Elizabeth Squires-Wheeler

Eye-tracking dysfunction in offspring from the New York High-Risk Project: diagnostic specificity and the role of attention

Eye tracking abnormalities were studied in the offspring of schizophrenic, unipolar depressed and bipolar probands from the New York High-Risk Project to examine their familial specificity. Offspring of schizophrenic and depressed probands both had significant global performance deficits based on spectral purity measurements, but only the offspring of schizophrenic probands had an increased rate of intrusive anticipatory saccades. The greater specificity of high anticipatory saccade rate than global performance impairment suggests that this eye movement abnormality may provide a more specific biological marker of risk for schizophrenia than the global measure of eye tracking performance used in this study. Attention facilitation effectively normalized all performance deficits in the offspring of schizophrenic patients, suggesting that a problem sustaining focused visual attention may contribute to eye tracking deficits observed in the relatives of schizophrenic probands.

DSM-III-R SCHIZOTYPAL PERSONALITY TRAITS IN OFFSPRING OF SCHIZOPHRENIC DISORDER, AFFECTIVE DISORDER, AND NORMAL CONTROL PARENTS

The aggregation of disorder in families identified by a schizophrenic disorder proband (index case) has provided indirect clues to the question of diagnostic boundaries of schizophrenic spectrum categories. The Danish Adoption Studies provided quasi-experimental evidence for the range of expression of a putative schizophrenic spectrum disorder which was subsequently denoted schizotypal personality disorder (STPD) in DSM-III-R. It has been hypothesized that such schizophrenic spectrum categories bear a genetic relationship to schizophrenic disorder and thus are continuous with schizophrenia in terms of etiology and pathogenesis. For meaningful use of such spectrum categories in genetic analyses, i.e., linkage analysis, it is important that rates of spectrum traits and disorder in normal control and in psychiatric control populations are known. The rate of DSM-III-R schizotypal traits and disorder was assessed in three offspring groups (ages 18-29) defined by parental diagnoses, including schizophrenic disorder (N = 90), affective disorder (N = 79), and no parental disorder (N = 161). The assessment was conducted by trained social workers and psychologists by means of a direct interview (Personality Disorder Examination). The interviewers were blind to the parental status and to previous psychiatric assessments of these offspring. The rates of three, four and five schizotypal features were elevated in the offspring with parental psychiatric disorder in contrast to the offspring with no parental psychiatric disorder. However, the rates between the offspring of the schizophrenic disorder parental group and the offspring of the affective disorder parental group did not differ significantly, thus failing to support the assumption of diagnostic specificity.

Latent structure of DSM-III-R Axis II psychopathology in a normal sample.

The Personality Disorder Examination was administered to 302 normal controls in the New York High-Risk Project in order to elicit Axis II diagnoses (revised 3rd edition of the Diagnostic and Statistical Manual of Mental Disorders; American Psychiatric Association, 1987) and quantitative dimensions of psychopathology. LISREL confirmatory factor analysis was used to evaluate the Axis II hypothesis of 3 orthogonal factors. There was considerable overlap among personality disorders. The best fitting LISREL model was of 3 oblique factors that were different for male and female subjects. Given that our choice of variables to constrain in order to mathematically identify our models was partially based on analysis of intercorrelations in our data set, our methods were not purely confirmatory. We present our results not to confirm specific hypotheses but to generate explicit hypotheses that can be tested in independent samples.

A longitudinal study relating P3 amplitude to schizophrenia spectrum disorders and to global personality functioning

Auditory and visual event-related potentials (ERPs) were recorded from first-degree relatives (adolescent offspring) of index cases with schizophrenic disorder, affective disorder, or no psychiatric disorder (normal controls) at a mean age of 15 years. Nearly a decade later, these subjects (at a mean age of 25 years) were evaluated for Research Diagnostic Criteria Schizophrenic Disorder, Schizoaffective Disorder, Unspecified Functional Psychosis, and for DSM-III-R Axis II schizophrenia-related traits and disorders including schizotypal, schizoid, and paranoid features. It was hypothesized, based on Duncan et al (1987a, Duncan 1988), that reduction of P3 amplitude in the auditory (but not the visual) modality would predict subsequent schizophrenic-related outcomes in subjects from the schizophrenic disorder parental group. This specific expectation was not statistically supported. An unanticipated and statistically robust result linking P3 decrements (in both auditory and visual modalities) with poorer Global Personality Functioning was observed for offspring from both psychiatric parental groups and the offspring of the normal control group. These data are consistent with the results of a large number of clinical studies of the P3 component that have demonstrated reductions in P3 amplitude in individuals expressing a wide range of behavioral dysfunctions. Their importance lies in the fact that these P3 amplitude decrements were detected long before the overt behavioral symptoms were identified, and were nonspecific with respect to parental psychiatric diagnostic group.

Early life precursors of psychiatric outcomes in adulthood in subjects at risk for schizophrenia or affective disorders

In the New York High-Risk Project (NYHRP), 186 offspring of schizophrenic, affectively ill, and psychiatrically normal parents have been followed prospectively from 1971-72 to the average age of 27 years in 1990 with the goal of identifying early precursors of later psychopathology. In this report, we use path analyses to examine the relationship of several life-history variables to three pathological outcomes in the offspring: namely, psychosis, psychiatric hospitalization, and psychological dysfunction. The chief direct relationship with these outcomes is the effect of having a schizophrenic parent. The latter effect is also mediated indirectly by IQ.

The temporal lobes, reversed asymmetry and the genetics of schizophrenia

Mechanisms determining temporal lobe structural asymmetries may be involved in the pathogenesis of schizophrenia. To investigate the temporal lobes in familial schizophrenia, computed tomographic scans were obtained from 51 subjects (seven families). Enlargement of sylvian fissures and temporal lobe sulcal spaces was observed in family members with schizophrenia. The posterior one-third of the sylvian fissure was larger on the left side in subjects with schizophrenia, and larger on the right side in unaffected individuals. This disturbed pattern of posterior sylvian fissure asymmetry suggests that adjacent language regions may be affected in schizophrenia. An intermediate degree of disturbance in subjects who had schizophrenia-related illnesses or were obligate carriers suggests that genetic factors may be important determinants of temporal lobe asymmetries in familial schizophrenia.

The New York High-Risk Project : Comorbidity for axis I disorders is preceded by childhood behavioral disturbance

The relationship between childhood behavioral disturbance and comorbidity for adult psychiatric disorders has not been sufficiently investigated. Subjects of this report (N = 185) were offspring of parents with schizophrenia or affective disorder and of normal parents from the New York High-Risk Project. Data on childhood behavior at the mean age of 9.5 years were obtained in a parent interview at initial assessment in 1971-72. Adulthood outcomes were assessed through standardized interviews, and lifetime axis I diagnoses were based on Research Diagnostic Criteria. Subjects with comorbidity for axis I disorders exhibited significantly more behavioral problems as children, compared with those who developed either one or no psychiatric disorder in adulthood. This association was not biased by gender or parental diagnosis of psychiatric disorder. The findings emphasize that psychiatric comorbidity can be traced back to childhood and underline the importance of longitudinal observations in psychiatric research.

Developmental abnormalities and cortical sulcal enlargement in psychosis

Neurodevelopmental abnormalities and cortical sulcal enlargement both occur in schizophrenia. To test the hypothesis that these abnormalities were related, CT scans from 164 psychotic patients (80 with schizophrenia) were reviewed. Neurodevelopmental abnormalities were observed in 11%. Abnormalities were equally prevalent in schizophrenia and other psychotic disorders. Cortical sulcal enlargement was observed in 39% of patients with schizophrenia, and was not associated with developmental abnormalities. Different mechanisms may contribute to distinct structural abnormalities.

Eye tracking dysfunction in offspring from the New York high-risk project

Eye tracking abnormalities were studied in the offspring of schizophrenic, unipolar depressed and bipolar probands from the New York High-Risk Project to examine their familial specificity. Offspring of schizophrenic and depressed probands both had significant global performance deficits based on spectral purity measurements, but only the offspring of schizophrenic probands had an increased rate of intrusive anticipatory saccades. The greater specificity of high anticipatory saccade rate than global performance impairment suggests that this eye movement abnormality may provide a more specific biological marker of risk for schizophrenia than the global measure of eye tracking performance used in this study. Attention facilitation effectively normalized all performance deficits in the offspring of schizophrenic patients, suggesting that a problem sustaining focused visual attention may contribute to eye tracking deficits observed in the relatives of schizophrenic probands.

PERSONALITY FEATURES AND DISORDER IN THE SUBJECTS IN THE NEW YORK HIGH-RISK PROJECT.

One hundred and seventy-five offspring of parents in two psychiatrically ill groups and of normal controls in the New York High-Risk Project (NYHRP) were assessed for Axis II personality traits and disorders as defined by the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised (DSM-III-R). These offspring include: subjects at high risk for schizophrenia (HRSz, n = 48), all of whom have a parent with schizophrenic disorder; subjects at high risk for affective disorder (HRAff, n = 40), all of whom have a parent with affective disorder; and subjects at no increased risk for psychiatric illness (NC, n = 87), whose parents are psychiatrically normal. The trained interviewers, who administered a standardized direct interview, were blind to parental clinical status and to previous clinical status of the offspring.The rates for any personality disorder (PD) ranged from 7% to 20%. Comorbidity between Axis I and Axis II disorders was high for all groups.