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L Erlenmeyer-Kimling

Publications and source records attributed to L Erlenmeyer-Kimling.

At least 55 records · Page 3Linked to original sources

Psychometric deviance in offspring at risk for schizophrenia: II. Resolving heterogeneity through admixture analysis.

The longitudinal and prospective study of offspring at risk for schizophrenia is complicated by within-group heterogeneity in liability, as only a subgroup of those at risk will ultimately become affected. Here, we attempt to resolve such heterogeneity in the New York High-Risk Project by conducting an admixture analysis of values on a psychometric index of liability to schizophrenia derived from the Minnesota Multiphasic Personality Inventory (MMPI). We fit mixtures of components to the overall distribution in 171 children from three criterion groups: offspring at risk (HR) for schizophrenia, psychiatric comparison (PC) offspring at risk for affective illness, and normal comparison (NC) offspring not at increased risk for psychiatric morbidity. The distribution of psychometric scores was bimodal, and separation of two latent classes showed that there is a valid and nonarbitrary distinction between a subgroup of MMPI-deviant (primarily HR) offspring and a larger homogeneous group of MMPI-nondeviant HR, PC, and NC subjects. While continued followup is required to demonstrate a correspondence between these two classes and an underlying taxonomy of liability to schizophrenia, our findings demonstrate the utility of objective psychometric measurement and admixture analysis for resolving within-group heterogeneity in high-risk research. The wider implications of including our MMPI indicators in other genetic investigations of schizophrenia are discussed.

Adolescent↗

Report of a workshop on genetic linkage studies in schizophrenia.

A workshop on genetic linkage studies in schizophrenia was held at Columbia University's Arden House Conference Center in October 1989. This report summarizes the contents of invited talks by Drs. Arno Motulsky and T. Conrad Gilliam and the discussions at the five workshop sessions. Topics of the workshop sessions were (1) diagnostic boundaries and hierarchies in schizophrenia, (2) genetic models and linkage parameters, (3) selection and ascertainment of pedigrees, (4) future extensions of molecular genetics strategies, and (5) possibilities for future collaboration.

Genetic Linkage↗

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.

Adolescent↗

The continuous performance test, identical pairs version: II. Contrasting attentional profiles in schizophrenic and depressed patients.

The Continuous Performance Test-Identical Pairs version was administered to 14 schizophrenic patients, 17 depressed patients, and 28 normal controls. The task was divided into verbal and spatial stimuli, as well as no-distraction and distraction (verbal and auditory) conditions. Both patient groups displayed attentional impairments compared to normal subjects, but they differed from each other in specific profiles. Schizophrenic patients were characterized by a global impairment and a particular inability to focus on the critical stimuli, whether verbal or spatial. They also made an excess of random responses throughout the task but showed no evidence that attention declined from its initial level over time. Depressed patients did not display a global attentional deficit but did show a specific inability to attend to spatial as compared to verbal stimuli and, in particular, a confusion when the spatial stimuli were only slightly different. Performance on a secondary task in response to a change in expectation improved dramatically for depressed but not schizophrenic patients, suggesting a more efficient allocation strategy, a greater reserve of processing capacity, or more dependence on motivational factors in depressed patients. Schizophrenic and depressed patients were alike in extent of distractibility. Whereas normal controls improved with the onset of external distraction, schizophrenic and depressed patients deteriorated to an equal extent. Distractibility was thus concluded to be a correlate of acute psychiatric illness and not specific for schizophrenia.

Adult↗

A taxometric analysis of cognitive and neuromotor variables in children at risk for schizophrenia.

A taxometric model was applied to detect a subgroup or taxon of children conjectured to be at highest risk for developing schizophrenia or related disorders in a sample of offspring of schizophrenic, depressed, and normal parents. Measures of cognitive and neuromotor performance in childhood were used as indicator tests in the analyses. A taxon consisting chiefly of children of schizophrenic parents was detected. Forty-seven percent of those children were assigned to the taxon, compared with 16% of the children of depressed parents and 4% of the children of normal parents. Assignment to the taxon is assessed in relation to the current functional status of the subjects in young adulthood.

Child↗

Auditory event-related potentials in children at risk for schizophrenia: the complete initial sample.

Event-related potentials (ERPs) were recorded from children of schizophrenic parents, children of parents with affective disorders, and children of parents without a history of psychiatric illness. ERPs were elicited during a modification of the "oddball" paradigm, in which two infrequents (a change in pitch and a missing stimulus) were embedded in a series of frequent background events. The data were recorded from electrodes located at midline frontal, central, parietal, and occipital scalp sites. Diagnostic assessments of the parents were performed using the Schedule for Affective Disorders and Schizophrenia-Lifetime Version (SADS-L) and Research Diagnostic Criteria (RDC). Behavioral assessments of the children were made with a modified version (BGAS) of the Global Assessment Scale. ERP amplitudes for several electrophysiological events were compared among groups for target and nontarget stimuli using analyses of of variance of both factor score and baseline to peak measures. No systematic differences suggesting waveform abnormalities in the children of schizophrenic parents (high-risk subjects) were found. However, when the results were analyzed using only those children whose parents had a "pure" diagnosis of either schizophrenia or affective disorder, the children of affectively disordered parents (psychiatric control subjects) showed significantly lower N100 amplitudes (to the frequent event only) than either the normal control or high-risk subjects. No consistent behavioral differences among the three groups emerged. Since only a small percentage of children at risk will eventually develop schizophrenia, ERP amplitude frequency distribution analyses were also performed and compared among groups. However, these did not provide evidence of an outlying subgroup in any of the three groups. There were complex relationships between ERP component amplitudes and behavioral adjustment in adolescence but, in general, these did not distinguish high-risk and psychiatric control subjects from each other. There was no evidence of a relationship between deviant attentional functioning as measured in an earlier round of laboratory testing and ERP late component amplitude.

Adolescent↗

The Continuous Performance Test, identical pairs version (CPT-IP): I. New findings about sustained attention in normal families.

Thirty families, consisting of two parents and two adolescent children, were tested on a high-processing load Continuous Performance Test, the CPT-IP, which required identification of identical stimulus pairs within a continuously presented series of stimuli. The purpose of this study was to provide normative data for research concerned with the role of attention in psychopathology, especially schizophrenia and major affective disorder. Retest data collected from 23 of the 30 families showed the CPT-IP to be a reliable measure of attention. A major developmental effect was found in capacity to sustain attention to spatial vs. verbal stimuli, which suggested that spatial skills are most developed during childhood and adolescence, while verbal attentional skills tend to peak in adulthood. Factor analysis and family transmission patterns further suggested that the two types of attention (spatial and verbal) were independent and that each was heritable to some degree. Experimental distraction did not disrupt performance in any of the subjects and, in fact, tended to improve it in the adolescents, especially for spatial stimuli. We conclude that the CPT-IP is appropriate for use with families containing members differing widely in age and processing skills.

Adolescent↗

The specificity of DSM-III schizotypal personality traits.

The rate of DSM-III schizotypal personality traits was evaluated in three groups of adolescent offspring (ages 15-21), defined by the psychiatric diagnosis of their parents. Parental diagnoses included schizophrenic disorder (40 adolescents), affective disorder (35 adolescents), and 'no psychiatric disorder' (normal controls) parents (82 adolescents). The presence of the eight component features of schizotypal personality disorder was assessed from video-taped semistructured psychiatric interviews, subsequently rated by trained psychiatrists, blind to the parental psychiatric status of the subjects. The effect of age, sex, and social class on the pattern of prevalence results was examined. The expected specificity of DSM-III schizotypal personality traits to schizophrenia was not supported by the prevalence pattern of the traits. Rates of 2 or more, 3 or more, and 4 or more schizotypal personality features were highest in the parental psychiatric groups. The rates of schizotypal personality traits in adolescent offspring of affective disorder parents were as high as those previously reported for relatives of schizophrenic disorder probands.

Adolescent↗

High-risk research in schizophrenia: a summary of what has been learned.

High-risk research on schizophrenia has been concerned chiefly with two types of issues: (1) description of background factors in the early lives of high-risk subjects; and (2) identification of biological variables that may be markers of the genetic liability to schizophrenic disorders. It is concluded that efforts to describe background factors have led to some conflicting results, have shown little evidence of specificity of the factors under study to risk for schizophrenia, and may not be generalizable to most individuals who develop schizophrenia. Results of research focusing on biological variables are summarized under the headings of attention and information processing (AIP), smooth pursuit eye movement (SPEM), neurological signs, electrodermal responding, event related potentials, and ventricular size. Of these, certain AIP and SPEM dysfunctions show substantial evidence of serving as biological markers, certain other AIP impairments are promising in this regard, electrodermal responsivity is not, and the other three categories present uncertain or conflicting results. Several methodological issues that have hampered the first generation of high-risk research are discussed.

Humans↗

Psychometric validation of psychiatric diagnoses in the New York High-Risk Study.

The authors used the Minnesota Multiphase Personality Inventory (MMPI) to provide convergent validity for Research Diagnostic Criteria (RDC) diagnoses of parents with schizophrenia, mainly schizophrenic schizoaffective disorder (SAS), bipolar affective disorder, and unipolar affective disorder in the New York High-Risk Study. Examination of group profiles, as well as univariate and configural analyses of several MMPI variables, led to successful discrimination of the schizophrenic from both affective groups and a normal control group. The results support the validity of risk assessment for children in the study and also suggest that there is commonality between schizophrenia and SAS. Despite variations in clinical status at testing, the MMPI was useful in exploratory analyses to describe phenomenology specific for schizophrenia that was expressed as the predominance of disturbances in thought, social relations, motivation, and affective expressivity relative to a primary disturbance in mood. The results also suggest that there is some symptomatic overlap between schizophrenia and affective disorders regarding a disturbance in social relatedness predominant over a disturbance in mood (for unipolar states) and a disturbance in thought predominant over a disturbance in mood (for bipolar states).

Adult↗

The New York High-Risk Project: a followup report.

The New York High-Risk Project began in 1971 as a prospective, longitudinal study of (1) children of one or two schizophrenic parents and (2) comparison groups of children whose parents had other or no psychiatric disorders. The former were examined because they were known to be at high risk--some 10-25 percent for children with one affected parent and 35-45 percent with two affected parents--for developing schizophrenia or schizophrenia spectrum disorders during adolescence or adulthood (Erlenmeyer-Kimling 1977; Gottesman and Shields 1982). Children of parents with affective disorders were included because we wished to determine whether variables that might differentiate the children of schizophrenic parents from the children of normal parents also differentiated them from children of parents with other psychiatric disorders. Major goals of the program were (1) identification of biological and behavioral indicators of a genetic liability to develop schizophrenia and (2) longitudinal followup of the subjects to assess the predictive validity and specificity of variables tentatively flagged as early indicators. Other goals have included evaluation of the developmental course of such variables and documentation of the history of the development of schizophrenic disorders.

Adolescent↗

Sustained attention in children at risk for schizophrenia: findings with two visual continuous performance tests in a new sample.

In partial replication of an earlier study, 35 children at high risk for schizophrenia, 25 children at high risk for affective disorder, and 53 normal control children from a new sample of 7- to 12-year-old subjects were tested with two new visual continuous performance tests. Response levels and intrasubject variability were analyzed separately. Multivariate analyses on factor scores derived from response levels indicate that "groups" is a significant predictor for a factor reflecting discriminability (or sensitivity) for the more difficult of these tests but not for the less difficult one, and that high risk for schizophrenia is associated with lower performance. Factor scores and multiple regression analyses were used to dichotomize subjects as to whether or not they are low performance outliers. A significantly larger proportion of subjects from the high risk for schizophrenia group than from the control groups were low performance outliers. Among subjects that developed psychopathology in adolescence, subjects at high risk for schizophrenia were more likely to have contributed low performance outliers early during childhood.

Adolescent↗

Event-related potentials in children at risk for schizophrenia during two versions of the continuous performance test.

Event-related potentials (ERPs) were recorded from children of schizophrenic parents, children of parents with affective disorders, and children of parents without a history of psychiatric illness. ERPs were elicited during two versions of the continuous performance test (CPT), which differed in their level of processing complexity. The data were recorded from electrodes located at midline frontal, central, parietal, and occipital scalp sites. Diagnostic assessments of the parents were performed using the Schedule for Affective Disorders and Schizophrenia-Lifetime Version and Research Diagnostic Criteria. Clinical assessments of the children were made with a modified version of the Global Assessment Scale. ERP amplitudes for six electrophysiological events were compared among groups for target and nontarget stimuli using analyses of variance of both factor score and baseline to peak measures. There was one isolated between-group finding: frontal negative slow wave recorded at FZ was of greater magnitude in the high risk (HR) than in either the psychiatric (PC) or normal control (NC) groups. Since only a small percentage of children at risk will eventually develop schizophrenia, ERP amplitude deviance and frequency distribution analyses were also performed and compared among groups. ERP component amplitudes did not distinguish the groups when each component was considered separately. Deviance analyses, using a combination of the amplitudes of the six ERP components, also did not provide evidence of a deviant subgroup within any of the three groups. There appeared to be no relationship between ERP component amplitudes and behavioral adjustment in adolescence. Some evidence of a relationship between deviant attentional functioning and ERP component amplitude was found, but the pattern of findings within the attentionally deviant HR subgroup was opposite to that found for the HR group as a whole and more consistent with the pattern found for the NC group.

Adolescent↗

Electrodermal recovery data on children of schizophrenic parents.

Half-amplitude recovery of electodermal responses is compared in children of schizophrenic parents (high-risk subjects) and children of depressed or normal parents. The results are dissimilar to those reported by Mednick and colleagues on a Danish high-risk sample. No significant differences emerged among the three groups in our study. Recovery did not differ according to sex or severity of illness of the schizophrenic parent. Recoveries of high-risk subjects separated from their homes were not shorter than recoveries of subjects who remained home. Recovery time recorded in childhood was unrelated to global adjustment in adolescence.

Adolescent↗