Psychiatric heterogeneity in antisocial alcoholics: relation to familial alcoholism.

There is some indication that addicts who qualify for a diagnosis of antisocial personality disorder (ASP) do not comprise a homogeneous group with respect to psychopathology. This preliminary study attempted to determine the extent to which DSM-III diagnosed ASP alcoholics with alcoholism on both sides of their family could be differentiated with respect to childhood behavioral problems and additional adult psychopathology from ASP alcoholics with low degrees of familial alcoholism. Two groups of ASP alcoholic patients were compared: (1) 11 high familial (bilineal) alcoholics, and (2) 22 low familial (nonfamilial or unilineal) alcoholics. Few group differences were found in sociodemographic or alcohol-related characteristics, although the high familial group tended to be younger. However, the high familial alcoholism group tended to report more childhood antisocial behaviors and more childhood behavior problems overall. The high familial alcoholism group also reported more psychopathology on three of the 10 Minnesota Multiphasic Personality Inventory (MMPI) clinical scales, paranoia (P less than .05), schizophrenia (P less than .06), and masculine-feminine (P less than .025). Effect sizes for these three variables were in the moderate range. The group MMPI profile of the high familial alcoholism group was indicative of serious characterological disturbances, while that of the low familial alcoholism group was much more normal. The results of this preliminary study provided evidence suggesting that antisocial individuals with a high degree of familial alcoholism are more likely to manifest psychopathology than antisocial individuals with a lesser degree of familial alcoholism.     

Diagnostic subgroups of antisocial alcoholics: outcome at 1 year

Of 233 alcoholics initially evaluated and subdivided into groups with an additional diagnosis of antisocial personality disorder (ASP) only (N = 38), ASP plus drug abuse (N = 30), ASP plus major depressive disorder (N = 18), and those with no additional diagnosis (N = 147), 205 were followed up 1 year later. The ASP plus drug group, although younger and having fewer years of alcoholism, did worse in the 1-year follow-up on many indicators of alcoholism severity compared with the other antisocial groups and the alcoholism only group. The ASP plus depressed group demonstrated marked improvement on measures of psychopathology and alcoholism severity over the course of 1 year such that they were comparable on these measures at 1-year follow-up to the other antisocial groups. These findings may indicate that the ASP/drug alcoholic has a poor long-term prognosis compared with the ASP only alcoholic, while the ASP/depressed patient has a disorder comparable in prognosis to the ASP only alcoholic.     

Attention deficit disorder, alcoholism, and drug abuse: MMPI correlates.

Earlier research had demonstrated that alcoholics with attention deficit disorder residual type (ADDRT) differ from other alcoholics on the Minnesota Multiphasic Personality Inventory (MMPI). The purpose of this study was to explore the influence of drug abuse on the relationship of ADDRT and alcoholism as reflected on the MMPI. Groups of 48 male alcoholics, 28 ADDRT alcoholics, 25 ADDRT alcohol and drug abusers and 18 alcohol and drug abusers were all administered the MMPI. Significant differences were found between the alcoholic and ADDRT alcoholic groups on scales Pd, Sc, Si, F, and K. For the ADDRT alcohol and drug abusers versus the alcohol and drug abuser groups, they differed on scales K, Hs, D, Pd, Pa, Pt, Sc, Si, F, K, and L.     

A family study of familial positive vs. familial negative alcoholics

Of 259 alcoholics studied, 173 were primary alcoholics. Familial positive primary alcoholics tended to have earlier onset of alcoholism and males seemed to have more complications from drinking. Family study data indicated that the familial positive group had family pedigrees more likely to contain relatives with antisocial personality disorder. This relationship to antisocial personality may help in explaining previous research findings in familial positive alcoholics.     

Association of 5-HT1B receptor gene and antisocial behavior in alcoholism

Summary. The 5-HT1B receptor gene has been postulated to play a modulatory role in alcohol consumption and alcohol dependence, and was considered a candidate gene for alcoholism. More recently, the association of the 5-HT receptor gene polymorphism and antisocial personality traits in alcoholism has been discussed. This possible association was studied using material from our gene bank for alcoholism. The research instruments used to phenotype patients were partly adopted from the US Collaborative Study on the Genetics of Alcoholism (COGA) which include anxiety- and depression-related scales from personality inventories such as the temperament and character inventory (TCI), the NEO-Five-Factor Inventory (NEO-FFI) and the Minnesota Multiphase Personality Inventory (MMPI-2). Based on the examination of 164 alcoholic subjects, an association was found between a lower frequency of the 5-HT 1B 861C allele, antisocial personality traits and conduct disorder in alcohol-dependent subjects. Adult antisocial personality occurred more often in males than females. Possible implications of these findings are discussed.     

Clinical importance of age at onset in type 1 and type 2 primary alcoholics

Alcoholics have been proposed to be comprised of subtypes who differ in their age at onset and in type 1 vs type 2 characteristics. This study examined whether the clinical course of primary alcoholics was associated with age at onset as well as the type 1-vs-type 2 classification scheme. Interviews with 171 consecutive primary alcoholic men entering an alcohol treatment program revealed that age at onset of alcoholism was correlated with alcohol, drug, and childhood criminality problem histories. Neither classification of these alcoholics into discrete type 1 and type 2 categories nor placing them along a continuum of type 2 characteristics was consistently associated with severity of clinical histories. These findings underscore the clinical importance of age at onset and suggest the possibility that the type 2 prototype might represent a separate diagnosis, antisocial personality disorder, and not alcoholism itself.     

Clinical characteristics of familial versus sporadic alcoholism in a sample of male and female patients.

Presence of a family history of alcoholism may predict clinical characteristics in affected subjects, such as an earlier age at onset. More frequent and severe social maladjustment and somatic complications are also regularly cited for familial alcoholism, although subject to many other confusing factors. We analysed the clinical specificities of 79 alcohol-dependent inpatients according to the absence versus presence of family history of alcoholism. Patients were evaluated for lifetime psychiatric morbidity with the Diagnostic Interview for Genetic Studies (DIGS), for somatic complications with a systematic screening list, and first-degree relatives (N = 428) were assessed with the Family Inventory Schedule and Criteria (FISC). Age at onset and social complications were predicting familial versus sporadic alcoholism, even when considering censored data and/or interaction between variables. But differences became non-significant when excluding patients with antisocial personality. If age at onset effectively appears to be the most informative characteristic for predicting familial versus sporadic alcoholism, it seems that it may be necessary in future studies to systematically take into account antisocial personality diagnosis, because of a probable contamination.     

Prefrontal volumes in habitually violent subjects with antisocial personality disorder and type 2 alcoholism

Pathology of the prefrontal cortices has been suggested to be a part of neural networks underlying deviant behavioral patterns. Recently, reduced overall prefrontal cortical volumes have been proposed in subjects with antisocial personality disorder (ASP). It is not known whether there are specific patterns of volume loss within the prefrontal regions. Nor is it known if there are correlations between the prefrontal volumes and degree of psychopathology. In this study, total prefrontal, prefrontal white, and cortical (dorsolateral, orbitofrontal, medial frontal) prefrontal volumes were measured from magnetic resonance images in 24 non-psychotic, violent male subjects who had a diagnosis of ASP in combination with type 2 alcoholism, and 33 age-matched control males. The degree of psychopathy in the ASP subjects was assessed using the Psychopathy Checklist-Revised (PCL-R). Compared with the controls, the ASP subjects had significantly smaller volumes of all three cortical regions on the left, but this significance disappeared after controlling for differences in education and duration of alcoholism. For the dorsolateral and orbitofrontal cortices, only duration of alcoholism was significantly associated with the observed volume deficit, and for the medial frontal cortex it was the difference in education. Thus, the observed volume deficits in this sample were related more to alcoholism or differences in education rather than to the diagnosis of ASP. Moreover, no significant correlations between any of the volumes and the degree of psychopathy were found.     

A volumetric MRI study of the hippocampus in type 1 and 2 alcoholism

In recent years, magnetic resonance imaging (MRI) of the hippocampus has been extensively studied on neurological and psychiatric disorders. Particularly in studies on schizophrenia and mood disorders, findings regarding the hippocampal involvement have been most controversial. Previously, minor volume loss of the hippocampus in alcoholism, a major comorbidity alongside psychiatric disorders, has been reported but no data exist on the hippocampal volumes in subtypes of alcoholism. In this study, MRI was used to measure volumes of the hippocampus in late-onset type 1 alcoholics and early-onset type 2 alcoholics. The type 2 alcoholic subjects were also violent offenders with antisocial personality disorder, derived from a forensic psychiatric sample. All were non-psychotic and legally competent. Normal volunteers, representing a wide age range, served as a controls group. Compared to the controls, the right, but not left, hippocampi were significantly smaller in both alcoholic groups. While there was no correlation between the hippocampal volumes with age in the control subjects, there was tendency towards decreased volumes with aging and also with the duration of alcoholism in the type 1 alcoholic subjects. Surprisingly, there was a significant positive correlation between the right hippocampal volume and age in the type 2 alcoholics. This study provides further in vivo evidence that type 1 alcoholism, in general, is associated with a minor loss in hippocampal volume. It is suggested that type 2 alcoholism, in general, similarly displays a minor decrease in hippocampal volume, but this decrease is unevenly distributed within the type 2 category, being weighted towards the younger subjects. These effects suggest differences between the two alcoholic groups, and raise the possibility that the observed effects within the type 2 category are due to other factors than the cumulative acquired effects related to alcohol abuse, such as primary personality psychopathology.     

Alcoholism and personality

OBJECTIVE: The search for an alcoholic personality has been pursued with varying enthusiasm throughout the 20th century. This paper reviews the methodological issues, research designs and current theories relating alcoholism and personality. METHOD: A selected literature search using computerised databases was ordered via the four major research design strategies: cross sectional studies, high-risk studies, longitudinal studies and genetic epidemiology studies. RESULTS: Cross sectional studies have suggested that two broad bands of personality, impulsivity/novelty seeking and neuroticism/negative emotionality, are associated with alcoholism. Although high-risk studies have repeatedly shown that sons of male alcoholics are at increased risk of alcoholism, whether this risk is related to personality variables is unclear. Many authors believe that the presence of antisocial personality disorder is a confounder and that this may explain some of the contradictory findings. Longitudinal studies have consistently reported that antisocial behaviour and hyperactivity are related to later alcoholism. Negative emotionality seems to be less important and may largely be a consequence of the alcoholism itself. Genetic epidemiological studies suggest that personality measures play a modest but significant role in the genetic influence of alcoholism. The strongest relationships are with conduct disorder and antisocial behaviour. The postulated alcoholic subtypes (Type I, Type II or Type A/B) based on age of onset and personality style have been challenged by recent research. The most vulnerable to alcoholism may be those with both high impulsivity/high novelty seeking and high neuroticism/negative emotionality. CONCLUSION: Antisocial behaviour and hyperactivity are the most consistent behaviours associated with alcoholism. These behaviours are not specific for alcoholism and are associated with many other psychiatric conditions. Personality variables by themselves explain only a small proportion of the risk for alcohol dependence. There is no alcoholic personality nor are there personality measures which are specific to vulnerability to later alcohol dependence. Attempting to link alcoholism with theoretical, poorly validated models of personality is premature.     

Alcoholism as a medical disorder

This report is based upon a long-term study from the Washington University Psychiatry Clinic. The study began with a systematic clinical evaluation of 500 patients, which was followed by a “blind” study of first-degree relatives and a “blind” follow-up of the index subjects. The present report deals with the diagnosis of alcoholism at index, at follow-up, and among the first-degree relatives. The results indicate that the criteria used for the diagnosis of alcoholism select patients who show a satisfactory degree of diagnostic consistency over many years. Furthermore, the diagnostic criteria select cases associated with a significant increase in the familial risk of alcoholism.Alcoholism was the only psychiatric disorder found to be increased among first-degree relatives of alcoholic probands. On the other hand, alcoholism in the probands was found to be associated with secondary depression, secondary mania, antisocial personality, Briquet's Syndrome, and drug dependence. None of these disorders, however, was found at an increased prevalence among the first-degree relatives of the alcoholics, suggesting that these associated disorders may play a significant role in the seeking of psychiatric care by patients with alcoholism.     

Implications of family history of alcoholism, antisocial personality, and sex differences in alcohol dependence

In this study of 210 male and female alcoholic inpatients, significant associations were found 1) between antisocial personality diagnosis and early onset of all stages in alcohol dependence; 2) between bilineal family history of alcoholism and greater frequency of the consequences of impaired control, withdrawal symptoms, and the pathologic symptoms associated with chronic alcoholism; and 3) between being female and older at onset of the initial, but not final, stages of alcoholism and having more symptoms associated with chronic alcohol use. Antisocial personality, type of family history, and sex of the proband were not interactive but contributed separate additive effects.     

Interaction between a functional MAOA locus and childhood sexual abuse predicts alcoholism and antisocial personality disorder in adult women

Women who have experienced childhood sexual abuse (CSA) have an increased risk of alcoholism and antisocial personality disorder (ASPD). Among male subjects, a functional polymorphism (MAOA-LPR, monoamine oxidase A linked polymorphic region) in the promoter region of the monoamine oxidase A gene (MAOA) appears to moderate the effect of childhood maltreatment on antisocial behavior. Our aim was to test whether MAOA-LPR influences the impact of CSA on alcoholism and ASPD in a sample of 291 women, 50% of whom have experienced CSA; we also tested whether haplotypes covering the region where both MAOA and monoamine oxidase B (MAOB) genes are located predict risk of alcoholism and ASPD better than the MAOA-LPR locus alone. Participants included 168 alcoholics (39 with ASPD (antisocial alcoholics) and 123 controls (no alcoholics, no ASPD). Antisocial behavior was also modeled as a continuous trait: ASPD symptoms count. The MAOA-LPR low activity allele was associated with alcoholism (P=0.005), particularly antisocial alcoholism (P=0.00009), only among sexually abused subjects. Sexually abused women who were homozygous for the low activity allele had higher rates of alcoholism and ASPD, and more ASPD symptoms, than abused women homozygous for the high activity allele. Heterozygous women displayed an intermediate risk pattern. In contrast, there was no relationship between alcoholism/antisocial behavior and MAOA-LPR genotype among non-abused women. The MAOA-LPR low activity allele was found on three different haplotypes. The most abundant MAOA haplotype containing the MAOA-LPR low activity allele was found in excess among alcoholics (P=0.008) and antisocial alcoholics (P=0.001). Finally, a MAOB haplotype, which we termed haplotype C, was significantly associated with alcoholism (P=0.006), and to a lesser extent with antisocial alcoholism (P=0.03). In conclusions, MAOA seems to moderate the impact of childhood trauma on adult psychopathology in female subjects in the same way as previously shown among male subjects. The MAOA-LPR low activity allele appears to confer increased vulnerability to the adverse psychosocial consequences of CSA. Haplotype-based analysis of the MAOA gene appeared to strengthen the association, as compared to the MAOA-LPR locus alone. A MAOB haplotype was associated with alcoholism independently from ASPD.     

Behavioral symptoms and psychiatric diagnoses among 162 children in nonalcoholic or alcoholic families

OBJECTIVE: People with alcoholic relatives have high rates of alcohol abuse and dependence as adults, but their patterns of problems earlier in life are less clear. Many studies have not controlled for parental disorders other than alcoholism or for parents' socioeconomic status and general life functioning. The authors' goal was to conduct a study controlling for such factors. METHOD: Personal structured interviews and a behavioral checklist were administered to the parents of 162 children 7 years old or older whose fathers had participated in the 15-year follow-up of 453 sons of alcoholics with no history of antisocial personality disorder and sons of nonalcoholic comparison subjects originally selected from a university population. RESULTS: There was no significant relationship between a family history of alcoholism and childhood diagnoses of conduct, oppositional, or attention deficit disorders or with behavioral checklist summary scores. However, children with alcoholic relatives apparently have a slightly higher risk for drug abuse or dependence than those without alcoholic relatives. CONCLUSIONS: Once familial antisocial disorders and familial socioeconomic status are controlled for, a family history of alcoholism does not appear to relate to childhood externalizing disorders.     

Relationship of child psychopathology to parental alcoholism and antisocial personality disorder.

OBJECTIVE: To evaluate the contributions of familial factors, including parental diagnoses of alcoholism and/or antisocial personality disorder (ASPD), to the risk of developing various child psychiatric diagnoses. METHOD: Four hundred sixty-three children and their biological parents were interviewed with adult and child versions of the Semi-Structured Assessment for the Genetics of Alcoholism. Demographic and psychiatric data were compared across 3 groups of children on the basis of the presence of parental alcoholism and ASPD (no other parental diagnoses were examined). Generalized estimating equations analyses allowed the inclusion of multiple children from each family in the analyses. RESULTS: Among offspring, parental alcoholism was associated with increased risks for attention-deficit hyperactivity disorder, conduct disorder (CD), and overanxious disorder. Parental alcoholism plus ASPD was associated with increased risk for oppositional defiant disorder. Dysfunctional parenting style was associated with increased risks for CD, alcohol abuse, and marijuana abuse. Low family socioeconomic status was associated with increased risk for CD. CONCLUSIONS: Parental diagnoses of alcoholism and ASPD were associated with increased risks for a variety of childhood psychiatric disorders, and dysfunctional parenting style was associated with the diagnoses of CD, alcohol abuse, and marijuana abuse.     

Psychopathology in hospitalized alcoholics

This study utilized the DSM-III criteria and the National Institute of Mental Health Diagnostic Interview Schedule to assess the prevalence of lifetime psychopathology among hospitalized alcoholics. Antisocial personality (ASP) and substance-use disorder were common psychopathologies among male alcoholics and major depression and phobia were common among female alcoholics. The onset of most psychopathologies preceded the abuse of alcohol among women. In men, however, with the exception of ASP and panic disorder, the onset of psychopathology was subsequent to that of alcohol abuse and/or dependence. Diagnoses of ASP and substance abuse were characterized by early onset of regular intoxication and alcohol abuse. Gender and the presence of specific psychopathology appeared to modify the course and symptom picture of alcoholism. In general, alcoholic women showed a later onset of regular intoxication and a more rapid progression to alcohol abuse and dependence than alcoholic men.     

Possible interaction between MAOA and DRD2 genes associated with antisocial alcoholism among Han Chinese men in Taiwan

Both monoamine oxidase A (MAOA) and dopamine D(2) receptor (DRD2) genes have been considered as candidate genes for antisocial personality disorder with alcoholism (Antisocial ALC) [Parsian, A., 1999. Sequence analysis of exon 8 of MAO-A gene in alcoholics with antisocial personality and normal controls. Genomics. 45, 290-295.; Samochowiec, J., Lesch, K.P., Rottmann, M., Smolka, M., Syagailo, Y.V., Okladnova, O., Rommelspacher, H., Winterer, G., Schmidt, L.G., Sander, T., 1999. Association of a regulatory polymorphism in the promoter region of the monoamine oxidase A gene with antisocial alcoholism. Psychiatry. Res. 86, 67-72.; Schmidt, L.vG., Sander, T., Kuhn, S., Smolka, M., Rommelspacher, H., Samochowiec, J., Lesch, K.P., 2000. Different allele distribution of a regulatory MAO-A gene promotor polymorphism in antisocial and anxious-depressive alcoholics. J. Neural .Transm. 107, 681-689.]. However, the association between alcoholism and MAOA or DRD2 gene has not been universally accepted [Lee, J.F., Lu, R.B., Ko, H.C., Chang, F.M., Yin, S.J., Pakstis, A.J., Kidd, K.K., 1999. No association between DRD(2) locus and alcoholism after controlling the ADH and ALDH genotypes in Chinese Han population. Alcohol. Clin. Exp. Res. 23, 592-599.; Lu, R.B., Lin, W.W., Lee, J.F., Ko, H.C., Shih, J.C., 2003. Neither antisocial personality disorder nor antisocial alcoholism association with MAOA gene among Han Chinese males in Taiwan. Alcohol. Clin. Exp. Res. 27, 889-893.]. Since dopamine is metabolized to 3,4-dihydroxyphenyl-acetaldehyde (DOPAL) via monoamine oxidase (MAO) [Westerink, B.H., de Vries, J.B., 1985. On the origin of dopamine and its metabolite in predominantly noradrenergic innervated brain areas. Brain. Res. 330, 164-166.], the interaction between MAOA and DRD2 genes might be related to Antisocial ALC. The present study aimed to determine whether Antisocial ALC might be associated with the possible interactions of DRD2 gene with MAOA gene. Of the 231 Han Chinese subjects who were recruited for the study, 73 participants were diagnosed with Antisocial ALC and 158 subjects were diagnosed with antisocial personality disorder without alcoholism (Antisocial Non-ALC). The DRD2 TaqI A and MAOA-uVNTR (variable number of tandem repeat located upstream) polymorphisms were not found to be associated with Antisocial ALC. However, an association between DRD2 TaqI A polymorphisms and Antisocial ALC was shown only after stratification for the MAOA-uVNTR 4-repeat polymorphism. Additionally, after multiple logistic regressions, we found that, under stratification of MAOA-uVNTR 4-repeat polymorphism and in comparison with the DRD2 A1/A1 genotype as a reference group, the DRD2 A1/A2 genotype has a possible protective effect against alcoholism in individuals with antisocial personality disorder (ASPD). We concluded that the possible interactions between MAOA-uVNTR polymorphism and DRD2 TaqI A polymorphism might be related to Antisocial ALC among Han Chinese men in Taiwan.     

Platelet MAO in subtypes of alcoholism

A number of investigators have observed low platelet monoamine oxidase (MAO) activity in alcoholism. There is also preliminary evidence suggesting that low enzyme activity is principally associated with one of two putative subtypes of alcohol dependence, i.e., type II (male limited). The results of this study are consistent with two previous reports of reduced platelet MAO activity in type II male alcoholics as compared with type I male alcoholics and normal, healthy male controls. Type I (milieu-limited) alcoholics showed a smaller reduction in enzyme activity. The observed differences do not appear to be related to concurrent use of other psychoactive substances, characteristic differences in age between type I alcoholics and type II alcoholics, antisocial personality disorder, or variation in platelet size. Low platelet MAO activity in alcoholics is possibly related to both state and trait factors and may be a useful biochemical measure to assist with subtyping.     

Alcoholism and attention deficit disorder: MMPI correlates

Previous research suggests that the alcoholic population can be meaningfully divided into subtypes, one of which is attention deficit disorder, residual type (ADDRT). The purpose of this study was to identify differences in personality profiles, as measured by the Minnesota Multiphasic Personality Inventory (MMPI), between ADDRT alcoholics and other alcoholics. Groups of 50 male ADDRT alcoholics and 50 male nonADDRT alcoholics were administered the MMPI. Statistically significant differences were found for the D, PD, Pa, Pt. Sc. MA, Si, F and K scales: the ADDRT alcoholics scored significantly higher than the nonADDRT alcoholics on most of the scales, but significantly lower on the K scale.     

Reduced P3 amplitudes are associated with both a family history of alcoholism and antisocial personality disorder

1. 1. Previous research has demonstrated that the amplitude of the P3 component of the event-related electroencephalographic potential (ERP) is influenced by the presence/absence of a family history of alcoholism (FHA). The present study extended this line of research by examining the P3 effects of both FHA and antisocial personality disorder (ASP) in a 2 × 2 factorial design.

2. 2. The task required subjects to judge the orientation of an infrequently-occurring outline drawing, representing an aerial view of a human head.

3. 3. Analyses of P3 amplitudes elicited by this drawing revealed reductions attributable to the effects of both FHA and ASP, but not their interaction. These effects were most apparent at frontal electrode sites. Analyses of P3 latency revealed no consistent pattern of findings. However, the interval between P3 and manual reaction time was shorter in the ASP+ group relative to the ASP- group.