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.     

The relationship between taste sensitivity to phenylthiocarbamide and anhedonia

It has been proposed that taste sensitivity to bitter compounds such as, phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP), represents a genetic marker for an increased vulnerability to depressive illness. Previous explorations of this idea have proven equivocal. This study refines and further explores this idea by focusing specifically on anhedonia (diminished hedonic capacity), a key symptom in some depressive illness, linked also with sensory pleasure. It is hypothesized that diminished PTC taste sensitivity will be associated with more general decrements in hedonic capacity (anhedonia). An opportunity sample of 198 university students were assessed using paper strips impregnated with PTC, the same participants also completed a widely used assessment of hedonic capacity, the Snaith-Hamilton Pleasure Scale (SHAPS). Hedonic capacity scores positively correlated with PTC taste sensitivity; specifically, heightened hedonic capacity was associated with heightened sensitivity to the bitter taste of PTC. Furthermore, modest differences were observed between those least (non-tasters) and most (supertasters) sensitive to PTC, with non-tasters reporting significantly lower hedonic capacity scores than supertasters. PTC taste sensitivity may represent a peripheral risk factor for anhedonia.     

Phenylthiocarbamide tasting and family history of depression, revisited: low rates of depression in families of supertasters

Past studies suggest that phenylthiocarbamide (PTC) taste status is related to vulnerability to depression, such that those sensitive to PTC are more vulnerable. We questioned this, reasoning that those insensitive to PTC may be more vulnerable (because they may have lower hedonic tone and higher risk for alcohol abuse). Forty-two volunteers responded to questionnaires regarding family history of depression, and were assigned to supertaster, taster, or non-taster categories based on taste reactions to a 3.80 x 1.43 cm piece of commercially prepared paper treated with PTC. Supertasters were significantly less likely to report first-degree relatives with a history of depression than were tasters and non-tasters. Supertasters may be afforded some protection from depression; elucidating the mechanisms of this protection is a potentially interesting avenue for future research.     

Gender differences in the specificity of alcoholism transmission among the relatives of opioid addicts

Gender differences in the specificity of drug versus alcohol transmission were examined among 201 opioid addicts and their 877 first-degree relatives using direct interviews and a structured family history method based on the Schedule for Affective Disorders and Schizophrenia Research Diagnostic Criteria. A strong association of parental alcoholism with alcoholism among the proband addicts was found, suggesting some specificity for drug versus alcohol abuse. We also found that among the 477 siblings, those with alcoholism alone did not have parents with drug abuse and those parents with drug abuse did not have children with alcoholism alone. Rates of parental alcoholism were higher in alcoholic female than in alcoholic male probands, suggesting greater female "loading" was needed in order to become alcoholic. This increased loading in women was also found among the siblings, but alcoholic parents appeared to transmit a nonspecific tendency for either drug or alcohol abuse to their female children. Thus, it may take a greater "dose" of parental transmission for a woman to become a substance abuser, and transmission of alcoholism may be specific in men, but not in women.     

An examination of associations between the inability to taste phenylthiocarbamide (PTC) and clinical characteristics and trait markers in first-episode,nonaffective psychotic disorders

Research findings are mixed as to whether or not the inability to taste phenylthiocarbamide (PTC) might represent an endophenotypic trait marker for schizophrenia. We hypothesized associations between PTC-tasting status and select clinical characteristics and trait markers in patients with psychotic disorders that, if present, would provide support for the inability to taste PTC as a trait marker. In a first-episode psychosis sample (n=93), we measured PTC tasting, family history of psychosis, age at onset of prodrome and psychosis, severity of positive and negative symptoms, global impairment in functioning, neurological soft signs, and four neurocognitive domains (verbal learning/memory, visual learning/memory, verbal working memory, and spatial working memory). Associations between PTC-non-tasting and clinical/neurocognitive variables were examined with χ² tests and independent samples t tests. Among participants, 67.7% tasted PTC in comparison to a strip of control paper, and 25.8% were non-tasters. Tasters and non-tasters did not show statistically significant differences with respect to family history, age at onset, severity of symptoms, neurological soft signs, or the four neurocognitive domains. In conjunction with other findings, it is unlikely that PTC-non-tasting is a trait marker of schizophrenia, though a conclusive study is warranted.     

The social complications of chronic alcohol abuse: relative influence of family history and severity of alcohol dependence

Alcoholics with a family history of the disease are said to present more severe consequences than alcoholics without such a history. This study examined the frequency distribution of severe alcohol dependence and police arrests for public drunkenness across samples of alcoholics with (n = 77) and without (n = 37) a family history of alcoholism. Both the percentage of subjects presenting severe dependence and the history of police arrests were greater in the positive family history group, but these differences did not reach conventional levels of statistical significance. However, results of logistic regression analyses demonstrate that male sex, younger age and, above all, severity of alcohol dependence, are better correlates of the occurrence of police arrests than is the subject's family history of alcoholism. The picture presented by this sample of outpatient alcoholics appears to qualify some currently held assumptions of the influence of family history on the phenomenology of alcoholism.     

Phenylthiocarbamide (PTC) perception in Parkinson disease.

OBJECTIVE: To examine phenylthiocarbamide (PTC) sensitivity in Parkinson disease (PD) patients and healthy volunteers to determine whether taster status represented a simple vulnerability marker for PD. BACKGROUND: The inability to taste PTC has been associated with a number of medical illnesses not typically associated with taste impairment. Abnormalities in the function/expression of G protein-signaling pathways have been implicated in PTC perception and also in dopamine expression and regulation in PD. No study has yet probed whether PTC tasting is disrupted in PD. METHOD: PTC sensitivity was assessed in a small sample of 36 male PD patients and 20 healthy male comparison subjects using a standardized psychophysical method. RESULTS: A higher proportion of nontasters were found in patients relative to healthy comparison subjects. These differences were not explained by alterations in perception of basic taste intensity or age. Among patients, nontasters and tasters of PTC did not differ with regard to duration of illness, age of onset, severity of motor symptoms, or overall illness severity. CONCLUSIONS: These data suggest an increase in the frequency of PTC nontaster status in PD. As phenotypic variation in PTC sensitivity is genetic in origin, this may represent a surrogate risk factor for the development of PD.     

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.     

Heterogeneity in the inheritance of alcoholism. A study of male and female twins

Genetic influence on risk for alcoholism was examined in a US treatment sample of 50 monozygotic (MZ) and 64 dizygotic (DZ) male and 31 MZ and 24 DZ female same-sex twin pairs. For the DSM-III composite diagnosis of Alcohol Abuse and/or Dependence, statistically significant MZ/DZ differences in concordance were found with male, but not female, twins. For specific diagnoses, MZ/DZ differences were found in male subjects for both Alcohol Abuse and Alcohol Dependence, while MZ/DZ differences in female subjects were found only for Alcohol Dependence. The male MZ/DZ concordance difference for composite diagnosis but not for Alcohol Dependence could be accounted for statistically by differences in age of onset between MZ and DZ probands. As with alcohol, differences in MZ/DZ concordance were found for DSM-III composite diagnoses of Other Substance Abuse and/or Dependence with male, but not female, twins. Using Epidemiological Catchment Area data to estimate the population base rates of both alcohol and other substance use disorders allowed for heritability analyses that showed genetic factors to have only a modest influence on overall risk in both sexes (heritability estimates of approximately 0.35 for male subjects and 0.24 for female subjects). However, evidence for heterogeneity in the pattern of inheritance was also found, suggesting forms of alcoholism that may be moderately to highly heritable.     

Family history of alcoholism influences naltrexone-induced reduction in alcohol drinking.

BACKGROUND: The purpose of this study was to examine the interactive effects of family history of alcoholism (FH+, FH-) and naltrexone dose (0, 50, 100 mg/day) on alcohol drinking. METHODS: Ninety-two, non-treatment-seeking alcohol-dependent participants received naltrexone daily for 6 days. On the 6th day, they participated in a laboratory paradigm involving exposure to a priming dose of alcohol followed by a 2-hour drinking period in which they made choices between consuming alcoholic drinks and receiving money. RESULTS: Total number of drinks consumed during the drinking period was significantly decreased by the 100-mg dose of naltrexone in FH+ drinkers. Secondary analyses in male drinkers (n = 70) indicated that 100 mg of naltrexone significantly decreased drinking in FH+ participants and increased drinking in FH- drinkers. CONCLUSIONS: These results suggest that family history of alcoholism might be a significant clinical predictor of response to naltrexone and that FH+ men are more likely to benefit from naltrexone therapy for alcohol drinking.     

Tridimensional Personality Questionnaire scores of sons of alcoholic and nonalcoholic fathers

The authors studied 33 men whose fathers had severe alcohol-related problems and 33 subjects with no family history of alcoholism. The former supplied information about the course of their fathers' alcohol problems; all 66 men answered questions about their own drinking and drug use and completed the Tridimensional Personality Questionnaire. There were no significant relationships between any of the 18 questionnaire scores and a subject's quantity/frequency of drinking or his family history of alcoholism. There was only one significant correlation between the alcoholic fathers' type 2 characteristics, according to the type 1/type 2 theory, and the sons' questionnaire scores. The relevance of these findings to the theory is discussed.     

Female alcoholics. II. The expression of alcoholism in relation to gender and age

A sample of 233 consecutive alcohol-dependent female admissions were cross-matched for date of birth and admission with male subjects of similar ethnic background. Primary drug abusers were not included. A quarter of subjects of both sexes were married. There were no gender or age differences in the level of family history of alcoholism. Highly significant gender and age differences were found in alcohol-related behaviours, which were more prominent in the younger age groups and in male subjects. These crucial differences were highlighted by stratification of the results into age groups at decade intervals. Individual personality traits or a family history of alcoholism were found to determine the age of onset and pattern of alcoholism, whereas gender and maturational stage influenced the expression of alcohol-related behaviours that occur in treatment populations.     

The 5-year clinical course of high-functioning men with DSM-IV alcohol abuse or dependence

OBJECTIVE: One goal of diagnostic criteria is to predict the course of clinically relevant future problems. This study evaluated the ability of the DSM-IV categories of alcohol abuse and alcohol dependence to predict the onset and cessation of the 11 DSM-IV abuse/dependence criterion items. METHOD: The DSM-IV categorical approach was used to determine alcohol diagnoses for 435 highly educated young adult men, who constituted 97.3% of the 447 men appropriate for this study. Structured face-to-face follow-up interviews were administered 5 years later. RESULTS: At the beginning of the study, 14.5% (N=63) of the subjects were alcohol dependent, 18.2% (N=79) reported alcohol abuse, and 67.4% (N=293) carried no alcohol diagnosis. Across these three diagnostic groups, 68.3%, 46.8%, and 15.4%, respectively, experienced at least one of the 11 DSM-IV abuse/dependence criterion items over the next 5 years. Only 11.4% of those who reported alcohol abuse went on to develop alcohol dependence. In addition to their diagnosis, characteristics that predicted subsequent problems with alcohol included a family history of alcoholism, higher levels of alcohol intake and a greater number of alcohol problems in the 10 years preceding the diagnosis, and a history of drug use. CONCLUSIONS: Even in this highly educated and high-functioning group of men, alcohol abuse and dependence predicted the onset and cessation of alcohol-related problems.     

Family history and diagnosis of alcohol dependence in cocaine dependence

Genetic research in alcoholism has made major advances in recent decades. Twin, adoption, high-risk, and familial studies have demonstrated an inheritance factor in alcoholism. No studies have demonstrated a genetic or familial disposition to cocaine and marijuana dependence. Two hundred sixty-three inpatients were given a structured psychiatric interview retrospectively (150) and prospectively (113) to obtain a DSM-III-R diagnosis of substance dependence disorders in the probands and of alcohol dependence in family members. Our study reveals a large number of probands with cocaine dependence with a positive family history for alcohol dependence. Approximately 50% of probands with cocaine dependence had at least a first or second degree relative with a diagnosis of alcohol dependence when studied by the family history and study methods. As many as 89% of probands who met DSM-III-R criteria for cocaine dependence qualified for other substance dependence diagnoses. Our study finds a high prevalence of alcohol (68% and 89%) and cannabis dependence (53% and 46%) in patients with cocaine dependence. Furthermore, the age of onset of alcohol and other drug dependence is early for those with cocaine dependence and precedes the onset of cocaine dependence. The diagnoses of other alcohol and drug dependence in cocaine dependence and in family members of probands with cocaine dependence have important implications for etiology, prognosis, and treatment.     

P300 and alcohol consumption in normals and individuals at risk for alcoholism. A preliminary report

Pairs of college student subjects (36 male, 36 female) were matched on age, sex, and personal drinking history. One pair member had a parent who met the DSM III criteria of alcoholism, while the other pair member had no close alcoholic relative. The P300 event-related brain potential (ERP) was obtained from each subject with auditory stimuli in an "oddball" paradigm. Target stimuli occurred randomly on 20% of the trials in a frequency discrimination task, a relatively easy intensity discrimination task, and a more difficult intensity discrimination task. Subjects indicated when the target items occurred by moving their index finger. No significant overall effects were obtained for family history for either P300 latency or amplitude. P300 latency increased and amplitude decreased with increases in the reported amount of alcohol consumption in all subjects only for the difficult intensity task but were statistically significant only for individuals with a negative family history for alcoholism.     

Additional psychiatric illness by Diagnostic Interview Schedule in male alcoholics

Seventy-four male veterans entering an alcohol abuse treatment program were screened for additional psychiatric diagnoses using the Diagnostic Interview Schedule (DIS). Fifty-four of these also completed a questionnaire on personal and family drinking history. Over half (54.1%) had another diagnosis. The most common syndromes other than substance abuse were antisocial personality disorder, phobic disorder, and depression. In each of these cases, the presence of the additional disorder accelerated the course of the alcohol problem significantly. The difference in course between syndromes was dwarfed by the time of presentation by the difference between "pure" alcoholism and alcoholism with another diagnosis. The primary versus secondary distinction appeared to account for only a part of this effect.     

The genetics of alcoholisms and related disorders

The inheritance of alcohol abuse and other psychopathology in 862 men and 913 women adopted by non-relatives, was studied. Both male and female adoptees were at greater risk to develop alcohol abuse if their biological, but not their adoptive, parents were alcoholic. Three types of families with alcoholism were distinguished that differed in frequency of alcohol abuse, somatoform disorders in women and in relation to antisocial behaviour in male adoptees. The combination of both genetic and environmental risk factors was necessary for the development of alcoholism in the most common, milieu-limited type of alcoholism. In families with a less common, male-limited, type of vulnerability, alcohol abuse was highly heritable in men, but women had multiple somatic complaints and seldom abuse. In a third type of family the common vulnerability was expressed as antisocial behaviour with violent criminality and recurrent alcohol abuse in males, but as high frequency somatization in female relatives.     

Gender differences in prevalence,risk, and clinical correlates of alcoholism comorbidity in bipolar disorder

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.     

Effects of alcoholism and gender on brain metabolism

OBJECTIVE: Proton magnetic resonance spectroscopy was used to evaluate gender influences on alcohol-associated changes in brain metabolism. METHOD: Concentrations of N-acetylaspartate, choline-containing compounds, myo-inositol, and creatine plus phosphocreatine in frontal lobe gray matter and white matter were estimated in eight women and 17 men who were recently detoxified from long-term alcoholism. Twelve women and 13 men with no history of alcoholism were used as a comparison group. RESULTS: In male and female alcoholics, frontal lobe white matter concentrations of N-acetylaspartate were significantly lower (-8.8%) than those seen in nonalcoholic comparison subjects. In the frontal lobe gray matter region, a significant alcoholism status-by-gender interaction and follow-up analyses revealed that female alcoholics had significantly lower N-acetylaspartate concentrations (-10.73%) relative to female comparison subjects, while male alcoholics and male comparison subjects had similar levels of this metabolite (<1% difference). CONCLUSIONS: Lower concentrations of white matter N-acetylaspartate, which may indicate neuronal loss or dysfunction, is equally severe in men and women with comparable alcohol abuse histories. However, female alcoholics exhibited significantly less N-acetylaspartate in frontal gray matter relative to female nonalcoholic comparison subjects, which could mean that female alcoholics are more susceptible to gray matter injury than their male counterparts. However, this finding could also be explained by higher-than-expected levels of N-acetylaspartate in the healthy female comparison group.     

Event-related potentials to emotional and neutral stimuli in alcoholism

Several studies have demonstrated that the emotional value of stimuli affects P300 amplitude. In the present study, the influence of alcohol-related stimuli in alcoholic patients was investigated. Subjects were 10 alcoholic inpatients (3 female) and 10 age- and sex-matched controls. Eight alcohol-related and 8 neutral words served as stimuli in a visual oddball paradigm. Acohol-related words were targets (48 stimuli, 33%) and neutral words were standard stimuli (96 stimuli, 66%). Results showed that P300 amplitude for targets did not differ significantly between the two groups. However, P300 latency for targets as well as reaction time were significantly shorter in male alcoholic patients. In contrast, P300 latency was increased in female alcoholic patients but reaction time did not differ. These results suggest that male alcoholics process information linked to alcohol cues more rapidly than neutral cues, probably because a specific semantic network is activated in these patients. The decreased reaction time confirms the impulsive behavior frequently found in male alcoholism, as it has been described in type II alcoholism. Besides, the results imply that information processing was delayed in female alcoholic patients. Therefore this study demonstrates a gender-dependent impact of alcohol-related stimuli on information processing.