1: J Affect Disord 2001 Sep;66(1):13-8 Bipolar II depression in late life: prevalence and clinical features in 525 depressed outpatients. Benazzi F. Department of Psychiatry, Public Hospital Morgagni, 47100 Forli, Italy. f.benazzi@fu.nettuno.it BACKGROUND: Late-life bipolar II depression has not been well studied. The aim of the present study was to find the prevalence of late-life (50 years or more) bipolar II depression among unipolar and bipolar depressed outpatients, and to compare it with bipolar II depression in younger patients, looking for differences supporting the subtyping of bipolar II depression according to age at onset. METHODS: Consecutive 525 patients presenting for treatment of a major depressive episode were interviewed with the Structured Clinical Interview for DSM-IV, the Montgomery Asberg Depression Rating Scale, and the Global Assessment of Functioning Scale. RESULTS: Among patients less than 50 years, 53.4% had bipolar II depression. Among patients 50 years or more, 32.9% had bipolar II depression (significant difference). Atypical features were present in 60.9% of bipolar II patients less than 50 years, and in 26.1% of those 50 years or more (significant difference). Bipolar II patients 50 years or more had significantly higher age at onset than those less than 50 years. Bipolar II and unipolar patients 50 years or more were not significantly different, apart from comorbidity. Bipolar II patients less than 50 years had significantly more atypical features than unipolar ones. LIMITATIONS: Single interviewer, single nonblind assessment, cross-sectional assessment, exclusion of substance abuse and severe personality disorder patients, comorbidity not systematically assessed, modification of DSM-IV duration criterion for hypomania. CONCLUSIONS: Findings suggest that bipolar II depression and atypical features are less common in late life. Differences in age at onset and atypical features support the subtyping of bipolar II depression according to age at onset. PMID: 11532528 [PubMed - indexed for MEDLINE] 2: Bipolar Disord 2001 Aug;3(4):181-8 Substance abuse in bipolar disorder. Cassidy F, Ahearn EP, Carroll BJ. Duke-Umstead Bipolar Disorders Program, Duke University, Durham, NC 27710, USA. cassi002@mc.duke.edu BACKGROUND: High rates of substance abuse have been reported in the general population, with males more often affected than females. Although high rates of substance abuse have also been reported in bipolar patients, the relationship between substance abuse and bipolar disorder has not been well characterized. METHODS: Substance abuse histories were obtained in 392 patients hospitalized for manic or mixed episodes of bipolar disorder and rates of current and lifetime abuse calculated. Analyses comparing sex, subtype (manic vs. mixed) and clinical history variables were conducted. RESULTS: Rates of lifetime substance abuse were high for both alcohol (48.5%) and drugs (43.9%). Nearly 60% of the cohort had a history of some lifetime substance abuse. Males had higher rates of abuse than females, but no differences in substance abuse were observed between subjects in manic and mixed bipolar states. Rates of active substance abuse were lower in older age cohorts. Subjects with a comorbid diagnosis of lifetime substance abuse had more psychiatric hospitalizations. CONCLUSIONS: Substance abuse is a major comorbidity in bipolar patients. Although rates decrease in older age groups, substance abuse is still present at clinically important rates in the elderly. Bipolar patients with comorbid substance abuse may have a more severe course. These data underscore the significance of recognition and treatment of substance abuse in bipolar disorder patients. Publication Types: Review Review, Tutorial PMID: 11552957 [PubMed - indexed for MEDLINE] 3: Eur Psychiatry 2001 Aug;16(5):289-92 Bipolar sensation seeking is associated with a propensity to abuse rather than to temperamental characteristics. Henry C, Bellivier F, Sorbara F, Tangwongchai S, Lacoste J, Faure-Chaigneau M, Leboyer M. Service Universitaire de Psychiatrie, CHS Charles Perrens, 121 rue de la Bechade, F-33076 cedex, Bordeaux, France. chantal.henry@bordeaux.inserm.fr OBJECTIVE: As some temperament profiles may be markers of genetic vulnerability traits, we aimed to compare sensation seeking in euthymic bipolar patients and in controls. METHODS: One hundred ninety-four patients fulfilling DSM-IV diagnostic criteria for bipolar disorders (BP), 81% of whom presented type I BP, and 95 controls were included in this study. Euthymia was assessed using both the MADRS and Bech mania scales. Subjects were evaluated using the French abbreviated form of Zuckerman's Sensation Seeking Scale (SSS), which provide a total score (TS) and four subscores: Thrill and Adventure Seeking (TAS), Experience Seeking (ES), Disinhibition (Dis), and Boredom Susceptibility (BS). RESULTS: SSS total score differed significantly between men (17.2 +/- 0.5) and women (15.3 +/- 0.6) (P = 0.02) and all the subscores were negatively correlated with age. On adjustment for sex and age, we found that bipolar patients had a high Dis score (P = 0.003). However, if the same analysis was performed with a lifetime history of alcohol abuse or dependence as a covariable, no such difference was found (P = 0.436). The SSS demonstrated a high degree of test-retest reliability (ICC = 0.91). CONCLUSION: These results suggest that sensation seeking assessed with the SSS is not a temperament characteristic associated with bipolar disorders but is instead linked to a tendency towards alcohol abuse. PMID: 11514131 [PubMed - indexed for MEDLINE] 4: J Affect Disord 2001 Jul;65(2):105-15 Drug abuse and bipolar disorder: comorbidity or misdiagnosis? Sherwood Brown E, Suppes T, Adinoff B, Rajan Thomas N. Department of Psychiatry, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390-9070, USA. sbrow3@mednet.swmed.edu Bipolar disorder is a common, severe and cyclic psychiatric illness. A strong association between alcohol dependence and bipolar disorder has been reported in numerous studies. The abuse of other drugs including cocaine, amphetamines, opiates, cannabis, and prescription medications in bipolar patients is also an important public health concern and has been less extensively investigated. This review examines the abuse of drugs other than alcohol or nicotine in people with bipolar disorder. The high rates of milder affective symptoms but not mania observed in patients in drug abuse treatment settings suggests the symptoms may in many cases be associated with the drug use. However, such patients presenting in psychiatric settings might be suffering from cyclothymic and related attenuated bipolar disorders (type II). Substance abuse may be associated with medication non-compliance, more mixed or dysphoric mania and possibly an earlier onset of affective symptoms and more hospitalizations. The pharmacotherapy of patients with bipolar disorder and drug abuse is examined, including evidence on the use of mood stabilizers, neuroleptics and the newer atypical antipsychotics in this population. Publication Types: Review Review, Tutorial PMID: 11356233 [PubMed - indexed for MEDLINE] 5: Addict Behav 2001 May-Jun;26(3):341-8 Characterizing female bipolar alcoholic patients presenting for initial evaluation. Salloum IM, Cornelius JR, Mezzich JE, Kirisci L, Daley DC, Spotts CR, Zuckoff A. Center for Psychiatric and Chemical Dependency Services, Western Psychiatric Institute and Clinic, School of Medicine, University of Pittsburgh, PA 15213, USA. salloumim@msx.upmc.edu This study examined gender differences of age and race-matched group of bipolar disorder (BPO) patients with comorbid alcohol dependence (AD; n = 65; males = 35, females = 30) to a group of BPO patients without comorbid AD (n = 61; males = 22, females = 39). The two groups were also similar on marital status and frequency of BPO subtypes. The results revealed that female bipolar alcoholic patients were more likely to report depressive symptoms as compared to either male bipolar alcoholics or both male and female non-alcoholic bipolar patients. When compared to male bipolar alcoholics, they had higher frequency of depressed mood, slow motor behavior, low self-esteem, decreased libido, decreased appetite, and higher general anxiety symptoms. On the other hand, female bipolar alcoholics differed from female non-alcoholic bipolar patients on reports of mood lability, depressed mood, low self-esteem, suicidal indicators, decreased libido, and general anxiety symptoms. These results raise the question of whether alcohol increases the frequency of depressive symptoms among female bipolar patients. PMID: 11436926 [PubMed - indexed for MEDLINE] 6: Am J Psychiatry 2000 Dec;157(12):2048-50 Attempted suicide and alcoholism in bipolar disorder: clinical and familial relationships. Potash JB, Kane HS, Chiu YF, Simpson SG, MacKinnon DF, McInnis MG, McMahon FJ, DePaulo JR Jr. Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA. jpotash@jhmi.edu OBJECTIVE: This study examined the clinical and familial relationships between comorbid alcoholism and attempted suicide in affectively ill relatives of probands with bipolar I disorder. METHOD: In 71 families ascertained for a genetic linkage study, 337 subjects with major affective disorder were assessed by using the Schedule for Affective Disorders and Schizophrenia-Lifetime Version. RESULTS: Subjects with bipolar disorder and alcoholism had a 38.4% lifetime rate of attempted suicide, whereas those without alcoholism had a 21.7% rate. Attempted suicide among subjects with bipolar disorder and alcoholism clustered in a subset of seven families. Families with alcoholic and suicidal probands had a 40.7% rate of attempted suicide in first-degree relatives with bipolar disorder, whereas other families had a 19.0% rate. CONCLUSIONS: Comorbid alcoholism was associated with a higher rate of attempted suicide among family members with bipolar disorder. Attempted suicide and alcoholism clustered in a subset of families. These relationships may have a genetic origin and may be mediated by intoxication, mixed states, and/or temperamental instability. PMID: 11097977 [PubMed - indexed for MEDLINE] 7: Biol Psychiatry 2000 Dec 1;48(11):1037-44 Parsing the association between bipolar, conduct, and substance use disorders: a familial risk analysis. Biederman J, Faraone SV, Wozniak J, Monuteaux MC. Pediatric Psychopharmacology Unit of the Child Psychiatry Service, Massachusetts General Hospital, Boston, Massachusetts 02114-3139, USA. BACKGROUND: Bipolar disorder has emerged as a risk factor for substance use disorders (alcohol or drug abuse or dependence) in youth; however, the association between bipolar disorder and substance use disorders is complicated by comorbidity with conduct disorder. We used familial risk analysis to disentangle the association between the three disorders. METHODS: We compared relatives of four proband groups: 1) conduct disorder + bipolar disorder, 2) bipolar disorder without conduct disorder, 3) conduct disorder without bipolar disorder, and 4) control subjects without bipolar disorder or conduct disorder. All subjects were evaluated with structured diagnostic interviews. For the analysis of substance use disorders, Cox proportional hazard survival models were utilized to compare age-at-onset distributions. RESULTS: Bipolar disorder in probands was a risk factor for both drug and alcohol addiction in relatives, independent of conduct disorder in probands, which was a risk factor for alcohol dependence in relatives independent of bipolar disorder in probands, but not for drug dependence. The effects of bipolar disorder and conduct disorder in probands combined additively to predict the risk for substance use disorders in relatives. CONCLUSIONS: The combination of conduct disorder + bipolar disorder in youth predicts especially high rates of substance use disorders in relatives. These findings support previous results documenting that when bipolar disorder and conduct disorder occur comorbidly, both are validly diagnosed disorders. PMID: 11094136 [PubMed - indexed for MEDLINE] 8: Biol Psychiatry 2000 Sep 15;48(6):477-85 Comment in: Biol Psychiatry. 2000 Sep 15;48(6):427. The impact of substance abuse on the course of bipolar disorder. Strakowski SM, DelBello MP, Fleck DE, Arndt S. Department of Psychiatry, University of Cincinnati College of Medicine, Ohio 45267-0559, USA. BACKGROUND: Substance abuse occurs at high rates in bipolar disorder. The reasons for this co-occurrence are unknown. Alcohol use disorders have been associated with both earlier and later age of onset of bipolar disorder, in part based on the temporal associations of the two conditions. Both drug and alcohol use disorders are associated with impaired outcome of bipolar illness. This influence may involve both direct effects of alcohol or drugs on the initiation of affective symptoms and indirect effects on treatment compliance. To extend these previous findings we examined the temporal associations of substance abuse and affective symptoms in patients with new onset bipolar disorder. METHODS: Associations between affective symptoms and alcohol and cannabis use disorder symptoms were evaluated using regression and time-series correlative methods in 50 new-onset bipolar patients. RESULTS: The duration of alcohol abuse during follow-up was associated with the time patients experienced depression. The duration of cannabis abuse was associated with the duration of mania. Several subgroups could be identified with different temporal relationships among these disorders. CONCLUSIONS: Although the relationships among substance use and bipolar disorders are complex, systematic study of the courses of the disorders might clarify how these conditions interact longitudinally. As the numbers of subjects in specific subgroups are relatively small in this study, these results should be considered preliminary. PMID: 11018221 [PubMed - indexed for MEDLINE] 9: Bipolar Disord 2000 Sep;2(3 Pt 1):191-5 Lifetime prevalence of substance or alcohol abuse and dependence among subjects with bipolar I and II disorders in a voluntary registry. Chengappa KN, Levine J, Gershon S, Kupfer DJ. Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, School of Medicine, PA 15213-2593, USA. chengappakn@msx.upmc.edu OBJECTIVE: To evaluate the prevalence of substance abuse dependence and/or alcohol abuse dependence among subjects with bipolar I versus bipolar II disorder in a voluntary registry. METHOD: One hundred randomly selected registrants in a voluntary case registry for bipolar disorder were interviewed, using the Structured Clinical Interview for DSM-IV Axis I Disorders, to validate the diagnosis of this registry. Corroborative information was obtained from medical records, family members and the treating psychiatrist. Eighty-nine adults (18-65 years) met criteria for bipolar disorder (bipolar I = 71, bipolar II = 18) and were included in this analysis. RESULTS: Forty-one (57.8%) subjects with bipolar I disorder abused, or were dependent on one or more substances or alcohol, 28.2% abused, or were dependent on, two substances or alcohol, and 11.3% abused or were dependent on three or more substances or alcohol. Nearly 39% of bipolar II subjects abused or were dependent on one or more substances, nearly 17% were dependent on two or more substances or alcohol, and 11% were dependent on three or more substances or alcohol. Alcohol was the most commonly abused drug among either bipolar I or II subjects. CONCLUSIONS: Consistent with other epidemiologic and hospital population studies, this voluntary bipolar disorder registry suggests a high prevalence of comorbidity with alcohol and/or substance abuse dependence. Bipolar I subjects appear to have higher rates of these comorbid conditions than bipolar II subjects; however, as the number of bipolar II subjects was rather small, this suggestion needs confirmation. PMID: 11256686 [PubMed - indexed for MEDLINE] 10: Bipolar Disord 2000 Sep;2(3 Pt 2):269-80 Impact of substance abuse on the course and treatment of bipolar disorder. Salloum IM, Thase ME. Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, PA 15213, USA. salloumim@msx.upmc.edu OBJECTIVES: The objectives of this article are to review the prevalence, natural history, pathophysiology, and treatment of comorbid bipolar disorder with alcoholism and other psychoactive substance use disorders (PSUDs). METHODS: All identified bibliographies through a literature search of all Medline files and bibliographies of selected articles focusing on the prevalence, natural history, course, prognosis, inter-relationship, and treatment of bipolar disorder with comorbid alcoholism and other PSUDs were reviewed. RESULTS AND CONCLUSIONS: Comorbidity of bipolar disorder and alcoholism and other PSUDs is highly prevalent. The presence of this so called 'dual diagnoses' creates a serious challenge in terms of establishing an accurate diagnosis and providing appropriate treatment interventions. The inter-relationship between these disorders appears to be mutually detrimental. The course, manifestation, and treatment of each condition are significantly compounded by the presence of the other condition. Substance abuse and alcoholism appear to significantly complicate the course and prognosis of bipolar disorder resulting in increased suffering, disability, and costs. On the other hand, bipolar disorder may be a risk factor for developing PSUDs. Although, there are a number of hypotheses explaining the pathophysiological mechanism involved in such comorbidities, our understanding of the exact nature of such neurobiological mechanisms is still limited. While the antikindling agents and targeted psychotherapeutic techniques may be useful intervention strategies, there is still a significant lack of empirically based treatment options for these patients. Publication Types: Review Review, Tutorial PMID: 11249805 [PubMed - indexed for MEDLINE] 11: Compr Psychiatry 2000 Sep-Oct;41(5):339-43 Bipolar II disorder and comorbidity. Vieta E, Colom F, Martinez-Aran A, Benabarre A, Reinares M, Gasto C. Department of Psychiatry, Hospital Clinic, University of Barcelona, Spain. The validity and reliability of the diagnosis of bipolar II disorder has been questioned by means of comorbidity with nonaffective disorders, including substance abuse, personality disorders, and anxiety disorders. This study examined the comorbid diagnosis of a sample of bipolar II patients, comparing patients with comorbidity and those with "pure" bipolar II disorder. Forty Research Diagnostic Criteria (RDC) bipolar II patients were assessed by means of the Schedule for Affective Disorders and Schizophrenia, Lifetime Version (SADS-L) and Structured Clinical Interview for DSM-III-R axis I (SCID-II) for personality disorders. Patients fulfilling RDC criteria for any psychiatric disorder (except personality disorders) or DSM-IV criteria for any personality disorder were compared with patients without comorbidity. For practical reasons, cyclothymia was not considered as a comorbid diagnosis. Half of the sample had lifetime comorbidity with other psychiatric disorders, mainly personality disorders (33%), substance abuse or dependence (21%), and anxiety disorders (8%). However, only the rates of suicidal ideation (74% v 24%, chi square [chi2] = 9.03, P = .003) and suicide attempts (45% v 5%, chi2 = 8.53, P = .003) were significantly different between patients with and without comorbidity. In summary, although the rates of comorbidity are relatively high in bipolar II disorder, most clinical and course variables are strikingly similar in patients with and without comorbidity except for suicidal behavior, suggesting that comorbidity does not reduce the validity of the diagnosis of bipolar II disorder. PMID: 11011829 [PubMed - indexed for MEDLINE] 12: Am J Drug Alcohol Abuse 2000 Aug;26(3):369-78 The use of collateral reports for patients with bipolar and substance use disorders. Weiss RD, Greenfield SF, Griffin ML, Najavits LM, Fucito LM. Alcohol and Drug Abuse Program, McLean Hospital, Belmont, Massachusetts 02478, USA. rdwss@aol.com This study investigated the value of collateral informant reports of substance use for patients with current bipolar disorder and substance dependence. We collected collateral informant reports on 132 occasions for 32 patients and found a high level of agreement between collateral reports and self-report/urine screen data (75.0%). In only 3 instances did collateral informants report substance use for patients who denied use and had negative urine screens. Frequency of contact between informants and patients was associated significantly with the level of agreement. These findings suggest that obtaining collateral informant data when studying this population may be of limited value. PMID: 10976663 [PubMed - indexed for MEDLINE] 13: J Affect Disord 2000 Aug;59(2):107-17 Suicidal behavior in bipolar mood disorder: clinical characteristics of attempters and nonattempters. Oquendo MA, Waternaux C, Brodsky B, Parsons B, Haas GL, Malone KM, Mann JJ. MHCRC for the Study of Suicidal Behavior and the Stanley Foundation Center for Applied Neuroscience of Bipolar Disorders, Department of Neuroscience, New York State Psychiatric Institute, Columbia University, NY 10032, USA. OBJECTIVE: Bipolar Disorder is associated with a higher frequency of attempted suicide than most other psychiatric disorders. The reasons are unknown. This study compared bipolar subjects with a history of a suicide attempt to those without such a history, assessing suicidal behavior qualitatively and quantitatively, and examining possible demographic, psychopathologic and familial risk factors. METHODS: Patients (ages 18 to 75) with a DSM III-R Bipolar Disorder (n = 44) diagnosis determined by a structured interview for Axis I disorders were enrolled. Acute psychopathology, hopelessness, protective factors, and traits of aggression and impulsivity were measured. The number, method and degree of medical damage was assessed for suicide attempts, life-time. RESULTS: Bipolar suicide attempters had more life-time episodes of major depression, and twice as many were in a current depressive or mixed episode, compared to bipolar nonattempters. Attempters reported more suicidal ideation immediately prior to admission, and fewer reasons for living even when the most recent suicide attempt preceded the index hospitalization by more than six months. Attempters had more lifetime aggression and were more likely to be male. However, attempters did not differ from nonattempters on lifetime impulsivity. LIMITATIONS: The generalizability of the results is limited because this is a study of inpatients with a history of suicide attempts. Patients with Bipolar I and NOS Disorders were pooled and a larger sample is needed to look at differences. We could not assess psychopathology immediately prior to the suicide attempt because, only half of the suicide attempters had made attempts in the six months prior to admission. Patients with current comorbid substance abuse were excluded. No suicide completers were studied. CONCLUSIONS: Bipolar subjects with a history of suicide attempt experience more episodes of depression, and react to them by having severe suicidal ideation. Their diathesis for acting on feelings of anger or suicidal ideation is suggested by a higher level of lifetime aggression and a pattern of repeated suicide attempts. PMID: 10837879 [PubMed - indexed for MEDLINE] 14: J Clin Psychiatry 2000 May;61(5):361-7 Group therapy for patients with bipolar disorder and substance dependence: results of a pilot study. Weiss RD, Griffin ML, Greenfield SF, Najavits LM, Wyner D, Soto JA, Hennen JA. Alcohol and Drug Abuse Program, McLean Hospital, Belmont, Mass 02478, USA. weissr@mcleanpo.mclean.org BACKGROUND: The authors' goal was to pilot test a newly developed manual-based group psychotherapy, called Integrated Group Therapy (IGT), for patients with bipolar disorder and substance dependence. METHOD: In this open trial, patients with DSM-IV bipolar disorder and substance dependence (N = 45) were recruited in sequential blocks to receive either group therapy (N = 21) or 6 monthly assessments, but no experimental treatment (N = 24). RESULTS: When compared with patients who did not receive group therapy, patients who received IGT had significantly better outcomes on the Addiction Severity Index drug composite score (p < .03), percentage of months abstinent (p < .01), and likelihood of achieving 2 (p < .002) or 3 (p < .004) consecutive abstinent months. CONCLUSION: IGT is a promising treatment for patients with bipolar disorder and substance dependence, who have traditionally had poor outcomes. It is unclear, however, how much of the improvement among the group therapy patients is attributable to the specific content of the treatment. A study comparing this treatment with another active psychotherapy treatment is warranted. Publication Types: Clinical Trial Controlled Clinical Trial PMID: 10847311 [PubMed - indexed for MEDLINE] 15: Clin Psychol Rev 2000 Mar;20(2):191-206 The co-occurrence of bipolar and substance use disorders. Strakowski SM, DelBello MP. Department of Psychiatry, University of Cincinnati College of Medicine, OH 45267-0559, USA. strakosm@email.uc.edu Substance use disorders are exceptionally common in bipolar patients. Although the frequency of this co-occurrence is well-documented, the reasons for this association are not clear. In this review, the authors examine four potential hypotheses for why substance use and bipolar disorders co-occur: (a) substance abuse occurs as a symptom of bipolar disorder; (b) substance abuse is an attempt by bipolar patients to self-medicate symptoms; (c) substance abuse causes bipolar disorder; and (d) substance use and bipolar disorders share a common risk factor. None of these four hypotheses have unequivocal support for explaining all cases of bipolar and substance use disorder co-occurrence, and it is probable that all four mechanisms play some role in the excess of substance abuse observed in bipolar patients. Additional studies are warranted to clarify the complex relationships between these two conditions as better understanding of this co-occurrence could lead to better treatment for patients afflicted with both disorders. Publication Types: Review Review, Tutorial PMID: 10721497 [PubMed - indexed for MEDLINE] 16: Eur Psychiatry 2000 Mar;15(2):103-8 The DRD2 gene and the risk for alcohol dependence in bipolar patients. Gorwood P, Bellivier F, Ad inverted question markes J, Leboyer M. Hospital Louis Mourier (Service de Psychiatrie adulte du Professeur Ad inverted question markes). Colombes 92700, France. The high co-morbidity between bipolar disorder and alcohol dependence may have different explanations, one of them being the existence of common genetic factors for the two disorders. Several candidate genes may be involved but the genes acting in the dopaminergic pathway may be more specifically involved. We have thus tested the role of the gene encoding the D2 dopamine receptor (TaqI A1 allele) in the potentially shared vulnerability to alcohol dependence and bipolar disorder. One hundred and twenty-two French (for at least two generations) patients were recruited on the basis of hospital or outpatient files and were interviewed with the DIGS. The A1 allele frequencies were compared between four groups, namely, with bipolar patients and co-morbid alcohol dependence (N = 21), with bipolar patients without alcohol morbidity (N = 31), with alcohol dependence without mood disorder (N = 35) and unaffected controls (N = 35). The Hardy Weinberg equilibrium for the DRD2 Taq1 A1 genotypes was respected for the sample as a whole, and for each subsample. We observed that 42.9% of control subjects have at least one A1 allele, a frequency which is not significantly different from the one observed in the affected sample as a whole (39.1%), neither from patients with alcohol dependence (37.1%), patients with bipolar disorder (48.4%) nor patients with alcohol dependence and bipolar disorder (28.6%). The regression analysis based on the three variables (bipolar disorder, alcohol dependence and interaction between these two disorders) does not explain the presence of the A1 allele of the DRD2 gene. We thus found no evidence for a significant role of the A1 allele of the D2 dopamine receptor gene in the specific association between bipolar disorder and alcohol dependence in our sample. PMID: 10881206 [PubMed - indexed for MEDLINE] 17: Am J Drug Alcohol Abuse 2000 Feb;26(1):13-23 Detecting bipolar disorder among treatment-seeking substance abusers. Sloan KL, Kivlahan D, Saxon AJ. VA Puget Sound Health Care System-Seattle Division, Washington 98108, USA. klsloan@u.washington.edu Bipolar disorder is increasingly recognized to have frequent comorbidity with substance use disorders, but may be difficult to diagnose among patients with active substance use. The purpose of this paper is to describe a brief, self-report form for the efficient detection of bipolar disorder. The 19-item form was piloted in 373 consecutive applicants for substance abuse treatment at an urban Veterans Affairs (VA) medical center. Results show reasonable internal consistency (alpha = .850) and high rates of manic symptomatology (36%), previous bipolar diagnosis (30%, 51% of whom report prior psychiatric hospitalization), and exposure to mood stabilizers (20%, 66% of whom reported therapeutic benefit). Comparison of nine different scoring algorithms with chart diagnosis as the validating criterion found that self-report of bipolar diagnosis was optimally sensitive. Either self-report of bipolar diagnosis with hospitalization or self-report of exposure to mood stabilizers with therapeutic response was optimally specific. Symptom self-report items had significantly poorer sensitivity and specificity (F = 7.60, p < .01). We conclude that questions pertaining to diagnostic and treatment history (especially hospitalization or therapeutic medication response) are considerably superior to symptom-based screening for clinically diagnosed bipolar disorder. Further work using structured interview as the diagnostic criterion is under way to validate this instrument. PMID: 10718160 [PubMed - indexed for MEDLINE] 18: J Clin Psychopharmacol 2000 Feb;20(1):114-5 Naltrexone for individuals with comorbid bipolar disorder and alcohol dependence. Sonne SC, Brady KT. Publication Types: Letter PMID: 10653225 [PubMed - indexed for MEDLINE] 19: Am J Addict 2000 Fall;9(4):314-20 Utilization of psychosocial treatments by patients diagnosed with bipolar disorder and substance dependence. Weiss RD, Kolodziej ME, Najavits LM, Greenfield SF, Fucito LM. Alcohol and Drug Abuse Treatment Program, McLean Hospital, 115 Mill St., Belmont, MA 02478, USA. weissr@mcleanpo.mclean.org We investigated psychosocial treatment interventions, mood symptoms, and substance use among 24 patients with bipolar disorder and substance dependence. Patients were assessed for 6 months following hospital discharge. Psychotherapy and Alcoholics Anonymous (AA) attendance decreased over time. Moreover, the focus of patients' psychotherapy changed over time, with decreasing emphasis on the patients' specific disorders. Mood symptoms and substance use did not change significantly over time, although there was a trend toward more frequent drug use over time. These findings point to infrequent utilization over time of psychosocial treatments focusing specifically on bipolar and substance use disorder. PMID: 11256355 [PubMed - indexed for MEDLINE] 20: Am J Addict 2000 Summer;9(3):187-95 Is bipolar disorder a risk for cigarette smoking in ADHD youth? Wilens TE, Biederman J, Milberger S, Hahesy AL, Goldman S, Wozniak J, Spencer TJ. Pediatric Psychopharmacology Unit, Massachusetts General Hospital, Boston 02114, USA. wilens@helix.mgh.harvard.edu Despite emerging literature linking juvenile bipolar disorder (BPD) and substance abuse, little is known about a link between BPD and cigarette smoking. To this end, we evaluated the association between BPD and cigarette smoking in youth. Subjects were 31 bipolar adolescents derived from a cohort of boys with DSM-III-R ADHD (N = 128) and non-ADHD comparisons (N = 109) followed prospectively for 4 years into mid-adolescence. Information on cigarette smoking was obtained in a standardized manner blind to the proband's clinical status. Logistic regression models were used to determine risk for smoking at follow-up. BPD was associated with a higher risk for cigarette smoking in mid-adolescence, which was largely accounted for by conduct disorder. The developmental onset of BPD in adolescence (age 13-18 years) conferred a greater risk for cigarette smoking compared to those youths with the onset of their BPD prepubertally (< or = 12 years; odds ratio = 10.8, p < 0.01), even after controlling for conduct disorder and other confounds. The naturalistic treatment of BPD with combined counseling and pharmacotherapy appeared to reduce the risk for cigarette smoking. BPD, particularly when it onsets in adolescence, is a significant risk factor for the early initiation of cigarette smoking in these ADHD youths. These data coupled with the literature strongly suggest that juveniles with BPD need to be carefully monitored for the early initiation of cigarette smoking and substance abuse. PMID: 11000914 [PubMed - indexed for MEDLINE] 21: J Clin Psychiatry 2000;61 Supp 13:32-7 Difficulties in diagnosis and management of bipolar disorder: three case presentations. Brady KT. Medical University of South Carolina, Charleston 29425, USA. bradyk@musc.edu Bipolar disorder is associated with significant problems in patient management, including misdiagnosis, noncompliance, and comorbid substance use disorders. This article describes strategies for the management of difficult cases, with particular emphasis on the choice of therapeutic agents, such as mood stabilizers and atypical antipsychotics, for optimal control of symptoms and psychosocial interventions for reinforcement of therapeutic interventions. Special attention is given to the relationship between bipolar disorder and substance use disorders. PMID: 11153810 [PubMed - indexed for MEDLINE] 22: Ann Clin Psychiatry 1999 Dec;11(4):187-95 Prevalence of axis II comorbidity in bipolar patients with and without alcohol use disorders. Kay JH, Altshuler LL, Ventura J, Mintz J. West LA-VA Medical Center, Los Angeles, California 90073, USA. OBJECTIVE: This study sought to determine the prevalence of comorbid personality disorder in euthymic bipolar I patients. METHOD: Sixty-one outpatients were assessed using the Structured Clinical Interview for DSM-III-R Personality Disorders (SCID II) and/or the Personality Diagnostic Questionnaire-Revised (PDQ-R). RESULTS: Thirty-eight percent of bipolar patients met criteria for an Axis II diagnosis based on the SCID II. Bipolar subjects with a history of comorbid alcohol use disorder were significantly more likely to have a SCID II diagnosis (52%) compared to those bipolar subjects without an alcohol use disorder history (24%). Cluster A diagnoses were significantly more common in the bipolar/alcohol use disorder group. The PDQ-R consistently overdiagnosed Axis II disorders, finding 62% of the overall bipolar group to have an Axis II diagnosis. CONCLUSIONS: Euthymic bipolar patients may have an increased rate of personality disorders, but much less so than previously reported in studies that did not take into account (1) current mood state, (2) comorbidity for an alcohol use disorder, and (3) instrument used for assessment of Axis II psychopathology. Publication Types: Review Review, Tutorial PMID: 10596733 [PubMed - indexed for MEDLINE] 23: J Clin Psychiatry 1999 Nov;60(11):733-40 A history of substance abuse complicates remission from acute mania in bipolar disorder. Goldberg JF, Garno JL, Leon AC, Kocsis JH, Portera L. Payne Whitney Clinic, New York Presbyterian Hospital and Weill Medical College of Cornell University, NY 10021, USA. BACKGROUND: Substance abuse frequently complicates the course of bipolar illness, promotes mixed states, and contributes to poor outcome in mania. Preliminary open trials suggest that anticonvulsant mood stabilizers may enhance remission rates and outcome for bipolar patients with substance abuse. This study compared remission patterns for mixed or pure manic episodes among bipolar inpatients with or without substance abuse histories. METHOD: Hospital records were retrospectively reviewed for 204 DSM-III-R bipolar I inpatients. Clinical features were compared for those with or without substance abuse/dependence histories predating the index manic episode. Time until remission was analyzed by Kaplan-Meier survival analysis. Naturalistic treatment outcome with lithium or anticonvulsant mood stabilizers was compared for those with or without past substance abuse. RESULTS: Past substance abuse was evident in 34% of the bipolar sample and comprised most often alcoholism (82%), followed by cocaine (30%), marijuana (29%), sedative-hypnotic or amphetamine (21%), and opiate (13%) abuse. Substance abuse was more common among men (p < .05) and those with mixed rather than pure mania (p < .05). Remission during hospitalization was less likely among patients with prior substance abuse (p < .05), especially alcohol or marijuana abuse, and among mixed manic patients with past substance abuse (p < .05). Bipolar patients with substance abuse histories who received divalproex or carbamazepine remitted during hospitalization more often than did those who received lithium as the sole mood stabilizer (p < .05). CONCLUSION: These findings support previous reports suggesting that bipolar patients with past substance abuse have poorer naturalistic treatment outcomes, but may show a better response to anticonvulsant mood stabilizers than lithium. Publication Types: Clinical Trial PMID: 10584760 [PubMed - indexed for MEDLINE] 24: Psychiatr Clin North Am 1999 Sep;22(3):517-34, vii The evolving bipolar spectrum. Prototypes I, II, III, and IV. Akiskal HS, Pinto O. Department of Psychiatry, University of California at San Diego, La Jolla, USA. hakiskal@ucsd.edu This article argues for the necessity of a partial return to Kraepelin's broad concept of manic-depressive illness, and proposes definitions--and provides prototypical cases--to illustrate the rich clinical phenomenology of bipolar subtypes I through IV. Although considerable evidence supports such extensions of bipolarity encroaching upon the territory of major depressive disorder, further research is needed in this area. From a practice standpoint, the compelling reason for broadening the bipolar spectrum lies in the utility of mood stabilizers as augmentation or monotherapy in the treatment of major depressive disorders with soft bipolar features falling short of the current strict standards for the diagnosis of bipolar II and hypomania in DSM-IV and ICD-10. Publication Types: Review Review, Tutorial PMID: 10550853 [PubMed - indexed for MEDLINE] 25: Psychiatr Clin North Am 1999 Sep;22(3):609-27, ix Substance abuse and bipolar comorbidity. Sonne SC, Brady KT. Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, USA. sonnesc@musc.edu Bipolar disorder and substance abuse commonly co-occur. In fact, as many as 50% of individuals with bipolar disorder have been found to have a lifetime history of substance abuse or dependence. This article discusses the very important comorbidity of bipolar disorder as it is complicated by substance abuse, focusing on the prevalence, course, diagnostic considerations and treatment. Publication Types: Review Review, Tutorial PMID: 10550858 [PubMed - indexed for MEDLINE] 26: Am J Psychiatry 1999 Jul;156(7):1122 Valproate for alcoholics with bipolar disorder. Sonne SC, Brady KT. Publication Types: Letter PMID: 10401478 [PubMed - indexed for MEDLINE] 27: J Addict Dis 1999;18(1):83-93 Management of patients with bipolar mood disorder and substance dependence. Sutor B, Tinsley JA, Morse RM. Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN 55905, USA. Nine patients with bipolar mood disorder and concurrent substance dependence were treated in an 18-bed inpatient addiction unit over a 3-month period. A multidisciplinary team approach used a medicalized Minnesota model and stressed the establishment of a positive diagnosis and individualization of management strategies for each patient. Clinically significant affective symptoms that required acute psychiatric intervention developed in several patients during hospitalization. Manic symptoms developed in three patients during sedative withdrawal, requiring the team to differentiate manic symptoms from physiologic withdrawal; and two patients became severely depressed, requiring pharmacologic management and suicide-prevention strategies. SUMMARY: Our experience with the patients in this case series supports the contention that there is no simple, uniform approach to the substance-dependent patient with bipolar disorder. Treatment teams must be prepared to differentiate complex syndromes and to manage manic, depressive, and addictive behaviors. PMID: 10234565 [PubMed - indexed for MEDLINE] 28: J Clin Psychiatry 1999;60 Suppl 2:53-6; discussion 75-6, 113-6 The risk of suicide in patients with bipolar disorders. Simpson SG, Jamison KR. Department of Psychiatry, The Johns Hopkins University School of Medicine, Baltimore, MD 21287-7381, USA. Patients with bipolar disorder have a high risk of committing suicide, but determining the exact risk is complicated. For many years, the lifetime suicide risk in bipolar disorder was accepted as 15%, but recent researchers have suggested that the lifetime suicide risk may be lower. The group of bipolar patients at highest risk of suicide are young men who are in an early phase of the illness, especially those who have made a previous suicide attempt, those abusing alcohol, and those recently discharged from the hospital. The risk is also increased in patients who are in the depressed phase of bipolar illness, who have mixed states, or who have psychotic mania. Lithium prophylaxis appears to decrease suicide attempts. Publication Types: Review Review, Tutorial PMID: 10073388 [PubMed - indexed for MEDLINE] 29: J Subst Abuse Treat 1999 Jan;16(1):47-54 A relapse prevention group for patients with bipolar and substance use disorders. Weiss RD, Najavits LM, Greenfield SF. Alcohol and Drug Abuse Program, McLean Hospital, Belmont, MA 02178, USA. rdwss@aol.com Although bipolar disorder is the Axis I disorder associated with the highest risk of having a coexisting substance use disorder, no specific treatment approaches for this dually diagnosed patient population have thus far been developed. This paper describes a 20-session relapse prevention group therapy that the authors have developed for the treatment of patients with coexisting bipolar disorder and substance use disorder. The treatment uses an integrated approach by discussing topics that are relevant to both disorders and by highlighting common aspects of recovery from and relapse to each disorder. PMID: 9888121 [PubMed - indexed for MEDLINE] 30: Harv Rev Psychiatry 1998 Sep-Oct;6(3):133-41 The effect of comorbid substance use disorders on the course of bipolar disorder: a review. Tohen M, Greenfield SF, Weiss RD, Zarate CA Jr, Vagge LM. Bipolar and Psychotic Disorders Program, McLean Hospital, Belmont, Mass, USA. Population-based studies have documented that among all patients with major psychiatric disorders, those with bipolar disorder have the highest prevalence of comorbid substance abuse and dependence. The cause of this high comorbidity rate has not been clearly established, and the relationship is probably bidirectional. Articles published in English from 1980 through 1997 containing the terms comorbidity, mania, outcome, and substance use were identified by searching Medline and then the bibliographies of the articles identified in this search. The literature review showed several risk factors to be associated with comorbid substance use disorders in bipolar disorder patients: early age of onset, gender, family history of substance use disorders, and presence of mixed mania. Methodological enhancements that have helped to advance understanding in this area include distinguishing between primary and secondary disorders, between the different subtypes of bipolar disorder, and between first and subsequent episodes of illness. In order to determine the temporal sequence of onset, longitudinal studies initiated at the onset of either illness need to be pursued. Increased understanding of the association between bipolar disorder and comorbid substance use disorder will facilitate improved detection and intervention, as well as more-effective preventive measures that could improve outcome for patients with bipolar disorder. Publication Types: Review Review, Tutorial PMID: 10372281 [PubMed - indexed for MEDLINE] 31: J Affect Disord 1998 Sep;50(2-3):91-6 Evidence supporting the independent inheritance of primary affective disorders and primary alcoholism in the families of bipolar patients. Duffy A, Grof P, Grof E, Zvolsky P, Alda M. Royal Ottawa Hospital, Department of Psychiatry, University of Ottawa, Ontario, Canada. BACKGROUND: This study explored the nature of the association between bipolar disorder and alcoholism. METHODS: The authors studied 814 first-degree relatives of 121 bipolar patients, divided on the basis of response to lithium prophylaxis. Logistic regression analysis was used to analyze the contribution of demographic, familial and clinical variables to the risk of primary alcoholism in the relatives. RESULTS: The risk of primary alcoholism in relatives was not related to the degree of affective loading in the family or to the proband's lithium response. CONCLUSION: This study does not support a shared genetic liability between bipolar disorder and alcoholism. LIMITATIONS: This study lacked a control group, but the analysis accounted for this. CLINICAL RELEVANCE: These disorders are not alternative forms of the same illness. PMID: 9858068 [PubMed - indexed for MEDLINE] 32: J Affect Disord 1998 Sep;50(2-3):81-9 Alcoholism and drug abuse in three groups--bipolar I, unipolars and their acquaintances. Winokur G, Turvey C, Akiskal H, Coryell W, Solomon D, Leon A, Mueller T, Endicott J, Maser J, Keller M. The National Institute of Mental Health Collaborative Program on the Psychobiology of Depression--Clinical Studies, Iowa, USA. OBJECTIVE: Previous work has shown that manic-depressive illness and alcohol abuse are linked. This study further explores the relationship of alcohol and drug abuse in bipolar I patients and unipolar depressives and a comparison group obtained through the acquaintance method. METHOD: Diagnosis was accomplished according to Research Diagnostic Criteria (RDC): controls = 469; bipolars = 277; unipolar depressives = 678. Systematic data were gathered using the SADS on lifetime and current drug abuse and alcoholism. Both patients and comparison subjects were then followed prospectively for 10 years. First degree family members were interviewed using the RDC family history method. RESULTS: The group of bipolar patients and the group of unipolar patients had higher rates of drug and alcohol abuse than the comparison group when primary and secondary affective disorder patients were combined. However, primary unipolar patients did not have higher rates of alcohol or drug abuse than the comparison group. In contrast, primary bipolar patients had higher rates of alcoholism, stimulant abuse, and ever having abused a drug than the primary unipolar group and the control group. In an evaluation of the bipolar patients, drug abusers were significantly younger at intake and had a significantly younger age of onset of bipolar disorder. There was a significant increase in family history of mania or schizoaffective mania in the drug-abusing bipolar patients as compared to the non-abusing bipolar patients. LIMITATION: As in all adult samples of patients with affective illness, the chronology of alcohol and substance problems vis-a-vis the onset of illness was determined retrospectively. CONCLUSIONS: (1) Alcoholism and drug abuse are more frequent in bipolar than unipolar patients. (2) The drug abuse of bipolar patients tends toward the abuse of stimulant drugs. (3) In a bipolar patient, familial diathesis for mania is significantly associated with the abuse of alcohol and drugs. (4) More provocatively, these findings suggest the hypothesis of a common familial-genetic diathesis for a subtype of bipolar I, alcohol and stimulant abuse. CLINICAL IMPLICATIONS: The present analyses, coupled with two previous ones from the CDS, suggest that drug abuse may precipitate an earlier onset of bipolar I disorder in those who already have a familial predisposition for mania. Furthermore, in dually diagnosed patients with manic-depressive and alcohol/stimulant abuse history, mood stabilization of the bipolar disorder represents a rational approach to control concurrent alcohol and drug problems, and should be studied in systematic controlled trials. PMID: 9858067 [PubMed - indexed for MEDLINE] 33: J Clin Psychiatry 1998 Sep;59(9):465-71 Course of psychiatric and substance abuse syndromes co-occurring with bipolar disorder after a first psychiatric hospitalization. Strakowski SM, Sax KW, McElroy SL, Keck PE Jr, Hawkins JM, West SA. Department of Psychiatry, University of Cincinnati College of Medicine, Ohio 45267-0559, USA. BACKGROUND: Patients with bipolar disorder frequently meet criteria for other psychiatric and substance abuse diagnoses. To clarify relationships among these disorders, the authors examined the course of syndromes co-occurring with bipolar disorder for 12 months after a first hospitalization. METHOD: Seventy-seven patients were recruited from consecutive inpatient admissions who met DSM-III-R criteria for bipolar disorder, manic or mixed with psychosis. The 12-month syndromal course of co-occurring DSM-III-R alcohol and drug abuse disorders, posttraumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), and other anxiety disorders were longitudinally recorded. RESULTS: The rates of all syndromes, except other anxiety disorders, were elevated. OCD demonstrated an interval course that frequently mirrored the course of the bipolar disorder. The courses of PTSD and substance abuse syndromes were separate from that of the bipolar disorder in many of those with both syndromes. Alcohol and drug abuse syndromes were strongly correlated. CONCLUSION: The obsessive-compulsive syndrome may represent an alternative expression of bipolar disorder in some patients. In contrast, PTSD appears to represent a truly separate disorder, which is possibly more prevalent in bipolar patients due to a shared risk factor. Substance abuse does not appear to simply result from attempts at self-medication or from the impulsivity of mania. These results suggest that future studies examining the course of syndromes co-occurring with bipolar disorder are warranted. PMID: 9771817 [PubMed - indexed for MEDLINE] 34: J Clin Psychiatry 1998 May;59(5):225-8 Tobacco smoking and bipolar disorder. Gonzalez-Pinto A, Gutierrez M, Ezcurra J, Aizpuru F, Mosquera F, Lopez P, de Leon J. Santiago Apostol Hospital, Vitoria, Alava, Spain. BACKGROUND: We sought to determine whether tobacco smoking is associated with bipolar disorder. METHOD: This case-control study carried out in Alava, in the north of Spain, included patients with a DSM-III-R diagnosis of bipolar disorder type I (N = 51) and a representative sample of the normal population (N = 517). Smoking history of bipolar patients was assessed with the Fagerstrom Test for Nicotine Dependence and was verified by family members of the patients. RESULTS: The frequencies of ever smoking and current daily smoking were, respectively, 63% (32/51) and 51% (26/51) for the bipolar patients and 45% (235/517) and 33% (169/517) for the control group (respective odds ratios [ORs] and 95% confidence intervals [CIs] were OR = 2.0, 95% CI = 1.1 to 3.8 and OR = 2.1, 95% CI = 1.2 to 4.0). The differences were significant (p = .03 and p = .042, respectively) for bipolar versus control males. Bipolar disorder (in both genders) was also significantly associated (OR = 4.4, 95% CI = 1.7 to 11.9, p = .0015) with heavy smoking (more than 1 pack per day). CONCLUSION: Despite its small sample size, this study suggests that smoking may be more prevalent in bipolar patients than in the normal population. Since most patients started to smoke before the onset of illness, vulnerability to bipolar illness may make subjects vulnerable to become tobacco smokers. PMID: 9632031 [PubMed - indexed for MEDLINE] 35: J Clin Psychiatry 1998 Apr;59(4):172-4 Medication compliance among patients with bipolar disorder and substance use disorder. Weiss RD, Greenfield SF, Najavits LM, Soto JA, Wyner D, Tohen M, Griffin ML. Alcohol and Drug Abuse Program, McLean Hospital, Belmont, Mass 02178, USA. BACKGROUND: This study examined patterns of medication compliance and reasons for noncompliance among patients with bipolar disorder and substance use disorder. METHOD: Forty-four patients with current bipolar disorder and substance use disorder were administered a structured interview regarding lifetime compliance with prescribed psychotropic medications. RESULTS: Patients who were prescribed both lithium and valproate were significantly (p = .03) more likely to report full compliance with valproate than with lithium. Side effects were the most common reason for lithium noncompliance, but were not cited as a reason for valproate noncompliance. Also, a common pattern of noncompliance among patients prescribed benzodiazepines, neuroleptics, and tricyclic antidepressants was the use of more medication than prescribed. CONCLUSION: Valproate may have greater acceptability than lithium among patients with bipolar disorder and substance use disorder. Clinicians should also be aware that these patients may take higher doses of medication than prescribed. PMID: 9590667 [PubMed - indexed for MEDLINE] 36: Gen Hosp Psychiatry 1998 Mar;20(2):98-101 Substance use disorders among inpatients with bipolar disorder and major depressive disorder in a general hospital. Lin CC, Bai YM, Hu PG, Yeh HS. Department of Psychiatry, Yu-Li Veterans Hospital, Hua-Lien, Taiwan, R.O.C. The prevalence and type of substance abuse and dependence were determined for 49 patients with mood disorders on a general hospital psychiatric unit. A standardized diagnostic interview was conducted with a high value of inter-rater reliability. This study found that 18.4% of mood disorder inpatients met the diagnostic criteria for psychoactive substance use disorders by DSM-III-R. Sedatives-hypnotics-anxiolytics was the most common substance use disorder (10.2%), followed by alcohol (6.1%). Patients with major depression had a higher rate of comorbidity with substance use disorders than did the bipolar disorder patients (p = 0.011). The prevalence of sedatives-hypnotics-anxiolytics use disorder among major depression patients was 35.7%, which was higher than that among bipolar disorder patients (0%). Male patients had a significantly higher percentage of substance use disorders than did female patients (p = 0.054). Seventy-seven percent of the patients with a dual diagnosis of mood and substance use disorder were not diagnosed as having substance use disorders by psychiatrists in charge. PMID: 9582594 [PubMed - indexed for MEDLINE] 37: J Am Acad Child Adolesc Psychiatry 1998 Feb;37(2):171-8 Comment in: J Am Acad Child Adolesc Psychiatry. 1999 Jan;38(1):4. Double-blind and placebo-controlled study of lithium for adolescent bipolar disorders with secondary substance dependency. Geller B, Cooper TB, Sun K, Zimerman B, Frazier J, Williams M, Heath J. Washington University School of Medicine, St. Louis, MO 63110, USA. OBJECTIVE: To perform a double-blind, placebo-controlled, random assignment, parallel group, pharmacokinetically dosed study of lithium for adolescents with bipolar disorders (BP) and temporally secondary substance dependency disorders (SDD). METHOD: Subjects were 16.3 +/- 1.2 years old and were comprehensively assessed during a 6-week outpatient protocol that included random weekly urine collection for drug assays and random and weekly serum collection for lithium levels. RESULTS: Using both intent-to-treat (N = 25) and completer (n = 21) analyses, there were significant differences on continuous and categorical measures between the active and placebo groups for both psychopathology measures and weekly random urine drug assays. The mean scheduled weekly serum lithium level of active responders was 0.9 mEq/L. Addiction to both alcohol and marijuana was the most frequent category of SDD. Mean age at onset of BP was 9.6 +/- 3.9 years and of SDD was 15.3 +/- 1.3 years. There were multigenerational mood disorders in 96% and multigenerational SDD in 56% of families. CONCLUSIONS: Lithium treatment of BP with secondary SDD in adolescents was an efficacious treatment for both disorders. These results warrant replication with a long-term maintenance phase. The mean 6-year interval between the onset of BP and onset of SDD strongly argues for earliest recognition of BP. Publication Types: Clinical Trial Randomized Controlled Trial PMID: 9473913 [PubMed - indexed for MEDLINE] 38: Arch Gen Psychiatry 1998 Jan;55(1):41-6 Cognitive impairment in euthymic bipolar patients with and without prior alcohol dependence. A preliminary study. van Gorp WG, Altshuler L, Theberge DC, Wilkins J, Dixon W. Department of Psychiatry, Cornell University Medical College, White Plains, NY, USA. wvangorp%westnyh@nyh.med.cornell.edu BACKGROUND: Few studies of the neurocognitive performance of patients with bipolar disorder have been performed while patients are in the euthymic state. METHODS: Twenty-five euthymic bipolar patients (12 with and 13 without a history of alcohol dependence) were compared with 22 normal control subjects on a neuropsychological test battery assessing a range of cognitive domains. The relationship between subjects' neurocognitive performance and the course-of-illness variables (lifetime episodes and duration of mania, depression, or both), as well as current lithium level, was determined. RESULTS: The results indicated differences across the groups, with the bipolar patients with and without alcohol dependence performing more poorly than controls on tests of verbal memory. Furthermore, bipolar subjects with a history of alcohol dependence had additional decrements in executive (i.e., frontal lobe) functions when compared with controls. For subjects in the bipolar group, lifetime months of mania and depression were negatively correlated with performance in verbal memory and several executive function measures. CONCLUSIONS: Our findings support the presence of persistent neurocognitive difficulties in patients with long-standing bipolar disorder who are not in the psychiatrically acute state or who are suffering the effects of alcohol abuse and suggest that there may be an aggregate negative effect of lifetime duration of bipolar illness on memory and frontal or executive systems. PMID: 9435759 [PubMed - indexed for MEDLINE] 39: J Affect Disord 1997 Nov;46(2):143-50 Alcohol problems and long-term psychosocial outcome in Chinese patients with bipolar disorder. Tsai SY, Chen CC, Yeh EK. Department of Psychiatry, Taipei Medical College and Hospital, Taiwan. tmcpsyts@mail.tmc.edu.tw BACKGROUND: A high comorbidity of alcohol use disorders among Western bipolar patients is recognized and worsens the outcome of bipolar illness. In view of lower prevalence of alcohol use disorders in some Asian groups, we attempted to investigate the alcohol problems among Chinese bipolar patients in Taiwan. METHODS: The clinical data of bipolar patients (DSM-III-R) having been followed-up naturally for at least 15 years were obtained by a combination of chart reviews and interviews with patients and family members. RESULTS: Based on a retrospective chart review of 158 patients, 8.2% of them were found to have alcohol problems. The lifetime prevalence of alcohol abuse was 6.9%, and of alcohol dependence 3.0% among 101 subjects accepting interview. According to the Global Assessment of Functioning Scale (APA, 1994) nearly one-third of them were clearly dysfunctional. LIMITATION: As subjects had a greater mean age, the age-related effects probably worsened the psychosocial outcome and reduced the incidence of new substance abuse. CONCLUSION: Chinese bipolar patients, despite a lower comorbidity of alcohol use disorders, do not have a more favorable long-term psychosocial outcome (marriage, work, and social adjustment) than Western patients. PMID: 9479618 [PubMed - indexed for MEDLINE] 40: J Am Acad Child Adolesc Psychiatry 1996 Jun;35(6):716-24 Increased prevalence of alcoholism in relatives of depressed and bipolar children. Todd RD, Geller B, Neuman R, Fox LW, Hickok J. Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA. OBJECTIVE: Previous publications from the "Nortriptyline in Childhood Depression: Follow-up Study" reported increased prevalence rates of mood disorders and alcoholism in the relatives of prepubertal depressed subjects. This article presents data on the association versus independent transmission of alcohol and mood disorders in the families of these subjects. METHOD: The follow-up study included 6- to 12-year-olds with major depressive disorder (MDD) and matched normal controls. After 2 to 5 years of follow-up, bipolarity developed in 31.7% of the MDD subjects. Family history data for the first- and second-degree relatives and first cousins of the 76 nonadopted MDD subjects and the 31 controls were obtained from the subjects' mothers, using the Family History-Research Diagnostic Criteria. RESULTS: The prevalence of alcoholism among the relatives of the MDD and bipolar probands was two to three times that reported for control relatives and twice that reported for the relatives of adult MDD and bipolar probands. Mood disorders and maternal alcoholism were independently transmitted while paternal alcoholism increased the risk for mood disorder in offspring. CONCLUSIONS: The potential psychosocial and genetic effects of familial alcoholism need to be considered for the clinical management and investigation of childhood-onset mood disorders. PMID: 8682752 [PubMed - indexed for MEDLINE]