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]