Types of alcoholics, II. Application of an empirically derived typology to treatment matching.

Data from 79 male alcoholics who were randomly assigned to either coping skills training or interactional group psychotherapy were used to replicate a multidimensional, empirically derived typology and to evaluate the typology's usefulness in matching patients to treatment. Consistent with previous cluster analysis research, indicators of risk for alcoholism, alcohol dependence, drinking history, and psychopathological impairment distinguished alcoholics along two broad dimensions of vulnerability and severity, with one subtype (type B alcoholics) manifesting an earlier onset of problem drinking, more familial alcoholism, greater dependence on alcohol, and more symptoms of antisocial personality than the other subtype (type A alcoholics). Analyses of outcome indicated that type A alcoholics fared better in interactional treatment and more poorly with coping skills training. Conversely, type B alcoholics had better outcomes with the coping skills treatment and worse outcomes with interactional therapy. Differences in treatment response were maintained for 2 years from the beginning of aftercare treatment.     

The HR/LR model: Further evidence as an animal model of sensation seeking

Sensation seeking is a personality trait characterized by risk-taking and the desire to experience novel stimuli. Evidence suggests that sensation seeking may increase an individual's psychological and neurobiological vulnerabilities to drug abuse. One potential animal model of human sensation seeking is high response to novelty in rats. High responders (HRs) prefer a novel environment to a familiar one and show an increase in locomotor activity in the new environment. These rats also show lower levels of anxiety-like behaviour on several tests. Furthermore, HRs display a much higher propensity to self-administer psychostimulants compared to low responders (LRs). HR rats and sensation seeking humans share a number of similarities, for instance both exhibit elevated mesolimbic dopamine activity, which has been implicated in central reward signaling and drug addiction. Evidence of common behavioural tendencies, physiological responses and gene expression patterns suggest that the HR model could be used as an animal model to investigate substance abuse in sensation seeking humans.     

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.     

Mental disorders among alcoholics. Relationship to age of onset and cerebrospinal fluid neuropeptides.

Eighty-one percent of 339 alcoholics participating in a research program were found to have associated mental disorders. Alcoholics with onset of heavy drinking before 20 years of age had significantly more antisocial personality traits, drug abuse, bipolar disorder, panic disorder, suicide attempts, and paternal alcoholism than alcoholics with onset after age 20 years. Alcoholics with onset before and after 20 years of age also differed significantly from each other for cerebrospinal fluid concentrations of diazepam-binding inhibitor and somatostatin. These results support the notion that age of onset may delineate subgroups of alcoholics with significant clinical and neurochemical differences.     

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.     

Factors predicting the onset of adolescent drinking in families at high risk for developing alcoholism.

BACKGROUND: With a longitudinal prospective design, the purpose of this study was 1) to assess, with survival analysis, the age of onset of drinking in relation to family history of alcoholism; 2) to examine the importance of selected neurobiological and psychosocial risk factors in predicting the onset to drink; and 3) to determine if the age of onset of substance dependence problems differed by risk group status. METHODS: One hundred twenty-five children and adolescents were evaluated annually (N = 638 evaluations), providing up to seven annual waves of longitudinal data. Survival analyses were performed to determine the age of onset of regular drinking and the age of onset for substance abuse/dependence. The age of onset of regular drinking outcome was modeled using familial density of alcoholism and four factors, which included neurobiological indices of development (postural sway and P300), personality characteristics, academic achievement, self-esteem, and trait anxiety. RESULTS: High-risk children/adolescents showed a significantly earlier age of onset of drinking and an earlier age of onset for substance abuse problems. Familial density of alcoholism predicted an earlier onset of drinking, as did having deficits in reading achievement, reduced P300 (visual and auditory), and greater postural sway for age. Higher scores on the Extraversion scale of the Junior version of the Eysenck Personality Inventory also predicted an earlier onset of drinking. CONCLUSIONS: Familial density of alcoholism (number of alcoholic first- and second-degree relatives) is an important predictor of adolescent alcohol initiation. Evidence is presented suggesting that part of the familial/genetic variation in outcome may be due to neurobiological factors and temperament.     

Markers for vulnerability to psychopathology: temperament traits associated with platelet MAO activity

The functional linkage between platelet MAO activity and psychopathology was explored by analyzing temperamental correlates in 40 male subjects by means of scales from the Eysenck Personality Questionnaire (EPQ), the Zuckerman Sensation Seeking Inventory, and the Karolinska Scales of Personality (KSP). Linear correlations were found with two sensation seeking scales, replicating earlier findings. However, nonlinear correlations predominated. Subjects with intermediate platelet MAO activity had higher scores in conformity scales and lower scores in anxiety and hostility scales than low and high MAO subgroups. Low MAO subjects showed a pattern of higher scores in KSP Impulsiveness, EPQ Neuroticism, and KSP Somatic Anxiety and Irritability and lower scores in KSP Socialization, in line with personality profiles found in alcoholics, psychopaths, and suicide attempters who also tend to have low platelet MAO activity. High MAO subjects scored lower in sensation seeking and conformity scales and higher in KSP Psychasthenia, Muscular Tension and Suspicion scales, consistent with clinical links between high platelet MAO activity and anxiety and paranoia.     

Female alcoholics. V: The relationship between family history of alcoholism and outcome 3-10 years after treatment

In a long-term follow-up study of 44 female alcoholics, a family history of alcoholism was related to younger age of onset of problem drinking, but did not necessarily imply a poorer outcome within this highly selected group of individuals. Alcoholism in father and his family was not related to either antisocial or borderline personality disorder nor outcome. However, alcoholism in mother and her family correlated with both borderline personality disorder and a significantly poorer outcome. The findings are discussed within different frames of reference, considering genetic mechanisms, psychodynamic factors and family systems theory.     

Age of alcoholism onset. I. Relationship to psychopathology

Numerous attempts have been made to subdivide populations of alcoholics into homogeneous subgroups. Although no consensus has been reached about the characteristics of these subgroups, a number of classification schemes have identified a subgroup of patients with a high genetic loading for alcoholism, an early onset of alcoholism, a severe course, and coexisting psychiatric problems consisting of aggressive tendencies or criminality. In a recent typology proposed by Cloninger on the basis of adoption studies, this subgroup has been classified as type 2. Another group of patients who were found to differ in their mode of inheritance and clinical characteristics was classified as type 1. The identification of etiologically homogeneous subgroups is easier in studies of adoptees than in studies of individuals who were not adopted. In an attempt to divide alcoholics into two groups of individuals presenting type 1 and type 2 characteristics, we used as a criterion the age of alcoholism onset because type 2 alcoholics as well as their fathers had been found to abuse alcohol at a younger age than type 1 patients. Patients with an onset of alcoholism before their 20th birthday were found to have a significantly higher incidence of paternal alcoholism and were twice as likely to have been incarcerated for crimes involving physical violence. We also observed other features not previously described in this patient subgroup. Patients who started abusing alcohol in their teens were three times as likely to be depressed and four times as likely to have attempted suicide as patients with a later onset of alcohol abuse.     

Striatal dopamine D1 receptors in type 1 and 2 alcoholics measured with human whole hemisphere autoradiography

A considerable number of human and animal studies have implied the importance of dopamine system and alterations in dopamine receptors in the context of alcoholism. However, it has remained unclear if the alcohol-abuse related dopaminergic deficit is specifically associated with certain receptor subtype. The aim of this study was to compare putative alterations of dopamine D(1) receptors in caudate and putamen of nine type 1 alcoholics, eight type 2 alcoholics and 10 healthy controls by using [(3)H]SCH 23390 as a radioligand in postmortem human whole hemisphere autoradiography. In addition, we compared the present results to our earlier studies on dopamine transporters and dopamine D(2) receptors in these same subjects and evaluated the putative correlations of dopamine D(1) receptor densities between the nucleus accumbens and the above-mentioned structures. Our results show that alcoholics do not have significantly different striatal dopamine D(1) receptor densities compared to controls. Neither were there any significant correlations between the dopamine D(1) receptors and the two other dopamine binding sites. However, the correlations of the dopamine D(1) receptors between nucleus accumbens and dorsal striatal structures were consistently and mostly statistically significantly positive in alcoholics, but not in controls, which may suggest some pathology related to addiction. In addition, considering the facts that dopamine D(1) receptors were more abundant in the mesolimbic nucleus accumbens than in the caudate or putamen and that there was a strong tendency towards lower binding among type 1 alcoholics may suggest the importance of dopamine D(1) receptors in reward and/or alcoholism.     

No association between C-45T polymorphism in the Sp1 binding site of the promoter region of the cholecystokinin gene and alcoholism

The activity of dopamine-containing neurons in the ventral tegmental area and nucleus accumbens may play a role in alcoholism. Cholecystokinin (CCK) co-exists in a large proportion of A10 dopamine neurons to exert some effect on dopamine-induced behavior. Recently, a C-45T polymorphism was discovered in the Sp1 binding site in the CCK gene promoter region. We investigated an association between the polymorphism and alcoholism in 209 Japanese DSM-III-R alcoholics and 113 Japanese control subjects. The patients and the control subjects had similar allele and genotype frequencies: the T allele frequencies were 0.27 in the patients and 0.28 in the control subjects and the CC, CT, and the TT genotype frequencies 0.53, 0.39, and 0.08 in the alcoholics and 0.53, 0.37, and 0.10 in the control subjects. Frequencies of clinical characteristics of Feighner's criteria for the lifetime diagnosis of alcoholism were not significantly different among the patient groups divided by the genotype. These findings indicate that the polymorphism has no major effect on the etiology of alcoholism.     

Alcoholism and alleles of the human D2 dopamine receptor locus. Studies of association and linkage

The association of the A1 allele of the D2 dopamine receptor gene with alcoholism was examined by comparing 32 unrelated white alcoholics with 25 unrelated white controls and by analysis of 17 nuclear families in multigenerational pedigrees of alcoholics in whom the A1 allele was segregating. All subjects had structured psychiatric interviews. Clinical assessment and genotyping were carried out independently. Thirteen (41%) of the 32 alcoholics carried the A1 allele compared with three (12%) of the 25 controls. The association with the A1 allele was significant when controls were compared with a subset of 10 alcoholics with severe medical problems (60% vs 12%), but not less severe cases. However, regardless of clinical severity or subtype, there was no evidence of linkage or cosegregation of the A1 allele and increased susceptibility to alcoholism in informative pedigrees. The possible association in the general population without linkage in families may be explained either by chance variation in our small samples or a modifying effect of the A1 allele that increases severity. Further study of the role of the D2 receptor gene in alcoholism is warranted.     

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.     

Alcoholism, ALDH2*2 allele and the A1 allele of the dopamine D2 receptor gene: an association study

The inactive form of aldehyde dehydrogenase-2 (ALDH2) is regarded as a protective factor against the development of alcoholism, and alcoholics with inactive ALDH2 are considered to be relatively homogeneous. This examination of a possible allelic association of the dopamine D2 receptor (DRD2) gene TaqI A polymorphism failed to detect significant differences between 583 Japanese alcoholics and 295 unrelated Japanese controls, or between alcoholic subjects with different ALDH2 genotypes. Despite the significantly higher frequency of the DRD2 A1 allele in the 207 alcoholics with inactive ALDH2 than in the 376 alcoholics with active ALDH2, multiple logistic regression analysis (controlled for the ALDH2 genotype) revealed no association between the TaqI A polymorphism and alcoholism. Nor did the frequency of the DRD2 TaqI A polymorphism differ in alcoholic subjects grouped by several pertinent clinical characteristics, including severity of alcoholism. Although there remains a possibility that the DRD2 TaqI A polymorphism plays some role in modifying the phenotype of the disease, these results suggest that neither the A1 allele nor the homozygous A1 genotype is associated with alcoholism.     

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.     

Platelet monoamine oxidase in alcoholism

We studied platelet monamine oxidase (MAO) activity using 14C-tyramine as substrate in hospitalized alcoholic patients in the early phases of abstinence and in nonhospitalized normal control volunteers. Platelet MAO was determined in 75 patients (67 men, 8 women) with alcoholism and 123 normal control volunteers (52 men, 71 women). The platelet MAO activity in alcoholic patients was significantly lower than in normal control volunteers. We also observed that the mean platelet MAO activity in male alcoholics was significantly lower than in normal males. The analysis of platelet MAO in alcoholics revealed a mixture of two normal distributions. Alcoholic patients falling into the low MAO component were younger in age, with a lower age of onset of alcoholism, and had higher frequencies of family history of alcoholism. They thus resembled type II alcoholics described by other investigators. Platelet MAO may thus serve as a useful biological marker for subtyping alcoholism and identifying high-risk groups at an early stage. The findings of this study are consistent with previous reports of low platelet MAO activity in alcoholic patients.     

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.