bipolar disorder and substance abuse


Attention Valued Visitor: A Drug Reference Page for FDA Approved General Anesthetics is now available!
Shawn Thomas ( is working to summarize the mechanisms of action of every drug approved by the FDA for a brain- related condition. In addition, new pages with more automated content will soon replace some of the older pages on the web site. If you have suggestions about content that you would like to see, e-mail if you have anything at all to share.



(Updated 1/12/04)

Cassidy F, Ahearn EP, Carroll BJ.
Substance abuse in bipolar disorder.
Bipolar Disord 2001 Aug;3(4):181-8
"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." [Abstract]

Goodwin RD, Stayner DA, Chinman MJ, Wu P, Tebes JK, Davidson L.
The relationship between anxiety and substance use disorders among individuals with severe affective disorders.
Compr Psychiatry. 2002 Jul-Aug;43(4):245-52.
"We sought to determine the association between anxiety disorders and substance use disorders among patients with severe affective disorders in a community-based outpatient treatment program. Two hundred sixty participants in a supported socialization program were assessed using the Structured Clinical Interview for DSM-III-R (SCID). Multivariate logistic regression analyses were used to determine the relationship between anxiety disorders and alcohol and substance use disorders among patients with severe and persistent affective disorders (i.e., major depression and bipolar disorder). Among patients with severe and persistent affective disorders, cocaine (odds ratio [OR] = 5.9 [1.4, 24.6]), stimulant (OR = 5.1 [1.2, 20.9]), sedative (OR = 5.4 [1.2, 24.7]), and opioid use disorders (OR = 13.9 [1.4, 138.7]) were significantly more common among those with, compared with those without, anxiety disorders. This association persisted after adjusting for differences in sociodemographic characteristics and comorbid psychotic disorders. Significant associations between panic attacks, social phobia, specific phobia, and obsessive-compulsive disorder (OCD) and specific substance use disorders were also evident. These findings are consistent with and extend previous results by documenting an association between anxiety disorders and substance use disorders, independent of comorbid psychotic disorders among patients in a outpatient psychiatric rehabilitation program. These data highlight the prevalence of comorbid anxiety disorders, a potentially undetected and therefore undertreated problem, among patients with severe affective disorders and substance use comorbidity. Future work is needed to determine the nature of this association and to determine whether treatment of one prevents onset of the other." [Abstract]

Skinstad AH, Swain A.
Comorbidity in a clinical sample of substance abusers.
Am J Drug Alcohol Abuse 2001 Feb;27(1):45-64
"The sample consisted of 125 male inpatients admitted to one of two substance abuse treatment centers in Iowa. They were diagnosed by means of the Diagnostic Interview Schedule Screening Interview-Quick-DIS version, the Structural Interview for DSM-III-R Personality Disorder (PD), revised, and the Substance Abuse Reporting System. The most frequently diagnosed comorbid Axis I conditions were anxiety and mood disorders, while the most frequently observed Axis II disorders were in Cluster B, borderline PD, and antisocial PD followed by Cluster C, avoidant PD, passive-aggressive PD and obsessive-compulsive PD; and then Cluster A; schizoid PD. Subjects diagnosed with Borderline PD showed the highest rate of comorbid psychopathology, including Axis I disorders of generalized anxiety disorder, major depression, cocaine dependence, and inhalant dependence. The most likely comorbid diagnosis for antisocial PD subjects was bipolar disorder. The schizoid PD and the NoPD groups were less likely to meet criteria for other Axis I disorders. A high rate of comorbid Axis II pathology was also found. Polysubstance dependent subjects were more likely to be diagnosed with anxiety disorder or bipolar disorder than were those who were not polysubstance dependent or were dependent only on alcohol. Polysubstance dependent men were at highest risk for Axis II disorders: 56% of them met criteria for a Cluster B PD, with borderline PD and histrionic PD most frequent." [Abstract]

Shrier LA, Harris SK, Kurland M, Knight JR.
Substance use problems and associated psychiatric symptoms among adolescents in primary care.
Pediatrics. 2003 Jun;111(6 Pt 1):e699-705.
"OBJECTIVE: Substance use disorders (SUDs) are associated with other mental disorders in adolescence, but it is unclear whether less severe substance use problems (SUPs) also increase risk. Because youths with SUPs are most likely to present first to their site of primary care, it is important to establish the presence and patterns of psychiatric comorbidity among adolescent primary care patients with subdiagnostic use of alcohol or other drugs. The objective of this study was to determine the association between level of substance use and psychiatric symptoms among adolescents in a primary care setting. METHODS: Patients who were aged 14 to 18 years and receiving routine care at a hospital-based adolescent clinic were eligible. Participants completed the Problem Oriented Screening Instrument for Teenagers Substance Use/Abuse scale, which is designed to detect social and legal problems associated with alcohol and other drugs, and the Adolescent Diagnostic Interview, which evaluates for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnoses of substance abuse/dependence and 8 types of psychiatric symptoms. We examined gender-specific associations of no/nonproblematic substance use (NSU), SUP, and SUD with psychiatric symptom presence (any symptoms within each type), score (symptom scores summed across all types), and number of types (number of different symptom types endorsed). RESULTS: Of 538 adolescents (68% female; mean +/- standard deviation age: 16.6 +/- 1.4 years), 66% were classified with NSU, 18% with SUP, and 16% with SUD, and 80% reported having at least 1 type of psychiatric symptom in the previous 12 months. Symptoms of anxiety were most common (60% of both boys and girls), followed by symptoms of depression among girls (51%) and symptoms of attention-deficit disorder (ADD) among boys (47%). Compared with those with NSU, youths with SUP and those with SUD were more likely to report symptom presence for several types of psychiatric symptoms. Girls with SUP or SUD had increased odds of reporting symptoms of mania, ADD, and conduct disorder; girls with SUD were at increased risk for symptoms of depression, eating disorders, and hallucinations or delusions. Boys with SUP had increased odds of ADD symptoms, whereas boys with SUD had increased odds of reporting hallucinations or delusions. Boys with SUP or SUD had increased odds of reporting symptoms of conduct disorder. Youths with SUP and SUD also had higher psychiatric symptom scores and reported a wider range of psychiatric symptom types (number of types) compared with youths with NSU. CONCLUSIONS: Like those with SUD, adolescents with subdiagnostic SUP were at increased risk for experiencing a greater number of psychiatric symptoms and a wider range of psychiatric symptom types than youths with NSU. Specifically, adolescents with SUP are at increased risk for symptoms of mood (girls) and disruptive behavior disorders (girls and boys). These findings suggest the clinical importance of SUP and support the concept of a continuum between subthreshold and diagnostic substance use among adolescents in primary care. Identification of youths with SUP may allow for intervention before either the substance use or any associated psychiatric problems progress to more severe levels." [Abstract]

Wilens TE, Biederman J, Millstein RB, Wozniak J, Hahesy AL, Spencer TJ.
Risk for substance use disorders in youths with child- and adolescent-onset bipolar disorder.
J Am Acad Child Adolesc Psychiatry 1999 Jun;38(6):680-5
"OBJECTIVE: Previous work in adults has suggested that early-onset bipolar disorder (BPD) is associated with an elevated risk for substance use disorders (SUD). To this end, the authors assessed the risk for SUD in child- versus adolescent-onset BPD with attention to comorbid psychopathology. METHOD: All youths (aged 13-18 years) with available structured psychiatric interviews were studied systematically. From clinic subjects (N = 333), 86 subjects with DSM-III-R BPD were identified. To evaluate the risk for SUD and BPD while attending to developmental issues, the authors stratified the BPD sample into those with child-onset BPD (< or = 12 years of age, n = 50) and those with adolescent-onset BPD (13-18 years of age, n = 36). RESULTS: In mid-adolescence, youths with adolescent-onset BPD were at significantly increased risk for SUD relative to those with child-onset BPD (39% versus 8%; p = .001). Compared with those with child-onset BPD, those with adolescent-onset BPD had 8.8 times the risk for SUD (95% confidence interval = 2.2-34.7; chi 7(2) = 9.7, p = .002). The presence of conduct disorder or other comorbid psychopathology within BPD did not account for the risk for SUD. CONCLUSIONS: Adolescent-onset BPD is associated with a much higher risk for SUD than child-onset BPD, which was not accounted for by conduct disorder or other comorbid psychopathology. Youths with adolescent-onset BPD should be monitored and educated about SUD risk. The identification and treatment of manic symptomatology may offer therapeutic opportunities to decrease the risk for SUD in these high-risk youths." [Abstract]

Biederman J, Faraone SV, Wozniak J, Monuteaux MC.
Parsing the association between bipolar, conduct, and substance use disorders: a familial risk analysis.
Biol Psychiatry 2000 Dec 1;48(11):1037-44
"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." [Abstract]

Frye MA, Altshuler LL, McElroy SL, Suppes T, Keck PE, Denicoff K, Nolen WA, Kupka R, Leverich GS, Pollio C, Grunze H, Walden J, Post RM.
Gender differences in prevalence, risk, and clinical correlates of alcoholism comorbidity in bipolar disorder.
Am J Psychiatry. 2003 May;160(5):883-9.
"OBJECTIVE: The prevalence of lifetime alcohol abuse and/or dependence (alcoholism) in patients with bipolar disorder has been reported to be higher than in all other axis I psychiatric diagnoses. This study examined gender-specific relationships between alcoholism and bipolar illness, which have previously received little systematic study. METHOD: The prevalence of lifetime alcoholism in 267 outpatients enrolled in the Stanley Foundation Bipolar Network was evaluated by using the Structured Clinical Interview for DSM-IV. Alcoholism and its relationship to retrospectively assessed measures of the course of bipolar illness were evaluated by patient-rated and clinician-administered questionnaires. RESULTS: As in the general population, more men (49%, 57 of 116) than women with bipolar disorder (29%, 44 of 151) met the criteria for lifetime alcoholism. However, the risk of having alcoholism was greater for women with bipolar disorder (odds ratio=7.35) than for men with bipolar disorder (odds ratio=2.77), compared with the general population. Alcoholism was associated with a history of polysubstance use in women with bipolar disorder and with a family history of alcoholism in men with bipolar disorder. CONCLUSIONS: This study suggests that there are gender differences in the prevalence, risk, and clinical correlates of alcoholism in bipolar illness. Although this study is limited by the retrospective assessment of illness variables, the magnitude of these gender-specific differences is substantial and warrants further prospective study." [Abstract]

Sloan KL, Kivlahan D, Saxon AJ.
Detecting bipolar disorder among treatment-seeking substance abusers.
Am J Drug Alcohol Abuse 2000 Feb;26(1):13-23
"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." [Abstract]

Chengappa KN, Levine J, Gershon S, Kupfer DJ.
Lifetime prevalence of substance or alcohol abuse and dependence among subjects with bipolar I and II disorders in a voluntary registry.
Bipolar Disord 2000 Sep;2(3 Pt 1):191-5
"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." [Abstract]

Escamilla MA, Batki S, Reus VI, Spesny M, Molina J, Service S, Vinogradov S, Neylan T, Mathews C, Meza L, Gallegos A, Montero AP, Cruz ML, Neuhaus J, Roche E, Smith L, Leon P, Freimer NB.
Comorbidity of bipolar disorder and substance abuse in Costa Rica: pedigree- and population-based studies.
J Affect Disord. 2002 Sep;71(1-3):71-83.
"BACKGROUND: The purpose of this study was to determine the prevalence of substance use disorders (substance abuse or substance dependence: SA/SD) in a large sample of Bipolar Type I (BPI) patients drawn from the Costa Rican population and to describe the effects of SA/SD on the course of their bipolar disorder. METHOD: 110 subjects from two high-risk (for BPI) Costa Rican pedigrees and 205 unrelated Costa Rican BPI subjects were assessed using structured interviews and a best estimate process. Chi(2) and survival analyses were performed to assess the effect of gender on comorbidity risk, and the effect of comorbidity on the clinical course of BPI. RESULTS: SA/SD (primarily alcohol dependence) occurred in 17% of the BPI patients from the population sample and 35% of the BPI patients from the pedigree sample. Comorbid SA/SD was strongly associated with gender chi(2) = 16.84, P = 0.00004). In comorbid subjects, alcohol dependence tended to predate the first manic episode (chi(2) = 6.54, P < 0.025). History of SA/SD did not significantly alter the prevalence of psychosis or age of onset of mania in BPI subjects. CONCLUSIONS: These results suggest that SA/SD comorbidity rates are lower in this type of population than in BPI patient populations in the US. Gender is a strong predictor of comorbidity prevalence in BPI patients from this population. Although SA/SD may be a risk factor for precipitating BPI in those at risk, in this population comorbid BPI subjects do not have a different onset or course of BPI in comparison to BPI patients without comorbidity." [Abstract]

Salloum IM, Thase ME.
Impact of substance abuse on the course and treatment of bipolar disorder.
Bipolar Disord 2000 Sep;2(3 Pt 2):269-80
"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." [Abstract]

Sutor B, Tinsley JA, Morse RM.
Management of patients with bipolar mood disorder and substance dependence.
J Addict Dis 1999;18(1):83-93
"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." [Abstract]

Potash JB, Kane HS, Chiu YF, Simpson SG, MacKinnon DF, McInnis MG, McMahon FJ, DePaulo JR Jr.
Attempted suicide and alcoholism in bipolar disorder: clinical and familial relationships.
Am J Psychiatry 2000 Dec;157(12):2048-50
"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." [Abstract]

Simon GE, Unutzer J.
Health care utilization and costs among patients treated for bipolar disorder in an insured population.
Psychiatr Serv 1999 Oct;50(10):1303-8
"OBJECTIVE: The study examined health care utilization and costs among patients treated for bipolar-spectrum disorders in an insured population. METHODS: Computerized data on prescriptions and on outpatient and inpatient diagnoses from a large health plan were used to identify patients treated for cyclothymia, bipolar disorder, or schizoaffective disorder. Three age- and sex-matched comparison groups consisting of general medical outpatients, patients treated for depression, and patients treated for diabetes were selected from health plan members. Utilization and cost of health services for the four groups over a six-month period were assessed using computerized accounting records. RESULTS: Total mean+/-SD costs for patients in the bipolar disorder group ($3,416+/-$6,862) were significantly higher than those in any of the comparison groups. Specialty mental health and substance abuse services accounted for 45 percent of total costs in the group with bipolar disorder (mean+/-SD=$1, 566+/-$3,243), compared with 10 percent in the group with depression. Among patients treated for bipolar disorder, 5 percent of patients accounted for approximately 40 percent of costs for specialty mental health and substance abuse services, 90 percent of inpatient costs for specialty mental health and substance abuse services, and 95 percent of out-of-pocket costs for inpatient care. In the bipolar disorder group, parity coverage of inpatient mental health and substance abuse services would increase overall health care costs by 6 percent. CONCLUSIONS: Health care costs for patients with bipolar disorder exceed those for patients treated for depression or diabetes, and specialty mental health and substance abuse treatment costs account for this difference. Costs to the insurer and costs borne by patients are accounted for by a small proportion of patients. Elimination of discriminatory mental health coverage would have a small effect on overall health care costs." [Abstract]

Carey KB, Carey MP, Simons JS.
Correlates of substance use disorder among psychiatric outpatients: focus on cognition, social role functioning, and psychiatric status.
J Nerv Ment Dis. 2003 May;191(5):300-8.
"This study compared psychiatric outpatients who were never, former, and current substance abusers on psychiatric, social, and cognitive functioning. Fifty-six outpatients with schizophrenia spectrum and bipolar disorders volunteered to complete diagnostic and social role function interviews, self-report inventories, and neuropsychological tests. Multinomial logit regression analyses indicated that current and former abusers reported greater subjective feelings of distress than those who never abused. Contrary to expectations, however, both groups of substance abusers performed better on nonverbal cognitive tests compared with those who never abused. Differences in social functioning were also observed: former abusers demonstrated better instrumental role functioning than those who never abused. This pattern of findings challenges assumptions about additive effects of comorbid disorders on cognitive and social functioning." [Abstract]

Preisig M, Fenton BT, Stevens DE, Merikangas KR.
Familial relationship between mood disorders and alcoholism.
Compr Psychiatry 2001 Mar-Apr;42(2):87-95
"Clinical and epidemiological studies have consistently revealed an association between alcohol use disorders and both bipolar and nonbipolar mood disorders. However, the evidence regarding the nature of these associations is unclear. The familial patterns of alcohol and affective disorders were examined using data from a controlled family study of probands with alcohol and anxiety disorders who were sampled from treatment settings and the community. The substantial degree of comorbidity between mood and anxiety disorders among probands allowed for the examination of comorbidity and familial aggregation of alcohol and mood disorders. The major findings are that (1) alcoholism was associated with bipolar and nonbipolar mood disorders in the relatives; (2) there was a strong degree of familial aggregation of alcohol dependence and both types of mood disorders were observed; and (3) there was no evidence of cross-aggregation (i.e., increase in mood disorders among probands with alcohol dependence, and vice versa) between alcoholism and mood disorders. The independent familial aggregation of bipolar disorder and alcoholism and the finding that the onset of bipolar disorder tended to precede that of alcoholism are compatible with a self-medication hypothesis as the explanation for the frequent co-occurrence of these disorders. In contrast, the independent familial aggregation and the tendency of an earlier onset of alcoholism than that of nonbipolar depression suggest that unipolar mood disorders are frequently secondary to alcoholism. Copyright 2001 by W.B. Saunders Company." [Abstract]

Tiihonen J, Hallikainen T, Lachman H, Saito T, Volavka J, Kauhanen J, Salonen JT, Ryynanen OP, Koulu M, Karvonen MK, Pohjalainen T, Syvalahti E, Hietala J.
Association between the functional variant of the catechol-O-methyltransferase (COMT) gene and type 1 alcoholism.
Mol Psychiatry 1999 May;4(3):286-9
"Catechol-O-methyltransferase (COMT) is an enzyme which has a crucial role in the metabolism of dopamine. It has been suggested that a common functional genetic polymorphism in the COMT gene, which results in 3 to 4-fold difference in COMT enzyme activity, may contribute to the etiology of mental disorders such as bipolar disorder and alcoholism. Since ethanol-induced euphoria is associated with the rapid release of dopamine in limbic areas, it is conceivable that subjects who inherit the allele encoding the low activity COMT variant would have a relatively low dopamine inactivation rate, and therefore would be more vulnerable to the development of ethanol dependence. The aim of this study was to test this hypothesis among type 1 (late-onset) alcoholics. The COMT polymorphism was determined in two independent male late onset (type 1) alcoholic populations in Turku (n = 67) and Kuopio (n = 56). The high (H) and low (L) activity COMT genotype and allele frequencies were compared with previously published data from 3140 Finnish blood donors (general population) and 267 race- and gender-matched controls. The frequency of low activity allele (L) was markedly higher among the patients both in Turku (P = 0.023) and in Kuopio (P = 0.005) when compared with the general population. When all patients were compared with the general population (blood donors), the difference was even more significant (P = 0.0004). When genotypes of all alcoholics (n = 123) were compared with genotypes of matched controls, the odds ratio (OR) for alcoholism for those subjects having the LL genotype vs those with HH genotype was 2.51, 95% CI 1.22-5.19, P = 0.006. Also, L allele frequency was significantly higher among alcoholics when compared with controls (P = 0.009). The estimate for population etiological (attributable) fraction for the LL genotype in alcoholism was 13.3% (95% CI 2.3-25.7%). The results indicate that the COMT polymorphism contributes significantly to the development of late-onset alcoholism." [Abstract]

->Back to Home<- //->Back to Bipolar Disorder Index<-

Recent Bipolar Disorder & Substance Abuse Research

1) Maher AR, Theodore G
Summary of the comparative effectiveness review on off-label use of atypical antipsychotics.
J Manag Care Pharm. 2012 Jun;18(5 Suppl B):1-20.
[PubMed Citation] [Order full text from Infotrieve]

2) Colombo RR, Schaufelberger MS, Santos LC, Duran FL, Menezes PR, Scazufca M, Busatto GF, Zanetti MV
Voxelwise evaluation of white matter volumes in first-episode psychosis.
Psychiatry Res. 2012 Jul 15;
The occurrence of white matter (WM) abnormalities in psychotic disorders has been suggested by several studies investigating brain pathology and diffusion tensor measures, but evidence assessing regional WM morphometry is still scarce and conflicting. In the present study, 122 individuals with first-episode psychosis (FEP) (62 fulfilling criteria for schizophrenia/schizophreniform disorder, 26 psychotic bipolar I disorder, and 20 psychotic major depressive disorder) underwent magnetic resonance imaging, as well as 94 epidemiologically recruited controls. Images were processed with the Statistical Parametric Mapping (SPM2) package, and voxel-based morphometry was used to compare groups (t-test) and subgroups (ANOVA). Initially, no regional WM abnormalities were observed when both groups (overall FEP group versus controls) and subgroups (i.e., schizophrenia/schizophreniform, psychotic bipolar I disorder, psychotic depression, and controls) were compared. However, when the voxelwise analyses were repeated excluding subjects with comorbid substance abuse or dependence, the resulting statistical maps revealed a focal volumetric reduction in right frontal WM, corresponding to the right middle frontal gyral WM/third subcomponent of the superior longitudinal fasciculus, in subjects with schizophrenia/schizophreniform disorder (n=40) relative to controls (n=89). Our results suggest that schizophrenia/schizophreniform disorder is associated with right frontal WM volume decrease at an early course of the illness. [PubMed Citation] [Order full text from Infotrieve]

3) Hsieh MH, Tang CH, Hung ST, Lee IH, Lin YJ, Yang YK
Comorbid prevalence of alcohol dependence, substance abuse, and external cause of injury in patients with bipolar disorder in a nationwide representative sample in Taiwan.
Bipolar Disord. 2012 Jul 13;
[PubMed Citation] [Order full text from Infotrieve]

4) Marshall DF, Walker SJ, Ryan KA, Kamali M, Saunders EF, Weldon AL, Adams KM, McInnis MG, Langenecker SA
Greater executive and visual memory dysfunction in comorbid bipolar disorder and substance use disorder.
Psychiatry Res. 2012 Jul 4;
Measures of cognitive dysfunction in Bipolar Disorder (BD) have identified state and trait dependent metrics. An influence of substance abuse (SUD) on BD has been suggested. This study investigates potential differential, additive, or interactive cognitive dysfunction in bipolar patients with or without a history of SUD. Two hundred fifty-six individuals with BD, 98 without SUD and 158 with SUD, and 97 Healthy Controls (HC) completed diagnostic interviews, neuropsychological testing, and symptom severity scales. The BD groups exhibited poorer performance than the HC group on most cognitive factors. The BD with SUD exhibited significantly poorer performance than BD without SUD in visual memory and conceptual reasoning/set-shifting. In addition, a significant interaction effect between substance use and depressive symptoms was found for auditory memory and emotion processing. BD patients with a history of SUD demonstrated worse visual memory and conceptual reasoning skills above and beyond the dysfunction observed in these domains among individuals with BD without SUD, suggesting greater impact on integrative, gestalt-driven processing domains. Future research might address longitudinal outcome as a function of BD, SUD, and combined BD/SUD to evaluate neural systems involved in risk for, and effects of, these illnesses. [PubMed Citation] [Order full text from Infotrieve]

5) Hallinen T, Soini EJ, Granström O, Ovaskainen Y, Leinonen E, Koponen HJ, Hänninen K
Differential use of extended and immediate release quetiapine: a retrospective registry study of Finnish inpatients with schizophrenia spectrum and bipolar disorders.
BMJ Open. 2012;2(4)
[PubMed Citation] [Order full text from Infotrieve]

6) Wasserman D, Rihmer Z, Rujescu D, Sarchiapone M, Sokolowski M, Titelman D, Zalsman G, Zemishlany Z, Carli V
[The European Psychiatric Association (EPA) guidance on suicide treatment and prevention].
Neuropsychopharmacol Hung. 2012 Jun;14(2):113-36.
Suicide is a major public health problem in the WHO European Region accounting for over 150,000 deaths per year. Suicidal crisis: Acute intervention should start immediately in order to keep the patient alive. Diagnosis: An underlying psychiatric disorder is present in up to 90% of people who completed suicide. Comorbidity with depression, anxiety, substance abuse and personality disorders is high. In order to achieve successful prevention of suicidality, adequate diagnostic procedures and appropriate treatment for the underlying disorder are essential. Treatment: Existing evidence supports the efficacy of pharmacological treatment and cognitive behavioural therapy (CBT) in preventing suicidal behaviour. Some other psychological treatments are promising, but the supporting evidence is currently insufficient. Studies show that antidepressant treatment decreases the risk for suicidality among depressed patients. However, the risk of suicidal behaviour in depressed patients treated with antidepressants exists during the first 10-14 days of treatment, which requires careful monitoring. Short-term supplementary medication with anxiolytics and hypnotics in the case of anxiety and insomnia is recommended. Treatment with antidepressants of children and adolescents should only be given under supervision of a specialist. Long-term treatment with lithium has been shown to be effective in preventing both suicide and attempted suicide in patients with unipolar and bipolar depression. Treatment with clozapine is effective in reducing suicidal behaviour in patients with schizophrenia. Other atypical antipsychotics are promising but more evidence is required. Treatment team: Multidisciplinary treatment teams including psychiatrist and other professionals such as psychologist, social worker, and occupational therapist are always preferable, as integration of pharmacological, psychological and social rehabilitation is recommended especially for patients with chronic suicidality. Family: The suicidal person independently of age should always be motivated to involve family in the treatment. Social support: Psychosocial treatment and support is recommended, as the majority of suicidal patients have problems with relationships, work, school and lack functioning social networks. Safety: A secure home, public and hospital environment, without access to suicidal means is a necessary strategy in suicide prevention. Each treatment option, prescription of medication and discharge of the patient from hospital should be carefully evaluated against the involved risks. Training of personnel: Training of general practitioners (GPs) is effective in the prevention of suicide. It improves treatment of depression and anxiety, quality of the provided care and attitudes towards suicide. Continuous training including discussions about ethical and legal issues is necessary for psychiatrists and other mental health professionals. (This article was originally published as: Wasserman D., Rihmer Z., Rujescu D., Sarchiapone M., Sokolowski M., Titelman D., et al. The European Psychiatric Association (EPA) guidance on suicide treatment and prevention. European Psychiatry 2012;27(2):129-141. doi:10.1016/j.eurpsy. 2011.06.003 Copyright 2011 Elsevier Masson SAS. All rights reserved. With permission.). [PubMed Citation] [Order full text from Infotrieve]

7) Daratha KB, Barbosa-Leiker C, H Burley M, Short R, Layton ME, McPherson S, Dyck DG, McFarland BH, Tuttle KR
Co-occurring mood disorders among hospitalized patients and risk for subsequent medical hospitalization.
Gen Hosp Psychiatry. 2012 Jun 13;
OBJECTIVE: The objective was to determine if patients hospitalized with a primary medical diagnosis and any co-occurring serious mental illness (SMI) were more likely than patients without any co-occurring SMI diagnosis to experience a subsequent medical hospitalization. METHOD: This was a longitudinal cohort study of 925,705 adult persons (aged 18+ years). Patients hospitalized in Washington State from 2004 to 2008 were followed through 2009 (for an average of 43 months). RESULTS: Compared to patients hospitalized for medical conditions without co-occurring SMI, patients with co-occurring dysthymia, bipolar and major depressive disorders were at an elevated risk for long-term subsequent hospitalization. Patients in the combined co-occurring mood disorders cohort were more likely (hazard ratio=1.13; 99% confidence interval=1.10-1.16; P<.001) than patients in the reference cohort to experience a subsequent medical hospitalization. A significant interaction between substance and mood disorders that increased risk for subsequent hospitalization was also observed. CONCLUSION: Hospitalized patients with co-occurring mood disorders are at high risk for repeat hospitalization for a medical reason. This high-risk population, including those with substance abuse, should be a focus of research efforts to identify and address ambulatory-care-sensitive conditions amenable to strategies that decrease complications and illness leading to subsequent hospitalizations. [PubMed Citation] [Order full text from Infotrieve]

8) Glick ID, Stillman MA, Reardon CL, Ritvo EC
Managing psychiatric issues in elite athletes.
J Clin Psychiatry. 2012 May;73(5):640-4.
[PubMed Citation] [Order full text from Infotrieve]

9) Meissner WG
Methods for treating neurological conditions (WO2011159945).
Expert Opin Ther Pat. 2012 Jul;22(7):847-52.
This patent application claims that inhibition of p21-activated kinases (PAK) reverses, partially reverses or delays clinical signs in neurological conditions (main claim for Huntington's disease (HD), substance abuse and addiction, Parkinson's disease, depression, bipolar disorder, anxiety disorder, posttraumatic stress disorder and neurofibromatosis). Several compounds with a pyrido-[2,3-d]pyrimidine-7(8H)-one core and high affinity to the catalytic domain of PAK1-4 are described in the patent. These PAK inhibitors are hypothesized to exert beneficial effects on clinical symptoms via modulation of dendritic spine morphology and/or synaptic function. Preliminary preclinical data suggest that PAK inhibition may be an interesting approach for the treatment of HD, neurofibromatosis and fragile X syndrome, while data for other neurological conditions are missing. Current limitations call for a comprehensive characterization of the role of PAK dysfunction in neurological disorders before further testing the effect of PAK inhibitors in relevant preclinical models. If ever, it will probably take many years before the most promising compounds will head to the clinic for further assessment in patients with neurological disorders. [PubMed Citation] [Order full text from Infotrieve]

10) Mirza RA, Eick-Cost A, Otto JL
The risk of mental health disorders among U.S. military personnel infected with human immunodeficiency virus, active component, U.S. Armed Forces, 2000-2011.
MSMR. 2012 May;19(5):10-3.
Mental health disorders (MHD) are reportedly more common among soldiers and airmen with HIV than their seronegative counterparts. This report documents the incidence rates of MHD among HIV-positive members of all service branches and compares the rates to those of two HIV-unexposed control groups: an HSV2-infected group and a group without documented HIV or HSV2 infections. Approximately 56 percent of HIV-infected service members received an incident diagnosis of a MHD six months or more after the initial detection of their infections. Cumulative incidence rates in nearly all MHD categories of interest were highest in the HIV group, intermediate in the HSV2 group and lowest in the referent group. The disorders more frequently diagnosed among HIV-infected service members compared to their uninfected counterparts were psychosis/schizophrenia, substance dependence, substance abuse, bipolar disorder, suicide ideation and depression. The findings are consistent with previous studies and reiterate the importance of long-term and comprehensive clinical monitoring of individuals diagnosed with HIV-1 infections. [PubMed Citation] [Order full text from Infotrieve]

11) Culpepper L
Does screening for depression in primary care improve outcome?
Curr Psychiatry Rep. 2012 Aug;14(4):345-52.
2012 marks one decade since the US Preventive Services Task Force recommended screening for depression. Advances since then include expanded understanding of the mechanisms underlying and influences of psychiatric disease on the development, course and outcomes of medical conditions. They also include collaborative care strategies to improve outcomes. However, the impact of such single disease approaches has been disappointing. Strategies that integrate management of multiple morbidities into primary care practice have greatly improved outcomes. Depression has been the only psychiatric condition incorporated into these strategies. Their expansion to integrate recognition and care of bipolar disease, anxiety disorders including PTSD, and substance abuse could further improve outcomes with modest marginal cost. Development of a screening and treatment monitoring instrument for multiple common psychiatric conditions is a prerequisite. One recently developed instrument, the M3, has the performance characteristics desirable, and provides opportunity to incorporate multiple common psychiatric conditions into multimorbidity integrated management. [PubMed Citation] [Order full text from Infotrieve]

12) Levy B, Manove E, Weiss RD
Recovery of cognitive functioning in patients with co-occurring bipolar disorder and alcohol dependence during early remission from an acute mood episode.
Ann Clin Psychiatry. 2012 May;24(2):143-54.
[PubMed Citation] [Order full text from Infotrieve]

13) Mantere O, Suominen K, Valtonen HM, Arvilommi P, Leppämäki S, Paunio T, Isometsä ET
Concomitants of family histories of mood disorders and alcoholism in a clinical cohort of patients with bipolar I and II disorder.
J Nerv Ment Dis. 2012 May;200(5):388-94.
We diagnosed 191 secondary-care outpatients and inpatients with DSM-IV BD I or II. Sociodemographic and clinical characteristics, including axis I and II comorbidity, neuroticism, and prospective life-chart were evaluated at intake and at 6 and 18 months. The family history (FH) of mood disorders, alcoholism, or any major psychiatric disorders among first-degree relatives was investigated in a semistructured interview. Most (74%) patients had some positive FH; 55% of mood disorder, 36% of alcoholism. Positive FH was associated with psychiatric comorbidity and depressive course in the proband. Based on a multinomial logistic regression model, patients with an FH of mood disorder and alcoholism had an odds ratio of 4.8 (p = 0.001) for having an anxiety disorder. Overall, the first-degree relatives of patients with BD have multiple types of mental disorders, which correlate with bipolar patients' course of illness and psychiatric comorbidity. The strongest associations are between FH of mood disorders and presence of comorbid anxiety disorders. [PubMed Citation] [Order full text from Infotrieve]

14) Partonen T
Clock gene variants in mood and anxiety disorders.
J Neural Transm. 2012 Apr 27;
Circadian clocks are driven by signals from the habitat to match the solar day and to reset their phase relative to local time. A key function of the circadian clocks allows individuals to anticipate routine environmental conditions and to adjust their behaviors to the change of conditions. In clinical practice mood, anxiety and alcohol use disorders are often comorbid conditions. Clinical data have demonstrated that there are abnormalities in the circadian rhythms in patients with mood disorders and those with alcohol use disorders. Recent findings of molecular genetics have yielded the first insight into the targets of interest. Circadian clock gene variants are a fruitful target for elucidation of the pathogenesis. The findings that have gained support indicate that genetic variants of RORA (rs2028122) and CRY1 (rs2287161) associate with depressive disorder, those of RORB (rs7022435, rs3750420, rs1157358, rs3903529) and NR1D1 (rs2314339) with bipolar disorder, and those of NPAS2 (rs11541353) and CRY2 (rs10838524) with seasonal affective disorder or winter depression. Concerning anxiety disorders and alcohol use disorders, the current findings are preliminary and need further verification to explain the association of ARNTL2, being suggestive only, with social phobia (rs2306073) and with alcohol abuse (rs7958822, rs4964057). [PubMed Citation] [Order full text from Infotrieve]

15) Price AL, Marzani-Nissen GR
Bipolar disorders: a review.
Am Fam Physician. 2012 Mar 1;85(5):483-93.
Bipolar disorders are common, disabling, recurrent mental health conditions of variable severity. Onset is often in late childhood or early adolescence. Patients with bipolar disorders have higher rates of other mental health disorders and general medical conditions. Early recognition and treatment of bipolar disorders improve outcomes. Treatment of mood episodes depends on the presenting phase of illness: mania, hypomania, mixed state, depression, or maintenance. Psychotherapy and mood stabilizers, such as lithium, anticonvulsants, and antipsychotics, are first-line treatments that should be continued indefinitely because of the risk of relapse. Monotherapy with antidepressants is contraindicated in mixed states, manic episodes, and bipolar I disorder. Maintenance therapy for patients involves screening for suicidal ideation and substance abuse, evaluating adherence to treatment, and recognizing metabolic complications of pharmacotherapy. Active management of body weight reduces complications and improves lipid control. Patients and their support systems should be educated about mood relapse, suicidal ideation, and the effectiveness of early intervention to reduce complications. [PubMed Citation] [Order full text from Infotrieve]

16) Jahangard L, Haghighi M, Bigdelou G, Bajoghli H, Brand S
Comparing efficacy of ECT with and without concurrent sodium valproate therapy in manic patients.
J ECT. 2012 Jun;28(2):118-23.
[PubMed Citation] [Order full text from Infotrieve]

17) Malhi GS, Bargh DM, Cashman E, Frye MA, Gitlin M
The clinical management of bipolar disorder complexity using a stratified model.
Bipolar Disord. 2012 May;14 Suppl 2:66-89.
[PubMed Citation] [Order full text from Infotrieve]

18) Miklowitz DJ
Family treatment for bipolar disorder and substance abuse in late adolescence.
J Clin Psychol. 2008;68(5):502-13.
The initial onset of bipolar disorder occurs in childhood or adolescence in about 50% of patients. Early-onset forms of the disorder have a poorer prognosis than adult-onset forms and are frequently characterized by comorbid substance abuse. Clinical trials research suggests that family psychoeducational approaches are effective adjuncts to medication in stabilizing the symptoms of bipolar disorder in adults and youth, although their efficacy in patients with comorbid substance use disorders has not been systematically investigated. This article describes the family-focused treatment (FFT) of a late adolescent with bipolar disorder and polysubstance dependence. The treatment of this patient and family required adapting FFT to consider the family's structure, dysfunctional alliance patterns, and unresolved conflicts from early in the family's history. The case illustrates the importance of conducting manual-based behavioral family treatments with a psychotherapeutic attitude, including addressing unstated emotional conflicts and resistances that may impede progress. [PubMed Citation] [Order full text from Infotrieve]

19) Hill SY, Weeks DE, Jones BL, Zezza N, Stiffler S
ASTN1 and alcohol dependence: family-based association analysis in multiplex alcohol dependence families.
Am J Med Genet B Neuropsychiatr Genet. 2012 May;159B(4):445-55.
A previous genome-wide linkage study of alcohol dependence (AD) in multiplex families found a suggestive linkage result for a region on Chromosome 1 near microsatellite markers D1S196 and D1S2878. The ASTN1 gene is in this region, a gene previously reported to be associated with substance abuse, bipolar disorder and schizophrenia. Using the same family data consisting of 330 individuals with phenotypic data and DNA, finer mapping of a 26 cM region centered on D1S196 was undertaken using SNPs with minor allele frequency (MAF) ? 0.15 and pair-wise linkage disequilibrium (LD) of r(2) < 0.8 using the HapMap CEU population. Significant FBAT P-values for SNPs within the ASTN1 gene were observed for four SNPs (rs465066, rs228008, rs6668092, and rs172917), the most significant, rs228008, within intron 8 had a P-value of 0.001. Using MQLS, which allows for inclusion of all families, we find three of these SNPs with MQLS P-values < 0.003. In addition, two additional neighboring SNPs (rs10798496 and rs6667588) showed significance at P = 0.002 and 0.03, respectively. Haplotype analysis was performed using the haplotype-based test function of FBAT for a block that included rs228008, rs6668092, and rs172917. This analysis found one block (GCG) over-transmitted and another (ATA) under-transmitted to affected offspring. Linkage analysis identified a region consistent with the association results. Family-based association analysis shows the ASTN1 gene significantly associated with alcohol dependence. The potential importance of the ASTN1 gene for AD risk may be related its role in glial-guided neuronal migration. [PubMed Citation] [Order full text from Infotrieve]