Posttraumatic stress disorder and substance use disorder in adolescent bipolar disorder

Objective: Anxiety disorders such as posttraumatic stress disorder (PTSD) and substance use disorders (SUD) are increasingly recognized as comorbid disorders in children with bipolar disorder (BPD). This study explores the relationship between BPD, PTSD, and SUD in a cohort of BPD and non‐BPD adolescents. Methods: We studied 105 adolescents with BPD and 98 non‐mood‐disordered adolescent controls. Psychiatric assessments were made using the Kiddie Schedule for Affective Disorders and Schizophrenia–Epidemiologic Version (KSADS‐E), or Structured Clinical Interview for DSM‐IV (SCID) if 18 years or older. SUD was assessed by KSADS Substance Use module for subjects under 18 years, or SCID module for SUD if age 18 or older. Results: Nine (8%) BPD subjects endorsed PTSD and nine (8%) BPD subjects endorsed subthreshold PTSD compared to one (1%) control subject endorsing full PTSD and two (2%) controls endorsing subthreshold PTSD. Within BPD subjects endorsing PTSD, seven (39%) met criteria for SUD. Significantly more SUD was reported with full PTSD than with subthreshold PTSD (χ² = 5.58, p = 0.02) or no PTSD (χ² = 6.45, p = 0.01). Within SUD, the order of onset was BPD, PTSD, and SUD in three cases, while in two cases the order was PTSD, BPD, SUD. The remaining two cases experienced coincident onset of BPD and SUD, which then led to trauma, after which they developed PTSD and worsening SUD. Conclusion: An increased rate of PTSD was found in adolescents with BPD. Subjects with both PTSD and BPD developed significantly more subsequent SUD, with BPD, PTSD, then SUD being the most common order of onset. Follow‐up studies need to be conducted to elucidate the course and causal relationship of BPD, PTSD and SUD.     

Comorbid substance use disorder in women with bipolar disorder associated with criminal arrest

OBJECTIVES: Previous research has indicated that comorbid substance abuse in patients with bipolar disorder (BPD) is strongly linked to criminal arrest. This study was conducted to further evaluate possible gender differences in substance use and risk of criminality in BPD. METHODS: Subjects were selected from all inmates with a DSM-IV diagnosis of BPD type I at Los Angeles County correctional facility. As a comparison, a sample of Los Angeles County patients with BPD type I who had not been arrested during the course of their psychiatric treatment within LA County was identified. The county's Management Information System (MIS) was utilized to obtain primary and secondary diagnoses as well as demographic information. RESULTS: The odds of having a comorbid substance use diagnosis for arrested female patients was more than 38 times that for community female patients (odds ratio = 38.75). Women were more likely to have been arrested for violent and substance use charges; men were more likely to have been arrested for theft and miscellaneous charges. CONCLUSIONS: Substance abuse appears to be a significant risk factor for arrest in patients with BPD and is especially significant for women with BPD. Our study suggests that comorbid BPD and substance use in women may significantly increase the risk of criminal arrest.     

A review of psychosocial outcome in patients with bipolar disorder

OBJECTIVE: The aim of this paper is to review outcome in patients with bipolar disorder as assessed by interepisode level of functioning, as until recently this dimension of outcome has been relatively under-emphasized. METHOD: Studies that examined psychosocial outcome in bipolar disorder were reviewed on the basis of rating measurements employed, length of follow-up, number of subjects followed and degree of impairment reported. Studies were included only if results from patients with bipolar and unipolar disorder were reported in such a way that the groups could be distinguished. RESULTS: When studies of psychosocial outcome in bipolar disorder are examined in aggregate, it appears that 30-60% of individuals with this disorder fail to regain full functioning in occupational and social domains. CONCLUSION: This review highlights the fact that inter-episode functional recovery is incomplete in some patients, suggesting that comprehensive rehabilitative assessment and intervention may be essential to reduce the morbidity associated with this disorder.     

Impact of substance abuse on the course and treatment of bipolar disorder

Objectives: The objectives of this article are to review the prevalence, natural history, pathophysiology, and treatment of comorbid bipolar disorder with alcoholism and other psychoactive substance use disorders (PSUDs).
Methods: All identified bibliographies through a literature search of all Medline files and bibliographies of selected articles focusing on the prevalence, natural history, course, prognosis, inter-relationship, and treatment of bipolar disorder with comorbid alcoholism and other PSUDs were reviewed.
Results and conclusions: Comorbidity of bipolar disorder and alcoholism and other PSUDs is highly prevalent. The presence of this so called 'dual diagnoses' creates a serious challenge in terms of establishing an accurate diagnosis and providing appropriate treatment interventions. The inter-relationship between these disorders appears to be mutually detrimental. The course, manifestation, and treatment of each condition are significantly compounded by the presence of the other condition. Substance abuse and alcoholism appear to significantly complicate the course and prognosis of bipolar disorder resulting in increased suffering, disability, and costs. On the other hand, bipolar disorder may be a risk factor for developing PSUDs. Although, there are a number of hypotheses explaining the pathophysiological mechanism involved in such comorbidities, our understanding of the exact nature of such neurobiological mechanisms is still limited. While the antikindling agents and targeted psychotherapeutic techniques may be useful intervention strategies, there is still a significant lack of empirically based treatment options for these patients.     

Relationships between insight and psychosocial adjustment in patients with bipolar I disorder

OBJECTIVES: The aim of this cross-sectional study was to examine the relationships between insight and psychosocial adjustment in outpatients with bipolar I disorder in clinical remission. METHODS: Using the Schedule of Assessment of Insight (SAI) and its expanded version (SAI-E), we evaluated 50 consecutive patients with bipolar I disorder in remission to determine their level of insight. We also evaluated their psychosocial adjustment using the Community Life Scale. Relationships among psychosocial adjustment, insight, residual affective symptoms, and demographic and clinical characteristics were examined. RESULTS: The results of the multiple regression analysis indicated that having a higher total SAI or SAI-E insight score and having no residual affective symptoms were significantly associated with better psychosocial adjustment in patients with bipolar I disorder. CONCLUSIONS: In this cross-sectional study, better insight and less residual affective symptoms were correlated with good psychosocial adjustment. To address the causality issue, a longitudinal study is needed.     

Comorbidity of eating disorders with bipolar disorder and treatment implications

OBJECTIVES: To review the scientific evidence examining the comorbidity among eating disorders and bipolar disorder (BD). METHODS: We reviewed all published English-language studies addressing the comorbidity of anorexia nervosa, bulimia, bulimia nervosa, and binge eating disorder in patients with BD and studies of comorbidity of BD in patients with eating disorders. In addition, we discuss the pharmacologic treatment implications from reviewed studies of agents used in BD and eating disorders. RESULTS: Community and clinical population studies of the lifetime prevalence rates of eating disorders in patients with BD, and of BD in patients with eating disorders, particularly when subthreshold and spectrum manifestations of these disorders are included, indicate high rates of comorbidity among these illnesses. CONCLUSIONS: Pharmacologic treatment approaches to patients with BD and a co-occurring eating disorder require examination of the possible adverse effects of the treatment of each syndrome on the other and attempts to manage both syndromes with agents that might be beneficial to both.     

Three-year outcomes of long-term patients with co-occurring bipolar and substance use disorders.

Little is known about the long-term outcomes of patients in the public mental health system who are disabled by co-occurring bipolar and substance use disorders. This article reports on the 3-year course of 51 patients with co-occurring bipolar and substance use disorders in the New Hampshire Dual Diagnosis Study. Participants received integrated dual disorders treatments in the state mental health system and were independently assessed with standardized measures at baseline and every 6 months for 3 years. Though psychiatric symptoms improved only modestly, participants improved steadily in terms of remission from substance abuse (61% in full remission at 3 years); they also achieved greater independent living (average 239 days in third year), competitive employment (49% in third year), regular social contacts with nonsubstance abusers (46% at 3 years), and quality of life (56% satisfied with life at 3 years). Different domains of outcome were only weakly related to each other. Long-term, disabled patients with co-occurring bipolar and substance use disorders have potential for remission from substance abuse and substantial improvements in functioning and quality of life.     

Gender differences in bipolar disorder type I and II

Objective: We investigated gender differences in bipolar disorder (BD) type I and II in a representative cohort of secondary care psychiatric in‐ and out‐patients. Method: In the prospective, naturalistic Jorvi Bipolar Study of 191 secondary care psychiatric in‐ and out‐patients, 160 patients (85.1%) could be followed up for 18 months with a life chart. Results: After adjusting for confounders, no marked differences in illness‐related characteristics were found. However, female patients with BD had more lifetime comorbid eating disorders (P < 0.001, OR = 5.99, 95% CI 2.12–16.93) but less substance use disorders (P < 0.001, OR = 0.29, 95% CI 0.16–0.56) than males. Median time to recurrence after remission was 3.1 months longer among men than women, female gender carrying a higher hazard of recurrence (P = 0.006, HR = 2.00, 95% CI 1.22–3.27). Conclusion: Men and women with type I and II BD have fairly similar illness‐related clinical characteristics, but their profile of comorbid disorders may differ significantly, particularly regarding substance use and eating disorders. In medium‐term follow‐up, females appear to have a higher hazard of recurrence than males.     

Comorbidity of anxiety disorders in patients with remitted bipolar disorder

Comorbidity between bipolar disorder and anxiety disorders has attracted considerable attention in recent years. However, a majority of the earlier studies examined anxiety disorders in acutely ill patients resulting in a possible confounding effect of the affective episodes. This study examines the prevalence of anxiety disorders in remitted bipolar subjects recruited from a psychiatric hospital in India and their effect on the severity of bipolar illness. A total of eighty remitted DSM-IV adult bipolar subjects and 50 non-psychiatric controls were recruited over a 10-month period. They were evaluated using a structured interview and various scales. The effect of anxiety disorders on bipolar severity was analyzed using multiple regression analyses. Anxiety disorders were highly prevalent in bipolar subjects compared to controls (49 [61%] vs. 7 [14%], χ² = 28.01, P < 0.001). Commonest lifetime anxiety disorder was obsessive-compulsive disorder (35%). Lifetime anxiety disorder had significant effect on all four indices of severity of illness, that included (1) percentage of time spent in episodes (Beta = 18.67, SE = 5.11, P < 0.001), (2) maximum period of continuous euthymia in the preceding 2 years (Beta = −5.26, SE = 1.71, P = 0.003), (3) presence of psychosis (Beta = 3.22, SE = 1.02, P = 0.002), and 4) response to mood stabilizers (Beta = −2.11, SE = 0.76, P = 0.006). The findings of this study confirm previous observations of the high prevalence and negative impact of comorbid anxiety disorders in bipolar disorder and also demonstrate that the findings are similar in culturally diverse settings. Future studies should systematically examine the various treatment options for anxiety disorders in bipolar patients. It is also necessary to examine the neurobiological and family/genetic correlates of anxious bipolar subjects to validate if they are a subgroup of bipolar disorders.     

The spectrum of substance abuse in bipolar disorder: reasons for use, sensation seeking and substance sensitivity

OBJECTIVES: To examine the spectrum of alcohol and substance abuse, including reasons for use, in patients with bipolar I disorder, compared with patients with substance use disorder and healthy controls, with a specific focus on the relationship between substance use, substance sensitivity, other comorbid psychiatric symptoms and traits related to sensation seeking. METHODS: This study included 104 patients with bipolar I disorder (BPD I), of whom 57 (54.8%) met DSM-IV criteria for lifetime alcohol or substance use disorder (BPD + SUD), 35 patients with substance use disorder (SUD) and no psychiatric disorder and 50 healthy controls. Assessments included the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID) and the Structured Clinical Interview for the Spectrum of Substance Use (SCI-SUBS). RESULTS: Patients with BPD + SUD and SUD had significantly higher scores on the SCI-SUBS domains of self-medication, substance sensitivity and sensation seeking compared with patients with BPD and healthy controls. Reasons for substance use did not differ between patients with BPD + SUD and patients with SUD. Those most frequently cited were: improving mood; relieving tension; alleviating boredom; achieving/maintaining euphoria; and increasing energy. CONCLUSIONS: Recourse to substances is associated with increased mood and anxiety symptoms, substance sensitivity, and sensation seeking among patients with BPD + SUD and SUD. Substance sensitivity and sensation seeking traits should be investigated in all patients with BPD as possible factors associated with a development of SUD, in order to warn patients of the specific risks related to improper use of medications and substances.     

Neuropsychological functions in patients with bipolar I and bipolar II disorder

Objectives:  The literature reports persistent cognitive impairments in patients with bipolar disorder even after prolonged remission. However, a majority of studies have focused only on bipolar I disorder (BP-I), primarily because bipolar II disorder (BP-II) is often underdiagnosed or misdiagnosed. More attention should be paid to the differences between BP-I and BP-II, especially the aspects of neuropsychological functioning. We examined the different neuropsychological functions in BP-I and BP-II patients and compared them with those of healthy controls.
Methods:  The study included 67 patients with interepisode bipolar disorder (BP-I: n = 30; BP-II: n = 37) and 22 healthy controls compared using a battery of neuropsychological tests that assessed memory, psychomotor speed, and certain aspects of frontal executive function.
Results:  The BP-I group performed poorly on verbal memory, psychomotor speed, and executive function compared to the BP-II and control groups. Both bipolar groups performed significantly less well than the control group on measures of working memory and psychomotor speed, while the BP-II group showed an intermediate level of performance in psychomotor speed compared to the BP-I and control groups. There was no difference between the groups on visual memory.
Conclusions:  BP-I was characterized by reduced performance in verbal memory, working memory, psychomotor speed, and executive function, while BP-II patients showed a reduction only in working memory and psychomotor speed. Cognitive impairment existed in both subtypes of bipolar disorder, and was greater in BP-I patients. Rehabilitation interventions should take into account potential cognitive differences between these bipolar subtypes.     

Suicide risk in bipolar patients: the role of co-morbid substance use disorders

Objective:  Bipolar disorder is associated with a high frequency of both completed suicides and suicide attempts. The primary aim of this study was to identify clinical predictors of suicide attempts in subjects with bipolar disorder.
Methods:  We studied 336 subjects with a diagnosis of bipolar I, bipolar II, or schizoaffective disorder (bipolar type). The Structured Clinical Interview for DSM-IV (SCID-I) was administered and subsequently two expert psychiatrists established a diagnosis. Predictors of suicide attempts were examined in attempters and non-attempters.
Results:  The lifetime rate of suicide attempts for the entire sample was 25.6%. A lifetime co-morbid substance use disorder was a significant predictor of suicide attempts: bipolar subjects with co-morbid substance use disorders (SUD) had a 39.5% lifetime rate of attempted suicide, while those without had a 23.8% rate (odds ratio=2.09, 95% CI=1.03–4.21, χ²=4.33, df=1, p=0.037).
Conclusions:  Lifetime co-morbid SUD were associated with a higher rate of suicide attempts in patients with bipolar disorder. This relationship may have a genetic origin and/or be explained by severity of illness and trait impulsivity.     

Sequencing of substance use and affective morbidity in 166 first-episode bipolar I disorder patients

Objectives:  Since bipolar disorder (BPD) patients have high rates of comorbid substance abuse, and the temporal relationships involved are unclear, we evaluated the sequencing of specific substance use and affective morbidity.
Methods:  Prospective follow-up (4.7 years) of 166 first-episode DSM-IV type I BPD patients with reliable, standardized assessments provided data for longitudinal analysis of temporal distribution of alcohol and cannabis use versus manic or depressive episodes or symptoms, using generalized estimating equation regression modeling.
Results:  By quarters, cannabis use selectively and strongly preceded and coincided with mania/hypomania, and alcohol use preceded or coincided with depression, whereas substance use was unassociated with mood states in preceding quarters.
Conclusions:  These preliminary findings suggest potentially predictive temporal associations, in which the abuse of cannabis or alcohol anticipated or corresponded with, but did not follow, affective morbidity, including selective association of cannabis with mania and alcohol with depression.     

Racial disparities in bipolar disorder treatment and research: a call to action

Objectives

Health disparities between individuals of African and European ancestry are well documented. The disparities in bipolar disorder may be driven by racial bias superimposed on established factors contributing to misdiagnosis, including: evolving empirically based diagnostic criteria (International Classification of Diseases [ICD], Research Diagnostic Criteria [RDC] and Diagnostic and Statistical Manual [DSM]), multiple symptom domains (i.e. mania, depression and psychosis), and multimodal medical and additional psychiatric comorbidity.

Methods

For this paper, we reviewed the phenomenological differences between bipolar individuals of African and European ancestry in the context of diagnostic criteria and clinical factors that may contribute to a potential racial bias.

Results

Published data show that bipolar persons of African ancestry, compared with bipolar persons of non‐African ancestry, are more often misdiagnosed with a disease other than bipolar disorder (i.e. schizophrenia). Additionally, studies show that there are disparities in recruiting patients of African ancestry to participate in important genomic studies. This gap in biological research in this underrepresented minority may represent a missed opportunity to address potential racial differences in the risk and course of bipolar illness.

Conclusion

A concerted effort by the research community to increase inclusion of diverse persons in studies of bipolar disorder through community engagement may facilitate fully addressing these diagnostic and treatment disparities in bipolar individuals of African ancestry.     

Concurrent tracking of alcohol use and bipolar disorder symptoms

OBJECTIVES: Alcohol use disorders (AUDs) are common co-occurring conditions in patients with bipolar disorder (BD), but it is unclear whether or not AUD and BD symptoms are temporally correlated. The primary aim of this analysis was to examine concurrent symptom tracking and how the relative onsets of AUD and BD influence the concurrent tracking of symptoms. METHODS: Participants met DSM-IV criteria for bipolar I disorder, manic or mixed, with no prior hospitalizations and minimal treatment. Patients were rated for alcohol use and bipolar symptom severity on a weekly basis for up to 7 years. For analysis purposes, patients were placed into groups with no AUD (BD Only; n = 21), onset of AUD either concurrent with or after the onset of bipolar symptoms (BD First; n = 32), and onset of AUD at least 1 year before the onset of bipolar symptoms (AUD First; n = 18). RESULTS: None of the patient groups demonstrate consistent positive or negative temporal correlations between alcohol use and affective symptoms. However, there were significant between-group differences on the relationship of symptom tracking and age of BD onset. For the AUD First group, the correlation between age of BD onset and symptom tracking was positive 0.41. However, for the BD First and BD Only groups the correlations were negative (-0.32 and -0.41, respectively). Moreover, for patients whose BD onset was < or =18 years old, the correlation between age of onset and tracking was -0.47. CONCLUSIONS: These findings suggest that although there is no direct temporal correlation of AUD and BD symptoms in subgroups of BD patients, age at illness onset contributes to the complex relationship between BD and AUD. For younger patients there may be a greater likelihood that alcohol use and bipolar symptoms increase or decrease in unison.     

Criminal conviction, impulsivity, and course of illness in bipolar disorder

Swann AC, Lijffijt M, Lane SD, Kjome KL, Steinberg JL, Moeller FG. Criminal conviction, impulsivity, and course of illness in bipolar disorder.
Bipolar Disord 2011: 13: 173–181. © 2011 The Authors.
Journal compilation © 2011 John Wiley & Sons A/S. Objective: Criminal behavior in bipolar disorder may be related to substance use disorders, personality disorders, or other comorbidities potentially related to impulsivity. We investigated relationships among impulsivity, antisocial personality disorder (ASPD) or borderline personality disorder symptoms, substance use disorder, course of illness, and history of criminal behavior in bipolar disorder. Methods: A total of 112 subjects with bipolar disorder were recruited from the community. Diagnosis was by Structured Clinical Interview for DSM‐IV (SCID‐I and SCID‐II); psychiatric symptom assessment by the Change version of the Schedule for Affective Disorders and Schizophrenia (SADS‐C); severity of Axis II symptoms by ASPD and borderline personality disorder SCID‐II symptoms; and impulsivity by questionnaire and response inhibition measures. Results: A total of 29 subjects self‐reported histories of criminal conviction. Compared to other subjects, those with convictions had more ASPD symptoms, less education, more substance use disorder, more suicide attempt history, and a more recurrent course with propensity toward mania. They had increased impulsivity as reflected by impaired response inhibition, but did not differ in questionnaire‐measured impulsivity. On logit analysis, impaired response inhibition and ASPD symptoms, but not substance use disorder, were significantly associated with criminal history. Subjects convicted for violent crimes were not more impulsive than those convicted for nonviolent crimes. Conclusions: In this community sample, a self‐reported history of criminal behavior is related to ASPD symptoms, a recurrent and predominately manic course of illness, and impaired response inhibition in bipolar disorder, independent of current clinical state.     

Treatment‐emergent mania/hypomania during antidepressant monotherapy in patients with rapid cycling bipolar disorder

Objective: To study treatment‐emergent mania/hypomania (TEM) associated with second‐generation antidepressant monotherapy in patients with rapid cycling bipolar disorder (RCBD). Methods: Data of patients with RCBD (n = 180) enrolled into two clinical trials were used to study the risk for TEM during second‐generation antidepressant monotherapy. History of TEM was retrospectively determined at the initial assessment by asking patients whether they were exposed to second‐generation antidepressants and if a hypomania/mania episode emerged during the first four weeks of treatment. Data were analyzed using t‐test, chi‐square, and logistic regression. Results: Of the 180 patients (bipolar I disorder, n = 128; bipolar II disorder, n = 52) with RCBD, 85% (n = 153) had at least one antidepressant treatment. Among these patients, 94.1% (144/153) had at least one antidepressant monotherapy treatment. Overall, 49.3% of patients had at least one TEM and 29.1% (116/399) of treatment trials were associated with TEM. In regression analysis, an inverse association between the number of mood episodes in the last 12 months and TEM was observed with an odds ratio of 0.9. However, gender, bipolar subtype, a lifetime history of comorbid anxiety disorder, substance use disorder, or psychosis, and age of mood disorder onset were not associated with TEM. For individual antidepressants, the rates of TEM varied from 42.1% for fluoxetine to 0% for fluvoxamine and mirtazapine. As a group, there was no difference between selective serotonin reuptake inhibitors and venlafaxine or bupropion in the incidence of TEM. Conclusions: Use of second‐generation antidepressants as monotherapy in RCBD is accompanied by clinically relevant rates of TEM. Even in patients with RCBD, differential vulnerabilities to antidepressant TEM may exist.     

Pathways to care for patients with bipolar disorder

Bipolar disorder is a chronic, debilitating psychiatric illness with serious ramifications for patients, their families, and society. Despite the availability of effective treatments, this disease often goes untreated due to medical, financial, legal/governmental, and cultural barriers. In this review we explore possible reasons for this problem. Misdiagnosis of bipolar disorders is a common medical barrier. One pathway to care for individuals with bipolar disorder is through referral from primary care, but primary care physicians generally have not received special training in the recognition and management of bipolar disorder. This often leads to diagnostic delays or errors, which prevents timely 'filtering' of patients into specialized care. Using data bases we explored these pathways. Legislation in the USA, such as the Emergency Medical Treatment and Active Labor Act (EMTALA), designed to ensure access to inpatient mental health care, has instead given hospitals financial incentives to limit inpatient mental health care capacities. Reimbursement of mental health care expenses is a significant issue impacting a patient's ability to gain access to care, as bipolar disorder is a costly disease to treat. Improving access to care among the bipolar community will require multilateral strategies to influence the actions and attitudes of patients, communities, providers, health care systems, and state/national governments. In other cultures, barriers to care differ according to a number of factors such as type of services, explanatory models of illness, misdiagnosis and perceptions of care givers. It is essential that clinicians are aware of pathways and barriers so that appropriate and accessible care can be provided.     

Birth‐cohort and dual diagnosis effects on age‐at‐onset in Brazilian patients with bipolar I disorder

Objective: Substance use disorders and birth‐cohort have been associated with an earlier onset in bipolar disorder (BD). This study aimed at evaluating the inter‐relations of these factors in age‐at‐onset in bipolar illness. Method: Two‐hundred and thirty patients with bipolar I disorder were cross‐sectionally evaluated. Patients were categorized into four age groups for analysis. Lifetime comorbidity and age‐at‐onset were derived from the Structured Clinical Interview for DSM‐IV. Results: There was a strong linear association between age group and age‐at‐onset. Lifetime alcohol and drug use disorders were also associated with age‐at‐onset. Illicit drug and alcohol use disorders and age group remained significant in the multivariate model. No interactions appeared. Conclusion: Both age group and dual diagnoses had strong and independent impacts on age‐at‐onset in out‐patients with BD. Substance abuse may be partly accountable for earlier symptom onset, but other features of BD in younger generations are still in need to be accounted for.