Rosemary Toomey

Genetic influences on DSM‐III‐R drug abuse and dependence: A study of 3,372 twin pairs

Research and clinical experience indicate that drug use disorders tend to run in families. The objective of this study was to distinguish between the family environment and genetic factors as the source of this observed family resemblance. Data were collected by telephone interview from members of the Vietnam Era Twin Registry, comprising male twin pairs who served in the U.S. military between 1965 and 1975. There were 3,372 pairs in which both twins participated. Drug use disorder was defined as receiving a diagnosis of drug abuse or dependence according to DSM-III-R; 10.1% of the sample had abused or been dependent on at least one illicit drug. A significant difference between concordance rates for monozygotic (26.2%) vs. dizygotic (16.5%) twins indicated a genetic influence on drug use disorder. Biometrical modeling indicated that genetic factors (34% of the variance), the environment shared by twins (28% of the variance), and the nonshared environment (38% of the variance) had significant influences of similar magnitudes on the individuals risk of developing a drug use disorder. These results support the application of molecular genetic approaches to elucidate the genetic influence on drug use disorder, as well as the potential efficacy of environmental intervention to reduce risk.

Thalamic and amygdala–hippocampal volume reductions in first-degree relatives of patients with schizophrenia: an MRI-based morphometric analysis

BACKGROUND Schizophrenia is characterized by subcortical and cortical brain abnormalities. Evidence indicates that some nonpsychotic relatives of schizophrenic patients manifest biobehavioral abnormalities, including brain abnormalities. The goal of this study was to determine whether amygdala-hippocampal and thalamic abnormalities are present in relatives of schizophrenic patients. METHODS Subjects were 28 nonpsychotic, and nonschizotypal, first-degree adult relatives of schizophrenics and 26 normal control subjects. Sixty contiguous 3 mm coronal, T1-weighted 3D magnetic resonance images of the brain were acquired on a 1.5 Tesla magnet. Cortical and subcortical gray and white matter and cerebrospinal fluid (CSF) were segmented using a semi-automated intensity contour mapping algorithm. Analyses of covariance of the volumes of brain regions, controlling for expected intellectual (i.e., reading) ability and diagnosis, were used to compare groups. RESULTS The main findings were that relatives had significant volume reductions bilaterally in the amygdala-hippocampal region and thalamus compared to control subjects. Marginal differences were noted in the pallidum, putamen, cerebellum, and third and fourth ventricles. CONCLUSIONS Results support the hypothesis that core components of the vulnerability to schizophrenia include structural abnormalities in the thalamus and amygdala-hippocampus. These findings require further work to determine if the abnormalities are an expression of the genetic liability to schizophrenia.

Neuropsychologic functioning among the nonpsychotic relatives of schizophrenic patients: the effect of genetic loading

BACKGROUND We previously reported that the nonpsychotic relatives of schizophrenic patients exhibited disturbances in executive functioning, verbal and visual memory, auditory attention, mental control, and verbal ability. In a 4-year follow-up, we showed that the discriminating power of most of these tests was stable over time. METHODS In this report we compare 41 nonpsychotic persons who have only one schizophrenic first-degree relative (simplex families) with 36 nonpsychotic persons who have two schizophrenic first-degree relatives (multiplex families). Our goal was to test a hypothesis that neuropsychologic deficits would be worse among the latter. RESULTS Relatives from multiplex families differed significantly from controls on estimated intelligence, immediate and delayed logical memories, and immediate visual reproductions. In contrast, in comparisons with controls, relatives from simplex families only differed on immediate logical memories. Comparisons between relatives from multiplex and simplex families showed that the former group had significantly worse scores for estimated intelligence, immediate and delayed logical memories, and immediate visual reproductions. We also found group x gender interactions: the worse performance of the multiplex group was seen for females. CONCLUSIONS These results are consistent with the idea that neuropsychologic deficits in relatives of schizophrenic patients reflect their degree of genetic predisposition to schizophrenia. They also suggest hypotheses about gender differences in the familial transmission of the disorder.

Poor perception of nonverbal social–emotional cues in relatives of schizophrenic patients

The present study compared nonverbal social perception in relatives of schizophrenic patients (n = 21) with that of normal controls (n= 19). We hypothesized that relatives would display deficits in social perception and we sought to determine the skills that are associated with this deficit. Relatives performed significantly worse than controls on the Profile of Nonverbal Sensitivity Test (PONS), despite comparable performance on skills hypothesized to be related to nonverbal social perception: visual perception, nonverbal problem solving, facial recognition, facial affect recognition, naming, social judgment, and vigilance. To further explore the relationships among these skills, we calculated correlations between the PONS score and associated skills separately within both the relative and control groups and assessed whether the values of these correlations differed between groups. Correlations that differed significantly indicated a greater association, within relatives, between slower reaction times on vigilance tasks and poor PONS performance. Further research is needed to clarify the nature of this relationship, to better characterize social perception deficits in relatives, and to determine whether these perceptual deficits are part of the genetic diathesis to schizophrenia.

Heterogeneity of schizophrenia: a study of individual neuropsychological profiles

Based on a strategy developed by Seidman et al. (Seidman, L.J., Faraone, S.V., Kremen, W.S., Pepple, J.R., Lyons, M.J., Tsuang, M.T., 1993. Neuropsychological dysfunctions in the non-psychotic first-degree relatives of schizophrenic patients, Poster presented at the annual meeting of the Society for Research and Psychopathology. Chicago, IL) we examined neuropsychological heterogeneity in schizophrenia using clinical neuropsychological descriptions of individual cases as the starting point. We blindly rated neuropsychological profiles of 74 schizophrenia patients and 91 normal controls based primarily on prototypes from the clinical literature in neuropsychology. Patients were classified as having the following profile types: within normal limits (WNL) (23%, n=17), frontal/abstraction (46%, n=34), widespread/diffuse (14%, n=10), left temporal/verbal memory (8%, n=6) and other (9%, n=7). As expected based on our classification scheme, the groups had different profile shapes (group x function interactions). They were also significantly different from one another in terms of overall severity (main effects); however, severity differences were not inherent in the definition of all groups. Longer duration of illness and greater overall cognitive impairment were observed as one went from the left temporal to the frontal to the widespread groups. Longitudinal studies are needed to determine whether the different neuropsychological profiles reflect true subgroup differences or within-person change over time. Further research-probably including neuroimaging and genetic studies-will also be needed to determine the validity and the utility of this strategy for identifying neuropsychological profile types.

Association of neuropsychological vulnerability markers in relatives of schizophrenic patients

We investigated the association of neuropsychological risk indicators in a matched sample of first-degree relatives of schizophrenic patients (n = 54) and normal controls (n = 72). We focussed on three functions previously identified in a smaller, initial sample as putative risk indicators of the schizophrenia genotype: abstraction, verbal memory and auditory attention. The expanded sample of relatives displayed significantly lower scores than controls on abstraction, verbal memory and auditory attention. The relatives demonstrated significant intercorrelations among these three functions. The significant correlations among relatives between attention and verbal memory and between attention and abstraction differed significantly from these correlations among controls. We discuss how the use of multiple risk indicators may help us better identify those relatives that carry the schizophrenia genotype.

Cognitive correlates to social cue perception in schizophrenia

Previous research has examined social skill learning in schizophrenic patients in relation to information-processing deficits and psychiatric symptoms. Relationships were examined in the current report between social cue perception, thought to be an early and necessary component of skill learning, and various information-processing deficits and psychiatric symptoms. Twenty-six inpatients with DSM-III-R diagnoses of schizophrenia completed measures of social cue perception, cognitive functioning, and psychiatric symptoms. Results showed that cue perception was significantly related to measures of early visual processing, recognition memory, and psychiatric symptoms of withdrawal/retardation. Implications of these findings for future research into the social-perceptual deficits of schizophrenic patients are discussed.

Sex differences in self-reported schizotypal traits in relatives of schizophrenic probands.

We used the Schizotypal Personality Questionnaire to evaluate schizotypal traits in 44 normal volunteers and 40 non-psychotic, biological relatives of schizophrenic probands. Relatives endorsed more cognitive-perceptual traits than did controls; a group-by-sex interaction indicated that male relatives accounted for this difference. Although not statistically significant, a similar pattern was observed for interpersonal traits. Thus, elevated rates of some schizotypal traits appear to be more prominent in male than in female relatives of schizophrenic probands, at least when assessed by self-report. Subscale analysis indicated that differences were accounted for primarily by suspiciousness and ideas of reference, suggesting that paranoid-like phenomena from both the cognitive-perceptual and interpersonal factors may constitute an important dimension of schizotypy in relatives. Unlike previous studies, we did not find any differences in constricted affect or disorganization signs. Interviews and other non-self-report techniques are probably best suited for an assessment of these features, although the question remains as to whether the combination of both approaches might provide some incremental discriminatory power.

Co‐twin control study of relationships among combat exposure, combat‐related PTSD, and other mental disorders

The well-documented association between combat-related PTSD (C-PTSD) and other mental disorders may be an artifact of shared familial vulnerability. This study uses a co-twin control design to examine whether the association between C-PTSD and other mental disorders persists after adjusting for shared familial vulnerability. Data were from male monozygotic twin pairs in the Vietnam Era Twin Registry. Logistic regression analyses demonstrated that combat exposure, adjusted for C-PTSD, was significantly associated with increased risk for alcohol and cannabis dependence and that C-PTSD mediated the association between combat exposure and both major depression and tobacco dependence. We conclude C-PTSD comorbidity persists after controlling for shared vulnerability. Combat exposure is directly and indirectly, through C-PTSD, associated with increased risk for other mental disorders.

A high risk twin study of combat-related PTSD comorbidity

Combat-related posttraumatic stress disorder (PTSD) is highly comorbid with other mental disorders. However, the nature of the relationship between PTSD and other mental disorders remains unclear. A discordant high-risk twin design was used on data from a sub-sample of the male-male twin pair members of the Vietnam Era Twin Registry to examine whether patterns of comorbidity are consistent with a psychopathological response to combat exposure or reflect familial vulnerability to psychopathology. Mental disorders were assessed via the Mental Health Diagnostic Interview Schedule Version III - Revised. Discordant monozygotic within-pair comparisons revealed that PTSD probands had higher symptom counts and diagnostic prevalences of mood and anxiety disorders than their non-combat exposed co-twins. Monozygotic co-twins of PTSD probands had significantly more mood disorder symptoms than monozygotic co-twins of combat controls or dizygotic co-twins of veterans with PTSD. These findings suggest that a) major depression, generalized anxiety disorder and panic disorder are part of a post-combat response syndrome; b) a shared familial vulnerability also contributes to the association between PTSD and major depression, PTSD and dysthymia, and c) this shared vulnerability is mediated by genetic factors.