003). It uses a fivepoint Likert-type scale. Twenty-five of the CTQ questions are split into five subscales of maltreatment: emotional abuse, physical abuse, sexual abuse, emotional neglect and physical neglect. The other three questions are used for detecting ‘false-negative’ answers involving a minimisation/denial scale. Statistical analyses Distributions of CTQ scores did not meet the assumption required for parametric analysis. Where appropriate, the bipolar group was divided into SCID (First et al., 1997) determined bipolar I and bipolar II subgroups. Chi-squared (χ2) test was used to compare sex distribution across bipolar and control groups. Age and BMI were normally distributed and were compared across bipolar and control groups using the independent samples t-test. The Mann–Whitney U-test and Spearman’s rank order correlations were used for all other comparisons of continuous variables. CTQ subscales for pooled bipolar and control data were examined using Spearman’s rho to identify significant correlations between subscales to determine suitability for inclusion in a regression analysis. Spearman’s rho was also used to examine relationships between CTQ subscale scores and the demographic variables, age, pre-morbid IQ (NART score) and years of education. CTQ subscale scores were compared between males and females. Step forward logistic regression of CTQ total scores and relevant demographic Australian & New Zealand Journal of Psychiatry, 48(6) 566 ANZJP Articles variables was performed to examine the overall relationship between trauma and bipolar disorder, with the binary outcome variable of bipolar or control group. A separate step forward logistic regression of the relevant CTQ subscales and demographic variables was performed to explore for relationships according to types of trauma. Results Patients and controls were matched for age, sex, pre-morbid IQ (NART score) and years of education, as reported in Table 1. A diagnosis of bipolar disorder was found to be significantly associated with a greater total CTQ score (Table 2). All subscale scores were significantly higher in the bipolar group, apart from sexual abuse. Similar results were found when the analysis was restricted to those with a diagnosis of bipolar I. In participants diagnosed with bipolar II, CTQ total, emotional abuse, emotional neglect and physical neglect scores were significantly greater than controls. Table 3 shows that in bipolar patients, CTQ scores did not differ between those with and those without suicidal ideation, although scores for the emotional neglect subscale showed a trend towards significance. Participants with a diagnosis of DSM-IV melancholia had significantly higher CTQ total scores, and significantly higher emotional neglect and emotional abuse scores than those without. Participants with a diagnosis of rapid cycling bipolar disorder had higher sexual abuse subscale scores than those who were not rapid cycling. In bipolar patients who reported one Table 1. Demographic and clinical characteristics of the bipolar group and control group. Bipolar patients % or mean (SD) Controls % or mean (SD) Comparison (p) Male (%) 53.3 54.5 χ2 = 0.02 (0.896) Age (mean years) 47.9 (9.4) 45.1 (13.1) t = 1.3 (0.193) BMI 29.8 (6.2) 26.0 (3.7) t = 3.0 (0.004) 110.6 (10.5) 113.3 (11.3) U = 1152.5 (0.089) 14.7 (3.3) 14.8 (4.3) U = 917.0 (0.554) NART IQ Years of education BMI: body mass index; NART IQ: National Adult Reading Test IQ. Table 2. CTQ scores in bipolar groups compared to controls.a All bipolar N = 60b Bipolar I N = 31b,c Comparison CTQ (SD) U p Bipolar II N = 25b,c Control N = 55% Comparison Comparison CTQ (SD) U p CTQ (SD) U p CTQ (SD) CTQ total 44.4 (19.1) 490.0 < 0.001 43.6 (20.6) 280.5 0.004 41.1 (13.1) 203.0 0.003 31.2 (8.0) Emotional abuse 10.4 (5.4) 780.0 < 0.001 10.2 (5.8) 470.0 0.012 9.7 (4.3) 294.0 0.005 6.8 (2.8) Physical abuse 7.5 (4.4) 903.0 0.005 7.9 (4.9) 461.0 0.005 6.0 (2.1) 439.5 0.387 5.4 (1.3) Sexual abuse 7.7 (5.4) 1092.5 0.131 7.9 (4.9) 584.5 0.182 7.1 (4.1) 428.5 0.224 6.2 (3.1) 12.4 (6.0) 767.0 < 0.001 12.7 (7.0) 459.5 0.011 11.1 (4.2) 299.0 0.008 8.2 (3.5) 7.9 (3.8) 787.5 < 0.001 8.1 (4.2) 446.0 0.002 7.2 (3.0) 306.5 0.003 5.7 (1.7) Emotional neglect Physical neglect aTable showing mean and SD of CTQ scores in different subject groups with a comparison using Mann–Whitney U-test of CTQ scores between the bipolar groups (all bipolar patients and those with a diagnosis of bipolar I or bipolar II) with controls. bNumbers vary due to the incomplete return of CTQs: all bipolar, N = 49–57; bipolar I, N = 25–31; bipolar II, N = 20–22; control, N = 39–45. cFour participants with bipolar disorder were not sub-classified as either bipolar I or II. CTQ: Childhood Trauma Questionnaire. Australian & New Zealand Journal of Psychiatry, 48(6) 567 vary due to the incomplete return of CTQs: history of attempted suicide, yes N = 23–29, no N = 21–23; current suicidal ideation, yes N = 11–13, no N = 34–40; rapid cycling, yes N = 6, no N = 38–46; DSM-IV melancholia, yes N = 21–24, no N = 23–27. CTQ: Childhood Trauma Questionnaire. aNumbers 0.046 222.0 (3.8) 6.9 (3.7) 8.9 137.0 0.976 (3.5) 7.8 9.3 9.2 Physical neglect (4.3) 6.6 (2.7) 218.5 0.029 6.8 (2.2) 8.2 (4.3) 235.0 0.597 (6.5) 0.031 210.0 (5.2) 10.9 (6.0) 129.5 0.807 14.3 (5.9) 12.6 12.5 13.7 Emotional neglect (6.4) 11.4 (5.4) 255.0 0.146 9.7 (5.9) 13.1 (6.0) 169.0 0.058 (6.7) 0.907 319.0 (5.3) 7.6 (6.0) 8.2 75.5 0.038 (5.0) 7.4 12.7 9.0 Sexual abuse (6.2) 6.7 (4.6) 265.0 0.198 8.4 (4.9) 7.7 (5.8) 190.0 0.184 (7.9) 0.227 264.5 (3.5) 7.0 (4.3) 7.8 116.0 0.503 (3.9) 7.2 10.2 8.3 Physical abuse (5.6) 6.9 (2.8) 322.5 0.831 6.8 (3.2) 7.9 (4.9) 234.0 0.569 (7.7) 0.216 259.0 (4.2) 8.9 (6.2) 113.5 0.479 11.6 (5.3) 10.1 12.3 11.5 Emotional abuse (5.9) 9.2 (5.0) 260.5 0.174 10.1 (5.6) 10.4 (5.6) 256.0 0.933 (6.4) 0.023 p U (14.9) 145.0 CTQ (SD) (20.8) 37.7 CTQ (SD) p U 92.0 0.451 49.8 (16.3) (SD) CTQ (32.6) 42.9 56.8 CTQ (SD) p U (20.3) 176.5 0.781 (SD) CTQ (19.4) 44.7 (SD) CTQ 42.8 0.051 p U Comparison (12.8) 158.5 CTQ (SD) (23.1) 38.3 CTQ (SD) No N = 42a Yes N = 14a No N = 24a Yes N = 31a 51.6 No N = 48a Yes N = 7a Comparison Rapid cycling Current suicidal ideation History of attempted suicide Table 3. Analyses of bipolar group clinical severity and clinical characteristics. CTQ total No N = 29a Yes N = 25a Comparison DSM-IV melancholia Comparison Watson et al. or more previous suicide attempts, CTQ total score was higher (p = 0.051), and scores significantly higher in the emotional abuse subscale. No significant correlations between CTQ total or CTQ subscale scores and length of current episode, number of previous hospitalizations, current severity of depression (HDRS-17 score), current alcohol intake were found (rs < 0.3, p > 0.1). Bivariate correlations between pooled bipolar and control scores of the five trauma subscales found significant correlations between all subscales (0.33 < rs < 0.64, p < 0.002), apart from between physical and sexual abuse (rs = 0.12, p = 0.17). All correlations were below 0.8 and therefore could be entered into a regression model without risk of multi-colinearity. Differences or associations with CTQ subscale scores and demographic characteristics were limited to age, which was significantly, but weakly, correlated with emotional neglect (rs = 0.14, p = 0.046) and sexual abuse scores which were significantly higher in females (U = 873.0, p < 0.001). NART scores or years of education were not significantly correlated with the CTQ subscales (rs < 0.2, p > 0.1). The factors considered to be plausible independent causal risk factors, i.e. CTQ total score, age and sex, were entered into step forward logistic regression, with the dependent variable of group (bipolar or control). This confirmed CTQ total score was the only significant predictor (β = 0.08, p = 0.001). The five subscale scores, age and sex, were then entered into a second step forward logistic regression, also with the dependent variable of group. Emotional neglect (β = 0.185, p < 0.001) remained the only significant predictor in the model (Table 4). Emotional abuse approached significance (p = 0.082). Discussion This paper demonstrates significant associations between childhood trauma and bipolar disorder. Higher CTQ scores were found in patients diagnosed with both bipolar I and bipolar II disorder compared to controls. Sexual abuse was the only subscale measure that was not higher in bipolar patients compared with controls. In bipolar patients with a diagnosis of DSM-IV melancholia, emotional neglect and physical neglect scores were higher. CTQ subscale scores were higher in those with a past history of attempted suicide or a diagnosis of rapid cycling bipolar disorder. Logistic regression showed CTQ total scores to differentiate bipolar patients from controls, and separately identified emotional neglect to be the only significant subscale of the CTQ to differentiate bipolar patients from controls. Emotional abuse approached significance and may therefore be considered as a potential contributor to the model. Our study is in line with the findings of two previous studies which also found that patients with a diagnosis of bipolar disorder reported higher rates of childhood trauma compared to healthy controls (Etain et al., 2010; Fowke et al., 2012). Exploring the subscales, we did not find Australian & New Zealand Journal of Psychiatry, 48(6) 568 ANZJP Articles Table 4. Logistic regression of CTQ subtypes predicting a diagnosis of bipolar disorder (I and II). Step 1 Age Gender Emotional abuse Physical abuse Sexual abuse Physical neglect Step 1a Emotional neglect Constant Score df 0.324 0.119 3.030 1.790 0.017 1.865 1 1 1 1 1 1 p 0.569 0.730 0.082 0.181 0.896 0.172 β Wald p 0.185 1.651 14.393 10.246 < 0.001 0.001 CTQ: Childhood Trauma Questionnaire. significant differences in the sexual abuse scale, which is in accord with one previous report (Etain et al., 2010) and is supported by a recent paper that found sexual abuse to be the least reported form of abuse by bipolar patients (Larsson et al., 2013), although other studies did find this association (Fowke et al., 2012; Hyun et al., 2000). Our findings differed in identifying emotional neglect, as opposed to an earlier finding of emotional abuse, to be the single significant subscale associated with bipolar disorder (Etain et al., 2010; Fowke et al., 2012). Methodological differences with the previous studies utilising the CTQ (Etain et al., 2010; Fowke et al., 2012) relate to the presence or absence of current episode and to the sample size. Our finding that a history of childhood trauma is related to a history of suicide attempts in bipolar patients is also in line with other studies (Alvarez et al., 2011; Carballo et al., 2008; Garno et al., 2005; Leverich et al., 2002), although two of these studies did not use a validated measure to retrospectively assess for childhood trauma (Carballo et al., 2008; Leverich et al., 2002). The allostatic impact of childhood trauma may be mediated through a range of biological systems with the hypothalamic–pituitary–adrenal (HPA) axis appearing to have a central role (Grande et al., 2012). It can also be argued that childhood trauma, at sensitive periods, may trigger an altered developmental pathway (Bateson et al., 2004), mediated in part by epigenetic processes (McGowan et al., 2009). For example, the regulation of hippocampal GR expression (McGowan et al., 2009) may induce ‘evolutionary appropriate’ responses such as increased vigilance, alertness to danger, responsivity to novel stressors and a willingness to explore new environments (Glover, 2011). The trade-off for such responses may be an increased risk of behavioural problems in childhood (Ramchandani et al., 2012) and of adult psychopathology including bipolar disorder (Watson et al., 2007) and suicidality (McGowan Australian & New Zealand Journal of Psychiatry, 48(6) et al., 2009). It is of interest that emotional neglect was the only subscale which significantly differentiated patients from controls. Emotional neglect suggests a pervasive deficiency in the parent–child relationship (Glaser, 2002), has been repeatedly linked with HPA axis dysregulation in adults (Gerra et al., 2008, 2010; Watson et al., 2007) and has been previously shown to be differentially related to depression (Spinhoven et al., 2010). It has been suggested that retrospective assessment of childhood trauma may be liable to recall bias in depressed patients (Lewinsohn and Rosenbaum, 1987). However, it should be noted that autobiographical recall of events (as measured using CTQ scores) in our study did not significantly correlate with severity of depression. CTQ scores have also been demonstrated to remain stable over time and to be independent of the current degree of abuse-related psychopathology (Paivio, 2001). Although there have been concerns that retrospective reporting overestimates associations between abuse and adult psychopathology compared to prospective assessment (Gilbert et al., 2009), a recent study found retrospective, compared to prospective, assessment of maltreatment predicted similar rates of mental disorder (Scott et al., 2012). A previous study has shown that recall bias accounted for less than 1% of reporting variance for measures of childhood abuse (Fergusson et al., 2011). However, emotional neglect is arguably the most subjective and difficult to define among forms of abuse, and hence further examination of the relationship between abuse and neglect and bipolar disorder in prospective studies which exclude recall bias would be useful. Investigations with euthymic bipolar patients would help to clarify the potential impact of current mood state. A weakness of this study is the relatively small sample size, which engenders the risk of type II errors. Further, the use of baseline data from a randomized controlled trial may have resulted in an under-sampling of more severe bipolar patients or those with comorbidities, which in turn may have resulted in an underestimation of the rates of childhood trauma in the bipolar group given the association between childhood trauma and poorer clinical outcomes (Garno et al., 2005; Leverich et al., 2002). Conclusions The association of perceived childhood trauma and depression is established (Nanni et al., 2012). This study adds to the literature suggesting a similar relationship in bipolar disorder, although confirmation in prospective studies is desirable. Emotional neglect may be particularly pernicious. Further consideration of its psychological and neurobiological mediation is warranted. Acknowledgements We are grateful to the participants who contributed to the research and to all those who helped in participant recruitment. Watson et al. Funding The study was funded by the Stanley Medical Research Institute (REF.: 03T-429) and the Medical Research Council (REF.: G0401207). Declaration of interest The authors declare that there is no conflict of interest. The funders did not influence the design or dissemination of the study. References Agid O, Shapira B, Zislin J, et al. (1999) Environment and vulnerability to major psychiatric illness: a case control study of early parental loss in major depression, bipolar disorder and schizophrenia. Molecular Psychiatry 4: 163–172. Alvarez M-J, Roura P, Osés A, et al. (2011) Prevalence and clinical impact of childhood trauma in patients with severe mental disorders. The Journal of Nervous and Mental Disease 199: 156–161. Bateson P, Barker D, Clutton-Brock T, et al. (2004) Developmental plasticity and human health. Nature 430: 419–421. Bernstein DP, Stein JA, Newcomb M, et al. (2003) Development and validation of a brief screening version of the Childhood Trauma Questionnaire. Child Abuse & Neglect 27: 169–190. Brown GR, McBride L, Bauer MS, et al. (2005) Impact of childhood abuse on the course of bipolar disorder: a replication study in U.S. veterans. Journal of Affective Disorders 89: 57–67. Carballo JJ, Harkavy-Friedman J, Burke AK, et al. (2008) Family history of suicidal behavior and early traumatic experiences: additive effect on suicidality and course of bipolar illness? Journal of Affective Disorders 109: 57–63. Cohen AN, Hammen C, Henry RM, et al. (2004) Effects of stress and social support on recurrence in bipolar disorder. Journal of Affective Disorders 82: 143–147. Daruy-Filho L, Brietzke E, Lafer E, et al. (2011) Childhood maltreatment and clinical outcomes of bipolar disorder. Acta Psychiatrica Scandinavica 124: 427–434. Douglas KM and Porter RJ (2012) The effect of childhood trauma on pharmacological treatment response in depressed inpatients. Psychiatry Research 18: 1–4. Etain B, Henry C, Bellivier F, et al. (2008) Beyond genetics: childhood affective trauma in bipolar disorder. Bipolar Disorders 10: 867–876. Etain B, Mathieu F, Henry C, et al. (2010) Preferential association between childhood emotional abuse and bipolar disorder. Journal of Traumatic Stress 23: 376–383. Fergusson DM, Horwood LJ, Boden JM (2011) Structural equation modeling of repeated retrospective reports of childhood maltreatment. International Journal of Methods in Psychiatric Research 20: 93–104. First M, Spitzer R, Gibbon M, et al. (1997) Structured Clinical Interview for DSM-IV Axis I Disorders, Research Version. New York: Biometrics Research. Fowke A, Ross S and Ashcroft K (2012) Childhood maltreatment and internalized shame in adults with a diagnosis of bipolar disorder. Clinical Psychology & Psychotherapy 19: 450–457. Garno JL, Goldberg JF, Ramirez PM, et al. (2005) Impact of childhood abuse on the clinical course of bipolar disorder. The British Journal of Psychiatry 186: 121–125. Gerra G, Zaimovic A, Castaldini L, et al. (2010) Relevance of perceived childhood neglect, 5-HTT gene variants and hypothalamus-pituitary-adrenal axis dysregulation to substance abuse susceptibility. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 153B: 715–722. Gerra G, Leonardi C, Cortese E, et al. (2008) Adrenocorticotropic hormone and cortisol plasma levels directly correlate with childhood neglect and depression measures in addicted patients. Addiction Biology 13: 95–104. Gilbert R, Widom CS, Browne K, et al. (2009) Burden and consequences of child maltreatment in high-income countries. Lancet 373: 68–81. 569 Glaser D (2002) Emotional abuse and neglect (psychological maltreatment): a conceptual framework. Child Abuse & Neglect 26: 697–714. Glover V (2011) Annual research review: Prenatal stress and the origins of psychopathology: an evolutionary perspective. Journal of Child Psychology and Psychiatry 52: 356–367. Grande I, Magalhães PV, Kunz M, et al. (2012) Mediators of allostasis and systemic toxicity in bipolar disorder. Physiology & Behavior 106: 46–50. Hamilton M (1960) A rating scale for depression. Journal of Neurology, Neurosurgery, and Psychiatry 23: 56–62. Horesh N and Iancu I (2010) A comparison of life events in patients with unipolar disorder or bipolar disorder and controls. Comprehensive Psychiatry 51: 157–164. Horesh N, Apter A and Zalsman G (2011) Timing, quantity and quality of stressful life events in childhood and preceding the first episode of bipolar disorder. Journal of Affective Disorders 134: 434–437. Hosang GM, Korszun A, Jones L, et al. (2012) Life-event specificity: bipolar disorder compared with unipolar depression. The British Journal of Psychiatry 201: 458–465. Hyun M, Friedman SD and Dunner DL (2000) Relationship of childhood physical and sexual abuse to adult bipolar disorder. Bipolar Disorders 2: 131–135. Judd LL, Akiskal HS, Schettler PJ, et al. (2002) The long-term natural history of the weekly symptomatic status of bipolar I disorder. Archives of General Psychiatry 59: 530–537. Judd LL, Akiskal HS, Schettler PJ, et al. (2003) A prospective investigation of the natural history of the long-term weekly symptomatic status of bipolar II disorder. Archives of General Psychiatry 60: 261–269. Judd LL, Akiskal HS, Schettler PJ, et al. (2005) Psychosocial disability in the course of bipolar I and II disorders: a prospective, comparative, longitudinal study. Archives of General Psychiatry 62: 1322–1330. Larsson S, Andreassen OA, Aas M, et al. (2013) High prevalence of childhood trauma in patients with schizophrenia spectrum and affective disorder. Comprehensive Psychiatry 54: 123–127. Leverich GS, McElroy SL, Suppes T, et al. (2002) Early physical and sexual abuse associated with an adverse course of bipolar illness. Biological Psychiatry 51: 288–297. Lewinsohn PM and Rosenbaum M (1987) Recall of parental behavior by acute depressives, remitted depressives, and nondepressives. Journal of Personality and Social Psychology 52: 611–619. McGowan PO, Sasaki A, D’Alessio AC, et al. (2009) Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nature Neuroscience 12: 342–348. McGuffin P, Rijsdijk F, Andrew M, et al. (2003) The heritability of bipolar affective disorder and the genetic relationship to unipolar depression. Archives of General Psychiatry 60: 497–502. Merikangas KR, Jin R, He J-P, et al. (2011) Prevalence and correlates of bipolar spectrum disorder in the world mental health survey initiative. Archives of General Psychiatry 68: 241–251. Nanni V, Uher R and Danese A (2012) Childhood maltreatment predicts unfavorable course of illness and treatment outcome in depression: a meta-analysis. American Journal of Psychiatry 169: 141–151. Nelson H and Willison J (eds) (1991) National Adult Reading Test (NART), 2nd edn. Windsor, UK: NFER-Nelson. Paivio SC (2001) Stability of retrospective self-reports of child abuse and neglect before and after therapy for child abuse issues. Child Abuse & Neglect 25: 1053–1068. Paykel ES (2003) Life events and affective disorders. Acta Psychiatrica Scandinavica 108: 61–66. Post RM (1992) Transduction of psychosocial stress into the neurobiology of recurrent affective disorder. The American Journal of Psychiatry 149: 999–1010. Ramchandani PG, Domoney J, Sethna V, et al. (2012) Do early fatherinfant interactions predict the onset of externalising behaviours in young children? Findings from a longitudinal cohort study. Journal of Child Psychology and Psychiatry 54: 56–64. Australian & New Zealand Journal of Psychiatry, 48(6) 570 Romero S, Birmaher B, Axelson DA, et al. (2009) Negative life events in children and adolescents with bipolar disorder. Journal of Clinical Psychiatry 70: 1452–1460. Savitz JB, Van der Merwe L, Stein DJ, et al. (2008) Neuropsychological task performance in bipolar spectrum illness: genetics, alcohol abuse, medication and childhood trauma. Bipolar Disorders 10: 479–494. Scott KM, McLaughlin KA, Smith DAR, et al. (2012) Childhood maltreatment and DSM-IV adult mental disorders: comparison of Australian & New Zealand Journal of Psychiatry, 48(6) ANZJP Articles prospective and retrospective findings. British Journal of Psychiatry 200: 469–475. Spinhoven P, Elzinga BM, Hovens JGFM, et al. (2010) The specificity of childhood adversities and negative life events across the life span to anxiety and depressive disorders. Journal of Affective Disorders 126: 103–112. Watson S, Gallagher P, Porter RJ, et al. (2012) A randomized trial to examine the effect of mifepristone on neuropsychological performance and mood in patients with bipolar depression. Biological Psychiatry 72: 943–949.
Purchase answer to see full attachment

Literature Review

435289 2012 ANP46410.1177/0004867411435289BassettANZJP Articles Review Borderline personality disorder and

ORDER A PLAGIARISM FREE PAPER NOW

bipolar affective disorder. Spectra or spectre? A review Australian & New Zealand Journal of Psychiatry 46(4) 327­–339 DOI: 10.1177/0004867411435289 © The Royal Australian and New Zealand College of Psychiatrists 2012 Reprints and permission: sagepub.co.uk/journalsPermissions.nav anp.sagepub.com Darryl Bassett1,2 Abstract Objective: Bipolar affective disorder and borderline personality disorder have long been considered to have significant similarities and comorbidity. This review endeavours to clarify the similarities and differences between these disorders, with an effort to determine whether they reflect different forms of the same illness or separate illness clusters. Method: The published literature relating to bipolar affective disorders, borderline personality disorders, and related areas of knowledge was reviewed using searches of several electronic databases (AMED, CINHAL, Embase, Ovid, ProQuest, MEDLINE, Web of Science, ScienceDirect) and published texts. These findings were combined with the personal clinical experience of the author, and information gathered from colleagues, to create a review of this topic. Results: Bipolar affective disorders and borderline personality disorders differ with respect to sense of self, disruption of relationships, family history of bipolar disorders, the benefits of medications, the extent of cognitive deficits, the form of affective dysregulation and mood cycling, the incidence of suicide and suicide attempts, the form of psychotic episodes, the incidence of early sexual abuse but not early trauma in general, the loss of brain substance, alterations in cortical activity, glucocorticoid receptor sensitivity, and mitochondrial dysfunction. They are similar with respect to non-specific features of affective dysregulation, the incidence of atypical depressive features, the incidence of self-mutilation, the incidence of transporter polymorphisms, possible genetic linkages, overall reduction in limbic modulation, reduction in the size of hippocampi and amygdala, and the incidence of sleep disruption. Conclusions: This review concludes that bipolar affective disorders and borderline personality disorder are separate disorders, but have significant elements in common. Keywords Atypical depressive disorder, bipolar disorder, bipolar spectrum, borderline personality disorder, cyclothymia Fundamentals The relationship between borderline personality disorder and bipolar affective disorder has been a topic of debate since at least 1979 (Boyce and Wilson, 2011; Siever and Gunderson, 1979; Stone, 1979). The presumed associations have been multiplied by increasing interest in patients who suffer less severe forms of mania but still suffer significant affective instability (the bipolar spectrum disorders) (Benazzi, 2009; Howland and Thase, 1993; Kwapil et al., 2011; Perugi et al., 2011; Thomas, 2004; Tiller and Schweitzer, 2010; Van Meter et al., 2011; Youngstrom et al., 2010). While such interest has captured recent attention, the concept of bipolar disorder with relatively mild forms of mania is not a recent development (Baethge et al., 2003; Brieger and Marneros, 1997; Slater and Roth, 1969). Our current major diagnostic systems have added to the confusion with long lists of criteria for each of these diagnostic groups, which permit the inclusion of a wide range of clinical presentations (Meares et al., 2011a). While bipolar disorder has been recognised as a diagnostic entity for a very long time (at least since Aretaeus of Cappadocia, circa AD 150–200) (Adams, 1972; Hornblower and Spawforth, 1School of Medicine, University of Notre Dame, Fremantle Australia of Psychiatry and Clinical Neurosciences, University of Western Australia, Nedlands, Australia 2School Corresponding author: Darryl Bassett, Suite 25, Hollywood Specialist Centre, 95 Monash Avenue, Nedlands, WA 6009, Australia. Email: dbassett@iinet.net.au Australian & New Zealand Journal of Psychiatry, 46(4) 328 1996), borderline personality disorder as currently defined is a relatively more recent construct (Stern, 1938). The problem of misdiagnosis of bipolar disorder has been well recognised and is the subject of considerable comment (Benazzi, 2000, 2006, 2008; Boyce and Wilson, 2011; Chilakamarri et al., 2011; George et al., 2003; Little and Richardson, 2010; Paris, 2010; Paris et al., 2007; Patfield, 2011; Ruggero et al., 2010a, 2010b; Smith et al., 2004; Tiller and Schweitzer, 2010; Yatham et al., 2009). One can readily appreciate that, among patients, a diagnosis of bipolar disorder gives a sense of optimism that treatment for their distressing illness is available. Conversely, in the context of our current service structure, a diagnosis of borderline personality disorder carries greater stigma and the implication that treatment may be unavailable (Aviram et al., 2006). A more biological diagnosis also externalises the locus of control, which is of appeal to some patients and therapists. Nevertheless, bipolar disorder is both frequently overdiagnosed and frequently missed (Hadjipavlou and Yatham, 2009; Leboyer and Kupfer, 2010). Evidence is steadily accumulating that bipolar disorder is associated with significant risks to brain structure and function, making early and effective treatment particularly important (Berk et al., 2009, 2010a, 2010b, 2011; Macneil et al., 2011). On the other hand, the positive misdiagnosis of bipolar disorder brings significant potential adverse consequences, including inappropriate medication exposure, insurance complications, employment implications, stigma and a distorted perception of health status. The failure to diagnose borderline personality disorder also has significant potential adverse consequences, as targeted psychotherapy and psychosocial management have proven efficacy. In the context of several shared elements, the complex phenomenological differences between the two disorders will emerge with greater clarity as they are examined in this paper (Berk et al., 2004). It would seem helpful to begin by reflecting upon what might be considered the ‘core’ elements of each group of disorders. Meares et al. (2011a) used factor analysis to define four core elements for borderline personality disorder: ‘painful incoherence’ (highly intense emotional pain reflecting a fragmented sense of self; the most significant factor); ‘role absorption’ (loss of identity); ‘inconsistency’; and ‘lack of commitment’ (the least significant factor) (Meares et al., 2011a). Although other significant features of borderline personality disorder such as a fear of abandonment, impulsivity, recurrent self-injurious behaviour, affective instability (rapidly fluctuating moods provoked by life events), episodic explosive rage and episodic psychotic phenomena were clearly significant, they were not regarded as ‘core’ features. Previous factor analyses identified disturbed relatedness (identity disturbance, chronic perceptions of internal emptiness, unstable relationships), behavioural dysregulation (self-injurious behaviour, impulsivity) and Australian & New Zealand Journal of Psychiatry, 46(4) ANZJP Articles affective dysregulation (inappropriate anger, efforts to avoid abandonment, affective instability) as the three prime features of borderline personality disorder (Clifton and Pilkonis, 2007). Significantly, Clifton and Pilkonis (2007) established that these latter factors correlated so highly together that they statistically reflected one comprehensive construct. It would be helpful to identify that construct in a clinically meaningful way. Like Meares et al. (2011a), I suggest that an ‘emotionally noxious sense of self” (an emotionally painful disruption of self-identity, a recurring fear of abandonment and chronic emptiness) is that core entity. Zanarini et al. (2007) argue for a similar concept, and also suggest that the interaction of this core element with a ‘kindling’ life event converts this predisposition into a clinical syndrome. However, Trull et al. (2011), in their discussion of the proposed diagnostic criteria for DSM-V, maintain that there is no single ‘latent’ group identity for borderline personality disorder and therefore a categorical diagnostic structure is unsatisfactory. Instead, they argue for a combination of the dimensions of clinical signs and symptoms derived from factor analyses, combined with the core features of affective dysregulation, impulsivity, and interpersonal hypersensitivity. This seems consistent with the notion of a fundamental core element of a noxious sense of self. Young et al. (2003), and Kellogg and Young (2006), have formulated the core elements of borderline personality disorder using a schema-based model. They describe these core schema elements as five modes which reflect the impact of childhood traumatic experiences: (1) ‘the abandoned and abused child’: fear of isolation and abandonment; (2) ‘the angry and impulsive child’: rage over perceived abuse, deprivation, rejection, subjugation and punishment; (3) ‘the detached protector’: emotional withdrawal, disconnection, isolation and behavioural avoidance; (4) ‘the punitive parent’: identification with a devaluing and rejecting parent; and (5) ‘the healthy adult mode’: the least common mode which allows the patient to meet essential needs and to seek containment of the recurring emotional pain. Their formulation is largely consistent with those described above, although they do not place emphasis upon self-observation and evaluation. However, their model has the added value of constructing a framework for a cognitive approach to psychotherapy. Bipolar disorder would seem to have a very different nature when the fundamental features of this disorder are considered. These consist of elements of depressive disorder (dysphoric mood, anhedonia, psychomotor disorder) and elements of mania (unusually and significantly increased energy evident in several forms, impaired judgement with disinhibition, unusually elevated or irritable mood), with subjective experiences linked to these elements (emotional emptiness, irrational guilt, suicidal thoughts, grandiose thoughts, elevated or depressed mood, increased creativity or impaired cognitive function, and a 329 Bassett number of other features) (Hosokawa et al., 2009; Parker, 2000, 2009; Parker et al., 2006). Importantly, disruption of a sense of self and an incapacity to maintain mutually satisfying relationships with others are not core features of bipolar disorder. As a consequence, the approach to effective psychotherapy for bipolar disorder is different to that for borderline personality disorder (Basco and Rush, 2005; Goodwin and Jamison, 2007d; Kellogg and Young, 2006; Linehan, 1993). Matters of difference Mania and hypomania in various ways define bipolarity, but some uncertainty arises when the milder forms of mania, such as those seen in cyclothymia, are considered (Akiskal and Benazzi, 2006; Alloy et al., 2011; Diagnostic and Statistical Manual of Mental Disorders, 2000; Goodwin and Jamison, 2007e; International Classification of Mental and Behaviour Disorders, 1994; Phelps, 2009; Smith et al., 2005). Perugi et al. (2011) report evidence of cyclothymic temperament in patients diagnosed with bipolar disorder, borderline personality disorder and atypical major depressive disorder, although their criteria for cyclothymia were not clearly defined (Perugi et al., 2011). Further, they did not separate cyclothymia as a syndrome from cyclothymic temperament as an element of personality. Ghaemi et al. (2004) maintain that cyclical patterns of mood shifts are a common element of bipolar disorder, recurrent major depressive disorder and atypical major depressive disorder, but that atypical depressive features and early onset are more common in bipolar disorder. The absence of mania in major depressive disorder and atypical major depressive disorder would seem critically important, despite the cyclical nature of their symptom profiles. As noted previously, a family history of major mood disorders helps to reinforce the diagnosis of a bipolar disorder (Galione and Zimmerman, 2010; Ghaemi et al., 2004; Mitchell et al., 2008; Souery et al., 2012), and the life trajectories of disabling symptoms of bipolar disorder tend to be more prolonged than with borderline personality disorder (Paris, 2004; Paris et al., 2007). However, both disorders are associated with a significant incidence of childhood trauma (approximately 50% in bipolar disorder and 60–80% in borderline personality disorder) (Alvarez et al., 2011; Ball and Links, 2009; Conus et al., 2010; Etain et al., 2008; Fowke et al., 2011; Garno et al., 2005; Herman et al., 1989; Hyun et al., 2000), and early life trauma may play an aetiological role in both (Holmes, 2003; Joyce et al., 2003; Watson et al., 2006). Patients with bipolar disorders and borderline personality disorders may differ in the form of childhood trauma, or their vulnerability to such trauma, but the possible details of such differences remain uncertain. Mackinnon and Pies (2006) offer support for the notion that rapid cycling of mood states is a common element of both bipolar and borderline states. The suggestion has some clinical support but appears inconsistent with the nonaffective components, as well as the details of affective disruptions discussed later, observed in both disorders. Self-mutilation has been observed with similar frequency in both bipolar disorder, particularly mixed states (Joyce et al., 2010), and borderline personality disorder. Therefore, such self-injury does not distinguish these disorders diagnostically. The separation of bipolar disorder and borderline personality disorder must then be achieved with criteria other than the presence of affective dysregulation and cyclicity of symptoms and signs alone. Importantly, however, the time course of the cyclicity is helpful: the presence of discrete, prolonged periods of affective symptoms, as opposed to rapidly shifting states, does suggest a bipolar diagnosis. Differences have also been identified in thinking styles between bipolar and borderline patients, with implications for their emotional health and relationship quality. Wupperman et al. (2009) identified significant deficiencies in mindfulness (attention, awareness and acceptance of the moment) in patients with borderline personality disorder. These included reduced interpersonal effectiveness, as well as passive and impulsive emotion regulation, even when they controlled for neuroticism. Nilsson et al. (2010), using the Temperament Evaluation of Memphis, Pisa, Paris and San Diego Autoquestionnaire, and the Young Schema Questionnaire, found that bipolar patients exhibited a higher level of maladaptive schemas and affective temperaments compared with controls. In contrast, borderline patients exhibited a higher level of cyclothymic temperament and reduced self-control. Quantitative clinical studies There have been numerous attempts to quantify the similarities and differences between bipolar disorder and borderline personality disorder, as well as their comorbidity (Paris et al., 2007). Perugi et al. (2011) studied a population of patients diagnosed with atypical major depressive disorder, 32% of whom they subsequently found could be diagnosed with bipolar disorder (24% without antidepressant-induced bipolarity and increased to 78% if hyperthymia or cyclothymic temperaments were considered indicative of bipolarity). When these atypically depressed patients were divided into those who also suffered from borderline personality disorder (42%), the only significant differences in demographic and a range of clinical features were shorter durations of the current illness and a higher rate of suicide attempts. The presence of bipolar features, however, defined in their study, did not identify comorbid borderline personality disorder in these atypical major depressive disorder patients. Galione and Zimmerman (2010) examined the clinical features of patients suffering depressive disorders (unipolar and bipolar), both with and without comorbid borderline Australian & New Zealand Journal of Psychiatry, 46(4) 330 ANZJP Articles Table 1. Significant differences between borderline personality disorder and bipolar disorder. Borderline personality disorder Bipolar disorder Altered sense of self No altered sense of self Relationships severely disrupted Relationships not as severely disrupted No family history of bipolar disorder Family history of bipolar disorder Increased glucocorticoid receptor sensitivity Reduced glucocorticoid receptor sensitivity Mood stabilizers modestly effective Mood stabilizers very effective Atypical antipsychotics modestly effective Atypical antipsychotics very effective Cognitive deficits less severe Cognitive deficits more severe Affective dysregulation between anger and depression prominent Affective dysregulation between euphoria and depression prominent Higher incidence of suicide attempts Higher incidence of completed suicide Very rapid mood cycling Less rapid mood cycling Early sexual abuse prominent Early sexual abuse not prominent Limited loss of gray matter More loss of gray matter Limited loss of white matter More loss of white matter Alterations of insula activity Uncertain changes in insula activity No changes in dorsolateral or dorsomedial prefrontal cortices Reduced activity of dorsolateral and dorsomedial prefrontal cortices No changes in cuneus and lingual Reduced activity of cuneus and lingual gyri No mitochondrial dysfunction Mitochondrial dysfunction Psychosis – non-specific features and sometimes persistent long-term Psychosis – most often linked to affective state and not persistent long-term personality disorder. They found the following differences when depressive disorders were comorbid with borderline personality disorder: earlier age of onset of depressive symptoms, greater frequency of depressive episodes, greater frequency of ‘atypical’ depressive symptoms, higher prevalence of comorbid anxiety disorders and substance abuse, and a greater number of suicide attempts. They also found that a history of bipolar disorder in first-degree relatives was not significantly associated with the presence of borderline personality disorder. They concluded that overall their data did not support the inclusion of borderline personality disorder as a component of the bipolar spectrum. On the other hand, it is interesting that Mitchell et al. (2008) found that the probability of a depressive disorder being part of a bipolar disorder was increased by the presence of features of atypical major depressive disorder, an earlier age of onset of first depressive episode, a history of multiple and shorter depressive episodes, and/or a family history of bipolar disorder. While there is overlap in their findings with the probability of borderline personality Australian & New Zealand Journal of Psychiatry, 46(4) disorder being present, the family history of bipolar disorder is again a prominent distinguishing feature. Paris et al. (2007), in their review of the bipolar disorder/borderline personality disorder interface, also concluded that bipolar disorder and borderline personality disorder were most likely separate disorders. Specifically, they found that while episodes of mania in bipolar disorder contrasted with more affective instability in borderline personality disorder, there was a significantly higher frequency of bipolar disorder in first-degree relatives of bipolar disorder patients, the benefits of mood stabilizers were more predictable in bipolar disorder than borderline personality disorder, and the prognosis for borderline personality disorder was generally better than for bipolar disorder. They also reviewed the relative incidence of borderline personality disorder and bipolar disorder comorbidity in several studies (Paris et al., 2007). They record that after combining the data, the median incidence of bipolar disorder-I in patients with borderline personality disorder was 9%. Similarly, the median incidence of bipolar disorder-II in patients with 331 Bassett Table 2. Similarities between borderline personality disorder and bipolar disorder. Affective dysregulation – non-specific Atypical depressive features more common than in major depressive disorder Self-mutilation common High heritability Transporter polymorphisms relevant Possible genetic linkage Fronto-limbic dysregulation: reduced modulation of limbic activity Reduced hippocampal size Increased activity of the amygdale Reduced size of the corpus callosum Low comorbidity between bipolar disorder and borderline personality disorder Early life trauma significant Some common sleep disruption Psychotic symptoms may arise borderline personality disorder was 11%. Cyclothymia was identified in 22% of patients with borderline personality disorder, but only one study was cited (Levitt et al., 1990). Conversely, borderline personality disorder was identified in 11% of patients with bipolar disorder-I and 16% of those with bipolar disorder-II. Perugi et al. (2003) found borderline personality disorder in 62% of patients with atypical major depressive disorder and cyclothymic temperament. These low rates of overlap argue in favour of the disorders being discrete entities. Henry et al. (2001) found that while affective instability was evident in both bipolar disorder and borderline personality disorder, there were important differences. Significantly, the instability seen in bipolar disorder was more often between euthymia and depression, euthymia and elation, or depression and elation. In contrast, the lability seen in borderline personality disorder was more often between euthymia and anger. Indeed, there is an increasing consensus that the high ranking of irritability in the DSM-IV criteria for bipolar disorder is a problem, and this is likely to be amended in the DSM-V system (Ghaemi et al., 2008). Benazzi (2006), using a measure of personality factors, found borderline personality traits were significantly more common in bipolar disorder-II than in major depressive disorder. However, while the ‘affective instability’ factor did not separate bipolar disorder and borderline personality disorder, the ‘impulsivity’ factor was significantly more common in borderline personality disorder compared with bipolar disorder. Other personality disorders were also identified in patients with bipolar disorder, with histrionic personality disorder being the most common co-morbid subtype. Yen et al. (2002) found that in women with borderline personality disorder, the level of affect intensity and affect control were significantly associated with the number of borderline traits. Both affect intensity (raised) and affect control (reduced) remained significant in association, even when controlled for depression. Affect control remained significant, even when controlled for affect intensity. Reich et al. (2011) found several significant differences in affective lability between bipolar and borderline disorders. Bipolar patients exhibited higher scores on the EuthymiaElation subscale of the Affective Lability Scale (ALS), as well as higher total scores using the Affect Intensity Measure. The latter scale also revealed higher Positive Emotion subscale scores in this group. In contrast, borderline personality disorder patients scored more highly on the AnxietyDepression subscale of the ALS. They also found that, using the Affective Lability Interview for Borderline Personality Disorder Scale, borderline patients exhibited more frequent shifts between euthymia and anxiety, anger and depression, as well as depression and anxiety. Becerra is currently conducting the first known study measuring emotional dysregulation using the Difficulties with Emotion Regulation Scale in patients with bipolar disorder. His preliminary data reveal a current mean score of 90 (maximum possible = 180) (Becerra R, 2011, unpublished data). This can be compared to a mean score of 126 in patients with borderline personality disorder (Gratz et al., 2006) and a mean of 80 in college students (Gratz and Roemer, 2004). While sufficient data is not yet available to permit a statistical analysis, the trend is toward a difference in scores between bipolar and borderline patients. Altamura et al. (2011) reported lower rates of comorbidity of bipolar disorder and borderline personality disorder than, for example, of panic disorder, substance abuse and attention deficit hyperactivity disorder. Similarly, comorbidity of both disorders has been identified with atypical major depressive disorder and major depressive disorder. A family history of bipolar disorder tends to be more prominent in patients with bipolar disorder than borderline personality disorder. While affective dysregulation can be identified in both disorders, there appear to be qualitative as well as quantitative differences. Finally, similar forms of cognitive deficits can be identified in both disorders, but the severity tends to be greater in bipolar disorder. Subtypes of bipolar disorder The current DSM-IV and ICD-10 descriptions of criteria for bipolar disorder-I, bipolar disorder-II, and cyclothymia (with the added variants of mixed affective episodes, rapid Australian & New Zealand Journal of Psychiatry, 46(4) 332 cycling, psychotic affective symptoms and schizoaffective disorder), contain essentially the same criteria for manic and depressed episodes, separated only by severity and duration of episodes. This is a clumsy and largely meaningless exercise, in which arbitrary criteria of duration are cited and severity remains a subjective evaluation by the observer. Only the variants of mixed affective episodes, rapid cycling and affective psychosis can be said to have further objectivity, and even then the frequency of episodes to identify ‘rapid cycling’ is itself arbitrary. Indeed, the decision to admit to a hospital, with all its significant non-clinical variables, is regarded by many as an inappropriate criterion for separating bipolar disorder-I from bipolar disorder-II (Akiskal and Benazzi, 2006). The presence of affective psychosis is not even given its own separate subtype in current classifications, although clinically these bipolar disorder-I patients suffer from a particularly destructive illness and there may be significant differences in the nature of this form of bipolar disorder. Cyclothymia is a useful, valid, but heterogeneous clinical entity (Akiskal and Benazzi, 2006; Akiskal et al., 2000; Howland and Thase, 1993). While cyclothymia can be considered a personality trait or temperament, it can also be defined as a form of bipolar disorder (DSM-IV and ICD10). It is usefully considered as a disorder which includes a range of bipolar signs and symptoms (Phelps, 2009), but the manic features are of a severity which is only spontaneously evident to ‘significant others’ (such as family or friends), and often evident to the patient only through reflection. While many observers may notice various emotional, cognitive and behavioural features consistent with bipolar disorders, they will frequently consider these to be personality traits, and not recognise their significantly disabling quality. This may rely on a less than precise definition of ‘significant others’, but it carries at least some objectivity. Patients rarely present with well-manicured illness syndromes and the interplay of significant bipolar features and numerous other disorders is considerable. In clinical practice, cyclothymia is diagnosed largely by historical review, collateral information from family and friends, current observation and self-report. Many patients suffering from cyclothymia are not spontaneously aware that their experience of pressured thoughts, fluctuating moods, bursts of expansive thinking, periods of heightened libido and significant fluctuations in sleeping habits, for example, are components of an illness. Yet these patients are usually well aware of the adverse consequences of their disorder, and are often perplexed by their own behaviour and internal experiences. The intrusion of personality disorders (defined by the persistence of major disruption of the experience of self and interpersonal relationships), and a variety of other psychological disorders (such as anxiety disorders, eating disorders, attention deficit disorders and substance abuse), only obfuscate our understanding of bipolarity if included Australian & New Zealand Journal of Psychiatry, 46(4) ANZJP Articles under the umbrella of bipolar spectrum disorders. It is more parsimonious to consider these as comorbid disorders, rather than forme frustes of bipolar disorders. Neuropsychological studies Neuropsychological studies have revealed deficits in cognitive function in both borderline personality disorder and euthymic bipolar disorder. The most prominent common features are defects in verbal learning and memory, and subtle impairment of executive functions have also been identified in both borderline personality disorder and bipolar disorder (Kurtz and Gerraty, 2009; Ruocco, 2005). However, Mann-Wrobel et al. (2011) report that the cognitive changes in bipolar disorder tend to be ‘generalized’ (evident in more brain regions) and potentially involve any cognitive functions. The precise deficits are modified by numerous illness and age-related factors. Only ‘crystallized’ verbal functions appeared relatively spared in their analysis. The severity of deficits from all of these studies tends to be greater in bipolar disorders and less generalized in borderline personality disorder (Kurtz and Gerraty, 2009; Ruocco, 2005). Genetics In 2000, Torgersen et al. (2000) reported a twin study of personality disorders, in which borderline personality disorder was revealed to be associated with a level of heritability of 0.7 (or 70%), consistent with measures of heritability in other personality disorders in that study. However, in 2008, he and his colleagues (Torgersen et al., 2008) reported a study of cluster B personality disorders, revealing a measure of heritability for borderline personality disorder traits of 0.35 (35%). Heritability in borderline personality disorder has been variously found in a number of studies to be between 0.35 and 0.8 (Torgersen et al., 2000, 2008). Kendler et al. (2011) also found significantly heritable personality traits in a large genetic study of personality disorders in general. Heritability in bipolar disorder has been estimated to be between 0.68 and 0.80 (Goodwin and Jamison, 2007a). Familial coaggregation of borderline personality disorder and bipolar disorder has been identified, but similar coaggregation has been identified with other mood disorders (major depressive disorder and atypical major depressive disorder) as well as anxiety disorders, somatoform disorders and substance abuse (Zanarini et al., 2009). More rigorous measures of genetic linkage between bipolar disorders and borderline personality disorder have not yet been employed. The serotonin transporter gene ‘short’ polymorphism has been found to be significantly associated with both borderline personality disorder (Maurex et al., 2010; Wagner et al., 2009) and bipolar disorder (Daray Bassett et al., 2010; Levinson, 2006), but the associations are not strong. Joyce et al. (2006) found a significant association between the 9-repeat allele of the DAT1 dopamine transporter gene and borderline personality disorder. This association persisted when relevant developmental factors (childhood abuse or neglect, borderline temperament) were controlled. The association was larger in older patients, suggesting a possibly greater significance in ‘poorer prognosis’ patients. Nemoda et al. (2010) present similar evidence of an association between dopamine transporter polymorphisms and borderline personality disorder. However, dopamine transporter polymorphisms appear significant in bipolar disorders as well (Pinsonneault et al., 2011). The similarities and differences remain uncertain. Neurobiology While reduced suppression of corticotrophic releasing hormone production by dexamethasone (using the Dexamethasone Suppression Test) has been well observed in depressive disorders (unipolar and bipolar), increased suppression has been observed in borderline personality disorder (Carrasco et al., 2007; Goodman et al., 2010; Zimmerman and Choi-Kain, 2009). Post-traumatic stress disorder has also been associated with increased suppression, but the presence or absence of this disorder did not alter the findings in these studies. There may be a similar reduction in blunting of the suppression of thyrotropinreleasing hormone (thyroliberin) production by thyroxine in borderline personality disorder (Carrasco et al., 2007). Decreased serotonergic responsivity and increased cholinergic responsivity have been observed in borderline personality disorder and major depressive disorder, with suggestions that a similar pattern may be the case in bipolar disorder (Goodman et al., 2010). Sleep architecture in borderline personality disorder is associated with a longer duration of rapid eye movement sleep, less slow-wave sleep and more stage 2 sleep than in major depressive disorder or healthy controls (De La Fuente et al., 2001, 2004). Similar disruptions of sleep architecture have been observed in bipolar disorder (Goodwin and Jamison, 2007e; Srinivasan et al., 2009), but more detailed research is required to clarify the similarities and differences which may be present in these two groups of disorders. Hallahan et al. (2011) performed a very thorough megaanalysis of morphometric MRI studies in bipolar disorder and found evidence of increases in the volumes of the right lateral ventricle, left temporal lobe and right putamen, while a reduced size of right and left amygdalae and hippocampi have been observed in borderline personality disorder (Nunes et al., 2009). Previous studies in bipolar disorders found inconsistent evidence of changes in the volumes of the third ventricle, subgenual prefrontal cortex, hippocampal/amygdala complex, thalamus and caudate 333 (Mcdonald et al., 2004). There is some evidence that adolescent females with borderline personality disorder may have reductions in dorsolateral prefrontal cortex and orbitofrontal gray matter, but the separation from healthy adolescent subjects is uncertain (Brunner et al., 2010). Disruption of white matter integrity has been the subject of attention, with abnormalities detected in the internal capsules and adjacent areas of the striatum, thalamus and frontal white matter in bipolar spectrum disorders (Haznedar et al., 2005). Benedetti et al. (2011) found structural white matter injury in the pathways between the amygdala and a variety of regions, including the cingulate gyri (subgenual, anterior and posterior), the parahippocampal gyri, the orbitofrontal cortex and the dorsolateral prefrontal cortex, in patients with bipolar disorder. Of further interest, disruption of white matter integrity has been detected in the internal capsules and left temporal regions of unaffected first-degree relatives of patients with bipolar disorder (Sprooten et al., 2011). Altered white matter integrity in the inferior frontal lobes has also been described in females with borderline personality disorder and a history of self-injury (Grant et al., 2007). The significance and consistency of white matter changes are uncertain and await further clarification in both bipolar and borderline personality disorders. Bandelow et al. (2010) suggest that many features of borderline personality disorder could potentially be explained as consequences of endogenous opioid dysfunction. These features include attention-seeking behaviours, over-activation of reward pathways with fear of abandonment, anhedonia and subjective emptiness as consequences of endogenous opioid deprivation and self-injury as an attempt to activate endogenous opioid function. They argue that the benefits of opioid receptor antagonists for self-injurious behaviour is supportive of their hypothesis. Unfortunately, the supportive evidence appears scant and confirmation of their hypothesis is lacking at this time. Vollm et al. (2004) found that, using a Go/No Go task in borderline personality disorder and antisocial personality disorder patients, metabolic activation measured by Functional Magnetic Resonance Imaging (fMRI) was distributed across the medial, superior and inferior frontal gyri extending to the anterior cingulate. This contrasted with healthy controls whose activation was mainly limited to the prefrontal cortex. Schulze et al. (2011) used fMRI to examine differences in metabolic activity associated with emotional reactivity in female patients with borderline personality disorder and healthy controls during a delayed reappraisal paradigm using aversive pictures and cognitive reappraisal strategies. They found that borderline personality disorder patients exhibited enhanced emotional reactivity as well as deficits in voluntarily reducing aversive emotions by cognitive reappraisal. Reviews by Mauchnik and Schmahl (2010) for borderline personality disorder, and Kupferschmidt and Zakzanis (2011), as well as Chen et al. (2011) for bipolar disorders, Australian & New Zealand Journal of Psychiatry, 46(4) 334 examined the neuroimaging research for both of these disorders. They note reports of reduced hippocampal and corpus callosum size in both borderline and bipolar patients, increased size of the amygdala in borderline patients, but inconsistent reports of alteration in the size of the amygdala in bipolar patients. In addition, they report reduced size of gray matter in the rostral and ventral regions of the anterior cingulate gyri in borderline patients, but no consistent reports of change in the anterior cingulate size of bipolar patients. Amygdala activity (measured by fMRI or Positron Emission Tomography scans) was reported to be increased in both borderline and bipolar patients, while hippocampal activity has been variously altered in bipolar patients. Activity of the anterior cingulate gyri and insular cortices were reportedly increased in borderline patients, but the reports of altered activity in these regions in bipolar patients have not been consistent. The reported failure of the activity of the insular cortices to increase when under emotional stress in borderline patients is of interest given their difficulty regulating emotional responses to such challenges. Bipolar patients have been reported to show reduced activity in the dorsolateral prefrontal cortices, the dorsomedial prefrontal cortices, the orbitofrontal cortices, the inferior frontal cortices and in the cuneus as well as lingual gyri. These changes in activity are of interest, given the evidence of fronto-limbic dysregulation and dorsoventral dysregulation in bipolar patients. The precise nature of morphological and metabolic changes in the brains of patients with bipolar and borderline personality disorders remains clouded by clinical heterogeneity, variations in technical assessment and the complexity of the neurobiology in these disorders. The physiological response to facially expressed emotion, as measured by cerebral blood flow, has been studied in both bipolar disorder and borderline personality disorder. The findings reveal complex variations related to the nature of the expressed emotion, but possible differences between bipolar disorder and borderline personality disorder were difficult to define (Minzenberg et al., 2007; Wessa and Linke, 2009). Meares et al. (2011b) report neurophysiological evidence of reduced inhibitory activity in the right hemisphere from fronto-medial structures in borderline personality disorder. However, similar defects in evoked potentials have been observed in bipolar disorder and schizophrenia, and may represent a marker of a broad neurophysiological dysfunction (Bestelmeyer et al., 2009). Indeed, one of the difficulties of biological markers in general is their broad failure to respect our current diagnostic systems. This is not really a surprise, since in no other branch of medicine does phenomenology accurately reflect pathophysiology. Importantly, however, all of these studies have provided further evidence of fronto-limbic dysregulation in both bipolar disorder and borderline personality disorder, compared with healthy controls. Australian & New Zealand Journal of Psychiatry, 46(4) ANZJP Articles The finding that the sensitivity of glucocorticoid receptors is reduced in bipolar disorder and increased in borderline personality disorder is of considerable interest, as it suggests a major separation in the neuroendocrine response to stress (Goodwin and Jamison, 2007c; Zimmerman and Choi-Kain, 2009). There is also some evidence that there may be reduced responsivity in serotonergic and acetylcholinergic circuits in both disorders. Altered function of endogenous opioid systems is a tempting hypothesis for some features of borderline personality disorder but is poorly supported. Dysregulation of neural circuits in the prefrontal regions, with disruption of some executive cognitive functions and reduced modulation by fronto-limbic pathways, appears supported in borderline personality disorder and in bipolar disorder (Berdahl, 2010). The differences in both structural and functional activity of neural circuits in both disorders remain uncertain, but exhibit similarities to changes in mental state and interpersonal functions. Andreazza et al. (2010) and Berk et al. (2011) note the significance of mitochondrial dysfunction in bipolar disorders, with likely relevance to the disruption of energy evident in the clinical states of these disorders. There are no reports of mitochondrial dysfunction in borderline personality disorders. Pharmacology It is evident that antidepressants, anticonvulsant-mood stabilizers and atypical antipsychotic medications have value in the management of both bipolar disorder and borderline personality disorder. However, the benefits in bipolar disorder appear significantly more prominent than in borderline personality disorder, and their use in the latter remains limited (Ripoll et al., 2011). Given the broad utility of antidepressants, antipsychotics and anticonvulsants across a wide range of disorders, treatment response does not appear to have diagnostic implications. The only exception appears to be lithium, which does not show efficacy in non-affective psychoses nor display clear utility in personality disorders (Bellino et al., 2008). Clinical observations Clinical observation and documentation by many clinicians suggest that borderline personality disorder is associated with an emotionally painful disruption of the sense of self, as well as rapidly changing affective instability, high impulsivity and a pattern of severely unsatisfactory interpersonal relationships (Meares et al., 2011a, 2011b; Paris et al., 2007). Bipolar disorder is much less commonly associated with such disruption of self-experience, and is less often associated with high impulsivity and repeatedly unsatisfactory relationships. Patients with bipolar disorder are more often observed to have a positive family history of bipolar 335 Bassett disorder, and their experience of affective instability is characterised by less rapid changes and less reactivity to environmental events than patients with borderline personality disorder. Psychosis can arise in both bipolar disorder and borderline personality disorder. The form of psychosis in bipolar disorder is most frequently mood congruent, but mood incongruent psychotic phenomena can arise. The psychotic episodes are almost always limited in duration and rarely extend beyond several months (Goodwin and Jamison, 2007b). The content of the psychotic episodes is usually dominated by delusional thinking, but a variety of perceptual disorders are common and severe disorganisation (delirious mania and catatonia) may develop (Goodwin and Jamison, 2007b). Psychotic phenomena in borderline personality disorder are less consistent in content, may be linked to early life trauma, and may persist for many years. However, severe psychotic disorganization is rare and usually very brief (mainly hours) (Adams and Sanders, 2011; Barnow et al., 2010). Acute psychiatric illness of many forms can test underlying personality structures, and the temporary emergence of behaviours suggestive of underlying personality disorder is common. During episodes of acute illness, patients with bipolar disorder (particularly mixed states) sometimes exhibit prominent affective instability, high impulsivity, self-injury, manipulative interpersonal behaviour and explosive rage. This may lead to an incorrect diagnosis of borderline personality disorder. Tiller has named this phenomenon ‘state borderline’ (Tiller J, 2002, personal communication). Longitudinal observation of the patient through historical assessment and personal observation by therapists is vitally important for accurate diagnosis. These observations chime with experience. Conclusions While bipolar disorder and borderline personality disorder have many clinical and biological features in common, the evidence suggests that they remain essentially distinct entities which may occur together or separately (see Tables 1 and 2). They share some elements of psychopathology and pathophysiology, but their differences are more significant. Acknowledgements I am indebted to several colleagues, who have given very generously of their time and expertise to critically comment upon the preparation of this paper. Professors Michael Berk and Sean Hood have been of considerable assistance. My good friends Drs Robert Segal and Nick de Felice have also provided invaluable comment. Dr Sherylee Bassett has given expert advice, assisted generously with literature searches, provided professional editing and tireless devotion to the quality of presentation. Their contributions are gratefully acknowledged. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Declaration of interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. References Adams B and Sanders T (2011) Experiences of psychosis in borderline personality disorder: A qualitative analysis. Journal of Mental Health 20: 381–391. Adams F (1972) Digital Hippocrates: the extant works of Aretaeus the Cappadocian: On the causes and symptoms of chronic disease. Chapter vi. On madness. Boston, MA: Milford House Inc., 1972 (republication of the 1856 edition). Available at: www.chlt.org/sandbox/dh/aretaeusEnglish/page.55.a.php (accessed 19 April 2011). Akiskal HS and Benazzi F (2006) The DSM-IV and ICD-10 categories of recurrent [major] depressive and bipolar ii disorders: Evidence that they lie on a dimensional spectrum. Journal of Affective Disorders 92: 45–54. Akiskal HS, Bourgeois ML, Angst J, et al. (2000) Re-evaluating the prevalence of and diagnostic composition within the broad clinical spectrum of bipolar disorders. Journal of Affective Disorders 59(suppl 1): S5–S30. Alloy LB, Urošević S, Abramson LY, et al. (2011) Progression along the bipolar spectrum: A longitudinal study of predictors of conversion from bipolar spectrum conditions to bipolar I and II disorders. Journal of Abnormal Psychology, Epub ahead of print 13 Jun 2011. Altamura AC, Serati M, Albano A, et al. (2011) An epidemiologic and clinical overview of medical and psychopathological comorbidities in major psychoses. European Archives of Psychiatry and Clinical Neuroscience 261: 489–508. Alvarez MJ, Roura P, Oses A, et al. (2011) Prevalence and clinical impact of childhood trauma in patients with severe mental disorders. Journal of Nervous and Mental Disease 199: 156–161. Andreazza AC, Shao L, Wang JF, et al. (2010) Mitochondrial complex I activity and oxidative damage to mitochondrial proteins in the prefrontal cortex of patients with bipolar disorder. Archives of General Psychiatry 67: 360–368. Aviram RB, Brodsky BS and Stanley B (2006) Borderline personality disorder, stigma, and treatment implications. Harvard Review of Psychiatry 14: 249–256. Baethge C, Salvatore P and Baldessarini RJ (2003) Cyclothymia, a circular mood disorder. History of Psychiatry 14: 377–399. Ball JS and Links PS (2009) Borderline personality disorder and childhood trauma: Evidence for a causal relationship. Current Psychiatry Reports 11: 63–68. Bandelow B, Schmahl C, Falkai P, et al. (2010) Borderline personality disorder: A dysregulation of the endogenous opioid system? Psychological Review 117: 623–636. Barnow S, Arens EA, Sieswerda S, et al. (2010) Borderline personality disorder and psychosis: A review. Current Psychiatry Reports 12: 186–195. Australian & New Zealand Journal of Psychiatry, 46(4) 336 Basco M and Rush A (2005) Cognitive-Behavioural Therapy for Bipolar Disorder. New York: The Guildford Press. Bellino S, Paradiso E and Bogetto F (2008) Efficacy and tolerability of pharmacotherapies for borderline personality disorder. CNS Drugs 22: 671–692. Benazzi F (2000) Borderline personality disorder and bipolar II disorder in private practice depressed outpatients. Comprehensive Psychiatry 41: 106–110. Benazzi F (2006) Borderline personality-bipolar spectrum relationship. Progress in Neuro-psychopharmacology and Biological Psychiatry 30: 68–74. Benazzi F (2008) A relationship between bipolar II disorder and borderline personality disorder? Progress in Neuropsychopharmacology and Biological Psychiatry 32: 1022– 1029. Benazzi F (2009) Cyclothymic temperament: The impact of age. Psychopathology 42: 165–169. Benedetti F, Absinta M, Rocca MA, et al. (2011) Tract-specific white matter structural disruption in patients with bipolar disorder. Bipolar Disorders 13: 414–424. Berdahl CH (2010) A neural network model of borderline personality disorder. Neural Networks 23: 177–188. Berk M, Berk L and Castle D (2004) A collaborative approach to the treatment alliance in bipolar disorder. Bipolar Disorders 6: 504–518. Berk M, Conus P, Kapczinski F, et al. (2010a) From neuroprogression to neuroprotection: Implications for clinical care. Medical Journal of Australia 193: S36–40. Berk M, Hallam K, Malhi GS, et al. (2010b) Evidence and implications for early intervention in bipolar disorder. Journal of Mental Health 19: 113–126. Berk M, Kapczinski F, Andreazza AC, et al. (2011) Pathways underlying neuroprogression in bipolar disorder: Focus on inflammation, oxidative stress and neurotrophic factors. Neuroscience and Biobehavioral Reviews 35: 804–817. Berk M, Malhi GS, Hallam K, et al. (2009) Early intervention in bipolar disorders: Clinical, biochemical and neuroimaging imperatives. Journal of Affective Disorders 114: 1–13. Bestelmeyer PE, Phillips LH, Crombie C, et al. (2009) The p300 as a possible endophenotype for schizophrenia and bipolar disorder: Evidence from twin and patient studies. Psychiatry Research 169: 212–219. Boyce P and Wilson F (2011) Bipolar disorder, borderline personality disorder or both? Medicine Today 12: 28–36. Brieger P and Marneros A (1997) Dysthymia and cyclothymia: Historical origins and contemporary development. Journal of Affective Disorders 45: 117–126. Brunner R, Henze R, Parzer P, et al. (2010) Reduced prefrontal and orbitofrontal gray matter in female adolescents with borderline personality disorder: Is it disorder specific? Neuroimage 49: 114–120. Carrasco JL, Diaz-Marsa M, Pastrana JI, et al. (2007) Hypothalamic-pituitary-adrenal axis response in borderline personality disorder without post-traumatic features. British Journal of Psychiatry 190: 357–358. Chen CH, Suckling J, Lennox BR, et al. (2011) A quantitative meta-analysis of fMRI studies in bipolar disorder. Bipolar Disorders 13: 1–15. Chilakamarri JK, Filkowski MM and Ghaemi SN (2011) Misdiagnosis of bipolar disorder in children and adolescents: Australian & New Zealand Journal of Psychiatry, 46(4) ANZJP Articles A comparison with ADHD and major depressive disorder. Annals of Clinical Psychiatry 23: 25–29. Clifton A and Pilkonis PA (2007) Evidence for a single latent class of diagnostic and statistical manual of mental disorders borderline personality pathology. Comprehensive Psychiatry 48: 70–78. Conus P, Cotton S, Schimmelmann BG, et al. (2010) Pretreatment and outcome correlates of past sexual and physical trauma in 118 bipolar I disorder patients with a first episode of psychotic mania. Bipolar Disorders 12: 244–252. Cooper JE (1994) International Classification of Mental and Behaviour Disorders Geneva: World Health Organization and London: Churchill Livingstone. Daray FM, Thommi SB and Ghaemi SN (2010) The pharmacogenetics of antidepressant-induced mania: A systematic review and meta-analysis. Bipolar Disorders 12: 702–706. De La Fuente JM, Bobes J, Morlan I, et al. (2004) Is the biological nature of depressive symptoms in borderline patients without concomitant Axis I pathology idiosyncratic? Sleep EEG comparison with recurrent brief, major depression and control subjects. Psychiatry Research 129: 65–73. De La Fuente JM, Bobes J, Vizuete C, et al. (2001) Sleep-EEG in borderline patients without concomitant major depression: A comparison with major depressives and normal control subjects. Psychiatry Research 105: 87–95. Etain B, Henry C, Bellivier F, et al. (2008) Beyond genetics: Childhood affective trauma in bipolar disorder. Bipolar Disorders 10: 867–876. Fowke A, Ross S and Ashcroft K (2011) Childhood maltreatment and internalized shame in adults with a diagnosis of bipolar disorder. Clinical Psychology and Psychotherapy Epub ahead of print 9 May 2011. DOI: 10.1002/cpp.752. Francis A (2000) Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Washington DC: American Psychiatric Association. Galione J and Zimmerman M (2010) A comparison of depressed patients with and without borderline personality disorder: Implications for interpreting studies of the validity of the bipolar spectrum. Journal of Personality Disorders 24: 763–772. Garno JL, Goldberg JF, Ramirez PM, et al. (2005) Impact of childhood abuse on the clinical course of bipolar disorder. British Journal of Psychiatry 186: 121–125. George EL, Miklowitz DJ, Richards JA, et al. (2003) The comorbidity of bipolar disorder and axis II personality disorders: Pre­valence and clinical correlates. Bipolar Disorders 5: 115–122. Ghaemi SN, Bauer M, Cassidy F, et al. (2008) Diagnostic guidelines for bipolar disorder: A summary of the International Society for Bipolar Disorders Diagnostic Guidelines Task Force Report. Bipolar Disorders 10: 117–128. Ghaemi SN, Hsu DJ, Ko JY, et al. (2004) Bipolar spectrum disorder: A pilot study. Psychopathology 37: 222–226. Goodman M, New AS, Triebwasser J, et al. (2010) Phenotype, endophenotype, and genotype comparisons between borderline personality disorder and major depressive disorder. Journal of Personality Disorders 24: 38–59. Goodwin F and Jamison K (2007a) Genetics. In: Goodwin FK and Jamison KR (eds) Manic-depressive Illness: Bipolar Disorders and Recurrent Depression, 2nd edition. New York: Oxford University Press, pp. 411–462. Bassett Goodwin FK and Jamison KR (2007b) Clinical description and diagnosis. In: Goodwin FK and Jamison KR (eds) Manic-depressive Illness: Bipolar Disorders and Recurrent Depression. New York: Oxford University Press, pp. 29–118. Goodwin FK and Jamison KR (2007c) Neurobiology. In: Goodwin FK and Jamison KR (eds) Manic-depressive Illness: Bipolar Disorders and Recurrent Depression, 2nd edition. New York: Oxford University Press, pp. 463–608. Goodwin FK and Jamison KR (2007d) Psychotherapy. In: Goodwin FK and Jamison KR (eds) Manic-depressive Illness: Bipolar Disorders and Recurrent Depression, 2nd edition. New York: Oxford University Press, pp. 869–906. Goodwin FK and Jamison KR (2007e) Sleep and circadian rhythms. In: Goodwin FK and Jamison KR (eds) Manic-depressive Illness: Bipolar Disorders and Recurrent Depression, 2nd edition. New York: Oxford University Press, pp. 659–698. Grant JE, Correia S, Brennan-Krohn T, et al. (2007) Frontal white matter integrity in borderline personality disorder with selfinjurious behavior. Journal of Neuropsychiatry and Clinical Neurosciences 19: 383–390. Gratz K and Roemer L (2004) Multidimensional assessment of emotion regulation and dysregulation: Development, factor structure, and initial validation of the difficulties in emotion regulation scale. Journal of Psychopathology and Behavioural Assessment 26: 41–54. Gratz KL, Rosenthal MZ, Tull MT, et al. (2006) An experimental investigation of emotion dysregulation in borderline personality disorder. Journal of Abnormal Psychology 115: 850–855. Hadjipavlou G and Yatham L (2009) Bipolar II disorder in context: Epidemiology, disability and economic burden. In: Parker G (ed) Bipolar II Disorder – Modelling, Measuring and Managing. Cambridge: Cambridge University Press, pp. 61–74. Hallahan B, Newell J, Soares JC, et al. (2011) Structural magnetic resonance imaging in bipolar disorder: An international collaborative mega-analysis of individual adult patient data. Biological Psychiatry 69: 326–335. Haznedar MM, Roversi F, Pallanti S, et al. (2005) Fronto-thalamostriatal gray and white matter volumes and anisotropy of their connections in bipolar spectrum illnesses. Biological Psychiatry 57: 733–742. Henry C, Mitropoulou V, New AS, et al. (2001) Affective instability and impulsivity in borderline personality and bipolar II disorders: Similarities and differences. Journal of Psychiatric Research 35: 307–312. Herman JL, Perry JC and Van Der Kolk BA (1989) Childhood trauma in borderline personality disorder. American Journal of Psychiatry 146: 490–495. Holmes J (2003) Borderline personality disorder and the search for meaning: An attachment perspective. Australian and New Zealand Journal of Psychiatry 37: 524–531. Hornblower S and Spawforth A (1996) The Oxford Classical Dictionary. Oxford; New York: Oxford University Press. Hosokawa T, Momose T and Kasai K (2009) Brain glucose metabolism difference between bipolar and unipolar mood disorders in depressed and euthymic states. Progress in Neuropsychopharmacology and Biological Psychiatry 33: 243–250. Howland RH and Thase ME (1993) A comprehensive review of cyclothymic disorder. Journal of Nervous and Mental Disease 181: 485–493. 337 Hyun M, Friedman SD and Dunner DL (2000) Relationship of childhood physical and sexual abuse to adult bipolar disorder. Bipolar Disorders 2: 131–135. Joyce PR, Light KJ, Rowe SL, et al. (2010) Self-mutilation and suicide attempts: Relationships to bipolar disorder, borderline personality disorder, temperament and character. Australian and New Zealand Journal of Psychiatry 44: 250–257. Joyce PR, Mchugh PC, Mckenzie JM, et al. (2006) A dopamine transporter polymorphism is a risk factor for borderline personality disorder in depressed patients. Psychological Medicine 36: 807–813. Joyce PR, Mckenzie JM, Luty SE, et al. (2003) Temperament, childhood environment and psychopathology as risk factors for avoidant and borderline personality disorders. Australian and New Zealand Journal of Psychiatry 37: 756–764. Kellogg SH and Young JE (2006) Schema therapy for borderline personality disorder. Journal of Clinical Psychology 62: 445–458. Kendler KS, Myers J and Reichborn-Kjennerud T (2011) Borderline personality disorder traits and their relationship with dimensions of normative personality: A web-based cohort and twin study. Acta Psychiatrica Scandinavica 123: 349–359. Kupferschmidt DA and Zakzanis KK (2011) Toward a functional neuroanatomical signature of bipolar disorder: Quantitative evidence from the neuroimaging literature. Psychiatry Research 193: 71–79. Kurtz MM and Gerraty RT (2009) A meta-analytic investigation of neurocognitive deficits in bipolar illness: Profile and effects of clinical state. Neuropsychology 23: 551–562. Kwapil TR, Barrantes-Vidal N, Armistead MS, et al. (2011) The expression of bipolar spectrum psychopathology in daily life. Journal of Affective Disorders 130: 166–170. Leboyer M and Kupfer DJ (2010) Bipolar disorder: New perspectives in health care and prevention. Journal of Clinical Psychiatry 71: 1689–1695. Levinson DF (2006) The genetics of depression: A review. Biological Psychiatry 60: 84–92. Levitt AJ, Joffe RT, Ennis J, et al. (1990) The prevalence of cyclothymia in borderline personality disorder. Journal of Clinical Psychiatry 51: 335–339. Linehan M (1993) Cognitive-behavioural Treatment for Borderline Personality Disorder. New York: The Guildford Press. Little J and Richardson K (2010) The clinician’s dilemma: Borderline personality disorder or bipolar spectrum disorder? Australasian Psychiatry 18: 303–308. Mcdonald C, Zanelli J, Rabe-Hesketh S, et al. (2004) Metaanalysis of magnetic resonance imaging brain morphometry studies in bipolar disorder. Biological Psychiatry 56: 411–417. Mackinnon DF and Pies R (2006) Affective instability as rapid cycling: Theoretical and clinical implications for borderline personality and bipolar spectrum disorders. Bipolar Disorders 8: 1–14. Macneil CA, Hasty MK, Berk M, et al. (2011) Psychological needs of adolescents in the early phase of bipolar disorder: Implications for early intervention. Early Intervention in Psychiatry 5: 100–107. Mann-Wrobel MC, Carreno JT and Dickinson D (2011) Metaanalysis of neuropsychological functioning in euthymic bipolar disorder: An update and investigation of moderator variables. Bipolar Disorders 13: 334–342. Australian & New Zealand Journal of Psychiatry, 46(4) 338 Mauchnik J and Schmahl C (2010) The latest neuroimaging findings in borderline personality disorder. Current Psychiatry Reports 12: 46–55. Maurex L, Zaboli G, Ohman A, et al. (2010) The serotonin transporter gene polymorphism (5-HTTLPR) and affective symptoms among women diagnosed with borderline personality disorder. European Psychiatry 25: 19–25. Meares R, Gerull F, Stevenson J, et al. (2011a) Is self disturbance the core of borderline personality disorder? An outcome study of borderline personality factors. Australian and New Zealand Journal of Psychiatry 45: 214–222. Meares R, Schore A and Melkonian D (2011b) Is borderline personality a particularly right hemispheric disorder? A study of P3a using single trial analysis. Australian and New Zealand Journal of Psychiatry 45: 131–139. Minzenberg MJ, Fan J, New AS, et al. (2007) Fronto-limbic dysfunction in response to facial emotion in borderline personality disorder: An event-related fMRI study. Psychiatry Research 155: 231–243. Mitchell PB, Goodwin GM, Johnson GF, et al. (2008) Diagnostic guidelines for bipolar depression: A probabilistic approach. Bipolar Disorders 10: 144–152. Nemoda Z, Lyons-Ruth K, Szekely A, et al. (2010) Association between dopaminergic polymorphisms and borderline personality traits among at-risk young adults and psychiatric inpatients. Behavioral and Brain Functions 6: 4. Nilsson AK, Jorgensen CR, Straarup KN, et al. (2010) Severity of affective temperament and maladaptive self-schemas differentiate borderline patients, bipolar patients, and controls. Comprehensive Psychiatry 51: 486–491. Nunes PM, Wenzel A, Borges KT, et al. (2009) Volumes of the hippocampus and amygdala in patients with borderline personality disorder: A meta-analysis. Journal of Personality Disorders 23: 333–345. Paris J (2004) Borderline or bipolar? Distinguishing borderline personality disorder from bipolar spectrum disorders. Harvard Review of Psychiatry 12: 140–145. Paris J (2010) Personality disorders and mood disorders: Phenomenological resemblances vs. pathogenetic pathways. Journal of Personality Disorders 24: 3–13. Paris J, Gunderson J and Weinberg I (2007) The interface between borderline personality disorder and bipolar spectrum disorders. Comprehensive Psychiatry 48: 145–154. Parker G (2000) Classifying depression: Should paradigms lost be regained? American Journal of Psychiatry 157: 1195–1203. Parker G (2009) Defining and measuring bipolar II disorder. In: Parker G (ed) Bipolar II Disorder – Modelling, Measuring and Managing. Cambridge: Cambridge University Press, pp. 46–60. Parker G, Hadzi-Pavlovic D and Tully L (2006) Distinguishing bipolar and unipolar disorders: An isomer model. Journal of Affective Disorders 96: 67–73. Patfield M (2011) Undiagnosis: An important new role for psychiatry. Australasian Psychiatry, 19, 107–109. Perugi G, Fornaro M and Hagop S (2011) Are atypical depression, borderline personality disorder and bipolar II disorder overlapping manifestations of a common cyclothymic diathesis? World Psychiatry 10: 45–51. Perugi G, Toni C, Travierso MC, et al. (2003) The role of cyclothymia in atypical depression: Toward a data-based Australian & New Zealand Journal of Psychiatry, 46(4) ANZJP Articles reconceptualization of the borderline-bipolar II connection. Journal of Affective Disorders 73: 87–98. Phelps J (2009) The bipolar spectrum. In: Parker G (ed) Bipolar II Disorder – Modelling, Measuring and Managing. Cambridge: Cambridge University Press, pp. 15–45. Pinsonneault JK, Han DD, Burdick KE, et al. (2011) Dopamine transporter gene variant affecting expression in human brain is associated with bipolar disorder. Neuropsychopharmacology 36: 1644–1655. Reich DB, Zanarini MC and Fitzmaurice G (2011) Affective lability in bipolar disorder and borderline personality disorder. Comprehensive Psychiatry, Epub ahead of print 30 May 2011. Ripoll LH, Triebwasser J and Siever LJ (2011) Evidence-based pharmacotherapy for personality disorders. International Journal of Neuropsychopharmacology 14: 1257–1288. Ruggero CJ, Carlson GA, Kotov R, et al. (2010a) Ten-year diagnostic consistency of bipolar disorder in a first-admission sample. Bipolar Disorders 12: 21–31. Ruggero CJ, Zimmerman M, Chelminski I, et al. (2010b) Borderline personality disorder and the misdiagnosis of bipolar disorder. Journal of Psychiatric Research 44: 405–408. Ruocco AC (2005) The neuropsychology of borderline personality disorder: A meta-analysis and review. Psychiatry Research 137: 191–202. Schulze L, Domes G, Kruger A, et al. (2011) Neuronal correlates of cognitive reappraisal in borderline patients with affective instability. Biological Psychiatry 69: 564–573. Siever LJ and Gunderson JG (1979) Genetic determinants of borderline conditions. Schizophrenia Bulletin 5: 59–86. Slater E and Roth M (1969) Clinical Psychiatry. London: Baillière, Tindall & Cassell. Smith DJ, Muir WJ and Blackwood DH (2004) Is borderline personality disorder part of the bipolar spectrum? Harvard Review of Psychiatry 12: 133–139. Smith DJ, Muir WJ and Blackwood DH (2005) Borderline personality disorder characteristics in young adults with recurrent mood disorders: A comparison of bipolar and unipolar depression. Journal of Affective Disorders 87: 17–23. Souery D, Zaninotto L, Calati R, et al. (2012) Depression across mood disorders: Review and analysis in a clinical sample. Comprehensive Psychiatry 53: 24–38. Sprooten E, Sussmann JE, Clugston A, et al. (2012) White matter integrity in individuals at high genetic risk of bipolar disorder. Biological Psychiatry 70: 350–356. Srinivasan V, Pandi-Perumal SR, Trakht I, et al. (2009) Pathophysiology of depression: Role of sleep and the melatonergic system. Psychiatry Research 165: 201–214. Stern A (1938) Psychoanalytic intervention of and therapy in the borderline group of neuroses. Psychoanalytic Quarterly, 7, 467–489. Stone MH (1979) Assessing vulnerability to schizophrenia or manic-depression in borderline states. Schizophrenia Bulletin 5: 105–110. Thomas P (2004) The many forms of bipolar disorder: A modern look at an old illness. Journal of Affective Disorders 79(suppl 1): S3–8. Tiller JW and Schweitzer I (2010) Bipolar disorder: Diagnostic issues. Medical Journal of Australia 193: S5–9. Torgersen S, Czajkowski N, Jacobson K, et al. (2008) Dimensional representations of DSM-IV cluster B personality disorders in Bassett a population-based sample of Norwegian twins: A multivariate study. Psychological Medicine 38: 1617–1625. Torgersen S, Lygren S, Oien PA, et al. (2000) A twin study of personality disorders. Comprehensive Psychiatry 41: 416–425. Trull TJ, Distel MA and Carpenter RW (2011) DSM-5 borderline personality disorder: At the border between a dimensional and a categorical view. Current Psychiatry Reports 13: 43–49. Van Meter A, Youngstrom EA, Youngstrom JK, et al. (2011) Examining the validity of cyclothymic disorder in a youth sample. Journal of Affective Disorders132: 55–63. Vollm B, Richardson P, Stirling J, et al. (2004) Neurobiological substrates of antisocial and borderline personality disorder: Preliminary results of a functional fMRI study. Criminal Behaviour and Mental Health 14: 39–54. Wagner S, Baskaya O, Lieb K, et al. (2009) The 5-HTTLPR polymorphism modulates the association of serious life events (SLE) and impulsivity in patients with borderline personality disorder. Journal of Psychiatric Research 43:1067–1072. Watson S, Chilton R, Fairchild H, et al. (2006) Association between childhood trauma and dissociation among patients with borderline personality disorder. Australian and New Zealand Journal of Psychiatry 40: 478–481. Wessa M and Linke J (2009) Emotional processing in bipolar disorder: Behavioural and neuroimaging findings. International Review of Psychiatry 21: 357–367. 339 Wupperman P, Neumann CS, Whitman JB, et al. (2009) The role of mindfulness in borderline personality disorder features. Journal of Nervous and Mental Disease 197: 766–771. Yatham LN, Kauer-Sant’anna M, Bond DJ, et al. (2009) Course and outcome after the first manic episode in patients with bipolar disorder: Prospective 12-month data from the systematic treatment optimization program for early mania project. Canadian Journal of Psychiatry 54: 105–112. Yen S, Zlotnick C and Costello E (2002) Affect regulation in women with borderline personality disorder traits. Journal of Nervous and Mental Disease 190: 693–696. Young JE, Klosko JS and Weishaar ME (2003) Schema Therapy: A Practitioner’s Guide. New York: The Guilford Press. Youngstrom E, Van Meter A and Algorta GP (2010) The bipolar spectrum: Myth or reality? Current Psychiatry Report 12: 479–489. Zanarini MC, Barison LK, Frankenburg FR, et al. (2009) Family history study of the familial coaggregation of borderline personality disorder with axis I and nonborderline dramatic cluster axis II disorders. Journal of Personality Disorders 23: 357–369. Zanarini MC, Frankenburg FR, Reich DB, et al. (2007) The subsyndromal phenomenology of borderline personality disorder: A 10-year follow-up study. American Journal of Psychiatry 164: 929–935. Zimmerman DJ and Choi-Kain LW (2009) The hypothalamicpituitary-adrenal axis in borderline personality disorder: A review. Harvard Review of Psychiatry 17: 167–183. Australian & New Zealand Journal of Psychiatry, 46(4)
Purchase answer to see full attachment

Literature Review

Literature Review

ORDER A PLAGIARISM FREE PAPER NOW

View Rubric

Max Points: 100

Details:

While the implementation plan prepares students to apply their research to the problem or issue they have identified for their capstone change proposal project, the literature review enables students to map out and move into the active planning and development stages of the project.

A literature review analyzes how current research supports the PICOT, as well as identifies what is known and what is not known in the evidence. Students will use the information from the earlier PICOT Statement Paper and Literature Evaluation Table assignments to develop a 750-1,000 word review that includes the following sections:

Title page
Introduction section
A comparison of research questions
A comparison of sample populations
A comparison of the limitations of the study
A conclusion section, incorporating recommendations for further research
Prepare this assignment according to the guidelines found in the APA Style Guide, located in the Student Success Center. An abstract is not required.

This assignment uses a rubric. Please review the rubric prior to beginning the assignment to become familiar with the expectations for successful completion.

You are required to submit this assignment to Turnitin. Please refer to the directions in the Student Success Center.

RUBRIC

Apply RubricsRUBRICRU

Literature Review

1
Unsatisfactory
0.00%

2
Less than Satisfactory
75.00%

3
Satisfactory
79.00%

4
Good
89.00%

5
Excellent
100.00%

80.0 %Content

10.0 %Introduction

An introduction is not present.

An introduction is present, but it does not relate to the body of the paper.

An introduction is present, and it relates to the body of the paper. There is nothing in the introduction to entice the reader to continue reading.

An introduction is present, and it relates to the body of the paper. Information presented in the introduction provides incentive for the reader to continue reading.

An introduction is present, and it relates to the body of the paper. Information presented in the introduction is intriguing and encourages the reader to continue reading.

20.0 %Comparison of Research Questions

No comparison of research questions is presented.

A comparison of research questions is presented, but it is not valid.

A cursory though valid comparison of research questions is presented.

A moderately thorough and valid comparison of research questions is presented.

A reflective and insightful comparison of research questions is presented.

20.0 %Comparison of Sample Populations

No comparison of sample populations is presented.

A comparison of sample populations is presented, but it is not valid.

A cursory though valid comparison of sample populations is presented.

A moderately thorough and valid comparison of sample populations is presented.

A reflective and insightful comparison of sample populations is presented.

20.0 %Comparison of the Limitations of the Study

No comparison of the limitations of the study is presented.

A comparison of the limitations of the study is presented, but it is not valid.

A cursory though valid comparison of the limitations of the study is presented.

A moderately thorough and valid comparison of the limitations of the study is presented.

A reflective and insightful comparison of the limitations of the study is presented.

10.0 %Conclusion and Recommendations for Further Research

No conclusion and recommendations for further research are presented.

A conclusion and recommendations for further research are presented, but they are not valid.

A conclusion and recommendations for further research are valid, but they are cursory.

A conclusion and recommendations for further research are valid and moderately thorough.

A conclusion and recommendations for further research are reflective and insightful.

15.0 %Organization and Effectiveness

5.0 %Thesis Development and Purpose

Paper lacks any discernible overall purpose or organizing claim.

Thesis is insufficiently developed or vague. Purpose is not clear.

Thesis is apparent and appropriate to purpose.

Thesis is clear and forecasts the development of the paper. Thesis is descriptive and reflective of the arguments and appropriate to the purpose.

Thesis is comprehensive and contains the essence of the paper. Thesis statement makes the purpose of the paper clear.

5.0 %Argument Logic and Construction

Statement of purpose is not justified by the conclusion. The conclusion does not support the claim made. Argument is incoherent and uses noncredible sources.

Sufficient justification of claims is lacking. Argument lacks consistent unity. There are obvious flaws in the logic. Some sources have questionable credibility.

Argument is orderly, but may have a few inconsistencies. The argument presents minimal justification of claims. Argument logically, but not thoroughly, supports the purpose. Sources used are credible. Introduction and conclusion bracket the thesis.

Argument shows logical progressions. Techniques of argumentation are evident. There is a smooth progression of claims from introduction to conclusion. Most sources are authoritative.

Clear and convincing argument that presents a persuasive claim in a distinctive and compelling manner. All sources are authoritative.

5.0 %Mechanics of Writing (includes spelling, punctuation, grammar, language use)

Surface errors are pervasive enough that they impede communication of meaning. Inappropriate word choice or sentence construction is used.

Frequent and repetitive mechanical errors distract the reader. Inconsistencies in language choice (register), sentence structure, or word choice are present.

Some mechanical errors or typos are present, but they are not overly distracting to the reader. Correct sentence structure and audience-appropriate language are used.

Prose is largely free of mechanical errors, although a few may be present. A variety of sentence structures and effective figures of speech are used.

Writer is clearly in command of standard, written, academic English.

5.0 %Format

2.0 %Paper Format (use of appropriate style for the major and assignment)

Template is not used appropriately or documentation format is rarely followed correctly.

Template is used, but some elements are missing or mistaken; lack of control with formatting is apparent.

Template is used, and formatting is correct, although some minor errors may be present.

Template is fully used; There are virtually no errors in formatting style.

All format elements are correct.

3.0 %Documentation of Sources (citations, footnotes, references, bibliography, etc., as appropriate to assignment and style)

Sources are not documented.

Documentation of sources is inconsistent or incorrect, as appropriate to assignment and style, with numerous formatting errors.

Sources are documented, as appropriate to assignment and style, although some formatting errors may be present.

Sources are documented, as appropriate to assignment and style, and format is mostly correct.

Sources are completely and correctly documented, as appropriate to assignment and style, and format is free of error.

100 %Total Weightage

 

Literature Review

Empirical research is the foundation of scholarly research and scholarly writing. An empirical article is defined as one that reports actual results of a research study. An empirical article includes a description of the study, an introduction, a research question, an explanation of the study’s methodology, a presentation of the results of the study, and a conclusion that discusses the results and suggests topics for further study.

As you search the library for scholarly research, you should limit your search to identify empirical articles. (You can use the “Empirical Research Checklist” from DNP-801 to assist in this determination.) After finding an empirical study, begin to assess the validity of the conclusion by determining if the conclusion answers the proposed research question and if the methodology is appropriate.

As you move forward in your doctoral journey, you will read research papers that will require you to assess the validity of the studies in question. To accomplish this, qualitative assessments about the research must be made by comparing, contrasting, and synthesizing what the research says.

In this assignment, you will continue to develop the skill of writing, by reviewing 15 research articles associated with your chosen topic and using the content to identify at least five major concepts and subthemes related to your topic.

General Requirements:

Use the following information to ensure successful completion of this assignment:

• Use the “Empirical Research Checklist” to assist in the determination of empirical articles.
• Use the “Research Article Chart” to provide a summary review of each component of your assignment.
• Doctoral learners are required to use APA style for their writing assignments. The APA Style Guide is located in the Student Success Center.
• This assignment uses a rubric. Please review the rubric prior to beginning the assignment to become familiar with the expectations for successful completion.
• You are required to submit this assignment to LopesWrite. Please refer to the directions in the Student Success Center.

Directions:

Part 1: Selection of 15 Articles

Select 15 empirical articles related to your PICOT question. Use the “Empirical Research Checklist” worksheet to ensure that each article you select meets all of the established criteria. At least one article must demonstrate a quantitative methodology.

Part 2: Research Article Chart

Using the articles acquired in Part 1, provide a summary review of each component using the “Research Article Chart” template.

Part 3: Synthesis of Research Studies

Based upon your review of the 15 research articles, identify at least five major concepts that relate to your project topic, and three subthemes related to each concept.

ORDER A PLAGIARISM FREE PAPER NOW

Using the information from the completed “Research Article Chart,” and the major concepts and subthemes you have identified, write a 2,000-3,000 word paper that synthesizes the content of the 15 research studies.

Summarize each major concept and focus on providing a detailed synthesis of the three identified subthemes that support that concept by addressing the following.

1. Introduction of the identified subtheme
2. Summary of the research questions posed by the studies
3. Summary of the sample populations used
4. Summary of the limitations of the studies
5. Summary of the conclusion and recommendations for further research