Familial correlates of risk: application to the Gershon and Goldin NIMH pedigree data.

Survival analysis of familial covariates of risk for affective illness demonstrated a significant effect on the proband's diagnosis when affection status included bipolar illness, but not major depressive disorder. A cohort effect was indicated only when broad spectra (including bipolar II and major depressive disorder) of illness were defined. Multifactorial analyses of familial correlations for affective illness evidenced neither sex-specific correlations nor prevalences. We suggest the examination of risk variables prior to undertaking familial analysis.

Alcohol-related symptoms in heterogeneous families of hospitalized alcoholics.

Heterogeneity in the clinical symptoms of alcohol abuse was examined in 243 men and 305 women from families of hospitalized alcoholics, who had demonstrated different patterns of inheritance of susceptibility to alcoholism. Discriminant analysis was utilized to identify nine alcoholic symptoms that distinguished male relatives of alcoholic men from those of alcoholic women. Inability to abstain from alcohol, fighting and reckless driving while intoxicated, and alcohol treatment other than Alcoholics Anonymous were more prevalent in families of male probands. Male relatives of female probands experienced later onset of loss of control over drinking associated with benders, and cirrhosis and feelings of guilt. Female relatives of alcoholic men and women showed a marked predominance of the latter (Type 1) features, whereas male relatives had different clinical features, depending on the associated mode of inheritance.

Genetic heterogeneity and the classification of alcoholism.

Recent progress toward a systematic pathophysiological model of alcoholism has led to identification of two distinct subtypes of alcoholism. These subtypes may be distinguished in terms of distinct alcohol-related symptoms, personality traits, ages of onset, and patterns of inheritance. Type 1 alcoholism is characterized by anxious (passive-dependent) personality traits and rapid development of tolerance and dependence on the anti-anxiety effects of alcohol. This leads to loss of control, difficulty terminating binges once they start, guilt feelings, and liver complications following socially encouraged exposure to alcohol intake. In contrast, type 2 alcoholism is characterized by antisocial personality traits and persistent seeking of alcohol for its euphoriant effects. This leads to early onset of inability to abstain entirely, as well as fighting and arrests when drinking. Empirical findings about sex differences, ages of onset, associated personality traits, and longitudinal course are described in a series of adoption and family studies in Sweden and the United States. Implications for future research and clinical practice are discussed.

A family study of dermatoglyphic traits in India: segregation analysis of accessory palmar triradii and the atd angle.

Accessory triradii and the atd angle were examined via complex segregation analysis in order to evaluate possible genetic effects on these dermatoglyphic traits, measured in an endogamous Brahmin caste of peninsular India. The phenotypes considered included: presence of accessory palmar triradii a' and d', associated with the interdigital areas II and IV, respectively; presence of an accessory axial triradius tt' associated with the proximal margin of the palm; and an arctanh-transformation of the atd angle measurement. For all accessory triradii considered in the present investigation familial resemblance was evident. The most parsimonious model which could account for the observed resemblance was a multifactorial model that includes polygenic effects as well as transmissible environmental effects that are inherited in the same pattern as polygenes. Evidence of familial resemblance was also found for the arctanh-transformed atd angle, which could be attributed, initially, to both a major effect and a multifactorial component. Tests of transmission of a putative major gene were performed which yielded results consistent with Mendelian transmission, although an alternative test of no transmission of the major effect also fit the data. In light of these contrasting results we are precluded from accepting with confidence the notion of a major gene influence on the atd angle. We have concluded that the accessory triradii a', d', and tt', and the atd angle are influenced by multifactorial effects, including additive polygenes and possible environmental factors, such as intrauterine effects.

Etiologic heterogeneity in alcoholism.

Etiologic heterogeneity in alcohol abuse was evaluated in 195 extended pedigrees, comprising 288 nuclear families of 140 male and 55 female Caucasian American hospitalized alcoholics. Previous adoption studies in Sweden demonstrated differential heritability of two patterns of alcohol abuse in men: type-2 alcoholism exhibited early onset of abuse associated with criminal behavior, while type-1 abuse began at a later age, uncomplicated by antisocial traits. Alcohol abuse in female Swedish adoptees was relatively homogeneous and similar to the late-onset, type-1 abuse. The notion of etiologic heterogeneity, as suggested by the Stockholm Adoption Studies, was examined in the American pedigrees by contrasting the models of familial transmission of susceptibility to alcoholism obtained via segregation analyses of families of male versus female probands. Families of male probands demonstrated significant familial resemblance, accounted for by a multifactorial-polygenic background in addition to a major (gene) effect. In contrast, familial resemblance in the pedigrees of female probands was attributed solely to a multifactorial-polygenic effect. We considered whether some families of male alcoholics were similar to families of female probands, who expressed type-1 abuse predominantly. Pedigrees of male probands were separated in two groups: (1) "female-like" families had a better likelihood for the model obtained for families of female probands than the one for families of all male probands, (2) "male-like" families had a better likelihood for the model of familial transmission describing families of all male probands. A statistically significant difference in the pattern of familial transmission was observed between the "male-like" and "female-like" groups. Discriminant function analysis of alcohol-related symptoms showed that the familial subtypes differed in clinical features as well. Alcohol abuse by male relatives in "male-like" families was characterized by the early onset of inability to abstain entirely from alcohol or lack of desire to stop drinking; in contrast, abuse in "female-like" families was characterized by late onset of guilt feelings and loss of control over binge drinking.

Neurogenetic mechanisms of learning: a phylogenetic perspective.

Common psychiatric disorders often involve abnormal patterns of adaptive response to environmental stimuli. Thus, an understanding of the pathophysiology and inheritance of such maladaptation requires specification of the underlying neural mechanisms involved in learning, which is broadly defined as the modification of behavior as a result of individual experience. The phylogenetic development of learning ability in animals is shown to proceed by a sequence of discrete steps in which non-associative learning is augmented successively by classical conditioning to aversive stimuli, followed by classical conditioning to food and other rewarding stimuli, then exploratory learning about novel habitats and operant conditioning of behavioral responses, and finally conceptual learning ability. As a result of this complex phylogenetic history, adaptive responses to the environment in mammals including human beings is multidimensional. A model of the structure of stimulus-response and cognitive-processing characteristics in human beings is described. The model is discussed in terms of its evolutionary advantages for survival and reproductive fitness as well as its importance in understanding susceptibility to psychiatric disorders, including personality and anxiety disorders.

A family study of dermatoglyphic traits in India: a search for major gene effects on palmar pattern ridge counts.

Palmar pattern ridge counts were subjected to segregation analysis in an attempt to identify possible major gene effects on these dermatoglyphic traits. The phenotypes considered were total palmar pattern ridge count, and ridge counts for the right interdigital III and IV and left interdigital IV individual palmar areas (sample sizes were too small for the other palmar areas). Evidence of familial resemblance was found for all of the phenotypes studied, and initial evidence for a major effect was found for all but the right palm interdigital III ridge count. However, this initial evidence could be attributed to nongenetic effects in each case, including skewness in the trait distribution. Tests for agreement with Mendelian transmission frequencies were found to be very useful in discriminating between a non-Mendelian major effect and a major gene. We concluded against a major gene effect for any of these traits, and multifactorial inheritance remains a plausible alternative explanation for the familial resemblance.