Does recovery from substance use disorder matter in patients with bipolar disorder?

OBJECTIVE: To examine the potential impact of recovery from substance use disorder (SUD) on the course of bipolar disorder among patients diagnosed with both bipolar and substance use disorders according to DSM-IV criteria. METHOD: As part of the multicenter Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), we examined bipolar disorder status (i.e., whether the patient is recovering or recovered), role functioning, and quality of life in the first 1000 patients to enter the STEP-BD study. We compared patients with no history of SUD, current SUD, and past SUD (i.e., lifetime SUD, but no current SUD) on these parameters. Data were collected between November 1999 and April 2001. RESULTS: A current clinical status of recovering or recovered from bipolar disorder was less likely among patients with current or past SUD compared to patients with no SUD (p < .002). Recovering/recovered status did not differ significantly between patients with current SUD versus past SUD. All 3 groups differed significantly on measures of role functioning as assessed by the Longitudinal Interval Follow-Up Evaluation-Range of Impaired Functioning Tool (LIFE-RIFT), with poorest role functioning among patients with current SUD, followed by patients with past SUD (p = .0002). Patients with current or past SUD reported significantly lower quality of life as measured by the LIFE-RIFT and the Quality of Life Enjoyment and Satisfaction Questionnaire and more lifetime suicide attempts (p < .001) than patients without an SUD; patients with past versus current SUD did not differ significantly on these measures. CONCLUSION: The results suggest that patients with bipolar disorder who experience sustained remission from an SUD fare better than patients with current SUD, but not as well as subjects with no history of SUD; differences among the 3 groups appear greatest in the area of role functioning.     

Cognitive endophenotypes in a family with bipolar disorder with a risk locus on chromosome 4

Objectives: We studied cognitive function in high‐risk relatives belonging to a single extended family showing linkage of bipolar disorder to a locus on chromosome 4. High‐risk relatives were defined as those that carried the risk haplotype of polymorphic markers, identified in a previous linkage study. This family provided a rare opportunity to characterize a neuropsychological endophenotype in a homogeneous sample of relatives with a common genetic risk factor. Methods: Fifteen family members carrying the risk haplotype (eight diagnosed with bipolar disorder or depression and seven with no psychiatric diagnosis), unrelated patients with bipolar disorder (n = 36) and major depressive disorder (n = 40), and healthy control subjects (n = 33) were administered the California Verbal Learning Test, Verbal Fluency Test, Hayling Sentence Completion Test, and Brixton Spatial Anticipation Test to assess verbal memory, verbal fluency, and executive function. Results: Compared with healthy controls, family members carrying the risk haplotype were impaired in indices of memory and executive function. There were no significant differences between unaffected and affected haplotype‐carrying family members in any cognitive measure. Pronounced deficits in the encoding stage of verbal memory and category verbal fluency were evident in individuals with the risk haplotype. Conclusions: Verbal learning and semantic verbal fluency impairments may represent a cognitive endophenotype for both bipolar disorder and major depression in relatives of bipolar disorder patients, as impairment was also present in high‐risk relatives who had not developed any affective disorder symptoms. These findings suggest that impairment in semantic organization may be linked to the genetic aetiology of bipolar disorder.     

Neurocognitive function in clinically stable men with bipolar I disorder or schizophrenia and normal control subjects.

BACKGROUND: Patients with bipolar disorder and schizophrenia have been shown to have neurocognitive deficits when compared with control subjects. The degree and pattern of impairment between psychiatric groups have rarely been compared, especially when subjects are psychiatrically stable. METHODS: Using a standard neurocognitive battery, we compared euthymic outpatients with bipolar disorder (n = 40), stable patients with schizophrenia (n = 20), and subjects with no psychiatric disorder (n = 22). The neurocognitive domains assessed included executive functioning, verbal memory, visual memory, procedural learning, visuoconstructive ability, and language functions. Effect sizes were calculated for each cognitive domain across groups. RESULTS: Stable schizophrenic subjects demonstrated a generalized cognitive impairment across most domains compared with control subjects, with average effect sizes of .9. Euthymic bipolar subjects were significantly impaired compared with control subjects only in executive functioning (Wisconsin Card Sorting Task) and verbal memory (California Verbal Learning Test) domains (effect sizes in the .8-.9 range). Performance on the executive function measures was bimodal among bipolar subjects, suggesting two subgroups: one with relatively normal and one with impaired executive functioning. No significant differences between the bipolar patient group and control subjects were observed in visuoconstructive ability, procedural learning, or language function. CONCLUSIONS: Both euthymic bipolar subjects and relatively stable schizophrenic subjects differed from control subjects in neurocognitive function. Among schizophrenic subjects, a generalized cognitive impairment was observed, and the degree of impairment was greater in the schizophrenic compared with the bipolar subjects. Subjects with bipolar disorder were impaired in two specific domains (verbal memory and executive function). Furthermore, within the bipolar group there was a subset with relatively normal executive functioning and a subset with significant impairment. Possible reasons for the persistence of these neurocognitive deficits in some subjects with bipolar disorder during periods of euthymia are reviewed.     

Bipolar disorder and co-occurring cannabis use disorders: Characteristics,co-morbidities and clinical correlates

This study examines rates of co-morbid mental disorders and indicators of the course of illness among individuals with bipolar disorder and cannabis use disorders (CUD). Data were drawn from the National Epidemiological Survey of Alcohol and Related Conditions (NESARC Wave 1, 2001–2002), a nationally representative sample of adults living in the United States. Among individuals with lifetime prevalence of bipolar disorder (N=1905) rates of CUD in the past 12 months were 7.2%, compared to 1.2% in the general population. Logistic regression models adjusting for sociodemographic variables indicated that individuals with bipolar disorder and co-occurring CUD were at increased risk for nicotine dependence (Adjusted Odds Ratio (AOR)=3.8), alcohol (AOR=6.6) and drug (AOR=11.9) use disorders, as well as antisocial personality disorder (AOR=2.8) compared to those without CUD. Among individuals with co-occurring CUD, age of onset of bipolar disorder was significantly lower and median number of manic, hypomanic and depressive episodes per year was significantly greater compared to individuals without CUD. Co-occurring CUD is associated with significant co-morbidities and a more severe course of illness among individuals with bipolar disorder. Comprehensive evaluation of patients with bipolar disorder should include a systematic assessment of CUD.     

Functional impairment in the remission phase of bipolar disorder

OBJECTIVES: The purpose of this study was to evaluate functional impairment in a group of patients with bipolar disorder in remission and to determine the extent of relationships between overall functioning and current depressive, manic and panic spectrum symptoms. METHOD: A subset of the patient population at the Pittsburgh site of the Systematic Treatment Enhancement Program in Bipolar Disorder (STEP-BD) study was evaluated in this study. The subsample comprises 103 male and female subjects with bipolar I disorder (n = 70), bipolar II disorder (n = 24), schizoaffective disorder - bipolar type (n = 4), or bipolar disorder NOS (n = 5). Subjects were evaluated in a period of remission (at least 4 weeks with no more than two depressive or manic symptoms). Subjects were assessed for overall functional status using the Work and Social Adjustment Scale (WSAS) and for current bipolar and panic spectrum symptoms using the Mood Spectrum Self-Report questionnaire (MOODS-SR) and Panic-Agoraphobic Spectrum Self-Report questionnaire (PAS-SR). RESULTS: The median WSAS total score in these remitted subjects was 14, indicating significant functional impairment. Regressing WSAS on current depressive, manic, and panic spectrum total scores, we observed a highly significant depressive spectrum effect (t = 4.9, df = 94, p < 0.0001), but non-significant panic and manic spectrum effects (t = 1.3, df = 94, p = 0.19 and t = -1.8, df = 94, p = 0.07, respectively). CONCLUSION: Bipolar disorder is associated with functional deficits even during periods of sustained and substantial remission. The degree of functional impairment is correlated with the degree of depressive spectrum symptoms.     

Study of impulse-control disorders among alcohol-dependent patients.

BACKGROUND: Impulse-control disorders (ICDs) include intermittent explosive disorder, kleptomania, trichotillomania, pyromania, and pathological gambling. Several studies have suggested that the incidence of pathological gambling is substantially higher in alcoholics than in the general population. The rate of co-occurrence of other ICDs and alcohol dependence has never been systematically investigated. In our study, we assessed the frequency of all ICDs in a population of alcohol-dependent patients. We also examined the possibility that the presence of an ICD can correspond to earlier onset and more severe forms of alcoholism, which have a greater association with antisocial personality. METHOD: All patients hospitalized at our psychiatric unit for detoxification between January and August 1997 met DSM-IV criteria for alcohol dependence and were included in this study. Diagnosis of alcohol dependence was confirmed with the Mini-International Neuropsychiatric Interview. ICDs were investigated using the Minnesota Impulsive Disorders Interview. All patients completed the Michigan Alcoholism Screening Test. RESULTS: Among the 79 patients included in the study, 30 (38.0%) met criteria for an ICD. Included in the study were 19 cases of intermittent explosive disorder, 7 cases of pathological gambling, 3 cases of kleptomania, and 1 case of trichotillomania. Patients with co-occurring ICDs were significantly younger than patients without an ICD (mean age = 40.7 vs. 44.5 years; p = .03). Patients with co-occurring pathological gambling were significantly younger at the onset of alcohol dependence than patients without ICDs (mean age = 19.5 vs. 25.9 years; p = .0008). Pathological gamblers had significantly longer duration of alcohol dependence compared with patients without ICDs (26.0 vs. 17.9 years; p = .02). Patients with co-occurring intermittent explosive disorder had the shortest duration of alcohol dependence of all patients (9.9 years). Prevalence of antisocial personality disorder was no different in patients with or without co-occurring ICDs. CONCLUSION: Thirty-eight percent of the alcohol-dependent patients studied presented with an ICD. Patients with ICDs were younger than those without an ICD. The presence of an ICD was not associated with a specific form of alcohol dependence or with antisocial personality. Co-occurrence of pathological gambling, however, was associated with lower age at onset of alcohol dependence, a higher number of detoxifications, and a longer duration of alcohol dependence than was absence of an ICD.     

Medication adherence and attitudes in patients with bipolar disorder and current versus past substance use disorder

We examined the impact of substance use disorder (SUD) history among patients with bipolar I disorder (BD) in regards to medication-taking behaviors and attitudes. Interviews were conducted with inpatients hospitalized for BD, which included diagnostic instruments and measures of attitudes concerning psychiatric medications. We compared patients with BD and no history of SUD (BD-NH), BD and past history of SUD (BD-PH), and BD and current SUD (BD-C). The primary outcome variable was a standardized medication adherence ratio (SMAR) of [medication taken]/[medication prescribed]. Fifty-four patients with a BD diagnosis participated, which included BD-NH (n=26), BD-PH (n=19), and BD-C (n=9). The SMAR was significantly different among the three groups; post-hoc analyses revealed the SMAR was significantly lower among BD-C (M=0.70) compared to BD-NH (M=0.90) and BD-PH (M=0.97) patients. This finding remained significant after controlling for numerous patient characteristics. Attitudes regarding medications, measured by the Drug Attitude Inventory (DAI), were positive among a significantly higher percentage of BD-PH (89.47%) and BD-NH (65.38%) compared to BD-C (44.44%) patients. In conclusion, patients with BD-C demonstrated poor medication adherence and attitudes concerning medication management. Helping patients with BD achieve remission from SUD may lead to a more successful course of BD pharmacotherapy.     

Cognitive function across manic or hypomanic, depressed, and euthymic states in bipolar disorder

OBJECTIVE: The study aims were to address neuropsychological functioning across different states of bipolar illness and to determine relationships among clinical features, neuropsychological performance, and psychosocial functioning. METHOD: Several domains of cognitive function were examined in 30 depressed bipolar patients (DSM-IV criteria for major depression, Hamilton Depression Rating Scale score > or = 17), 34 manic or hypomanic bipolar patients (DSM-IV criteria for manic or hypomanic episode, Young Mania Rating Scale score > or = 12), and 44 euthymic bipolar patients (6 months of remission, Hamilton depression scale score < or = 8, and Young Mania Rating Scale score < or = 6). The comparison group consisted of 30 healthy subjects without history of neurological or psychiatric disorders. A neuropsychological battery assessed executive function, attention, and verbal and visual memory. RESULTS: The three groups showed cognitive dysfunction in verbal memory and frontal executive tasks in relation to the comparison group. Low neuropsychological performance was associated with poor functional outcome. Impairment of verbal memory was related to the duration of illness and the numbers of previous manic episodes, hospitalizations, and suicide attempts. CONCLUSIONS: A poorer performance was observed in all bipolar groups regarding executive function and verbal memory in relation to the healthy comparison subjects. These cognitive difficulties, especially related to verbal memory, may help explain the impairment regarding daily functioning, even during remission. Further studies should focus on testing, whether optimizing prophylactic pharmacological treatment and psychoeducation might reduce cognitive impairment, and whether bipolar patients would benefit from neuropsychological rehabilitation in order to reduce the impact of cognitive impairment in their overall functioning.     

Presence of co-morbid substance use disorder in bipolar patients worsens their social functioning to the level observed in patients with schizophrenia

Bipolar disorder has been considered to have a better prognosis than schizophrenia at the very beginning of its definition. However, psychosocial functioning may vary not only because of the characteristics of the disorder, but also of co-morbid conditions, especially regarding substance use disorder (SUD). The purpose of this study was to compare the social adjustment level of patients with bipolar disorder with that observed in patients with schizophrenia, taking into account substance use disorder (SUD). Forty subjects with schizophrenia and 40 subjects with bipolar disorder, in the stable phase of the disorder, were matched for age, gender and presence of SUD (DSM-IV criteria). The social adjustment scale was completed with socio-demographic and clinical characteristics of illness. The global adaptation score of bipolar patients with SUD was poorer than bipolar patients without SUD, but was not observed as being significantly different from that of patients with schizophrenia, with or without associated SUD. Suicide attempts, poor compliance, longer hospitalisation, shorter remissions and criminal activity were also more frequently observed in the group of patients with bipolar disorder and SUD. Presence of substance use disorder seems to have a greater weight than the main diagnostic (schizophrenia versus bipolar disorder) to predict worse social adjustment and poorer outcome.     

Health-related quality of life and functioning of middle-aged and elderly adults with bipolar disorder

OBJECTIVE: Data characterizing bipolar disorder in older people are scarce, particularly on functional status. We evaluated health-related quality of life and functioning (HRQoLF) among older outpatients with bipolar disorder as well as the relationship of HRQoLF to bipolar illness characteristics. METHOD: We compared community-dwelling middle-aged and older adults (age range, 45 to 85 years) with bipolar disorder (N=54; mean age=57.6 years), schizophrenia (N=55; mean age=58.5 years), or no psychiatric illnesses (N=38; mean age=64.7 years) on indicators of objective functioning (e.g., education, occupational attainment, medical comorbidity) and health status (e.g., Quality of Well-Being scale [QWB] and the Medical Outcomes Study-Short Form Health Survey [SF-36]). Within the group with bipolar disorder, we examined the relationship between HRQoLF and clinical variables (e.g., phase and duration of illness, psychotic symptoms, cognitive functioning). RESULTS: Patients with bipolar disorder were similar in educational and occupational attainment to the normal comparison group, but they obtained lower scores on the QWB and SF-36 (with large effect sizes). Compared with schizophrenia, bipolar disorder was associated with better educational and work histories but similar QWB and SF-36 scores and more medical comorbidity. Patients in remission from bipolar disorder had QWB scores that were worse than those of normal comparison subjects. Greater severity of psychotic and depressive symptoms and cognitive impairment were associated with lower HRQoLF. CONCLUSIONS: Bipolar disorder was associated with substantial disability in this sample of older adults, similar in severity to schizophrenia. Remission of bipolar disorder was associated with significant but incomplete improvement in functioning, whereas psychotic and depressive symptoms and cognitive impairment seemed to contribute to lower HRQoLF.     

Deficits in sustained attention in schizophrenia and affective disorders: stable versus state-dependent markers

OBJECTIVE: The authors compared sustained attention deficits measured by the Continuous Performance Test in patients with various affective disorders and patients with schizophrenia and examined whether Continuous Performance Test deficits in patients with affective disorders improve with remission of affective disorder symptoms. METHOD: Patients with schizophrenia (N=41), major depression without psychotic features (N=22), bipolar disorder without psychotic features (N=22), and bipolar disorder with psychotic features (N=46) completed Continuous Performance Test sessions with an undegraded version of the test and a 25% degraded version in which the stimulus images were visually distorted. Subjects were also interviewed with the Chinese version of the Diagnostic Interview for Genetic Studies. All inpatients with schizophrenia (N=41) and bipolar disorder (N=15) were assessed both at admission and discharge. Subjects' Continuous Performance Test scores were standardized in comparison with scores for a community sample of 345 subjects, with adjustment for age, sex, and level of education. RESULTS: Compared with the general population, all patient groups except the group with nonpsychotic major depression were significantly impaired in their ability to discriminate target stimuli from nontarget stimuli on the Continuous Performance Test. Patients with schizophrenia had the severest impairment, followed by patients with bipolar disorder with psychotic features and those with bipolar disorder without psychotic features. From admission to discharge, Continuous Performance Test deficits in schizophrenia remained unchanged, but inpatients with bipolar disorder showed significant improvement on the degraded Continuous Performance Test. All patients adopted a similar response criterion (the amount of perceptual evidence the person requires to decide that a stimulus is a target) to that in the general population, except that the patients with schizophrenia had a less stringent response criterion during the degraded Continuous Performance Test. CONCLUSIONS: Continuous Performance Test deficits are stable vulnerability indicators for schizophrenia, mediating indicators for bipolar disorder, and state-dependent indicators for major depression.     

Substance use disorders in bipolar disorder: An update

Substance use disorders (SUDs) commonly co-occur during the course of bipolar type I disorder, and they can negatively affect illness outcome. This paper reviews recent research examining SUDs in bipolar disorder. These studies confirmed the high prevalence rate of SUDs but found that they are less common in younger patients (< age 17 years). Two new longitudinal studies suggest that a co-occurring SUD worsens the prognosis of bipolar disorder and leads to more affective symptoms and suicide attempts. Two new studies have examined the treatment of bipolar patients with a comorbid SUD. These studies suggest that valproate (as an adjunct to lithium) and aripiprazole may be useful in the treatment of the affective symptoms of bipolar patients with a comorbid SUD and may also help with the treatment of the SUD.     

The International Society for Bipolar Disorders–Battery for Assessment of Neurocognition (ISBD‐BANC)

Yatham LN, Torres IJ, Malhi GS, Frangou S, Glahn DC, Bearden CE, Burdick KE, Martínez‐Arán A, Dittmann S, Goldberg JF, Ozerdem A, Aydemir O, Chengappa KNR. The International Society for Bipolar Disorders–Battery for Assessment of Neurocognition (ISBD‐BANC).
Bipolar Disord 2010: 12: 351–363. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S. Objectives: Although cognitive impairment is recognized as an important clinical feature of bipolar disorder, there is no standard cognitive battery that has been developed for use in bipolar disorder research. The aims of this paper were to identify the cognitive measures from the literature that show the greatest magnitude of impairment in bipolar disorder, to use this information to determine whether the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB), developed for use in schizophrenia, might be suitable for bipolar disorder research, and to propose a preliminary battery of cognitive tests for use in bipolar disorder research. Methods: The project was conducted under the auspices of the International Society for Bipolar Disorders and involved a committee that comprised researchers with international expertise in the cognitive aspects of bipolar disorder. In order to identify cognitive tasks that show the largest magnitude of impairment in bipolar disorder, we reviewed the literature on studies assessing cognitive functioning (including social cognition) in bipolar disorder. We further provided a brief review of the cognitive overlap between schizophrenia and bipolar disorder and evaluated the degree to which tasks included in the MCCB (or other identified tasks) might be suitable for use in bipolar disorder. Results: Based on evidence that cognitive deficits in bipolar disorder are similar in pattern but less severe than in schizophrenia, it was judged that most subtests comprising the MCCB appear appropriate for use in bipolar disorder. In addition to MCCB tests, other specific measures of more complex verbal learning (e.g., the California Verbal Learning Test) or executive function (Stroop Test, Trail Making Test–part B, Wisconsin Card Sorting Test) also show substantial impairment in bipolar disorder. Conclusions: Our analysis reveals that the MCCB represents a good starting point for assessing cognitive deficits in research studies of bipolar disorder, but that other tasks including more complex verbal learning measures and tests of executive function should also be considered in assessing cognitive compromise in bipolar disorder. Several promising cognitive tasks that require further study in bipolar disorder are also presented.     

Treatment of Functional Impairment in Patients with Bipolar Disorder

Traditionally, functional impairment has received little attention in bipolar disorder, despite the fact that many patients experience significant impairments in daily life. In the last decade, research has changed its focus from clinical remission to functional recovery in bipolar patients as a priority. A literature review of this topic will allow us provide an overview of the relevance of functional impairment as well as the potential factors that can predict or contribute to low functioning in bipolar disorder (BD). Treatment approaches should consider not only euthymia as a goal but also cognitive and functional improvement of patients with such a complex disorder. Functional remediation and psychoeducation among psychological interventions may help to enhance functioning. The combination of cognitive enhancers and cognitive/functional remediation programs may help in improving cognitive and functional impairments. Early interventions are essential to prevent cognitive deficits and disability.     

The catechol O-methyltransferase Val158Met polymorphism and herpes simplex virus type 1 infection are risk factors for cognitive impairment in bipolar disorder: additive gene-environmental effects in a complex human psychiatric disorder

BACKGROUND: Bipolar disorder is associated with deficits in cognitive functioning. The etiology of cognitive impairment in bipolar disorder may relate to both genetic and environmental factors. A valine/methionine polymorphism of the catechol O-methyltransferase gene at amino acid 158 (COMT Val158Met polymorphism) has been identified as a risk factor for cognitive impairment in schizophrenia. Serological evidence of infection with herpes simplex virus type 1 (HSV-1) has also been identified as a risk factor for cognitive impairment in bipolar disorder. METHODS: We used Taqman technology to measure COMT Val158Met alleles in 107 individuals with bipolar disorder and in 95 controls. We also measured antibodies to HSV-1 in sera obtained from the same individuals. Cognitive functioning was assessed with the Repeatable Battery for the Assessment of Neuropsychological Status and the Letter-Number Sequencing Test. The effects of the COMT Val158Met polymorphism and antibodies to HSV-1 on cognitive functioning were analyzed with multinomial logistic regressions. RESULTS: The COMT Val158Val genotype and serological evidence of infection with HSV-1 are independent risk factors for cognitive impairment in individuals with bipolar disorder, particularly in the domains of immediate and delayed memory. Individuals with bipolar disorder with the COMT158 Val/Val genotype and serological evidence of HSV-1 infection were more than 85 times more likely to be in the lowest quintile of cognitive functioning when compared with the highest quintile when controlling for potential confounding variables such as symptom severity and education. Control individuals did not display this association. CONCLUSION: Both the COMT Val158Met polymorphism and serological evidence of HSV-1 infection affect cognitive functioning in individuals with bipolar disorder.     

The duration of inpatient admission predicts cognitive functioning at discharge in patients with bipolar disorder

Previous studies of cognitive functioning in bipolar disorder generally indicate that a more severe course of illness is associated with greater cognitive impairment. In particular, a history of greater number and longer duration of mood episodes predicts enduring cognitive deficits in euthymic patients. Shifting the focus of this investigation to the cognitive effects of a discrete mood episode, the current study aimed to explore whether patients who require a longer hospitalization to stabilize from an acute episode of mood disturbance present with more compromised cognitive functioning during the phase of early recovery. For this purpose, the study examined the link between the duration of inpatient admission and neuropsychological test scores at the time of discharge in 41 patients with bipolar disorder. Participants were assigned to long (n = 20) and short (n = 21) stay groups using a median split (M = 12). Results indicated that longer admissions were associated with more severe deficits in executive functioning at discharge after controlling for residual mood symptoms and previous number of psychiatric admissions. Findings from the current study may inform discharge planning for patients with bipolar disorder after an extended hospital stay.     

Substance use disorder comorbidity in major depressive disorder: an exploratory analysis of the Sequenced Treatment Alternatives to Relieve Depression cohort

Patients with major depressive disorder (MDD) often present with concurrent substance use disorders (SUD) involving alcohol and/or illicit drugs. This analysis compares the depressive symptomatic presentation and a range of clinical and demographic features of patients with MDD and concurrent SUD symptoms vs those without SUD symptoms, to clarify how these two differ and to determine whether concurrent SUD symptoms may alter the clinical presentation of MDD. The first 1500 outpatients with nonpsychotic MDD enrolled in the Sequenced Treatment Alternatives to Relieve Depression study were divided into those with and without concurrent SUD symptoms as ascertained by a self-report instrument, the Psychiatric Diagnostic Screening Questionnaire (PDSQ). Of the 1484 cases with completed baseline PDSQ, 28% (n = 419) of patients with MDD were found to endorse symptoms consistent with current SUD. Patients with symptoms consistent with SUD were more likely to be men (P < .0001), to be either divorced or never married (P = .018), to have a younger age of onset of depression (P = .014), and to have a higher rate of previous suicide attempts (P = .014) than those without SUD symptoms. Patients with major depressive disorder who have symptoms consistent with SUD endorsed greater functional impairment attributable to their illness than those without concurrent SUD symptoms (P = .0111). The presence of SUD symptoms did not alter the overall depressive symptom pattern of presentation, except that the dual-diagnosed patients had higher levels of hypersomnia (P = .006), anxious mood (P = .047), and suicidal ideation (P = .036) compared to those without SUD symptoms. In conclusion, gender, marital status, age of onset of major depression, functional impairment, and suicide risk factors differ in depressed patients with concurrent SUD symptoms compared to those without SUD comorbidity.     

Psychotic spectrum disorders and alcohol abuse: a review of pharmacotherapeutic strategies and a report on the effectiveness of naltrexone and disulfiram

The rate of substance-use disorders in patients with mental illnesses within the psychotic spectrum, such as schizophrenia, schizoaffective disorder, and bipolar disorder, is higher than the rate observed in the general population and is associated with significant morbidity and mortality. Although there are currently 3 medications approved by the Food and Drug Administration for the treatment of alcohol dependence, no medications have been approved for the specific treatment of dually diagnosed patients. A small but growing body of literature supports the use of 2 of these medications, disulfiram and naltrexone, in dually diagnosed individuals. This article outlines a review of the literature about the use of disulfiram and naltrexone for alcoholism and in patients with comorbid mental illness. In addition, results are presented of a 12-week randomized clinical trial of disulfiram and naltrexone alone and in combination for individuals with Axis I disorders and alcohol dependence who were also receiving intensive psychosocial treatment. Individuals with a psychotic spectrum disorder, including schizophrenia, schizoaffective disorder, and bipolar disorder, had worse alcohol outcomes than those without a psychotic spectrum disorder. Individuals with a psychotic spectrum disorder had better alcohol-use outcomes on an active medication compared with placebo, but there was no clear advantage of disulfiram or naltrexone or of the combination. Retention rates and medication compliance in the study were high and exceeded 80%. Pharmacotherapeutic strategies should take into account the advantages and disadvantages of each medication. Future directions of pharmacotherapeutic options are also discussed.     

Clinical predictors of functional outcome of bipolar patients in remission

Objectives:  A number of studies have now shown that subjects with bipolar disorder (BD) have significant psychosocial impairment during interepisode intervals. This study was carried out to assess the level of functioning as well as to identify potential predictors of functioning in a well-defined, euthymic bipolar sample.
Methods:  The study included 71 euthymic bipolar patients and 61 healthy controls. The Functioning Assessment Short Test (FAST) was used to assess multiple areas of functioning such as autonomy, occupational functioning, cognitive functioning, interpersonal relationships, financial issues, and leisure time. Multivariate analysis was used to determine the global and specific clinical predictors of outcome.
Results:  Sixty percent (n = 42) of the patients had overall functional impairment (defined as a FAST total score > 11) compared to 13.1% (n = 8) of the control group (p = 0.001). Bipolar patients showed a worse functioning in all the areas of the FAST. Only four variables—older age, depressive symptoms, number of previous mixed episodes, and number of previous hospitalizations—were associated with poor functioning, on a linear regression model, which accounted for 44% of the variance ( F  =   12.54, df = 58, p < 0.001).
Conclusions:  A substantial proportion of bipolar patients experience unfavorable functioning, suggesting that there is a significant degree of morbidity and dysfunction associated with BD, even during remission periods. Previous mixed episodes, current subclinical depressive symptoms, previous hospitalizations, and older age were identified as significant potential clinical predictors of functional impairment.     

Impaired functioning in euthymic patients with bipolar disorder--HSV-1 as a predictor

There is a possible association between infectious agents and psychiatric disorders. Previous studies in the US provided evidence for cognitive impairment correlated with Herpes simplex virus type 1 (HSV-1) infection. For a replication study in Europe we chosed individuals diagnosed with bipolar disorder to analyse the correlation with HSV-1 infection. Antibody prevalence was analyzed by using solid phase immunoassay techniques. Cognitive functioning was tested with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Form A, the Trail Making Test A&B, and two subtests from the WAIS III: the Letter Number Sequencing Task and the subtest on information. History and psychopathology was assessed using structured interviews and validated rating scales (SCID, HRSD-21, YMRS, PANSS). Additionally, we investigated social functioning and quality of life using self-assessment-scales (SAS, LQLP). Prevalence rates of antibodies against diverse infectious agents did not differ significantly between patients and controls. We found a significant correlation between cognitive impairment in patients with bipolar disorder and the prevalence of antibodies directed against HSV-1. Cognitive functions were significantly impaired including language, attention, and immediate memory.The results of this study confirm previous findings suggesting that HSV-1 affects cognitive functions in patients with bipolar disorder. This may also result in more impaired functioning, less quality of life and difficulties in social adjustment.