Both Bipolar Disorder Research Articles

Comparing adaptive coding of reward in bipolar I disorder and schizophrenia.

Deficits in neural processing of reward have been described in both bipolar disorder (BD) and schizophrenia (SZ), but it remains unclear to what extent these deficits are caused by similar mechanisms. Efficient reward processing relies on adaptive coding which allows representing large input spans by limited neuronal encoding ranges. Deficits in adaptive coding of reward have previously been observed across the SZ spectrum and correlated with total symptom severity. In the present work, we sought to establish whether adaptive coding is similarly affected in patients with BD. Twenty-five patients with BD, 27 patients with SZ and 25 healthy controls performed a variant of the Monetary Incentive Delay task during functional magnetic resonance imaging in two reward range conditions. Adaptive coding was impaired in the posterior part of the right caudate in BD and SZ (trend level). In contrast, BD did not show impaired adaptive coding in the anterior caudate and right precentral gyrus/insula, where SZ showed deficits compared to healthy controls. BD patients show adaptive coding deficits that are similar to those observed in SZ in the right posterior caudate. Adaptive coding in BD appeared more preserved as compared to SZ participants especially in the more anterior part of the right caudate and to a lesser extent also in the right precentral gyrus. Thus, dysfunctional adaptive coding could constitute a fundamental deficit in severe mental illnesses that extends beyond the SZ spectrum.

Disease Burden Of Co-Occurring Borderline Personality Disorder In Patients With Bipolar Disorder

IntroductionIn recent years, advances in the areas of both bipolar disorder (BD) and borderline personality disorder (BPD) have generated considerable interest in the relationship between these two conditions, since that they are commonly comorbid.ObjectivesWe aimed to investigate the impact of BPD on course of illness in patients with BP.MethodsWe conducted a cross-sectional, descriptive and analytical study among 30 psychiatric outpatients diagnosed with BD in the Psychiatry « B » department, Hedi Chaker Hospital (Sfax, Tunisia). The McLean Screening Instrument for Borderline Personality Disorder (MSI-BPD) was used to screen for BPD. Clinical outcomes (hospital stays, comorbidities, suicidality…) were compared between BD- patients with or without BPD comorbidity.Results The mean age was 41.63 years, with a sex ratio of ½. Among the patients, 2/3 were diagnosed with BD-I, while 1/3 presented a BD-II. Physical comorbidities, comorbid anxious and eating disorders were noted respectively in 36.7%; 16.7% and 43.3% of patients. Suicidal attempts were reported in 46.7% of cases. According to MSI-BPD, a comorbid BPD was noted in 30% of our sample. Patients with BD-II were significantly more likely to present BDP traits (50%) than those with BD-I (20%) (p<0.001). Patients with BPD were significantly more likely to attempt suicide (p=0.033), and to present physical comorbidities (p<0.001) and comorbid eating disorders (p<0.001).ConclusionsOur study showed that BPD darkens the prognosis of BD, because of worse outcomes related to suicide, physical and psychiatric comorbidities. Thus, its co-occurrence complicates the management of BD.DisclosureNo significant relationships.

Precision psychiatry with immunological and cognitive biomarkers: a multi-domain prediction for the diagnosis of bipolar disorder or schizophrenia using machine learning

Precision psychiatry is attracting increasing attention lately as a recognized priority. One of the goals of precision psychiatry is to develop tools capable of aiding a clinically informed psychiatric diagnosis objectively. Cognitive, inflammatory and immunological factors are altered in both bipolar disorder (BD) and schizophrenia (SZ), however, most of these alterations do not respect diagnostic boundaries from a phenomenological perspective and possess great variability in different individuals with the same phenotypic diagnosis and, consequently, none so far has proven to have the ability of reliably aiding in the differential diagnosis of BD and SZ. We developed a probabilistic multi-domain data integration model consisting of immune and inflammatory biomarkers in peripheral blood and cognitive biomarkers using machine learning to predict diagnosis of BD and SZ. A total of 416 participants, being 323, 372, and 279 subjects for blood, cognition and combined biomarkers analysis, respectively. Our multi-domain model performances for the BD vs. control (sensitivity 80% and specificity 71%) and for the SZ vs. control (sensitivity 84% and specificity 81%) pairs were high in general, however, our multi-domain model had only moderate performance for the differential diagnosis of BD and SZ (sensitivity 71% and specificity 73%). In conclusion, our results show that the diagnosis of BD and of SZ, and that the differential diagnosis of BD and SZ can be predicted with possible clinical utility by a computational machine learning algorithm employing blood and cognitive biomarkers, and that their integration in a multi-domain outperforms algorithms based in only one domain. Independent studies are needed to validate these findings.

Reduced density of oligodendrocytes and oligodendrocyte clusters in the caudate nucleus in major psychiatric illnesses

Functional dysconnectivity in schizophrenia and affective disorders may be associated with myelin and oligodendrocyte abnormalities. Altered network integration involving the caudate nucleus (CN) and metabolic abnormalities in fronto-striatal-thalamic white matter tracts have been reported in schizophrenia and impaired patterns of cortico-caudate functional connectivity have been found in both bipolar disorder (BPD) and schizophrenia compared to healthy controls. Postmortem studies have found ultrastructural dystrophy and degeneration of oligodendrocytes and dysmyelination in the CN in schizophrenia and BPD. We aimed to test the hypothesis that oligodendrocyte density may be reduced in the CN in major psychiatric disorders and may thereby form the cellular basis for the functional dysconnectivity observed in these disorders. Optical disector was used to estimate the numerical density (Nv) of oligodendrocytes and oligodendrocyte clusters (OLC) in the CN of cases with schizophrenia, BPD and major depressive disorder (MDD) and in normal controls (15 cases per group). A significant reduction in the Nv of oligodendrocytes was found in schizophrenia and BPD as compared to the control group (p < 0.05), and the Nv of OLC was significantly lowered in schizophrenia and BPD compared to controls (p < 0.05). There were no significant differences between MDD and control groups. The Nv of OLC was significantly decreased in the left hemisphere in schizophrenia as compared to the left hemisphere of the control group (−52%, p < 0.01). The data indicates that a decreased density of oligodendrocytes and OLC could contribute to the altered functional connectivity of the CN in subjects with severe mental illnesses.

SA65 - IDENTIFYING VARIANTS IN NF1A GENE TO BE ASSOCIATED WITH SEASONAL PATTERN AND SUSCEPTIBILITY FOR DEPRESSION THROUGH A CANDIDATE GENE APPROACH

Background Seasonal Pattern (SP) was reported in depressive patients of both Bipolar Disorder (BD) and Major Depressive Disorder (MDD). In this study, we aimed to investigate genetic contributions of seasonal pattern of major depressive episodes in both BD and MDD patients, including genes in relevant biological pathways indicated in previous studies. To further clarify the roles of the variants in depression, we conducted analyses using a case-control study design to examine whether the genetic variants for SP also possess effects on susceptibility to depression. Methods We recruited 472 BD (83%) and MDD (17%) patients in Taiwan. SP of depressive episode were defined according to interview questions as “Which season do you feel the worst?” in their first, the most serious, and the most recent episode within a year. Subjects answered a specific season in two of the three episode categories were considered SP+, while others were categorized as non-SP (SP-). The other dataset for depression was obtained from the Taiwan biobank with about 10,000 people. Cases were defined by self-report MDD history or having the sum-score greater than 3 in the Patient Health Questionnaire-4. We examined 15 genes (824 single nucleotide variants) including the melatonin pathway (MTNR1a, MTNR1b, AANAT), serotonin pathway (TPH2, HTR2A, HTR2B, SLC6A4), circadian feedback loop (NPAS2, CRY2, ARNTL, ARNTL2, RORA, RORB, PER) and NF1A gene that identified from a previous genome-wide association study of seasonal mania. Association analyses were performed by multivariate logistic regression, adjusting for gender, age, and diagnosis. We corrected for multiple testings using false discovery rate method. Results After excluding subjects with missing covariates, there were a total of 464 subjects with 162 (35%) in the SP+ and 302 (65%) in the SP- groups. No differences were observed in gender, age or diagnosis distribution between the two SP groups. Nominal associations with p-value The 20 markers were tested again for depression in 9862 individuals from Taiwan biobank. Although none of them showed genome-wide significance, 6 SNPs had nominal p-values Discussion We found that NF1A gene maybe a susceptible gene for depression and modifiable gene for SP. Some genetic variants in this gene are related to both seasonal pattern of depressive episodes and depression with nominal significance, indicating partially shared genetic components between the development of mood symptoms and seasonality in depression. Further investigation is needed for replication with more stringent seasonal pattern evaluation, and for exploring the exact biological functions of the identified genetic variants.

Abnormalities in High-Energy Phosphate Metabolism in First-Episode Bipolar Disorder Measured Using 31P-Magnetic Resonance Spectroscopy

BackgroundBrain energy metabolism is critical for supporting synaptic function and information processing. A growing body of evidence suggests abnormalities in brain bioenergetics in psychiatric disorders, including both bipolar disorder (BD) and schizophrenia. 31P magnetic resonance spectroscopy provides a noninvasive window into these processes in vivo. Using this approach, we previously showed that patients with BD show normal adenosine triphosphate (ATP) and phosphocreatine levels at rest but cannot maintain normal ATP levels in the visual cortex during times of high energy demand (photic stimulation). Because ATP is replenished from phosphocreatine via the creatine kinase reaction, we have now measured the creatine kinase forward reaction rate constant in BD. MethodsWe studied 20 patients experiencing a first episode of BD and 28 healthy control participants at 4T and quantified creatine kinase forward reaction rate constant using 31P magnetization transfer magnetic resonance spectroscopy as described previously. ResultsWe found a significant reduction in creatine kinase forward reaction rate constant in the BD group (F = 4.692, p = .036), whereas brain ATP and phosphocreatine concentrations, as well as brain parenchymal pH, were normal. ConclusionsThese results pinpoint a specific molecular mechanism underlying our previous observation of an inability to replenish brain ATP during times of high energy demand in BD.

Pituitary gland in Bipolar Disorder and Major Depression: Evidence from structural MRI studies: Special Section on “Translational and Neuroscience Studies in Affective Disorders”. Section Editor, Maria Nobile MD, PhD. This Section of JAD focuses on the relevance of translational and neuroscience studies in providing a better understanding of the neural basis of affective disorders. The main aim is to briefly

BackgroundThe function of the hypothalamo-pituitary-adrenal axis (HPA) has been widely investigated in mood disorders based on its role in regulating stress response. Particularly, Magnetic Resonance Imaging (MRI) reports have explored pituitary gland (PG) in both bipolar disorder (BD) and major depressive disorder (MDD). In this context, the present review summarizes the results from MRI studies with the final aim of commenting on the presence of common or distinct PG structural alterations between these two disabling illnesses. MethodsA bibliographic search on PUBMED of all MRI studies exploring PG volumes in BD and MDD as well as first-degree relatives (RELs) from 2000 up to October 2016 was performed. ResultsFollowing the screening process of the available literature it can be said that a) PG enlargement has been found in both BD and MDD, therefore potentially representing a common neurobiological marker characterizing mood disorders, and b) PG volumes are moderated by age and sex in both illnesses, although the direction and the extent of this moderation are still not fully clear. LimitationsFew MRI studies with heterogeneous results. ConclusionsThese hypotheses must be taken with caution especially because the heterogeneity of the results of the studies reviewed does not allow for a definite answer about the role of PG in affective disorders. Therefore, larger longitudinal studies investigating PG volumes in BD and MDD patients at the early phases of the illness, by considering females and males separately, are needed to further corroborate these findings.

Impulsivity and brain volume in patients with bipolar disorder type I and bipolar disorder type II

IntroductionImpulsivity is a key feature of both bipolar disorder (BD) type I (BDI) and type II (BDII).ObjectiveStructural neuroimaging studies help clarifying brain mechanisms underpinning the regulation of impulsivity in BDI and BDII.AimsTo address the question whether grey matter (GM) alterations relate differently with impulsivity in BDI and BDII.MethodsWe assessed 54 euthymic outpatients, diagnosed with BDI (n = 28) or BDII (n = 26) according to DSM-IV-TR criteria. They underwent a 3 T magnetic resonance imaging (MRI) investigation. GM brain volumes were analyzed on a voxel-by-voxel basis using Statistical Parametric Mapping 8. The Barratt Impulsiveness Scale (BIS), version 11A, was used to assess trait impulsivity.ResultsBDI and BDII patients present an inverse relationship between impulsivity and GM volume in two cerebral areas: the right cerebellum (right crus I) and the interface between the left angular gyrus and the left inferior parietal cortex (Brodmann Area 39, 7, 40). More specifically, a negative relationship for BPI and a positive relationship for BPII were found in both areas.ConclusionsResults suggest that the different diagnosis between BDI and BDII could have a significant effect on GM changes according to impulsivity severity and point up the importance of considering the BP subtype distinction in neuroimaging studies on this topic.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Genetic Studies on the Tripartite Glutamate Synapse in the Pathophysiology and Therapeutics of Mood Disorders.

Both bipolar disorder (BD) and major depressive disorder (MDD) have high morbidity and share a genetic background. Treatment options for these mood disorders are currently suboptimal for many patients; however, specific genetic variables may be involved in both pathophysiology and response to treatment. Agents such as the glutamatergic modulator ketamine are effective in treatment-resistant mood disorders, underscoring the potential importance of the glutamatergic system as a target for improved therapeutics. Here we review genetic studies linking the glutamatergic system to the pathophysiology and therapeutics of mood disorders. We screened 763 original genetic studies of BD or MDD that investigated genes encoding targets of the pathway/mediators related to the so-called tripartite glutamate synapse, including pre- and post-synaptic neurons and glial cells; 60 papers were included in this review. The findings suggest the involvement of glutamate-related genes in risk for mood disorders, treatment response, and phenotypic characteristics, although there was no consistent evidence for a specific gene. Target genes of high interest included GRIA3 and GRIK2 (which likely play a role in emergent suicidal ideation after antidepressant treatment), GRIK4 (which may influence treatment response), and GRM7 (which potentially affects risk for mood disorders). There was stronger evidence that glutamate-related genes influence risk for BD compared with MDD. Taken together, the studies show a preliminary relationship between glutamate-related genes and risk for mood disorders, suicide, and treatment response, particularly with regard to targets on metabotropic and ionotropic receptors.

Discriminating Bipolar Disorder from Major Depression using Whole-Brain Functional Connectivity: a Feature Selection Analysis with SVM-FoBa Algorithm

It is known that both bipolar disorder (BD) and major depressive disorder (MDD) can manifest depressive symptoms, especially in the early phase of illness. Therefore, discriminating BD from MDD is a major clinical challenge due to the absence of biomarkers. Feature selection is especially important in neuroimaging applications, yet high feature dimensions, low sample size and poor model understanding present huge challenges. Here we developed an advanced feature selection algorithm, “SVM-FoBa”, which enables adaptive selection of informative feature subsets from high dimensional resting-state functional connectives (rsFC) data. By comparing SVM-FoBa with conventional feature selection methods on several public biomedical data sets, the proposed method was proven to be increasingly superior as the feature dimension became high. When applying SVM-FoBa to brain data, with 38 significant rsFCs chosen from 6670 in total, an 88 % classification accuracy between BD and MDD was achieved using leave-one-out cross-validation. Further, by conducting weight analysis, the most discriminative FCs were revealed, providing which adds to our understanding of functional deficits and may serve as potential biomarkers for mood disorders.

Deficits in axon-associated proteins in prefrontal white matter in bipolar disorder but not schizophrenia.

Brain imaging studies have implicated white matter dysfunction in the pathophysiology of both bipolar disorder (BD) and schizophrenia (SCZ). However, the contribution of axons to white matter pathology in these disorders is not yet understood. Maintenance of neuronal function is dependent on the active transport of biological material, including synaptic proteins, along the axon. In this study, the expression of six proteins associated with axonal transport of synaptic cargoes was quantified in postmortem samples of prefrontal white matter in subjects with BD, those with SCZ, and matched controls, as a measure of axonal dysfunction in these disorders. Levels of the microtubule-associated proteins β-tubulin and microtubule-associated protein 6 (MAP6), the motor and accessory proteins kinesin-1 and disrupted-in-schizophrenia 1 (DISC1), and the synaptic cargoes synaptotagmin and synaptosomal-associated protein-25 (SNAP-25) were quantified in white matter adjacent to the dorsolateral prefrontal cortex in subjects with BD (n = 34), subjects with SCZ (n = 35), and non-psychiatric controls (n = 35) using immunoblotting and an enzyme-linked immunosorbent assay (ELISA). Protein expression of β-tubulin, kinesin-1, DISC1, synaptotagmin, and SNAP-25 was significantly lower in subjects with BD compared to controls. Levels of axon-associated proteins were also lower in subjects with SCZ, but failed to reach statistical significance. These data provide evidence for deficits in axon-associated proteins in prefrontal white matter in BD. Findings are suggestive of decreased axonal density or dysregulation of axonal function in this disorder.

The Use of Quetiapine for Comorbid Bipolar and Obsessive Compulsive Disorders

Background: Both Bipolar Disorder (BD) and Obsessive Compulsive Disorder (OCD) are chronic psychiatric conditions, the first characterized by depressive and manic mood episodes and the latter characterized by obsessions and compulsions. The comorbidity between BD and OCD is not rare, and the presence of both conditions conveys important complications. The treatment supposes a challenge since antidepressants, first choice of treatment for OCD, carry an important risk for bipolar patients. Objective: In the present review our aim was to find evidence on Quetiapine's efficacy in the treatment of bipolar disorder with comorbid OCD. Method: We performed a literature review on the treatment options for comorbid BD and OCD, Quetiapine’s use in OCD and anxiety disorders and finally a MEDLINE search about the use of Quetiapine for this specific indication. Conclusion: The use of Quetiapine could be justified in patients with cycling OCD and in those who have shown benefit from this antipsychotic for BD and can tolerate adjunctive antidepressants. Still, clinical trials including this specific comorbid population should be performed to consider Quetiapine as part of BD-OCD patient’s treatment. Keywords: Bipolar disorder, obsessive compulsive disorder, comorbid, treatment, antipsychotic, quetiapine, SSRI.

Problematic Boundaries in the Diagnosis of Bipolar Disorder and Borderline Personality Disorder in First Depressive Episode

Introduction It is clinically important to recognize both bipolar disorder (BD) and borderline personality disorder (BPD) in patients seeking treatment for depression, and it is important to distinguish between the two. However, in routine clinical practice, the differentiation remains difficult. Objective and Methods The aim of the study was to illustrate the difficulty in the practice, to distinguish BD and BPD in depressed patients through a case report. Clinical label Mr IK 27-year-old, without medicals history. He is a single man with an animated life, professional instability, substance abuse, sensibility in the refusal, a tendency to impulsiveness and a feeling of meaning devoid. He was hospitalized for three consecutive suicide attempts. We found an unstable patient on the psychomotor plan, with depressive humour and anhedonia. The final diagnosis was major depressive episode without signs of bipolarity. He was putted under fluoxetine. The evolution was marked by a turn maniac. Diagnosis of BD and BPD were discussed. Aspect of the BPD appears and confirmed by Rorschach test. Conclusion At present the links between BD and BPD remains a subject of controversy. This case suggests that BPD needs to be diagnosed with a narrower set of criteria that cover all of its domains.

Connecting Childhood Maltreatment to Bipolar Disorder: A Biological Mechanism

Childhood trauma is associated with risk for both bipolar disorder (BD) and specific illness characteristics, including early onset, rapid cycling,

The impact of childhood trauma on cognitive functioning in patients recently recovered from a first manic episode: Data from the Systematic Treatment Optimization Program for Early Mania (STOP-EM).

Background: Both bipolar disorder (BD) and childhood trauma are associated with cognitive impairment. People with BD have high rates of childhood trauma, which confer greater overall disease severity, but, it is unknown if childhood trauma is associated with greater neurocognitive impairment in BD patients early in the course of their illnesses. In this study, we investigated the impact of childhood trauma on specific cognitive dysfunction in patients who recently recovered from their first episode of mania. Methods: Data were available for 64 patients and 28 healthy subjects matched by age, gender and pre-morbid IQ, recruited from a large university medical center. History of childhood trauma was measured using the Childhood Trauma Questionnaire. Cognitive function was assessed through a comprehensive neuropsychological test battery. Results: Trauma was associated with poorer cognitive performance in patients on cognitive measures of IQ, auditory attention and verbal and working memory, and a different pattern was observed in healthy subjects. Limitations: We had a modest sample size, particularly in the group of healthy subjects with trauma. Conclusions: Childhood trauma was associated with poorer cognition in BD patients who recently recovered from a first episode of mania compared to healthy subjects. The results require replication, but suggest that the co-occurrence of trauma and bipolar disorder can affect those cognitive areas that are already more susceptible in patients with BD.

Lithium Treatment of a Bipolar Patient with Wilson's Disease: A Case Report

We present the case of a male patient with a family history of both bipolar disorder (BD) and Wilson's disease (WD). Wilson's disease was diagnosed for this patient in 2008, at the age of 28 years, and shortly thereafter his bipolar illness began with depressive episodes. The patient has been treated with zinc sulphate for WD and with antidepressants for depression. In 2009, lithium was added, and in 2010 antidepressants were discontinued. During treatment with zinc sulphate, a gradual improvement of hepatic indices and a decrease of mandibulofacial dystonia was noted. In 2011, a hypomanic state occurred which subsided with an increase of the lithium dose. Since then, the patient has been mostly in a euthymic mood with subclinical hypomanic periods. We suggest that lithium may be a viable option for treating bipolar illness in patients with Wilson's disease.

Genetic association of the Phosphoinositide‐3 kinase in schizophrenia and bipolar disorder and interaction with a BDNF gene polymorphism

Phosphoinositide-3-kinase, class III (PIK3C3) is a member of the phosphoinosite-3-kinases family, involved in cell signaling, membrane trafficking, and neurodevelopment. Previous studies have indeed shown an association between PIK3C3 gene variants and both bipolar disorder (BD) and schizophrenia (SZ). Brain-derived neurotrophic factor (BDNF) is a neurodevelopmental factor, which can regulate the PI3K signaling pathway. Associations have been reported between BDNF gene polymorphisms and affective and psychotic disorders. The aim of the present study was to replicate an association between PIK3C3 and BDNF gene variants in SZ and BD and a putative epistasis between the two genes. Patients meeting the DSM-IV criteria of BD and SZ were included in this study (98 BD and 79 SZ) as well as 158 healthy controls. Blood DNA was extracted and genotyping was performed either by the polymerase chain reaction (PCR) technique followed by enzymatic digestion or by the high-resolution melt (HRM) method. Genotype and haplotype association was assessed with the UNPHASED statistical program.The results showed one nominal association with BD (P < 0.02) and two risk haplotypes in both SZ (P < 0.001) and BP (P < 0.0005), which survived multiple testing correction. A modest interaction between a BDNF variant and PI3KC3 polymorphism was observed (P < 0.04).These preliminary results confirm the genetic association of PI3K gene variants with both SZ and BD, and support the hypothesis that SZ and BD share a genetic background.

P01-223-Recovery of cognitive functioning in patients with co-occurring bipolar disorder and alcohol dependence during early remission from an acute mood episode

IntroductionPreliminary data suggest that patients who suffer from both bipolar disorder (BD) and alcohol dependence (AD) may be more vulnerable to cognitive dysfunction than patients with a single diagnosis, especially during periods that are clinically unstable.ObjectiveThe purpose of this study was to examine the cognitive recovery of dually-diagnosed patients during remission from an acute mood disturbance.AimThe study aimed to replicate our previous comparison of cognitive functioning between BD patients with and without AD, while on the inpatient unit, and to extend this investigation in a longitudinal design post-discharge.MethodFifty-five adult inpatients with bipolar I disorder completed a neuropsychological battery, mood measures and substance abuse measures upon discharge from the hospital and at a 3 month follow up. Analyses provided group comparisons on these measures between patients who presented with co-occurrence of AD (n = 21) in the year prior to hospital admission and patients without a Substance Use Disorder (SUD; n = 34).ResultsCompared to patients without SUD, dually-diagnosed patients scored significantly more poorly on measures of visual memory, verbal memory and executive functioning both at hospital discharge and follow-up. They also exhibited more limited recovery of these functions over the course of this period. Mood symptoms decreased in both groups from discharge to follow up.ConclusionsPatients with co-occurring BD and AD may suffer from more severe cognitive dysfunction and less favorable recovery of cognitive deficits than BD patients without SUD over the course of remission from a mood episode.

The relative roles of bipolar disorder and psychomotor agitation in substance dependence.

Previous studies have shown that both bipolar disorder (BPD) and psychomotor agitation (PMA) are associated with substance dependence. These two findings have yet to be integrated, despite evidence that PMA is closely linked with the bipolar spectrum. Accordingly, the current study examined whether BPD and PMA had unique or overlapping associations with substance dependence disorders. Participants were 2,300 individuals seeking outpatient psychiatric treatment. Before treatment, participants were assessed using structured clinical interviews, which yielded DSM-IV psychiatric diagnoses and clinical ratings of mood symptoms. Current PMA and lifetime BPD were present in 483 and 172 (bipolar I, n = 71; bipolar II, n = 101) participants, respectively. Current PMA and lifetime BPD each were associated with increased prevalence of lifetime nicotine, alcohol, and drug dependence (ORs >or= 1.52, ps <or= .0004). These associations remained significant when controlling for demographic characteristics and comorbid psychiatric disorders, except the link between agitation and alcohol dependence, which was reduced to a trend (p = .058). Although BPD and PMA were associated with each other, these two factors demonstrated unique, nonoverlapping relationships to nicotine, alcohol, and drug dependence. Individuals with both PMA and BPD exhibited especially high rates of comorbid substance dependence. The present results replicate and extend previous findings documenting the relations of BPD and PMA to substance dependence. BPD and PMA may represent independent psychopathological correlates of substance dependence. Future research should explore the theoretical and clinical significance of these potentially distinct relations to substance dependence.

Conceptualizing impulsivity and risk taking in bipolar disorder: importance of history of alcohol abuse.

Elevated levels of impulsivity and increased risk taking are thought to be core features of both bipolar disorder (BD) and addictive disorders. Given the high rates of comorbid alcohol abuse in BD, alcohol addiction may exacerbate impulsive behavior and risk-taking propensity in BD. Here we examine multiple dimensions of impulsivity and risk taking, using cognitive tasks and self-report measures, in BD patients with and without a history of alcohol abuse. Thirty-one BD subjects with a prior history of alcohol abuse or dependence (BD-A), 24 BD subjects with no history of alcohol abuse/dependence (BD-N), and 25 healthy control subjects (HC) were assessed with the Barratt Impulsiveness Scale (BIS) and the computerized Balloon Analogue Risk Task (BART). Both BD groups scored significantly higher than controls on the BIS. In contrast, only the BD-A group showed impaired performance on the BART. BD-A subjects popped significantly more balloons than the BD-N and HC groups. In addition, subjects in the BD-A group failed to adjust their performance after popping balloons. Severity of mood symptomatology was not associated with performance on either task. The current study supports a primary role of prior alcohol abuse in risk-taking propensity among patients with bipolar disorder. In addition, findings suggest that impulsivity and risky behavior, as operationalized by self-report and experimental cognitive probes, respectively, are separable constructs that tap distinct aspects of the bipolar phenotype.