Bipolar disorder and substance abuse.

Substance use disorders are overrepresented in individuals with bipolar and bipolar spectrum disorders. Although awareness of this phenomenon has increased over the past 20 years, few empirically based treatment strategies have been developed for this challenging patient population. This review examines the relationship between bipolar and substance use disorders and treatment options that have been studied in this patient population. First, we examine the high prevalence rates of substance use disorders in individuals diagnosed with bipolar disorder, the common problems associated with establishing a bipolar disorder diagnosis in individuals who abuse substances, the possible explanations for the frequent coexistence of bipolar and substance use disorders, and the negative effect of substance abuse on the course of and treatment outcomes for bipolar disorder. The review then focuses on treatment approaches for this patient population, including integrated group therapy for co-occurring bipolar and substance use disorders and pharmacotherapies that target both disorders. Finally, we present suggestions for medications that might be tested for their efficacy in treating both disorders in specific subgroups of patients with bipolar and substance use disorders.     

Bipolar obsessive-compulsive disorder and personality disorders

OBJECTIVES: Relatively few systematic data exist on the clinical impact of bipolar comorbidity in obsessive-compulsive disorder (OCD) and no studies have investigated the influence of such a comorbidity on the prevalence and pattern of Axis II comorbidity. The aim of the present study was to explore the comorbidity of personality disorders in a group of patients with OCD and comorbid bipolar disorder (BD). METHODS: The sample consisted of 204 subjects with a principal diagnosis of OCD (DSM-IV) and a Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score>or=16 recruited from all patients consecutively referred to the Anxiety and Mood Disorders Unit, Department of Neuroscience, University of Turin over a period of 5 years (January 1998-December 2002). Diagnostic evaluation and Axis I comorbidities were collected by means of the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I). Personality status was assessed by using the Structured Clinical Interview for DSM-IV Axis II Disorders (SCID-II). Socio-demographic and clinical features (including Axis II comorbidities) were compared between OCD patients with and without a lifetime comorbidity of BD. RESULTS: A total of 21 patients with OCD (10.3%) met DSM-IV criteria for a lifetime BD diagnosis: 4 (2.0%) with BD type I and 17 (8.3%) with BD type II. Those without a BD diagnosis showed significantly higher rates of male gender, sexual and hoarding obsessions, repeating compulsions and lifetime comorbid substance use disorders, when compared with patients with BD/OCD. With regard to personality disorders, those with BD/OCD showed higher prevalence rates of Cluster A (42.9% versus 21.3%; p=0.027) and Cluster B (57.1% versus 29.0%; p=0.009) personality disorders. Narcissistic and antisocial personality disorders were more frequent in BD/OCD. CONCLUSIONS: Our results point towards clinically relevant effects of comorbid BD on the personality profiles of OCD patients, with higher rates of narcissistic and antisocial personality disorders in BD/OCD patients.     

The Maudsley Bipolar Disorder Project: executive dysfunction in bipolar disorder I and its clinical correlates.

BACKGROUND: Cognitive abnormalities are increasingly recognized as a feature of bipolar I disorder (BDI,) but there is limited information regarding the pattern and severity of cognitive impairment during remission and its relationship with clinical variables. METHODS: Forty-four remitted BDI patients recruited from a representative treatment sample and an equal number of matched healthy volunteers underwent comprehensive clinical and cognitive assessments. Cognitive evaluation covered the domains of IQ, memory, and executive function. The profile of cognitive deficits in patients was examined, and the correlation of executive function with clinical features and treatment variables was explored. RESULTS: Remitted BDI patients were impaired in tests of executive function compared with healthy participants. Within the patient group, current antipsychotic treatment predicted worse performance across all executive function tests, whereas duration of illness predicted loss of inhibitory control. Residual mood symptoms, regardless of polarity, had a negative impact primarily on measures of attentional interference. CONCLUSIONS: These results suggest that impaired executive function might be an important feature of BDI. Antipsychotic treatment, duration of illness, and level of symptoms are the most significant contributors to the observed impairment.     

Differential dysfunctions related to alcohol and cannabis use disorder symptoms in reward and error-processing neuro-circuitries in adolescents

Alcohol and cannabis are two of the most commonly used substances by adolescents and are associated with adverse medical and psychiatric outcomes. These adverse psychiatric outcomes may reflect the negative impact of alcohol and/or cannabis abuse on neural systems mediating reward and/or error detection. However, work indicative of this has mostly been conducted in adults with Alcohol and/or Cannabis Use Disorder (i.e., AUD and CUD), with relatively little work in adolescent patients. Furthermore, of the work that has been conducted in adolescents, groups were based on categorical diagnoses of AUD and/or CUD, so the relationship between AUD and/or CUD symptom severity in adolescents and neural dysfunction is unclear. We used a Monetary Incentive Delay (MID) task to examine the relationship between AUDIT and/or CUDIT scores and functional integrity of neuro-circuitries mediating reward processing and error detection within 150 adolescents. Our findings indicate that AUDIT score is negatively related to activity in reward processing neuro-circuitry in adolescents. However, CUDIT score is negatively related to activity in brain regions involved in error detection. Each of these relationships reflected a medium effect size (Partial-η² 0.09-0.14). These data suggest differential impacts of AUD and CUD on reward versus error detection neuro-circuitries within the adolescent brain.     

Bipolar disorder,testosterone administration,and homicide: A case report

Objective. Homicide is a major public health and social concern in the United States. Studies have found higher rates of psychiatric disorders in homicide offenders than in the general population. The aim of this article is to report and to discuss a case of a patient with bipolar disorder and hypogonadism who murdered his wife shortly after a testosterone injection. Methods. A case study and a review of the relevant literature. Results. Our case study as well as several case reports in the literature suggests that testosterone administration or high testosterone levels may be associated with homicidal behavior. Conclusion. Further studies of the role of testosterone in the neurobiology of violent and homicidal behavior may lead to improvements in the prevention of homicides.     

Clozapine use and relapses of substance use disorder among patients with co-occurring schizophrenia and substance use disorders

BACKGROUND: Previous correlational research with schizophrenic patients has suggested that the second-generation antipsychotic medication clozapine helps to induce remissions of substance use disorder in patients with co-occurring psychosis and substance abuse. This research, however, could be biased by selection factors. Studying patients who are currently in substance abuse remission could control for level of motivation to stop using substances and other methodological confounds. METHODS: To test whether clozapine was associated with prevention of substance abuse relapses, we examined patients with schizophrenia or schizoaffective disorder who were in their first 6-month remission of substance use disorder during a prospective 10-year follow-up study. All patients received yearly multimodal assessments of substance use. Antipsychotic medications were prescribed by community doctors as part of usual clinical care. RESULTS: Patients using clozapine at the first 6-month period of substance abuse remission (n = 25) were much less likely to relapse over the next year compared with those on other antipsychotic medications (n = 70): 8.0% vs 40.0%, chi(2) = 8.73 (df = 1), P = .003. Although medication assignment was not randomized, several potential confounders were similar between the groups. CONCLUSION: Clozapine should be considered for the treatment of patients with schizophrenia and co-occurring substance use disorder to prevent relapses to substance abuse.     

Psychiatric comorbidity associated with co-occurring autism spectrum disorder and substance use disorder

BackgroundAlthough both autism spectrum disorder (ASD) and substance use disorder (SUD) are both commonly comorbid with other psychiatric conditions, there is a paucity of research on the overlap of these disorders. The primary aim of the present study was to identify the prevalence of psychiatric comorbidities in young adults with SUD and ASD compared to those with ASD only.MethodMultivariate logistic regression controlling for age was used to compare the prevalence of psychiatric disorders in a sample of treatment-seeking adult outpatients with a) ASD without SUD and b) ASD with SUD. Psychiatric and SUD diagnoses were determined by semi-structured interview (SCID for DSM IV).ResultsThe sample included 42 patients with ASD only (mean age ± SD = 26.2 ± 8.9 years) and 21 with ASD and SUD (35.2 ± 12.6). High rates of psychopathology were found in both groups. Comorbid conduct disorder (CD) was significantly more prevalent in the ASD + SUD group (25 %) compared to those without SUD (5%; p < 0.05). There were no other significant differences between groups in the rates of non-conduct comorbid psychopathology.ConclusionIn both groups, rates of psychopathology were high with CD being significantly more common in young adults with ASD and SUD. These findings highlight the importance of screening for CD in individuals with ASD to mitigate the potential development of comorbid SUD. Further research is needed to determine if CD is a true risk factor for SUD in the ASD population and identify other risk factors.     

Cigarette smoking and its relationship to mood disorder symptoms and co-occurring alcohol and cannabis use disorders following first hospitalization for bipolar disorder

Heffner JL, DelBello MP, Anthenelli RM, Fleck DE, Adler CM, Strakowski SM. Cigarette smoking and its relationship to mood disorder symptoms and co‐occurring alcohol and cannabis use disorders following first hospitalization for bipolar disorder. Bipolar Disord 2012: 14: 99–108. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objectives: Cigarette smoking is highly prevalent among individuals with bipolar disorder (BD) and may adversely affect symptoms of the disorder, as well as the co‐occurrence of other substance use disorders. However, anecdotal reports suggesting that smoking cessation caused a worsening of mood in smokers with BD have raised concerns about quitting. In the present study, we prospectively evaluated the course of BD, alcohol use disorders, and cannabis use disorders in relation to smoking and examined the relationship between smoking abstinence and changes in mood. Methods: Participants (N = 161) were adolescents (n = 80) and adults (n = 81) with bipolar I disorder who were hospitalized for their initial mixed or manic episode. Participants were followed up to eight years post‐hospitalization (median follow‐up = 122 weeks) as part of a naturalistic, observational study of the longitudinal course of BD and substance use. Results: The course of BD symptoms in the 12 months following index hospitalization did not differ by smoking status in either the adolescent or the adult subsample. Among adolescents, smoking was associated with an increased risk of having a cannabis or alcohol use disorder, almost all of which were new‐onset disorders, in the year following first hospitalization. Neither adolescents nor adults who were abstinent from smoking for at least two months experienced significant increases in depressive or manic symptoms. Conclusions: Although cigarette smoking did not predict a worse course of BD, smoking was associated with an increased risk of developing alcohol and cannabis use disorders in adolescents with BD. Importantly, these data provide no evidence to suggest that abstinence from smoking is associated with worsening symptoms of depression or mania in the short term.     

Differential prevalence and demographic and clinical correlates of second-generation antipsychotic use in bipolar I versus bipolar II disorder

AimsTo assess second-generation antipsychotic (SGA) use, demographics, and clinical correlates in patients with bipolar I disorder (BDI) versus bipolar II disorder (BDII).MethodsStanford Bipolar Disorder (BD) Clinic outpatients enrolled during 2000–2011 were assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation. Current SGA use, demographics, and clinical correlates were assessed for BDI versus BDII.ResultsAmong 503 BD outpatients, in BDI versus BDII, SGA use was more than twice as common (44.0% versus 21.2%), and doses were approximately twice as high. BDI patients taking (N = 107) versus not taking (N = 136) SGAs less often had current full time employment and college degree; and more often had lifetime psychiatric hospitalization, current depression, and current complex pharmacotherapy, and had a higher mean current Clinical Global Impression for Bipolar Version Overall Severity score, and these persisted significantly after covarying for employment and education. Prior psychiatric hospitalization was the most robust correlate of SGA use in BDI patients. In contrast, these demographic and clinical correlates of SGA use were not statistically significant among patients with BDII, although BDII (but not BDI) patients taking (N = 55) versus not taking (N = 205) SGAs were more likely to have current mood stabilizer use (67.3% versus 51.7%).LimitationsAmerican tertiary bipolar disorder clinic referral sample, cross-sectional design.ConclusionsCurrent SGA use was robustly associated with prior psychiatric hospitalization in BDI and to a more limited extent with current mood stabilizer use in BDII. SGA use associations with other unfavorable illness characteristics in BDI were less robust.     

Risky sexual behavior among adolescents: The role of decision-making,problems from cannabis use and externalizing disorder symptoms

Introduction: Previous research has demonstrated that externalizing symptoms, cannabis use problems, and poor decision-making abilities are each independently related to risky sexual behavior (RSB). However, few studies have examined the joint effect of these factors on RSB among a sample of adolescents. Methods: The current study addresses this gap in the literature by examining how externalizing disorder symptoms, cannabis use, and decision-making abilities interact to predict RSB among a sample of adolescents (n = 204; M_age = 15.5) at-risk for escalation in cannabis use. Poisson regression was used for all analyses, and simple slope difference tests were used for all post-hoc analyses. Results: A greater number of externalizing symptoms, more problems from cannabis use, and more risk disadvantageous choices on the Cups Task (CT) total trials and more risk disadvantageous choices on the CT-gain trials predicted greater RSB endorsement. Findings also highlight significant interactions between cannabis use problems and CT-total and -gain trial performance, as well as between cannabis use problems and externalizing symptoms in predicting RSB.Conclusion: Current treatment and prevention approaches to reduce RSB among adolescents may benefit from incorporating techniques that improve decision-making skills.     

Prospective associations between cannabis use, abuse, and dependence and panic attacks and disorder

The present study prospectively evaluated cannabis use, abuse, and dependence in relation to the development of panic attacks and panic disorder. Participants at the start of the study were adolescents (n=1709) with a mean age of 16.6 years (SD=1.2; time 1) and were re-assessed 1 year later (time 2) and then again as young adults (time 3; mean age=24.2 years, SD=0.6). Results indicated that cannabis use and dependence were significantly prospectively associated with an increased odds for the development of panic attacks and panic disorder. However, cannabis was not incrementally associated with the development of panic after controlling for daily cigarette smoking. The theoretical and clinical implications of these findings are discussed.     

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.     

Women are taking the hit: Examining the unique consequences of cannabis use across the female lifespan

Cannabis use has risen dramatically in recent years due to global decriminalization and a resurgence in the interest of potential therapeutic benefits. While emerging research is shaping our understanding of the benefits and harms of cannabis, there remains a paucity of data specifically focused on how cannabis affects the female population. The female experience of cannabis use is unique, both in the societal context and because of the biological ramifications. This is increasingly important given the rise in cannabis potency, as well as the implications this has for the prevalence of Cannabis Use Disorder (CUD). Therefore, this scoping review aims to discuss the prevalence of cannabis use and CUD in women throughout their lifespan and provide a balanced prospective on the positive and negative consequences of cannabis use. In doing so, this review will highlight the necessity for continued research that goes beyond sex differences.     

Shared genetic factors influence risk for bipolar disorder and alcohol use disorders

Bipolar disorder and alcohol use disorder (AUD) have a high rate of comorbidity, more than 50% of individuals with bipolar disorder also receive a diagnosis of AUD in their lifetimes. Although both disorders are heritable, it is unclear if the same genetic factors mediate risk for bipolar disorder and AUD. We examined 733 Costa Rican individuals from 61 bipolar pedigrees. Based on a best estimate process, 32% of the sample met criteria for bipolar disorder, 17% had a lifetime AUD diagnosis, 32% met criteria for lifetime nicotine dependence, and 21% had an anxiety disorder. AUD, nicotine dependence and anxiety disorders were relatively more common among individuals with bipolar disorder than in their non-bipolar relatives. All illnesses were shown to be heritable and bipolar disorder was genetically correlated with AUD, nicotine dependence and anxiety disorders. The genetic correlation between bipolar and AUD remained when controlling for anxiety, suggesting that unique genetic factors influence the risk for comorbid bipolar and AUD independent of anxiety. Our findings provide evidence for shared genetic effects on bipolar disorder and AUD risk. Demonstrating that common genetic factors influence these independent diagnostic constructs could help to refine our diagnostic nosology.     

Behavioral therapies for co-occurring substance use and mood disorders.

There has been marked progress in recent years in the development of effective behavioral therapies for substance use disorders and in the largely independent development of behavioral therapies for mood disorders. Until recently, however, there were few well-specified behavioral approaches that incorporated an integrated approach for individuals in whom these disorders co-occur. The emerging literature on the efficacy of several types of behavioral therapy for engaging individuals with co-occurring mood and substance use disorders in treatment, reducing substance use and affective symptoms, enhancing adherence, and preventing disengagement and relapse is reviewed, followed by discussion of the challenges likely to be met in integrating these behavioral approaches into clinical practice.     

Quality of life and risk of psychiatric disorders among regular users of alcohol,nicotine, and cannabis: An analysis of the National Epidemiological Survey on Alcohol and Related Conditions (NESARC)

Research is limited on the effects of regular substance use on mental health-related outcomes. We used a large nationally representative survey to examine current and future quality of life and risk of psychiatric disorders among past-year regular (weekly) users of alcohol, nicotine, and cannabis. Data on psychiatric disorders and quality of life from two waves (Wave 1 N = 43,093, Wave 2 N = 34,653) of the National Epidemiological Survey on Alcohol and Related Conditions (NESARC) were used to test study aims. In cross-sectional analyses, regular nicotine and cannabis use were associated with higher rates of psychiatric disorder, though regular alcohol use was associated with lower rates of disorders. Prospective analyses found that regular nicotine use predicted onset of anxiety, depressive, and bipolar disorders. Regular alcohol use predicted lower risk of these disorders. Regular cannabis use uniquely predicted the development of bipolar disorder, panic disorder with agoraphobia, and social phobia. Lastly, regular alcohol use predicted improvements in physical and mental health-related quality of life, whereas nicotine predicted deterioration in these outcomes. Regular cannabis use predicted declines in mental, but not physical health. These data add to the literature on the relations between substance use and mental and physical health and suggest increased risk of mental health problems among regular nicotine and cannabis users and better mental and physical health among regular alcohol users. Examination of mechanisms underlying these relationships is needed.     

Bipolar disorder: Functional neuroimaging markers in relatives

Neural models of anatomical and functional alterations have been proposed for bipolar disorders (BD). However, studies in affected patients do not allow disentangling alterations linked to the liability to BD from those associated with the evolution, medication and comorbidities of BD. Explorations in high risk subjects allow the study of these risk markers. We reported and summarized all functional magnetic resonance imaging (fMRI) studies focusing on first-degree relatives of BD patients. We found 29 studies reporting neural correlates of working memory (WM), emotional processing, executive functions and resting state in relatives of BD patients, compared to healthy subjects. Overall, the same regions that have been involved in patients, such as the inferior frontal gyrus and limbic areas, seem to be functionally altered in high-risk subjects.We conclude that the same brain regions already implicated in the pathophysiology of the disease such as the amygdala are also associated with the risk of BD. However longitudinal studies are required to understand their implication in the transition to BD.