Cassidy F, Ahearn EP, Carroll BJ.
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]
RD, Stayner DA, Chinman MJ, Wu P, Tebes JK, Davidson L.
between anxiety and substance use disorders among individuals with severe affective
Compr Psychiatry. 2002 Jul-Aug;43(4):245-52.
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
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]
LA, Harris SK, Kurland M, Knight JR.
Substance use problems and associated
psychiatric symptoms among adolescents in primary care.
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
TE, Biederman J, Millstein RB, Wozniak J, Hahesy AL, Spencer TJ.
for substance use disorders in youths with child- and adolescent-onset bipolar
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]
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]
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.
in prevalence, risk, and clinical correlates of alcoholism comorbidity in bipolar
Am J Psychiatry. 2003 May;160(5):883-9.
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
KL, Kivlahan D, Saxon AJ.
Detecting bipolar disorder among treatment-seeking
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."
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]
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.
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."
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]
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."
JB, Kane HS, Chiu YF, Simpson SG, MacKinnon DF, McInnis MG, McMahon FJ, DePaulo
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
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."
KB, Carey MP, Simons JS.
Correlates of substance use disorder among
psychiatric outpatients: focus on cognition, social role functioning, and psychiatric
J Nerv Ment Dis. 2003 May;191(5):300-8.
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
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]
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.
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]