Childhood Affective Indicators of Risk for Adulthood Psychopathology: The New York High-Risk Project Findings.

There are relatively few investigations of the emotion expressivity of children at risk for the later development of schizophrenia and schizophrenia-spectrum disorders. Using data from the New York High-Risk Project, we compared children's emotional expressivity during a semi-structured videotaped interview. Data were coded for 173 child subjects: 61 with schizophrenic parents (HRSz); 54 with affectively ill parents (HRAff); and 58 with psychiatrically "normal" parents (NC). A child's affective responses were rated for the presence of discrete positive, negative, or neutral emotions by coders naive to group membership. Responses were also rated for anxiety, flat affect, inappropriate affect, and emotional withdrawal/disengagement. Compared with the two other two groups, HRSz children displayed significantly more negative affect in response to questions regarding their most negative experiences and, when questioned about their self-concept, they displayed significantly less positive affect. Both HRSz and HRAff children showed more inappropriate affect than NC children. Significantly more HRSz children were rated as demonstrating a lack of emotional engagement. Children making inappropriate displays of positive affect while discussing a negative topic were most likely to manifest a psychiatric disorder as an adult. These findings suggest that inappropriate affect may be a nonspecific indicator of risk for psychopathology. Emotional withdrawal in childhood may be a potential indicator of risk for schizophrenia.

Thought disorder in mid-childhood as a predictor of adulthood diagnostic outcome: findings from the New York High-Risk Project.

BACKGROUND: Thought disorder has been proposed as an indicator of schizotypy, which is considered to be necessary but not sufficient for the development of schizophrenia. It is unclear whether thought disorder is an indicator of susceptibility (i.e. an endophenotype) for schizophrenia. The goal of the present study was to elucidate the role of thought disorder in relation to schizotypy by examining its presence in high-risk individuals during mid-childhood. Method The sample consisted of 265 subjects drawn from the New York High-Risk Project. Individuals at high risk for schizophrenia (i.e. offspring of parents with schizophrenia) were compared with individuals at low risk for schizophrenia (i.e. offspring of parents with affective disorder or offspring of psychiatrically normal parents). Videotaped interviews were rated for thought disorder using the Scale for the Assessment of Thought, Language, and Communication (TLC). The same subjects were administered diagnostic interviews in late adolescence/early adulthood. RESULTS: Although positive thought disorder was equally present in subjects with affective and non-affective psychoses, negative thought disorder (namely, poverty of speech and poverty of content of speech) was elevated only in subjects with schizophrenia-related psychosis. Logistic regression analyses revealed that negative thought disorder added to the prediction of schizophrenia-related psychosis outcomes over and above positive thought disorder. CONCLUSIONS: These findings suggest that negative thought disorder may have a specific association with schizotypy, rather than a more general association with psychosis. The findings also support consideration of negative thought disorder as an endophenotypic indicator of a schizophrenia diathesis.

Thought disorder in offspring of schizophrenic parents: findings from the New York High-Risk Project.

The goal of the present analyses was to examine the hypothesis that mild forms of thought disorder (TD) may serve as an indicator of genetic liability for schizophrenia. A subset of 232 subjects drawn from the New York High-Risk Project was used to compare individuals at high risk for schizophrenia (ie, offspring of parents with schizophrenia; n = 63) with 2 groups of individuals at low risk for schizophrenia (ie, offspring of parents with affective disorder [n = 52] and offspring of psychiatrically normal parents [n = 117]). Subjects were administered the Rorschach Inkblot Test, and their responses were assessed according to the Thought Disorder Index (TDI). The high-risk offspring displayed significantly more TD than the other 2 groups, as shown by significantly higher TDI scores. Moreover, they had more deviant verbalizations, according to their significantly higher scores on a composite Idiosyncratic Verbalizations score. As expected, the offspring who developed psychosis produced more TD in adolescence than those who did not develop psychosis. In the sample as a whole, TD scores during late adolescence/early adulthood were positively associated with schizotypal features during mid-adulthood. These findings support the assertion that the presence of TD serves as an endophenotypic marker of a schizophrenia diathesis.

Interval-timing deficits in individuals at high risk for schizophrenia.

A duration-bisection procedure was used to study the effects of signal modality and divided attention on duration classification in participants at high genetic risk for schizophrenia (HrSz), major affective disorder (HrAff), and normal controls (NC). Participants learned short and long target durations during training and classified probe durations during test. All groups classified visual signals as shorter than equivalent duration auditory signals. However, the difference between auditory and visual signal classification was significantly larger for the HrSz group than for the NC group. We posit a model in which there is a clock rate difference between auditory and visual signals due to an attentional effect at the level of a mode switch that gates pulses into an accumulator. This attentionally mediated clock rate difference was larger for the HrSz participants than for the NC participants, resulting in a larger auditory/visual difference for the HrSz group.

Handedness in children of schizophrenic parents: data from three high-risk studies.

This is the first report of data analyses from a consortium of longitudinal genetic-risk studies on offspring of schizophrenic parents (CLOSSER) who were followed from birth or mid-childhood to their early 20's or considerably older ages. Three of the CLOSSER studies provide data to enable us to address long-persisting questions in the schizophrenia literature concerning possible atypicality of hand dominance associated with the illness. Handedness, used as a proxy for cerebral lateralization, is a topic of considerable importance because of its potential to reveal mechanisms in the underlying pathophysiology of schizophrenia. We examine agreement among the CLOSSER studies with respect to possible deviance in handedness in subjects with schizophrenic parents (high-risk individuals) and specifically in those who have gone on to develop adult schizophrenia, compared with other subjects of these studies. Possible developmental delay in age at lateralization is also considered.

Positive and negative thought disorder and psychopathology in childhood among subjects with adulthood schizophrenia.

UNLABELLED: The New York High-Risk Project (NYHRP) is a longitudinal study of offspring of parents with schizophrenia or affective disorder and normal controls. Neuropsychological deficits had been observed at about age 9 in subjects with adulthood schizophrenia. We explored whether in these subjects, early signs of clinical schizophrenia-related symptoms, such as thought disorder or behavioral abnormalities, could also be observed. METHODS: We rated thought disorder and symptoms from videotaped interviews at age 9, using the Scale for the Assessment of Thought, Language and Communication (TLC), and the Mental Health Assessment Form (MHAF). With factor analyses we examined the structure of the ratings, and from interpretable factors, scales were assembled. MANOVAs were used to examine the effect of parental risk and adulthood psychiatric diagnosis (schizophrenia-related psychosis (SRP), major affective disorder (MAD), no disorder/other (NoDx/other)) as independent variables (IV) on thought disorder and symptoms as dependent variables. RESULTS: Global, positive and negative thought disorder, and negative symptoms were significantly higher in subjects with adulthood schizophrenia-related psychosis than both comparison groups. A significant interaction between the two IVs was effective with respect to positive thought disorder. This scale was particularly elevated among subjects with adulthood schizophrenia-related psychosis at parental risk for affective disorder (all of whom had adulthood schizoaffective disorder). CONCLUSIONS: We were able to show that global, negative and positive thought disorder and negative symptoms were present in subjects with adulthood schizophrenia already at mid-childhood, years before onset of psychosis. Further, we found a particularly high propensity to positive symptoms in subjects with adulthood schizophrenia who have also an affective component in their symptoms. This association, previously reported in acute schizophrenia, was here observed years before the first psychotic episode.

Wisconsin Card Sorting deficits in the offspring of schizophrenics in the New York High-Risk Project.

It has been suggested that performance on the Wisconsin Card Sorting Test (WCST) may be an indicator of vulnerability to schizophrenia. WCST deficits have been demonstrated in schizophrenic patients and their relatives, but not as yet in their offspring. This study aimed to further establish the indicator potential of WCST deficits by analyzing data collected as part of the New York High-Risk Project (NYHRP), a longitudinal study of attention, cognition and clinical functioning in the offspring of schizophrenic (HRSz, n=73), affective disordered (HRAff, n=61) and normal comparison (NC, n=120) parents. Parental Research Diagnostic Criteria diagnoses were established by semi-structured interview (SADS-L). WCST testing was carried out when offspring were in their mid-20s. HRSz subjects performed significantly more poorly on the WCST than HRAff and NC subjects. High-risk subjects who developed psychotic symptoms prior to or shortly after testing did not differ significantly from HRSz subjects who did not become ill. Thus, WCST performance in the offspring of schizophrenics resembles that of schizophrenic patients and may distinguish HRSz from offspring at risk for nonschizophrenic illness. WCST deficits may be a specific familial indicator of vulnerability, but appear not to distinguish between those subjects at risk for schizophrenia who do or do not become ill.

Family and twin strategies as a head start in defining prodromes and endophenotypes for hypothetical early-interventions in schizophrenia.

In an effort to share the experiences of 'genotype-hunters'-who have approached the difficult task of forecasting future schizophrenia in the young offspring or other relatives of index cases, in new samples guided by the prior probabilities of 15% in offspring or 50% in identical co-twins-with 'early-interventionists'-who focus on purported prodromal symptoms in children who would be treated pharmacologically to prevent the development of schizophrenia-we provide a focused review that emphasizes the hazards of false positives in both approaches. Despite the advantages prospective high-risk strategies have had from clinical and laboratory findings that implicate some prodromal signs and endophenotypes, e.g. attention, memory, and information processing evaluations, the yields are not sufficient for practical applications involving antipsychotic drugs for undiagnosed children. Even more caution than usual is required, given the suggestions that the developing neocortex is vulnerable to dopaminergic exposure.

Early neurobehavioral deficits as phenotypic indicators of the schizophrenia genotype and predictors of later psychosis.

Schizophrenia is a genetically complex disorder that requires sharper delineation of its phenotypic boundaries. Considerable attention has been devoted in recent family and high-risk studies to the identification of both subclinical and other phenotypes, such as neurobehavioral deficits, that may be indicators of the genetic liability to schizophrenia. In high-risk studies, candidate liability indicators that are evident by young ages are also evaluated for their ability to predict future schizophrenia or spectrum disorders. We report on assessments of verbal short-term memory, gross motor skills, and global attention administered in midchildhood to offspring of schizophrenic, affectively ill, and normal parents as predictors of adult psychoses and as possible indicators of schizophrenia-susceptibility genes.

The New York High-Risk Project: observations on the rating of early manifestations of schizophrenia.

The neurodevelopmental paradigm of schizophrenia (Sz) proposes a lifelong process of brain pathology as the cause of the disorder. Investigating the early phenotype of Sz, we rated videotapes of children at risk for Sz for early manifestations of thought disorder and Sz-related symptoms, using the Scale for the Assessment of Thought, Language, and Communication and parts of a diagnostic interview designed for psychiatric assessment of children. We found that thought disorder as well as negative symptoms were elevated in children with adulthood Sz-related psychosis. This discussion focuses on methodological problems that arise in making clinical judgments on early and still subtle functional deviations.

A new MMPI-derived indicator of liability to develop schizophrenia: evidence from the New York High-Risk Project.

A large body of research indicates that the liability to develop schizophrenia is largely genetically mediated, although phenotypic expression requires environmental triggers/insults and/or epigenetic and/or stochastic factors. In an effort to identify the precise environmental factors that precipitate a predisposition to schizophrenia, researchers have implemented a high-risk model-the prospective study of offspring born to schizophrenic parents. As it is difficult to ascertain exactly which of the "high-risk" participants will actually develop the disorder, we examined the validity of an experimental MMPI scale, Schizophrenia Proneness (SzP), and the Moldin-Gottesman psychometric index to identify such individuals. Results suggest that the SzP scale can be an effective predictor of schizophrenia-related psychoses. A revised psychometric index is offered for further study.

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.

Attention, memory, and motor skills as childhood predictors of schizophrenia-related psychoses: the New York High-Risk Project.

OBJECTIVE: Childhood neurobehavioral deficits in offspring of schizophrenic, affectively ill, and psychiatrically normal parents were evaluated as predictors of schizophrenia-related psychoses in adulthood. METHOD: The offspring were tested with neurobehavioral measures at 7-12 years of age and assessed in mid-adulthood for axis I diagnoses. The relationships of childhood deficits in attention, verbal memory, and gross motor skills to adulthood schizophrenia-related psychoses were examined in separate path analyses by using logistic regression equations. Sensitivity and specificity were determined for each of the childhood dysfunctions. RESULTS: For the offspring of schizophrenic parents, childhood deficits in verbal memory, gross motor skills, and attention identified 83%, 75%, and 58%, respectively, of the subjects with schizophrenia-related psychoses; 50% were identified by all three variables combined. False positive rates in subjects who did not develop schizophrenia-related psychoses ranged from 18% for those with deficits in attention during childhood to 28% for those with deficits in memory. The three variables had low deficit rates in the offspring of the other two parental groups and were not associated with other psychiatric disorders in any group. CONCLUSIONS: Schizophrenia-related psychoses in adulthood are distinguished in subjects at risk for schizophrenia by childhood deficits in verbal memory, gross motor skills, and attention. The findings suggest that deficits in these variables are relatively specific to schizophrenia risk and may be indicators of the genetic liability to schizophrenia.

Neurobehavioral deficits in offspring of schizophrenic parents: liability indicators and predictors of illness.

High-risk research in schizophrenia incorporates several different strategies for studying individuals who are defined by different criteria as being at risk for future development of schizophrenia. Variables from a wide range of domains have been included in these studies. Several reviews of high-risk research have attempted to cover the field broadly, whereas others have been more sharply focused on research subjects defined by specific criteria or on particular classes of variables. Among the review articles and collections of project reports on high-risk research in the past two decades are: Watt et al. [1984: Children at risk for schizophrenia: a longitudinal perspective]; Nuechterlein and Dawson [1984: Schizophr Bull 10:160-203]; Nuechterlein [1986: J Child Psychol Psychiatr 27:133-144]; Erlenmeyer-Kimling and Cornblatt [1987: J Psychiatr Res 26:405-426]; Goldstein and Tuma [1987: Schizophr Bull 13:369-371]; Asarnow [1988: Schizophr Bull 14:613-631]; Moldin and Erlenmeyer-Kimling [1994: Schizophr Bull 20:25-29]; Mirsky [1995: Schizophr Bull 21:179-182]; Gooding and Iacono [1995: Manual of developmental psychopathology] McNeil [1995: Epidemiol Rev 17:107-112] Olin and Mednick [1996: Schizophr Bull 22:223-240]; Cornblatt and Obuchowski [1997: Intl Rev Psychiatry 9:437-447]. This paper presents an overview of findings from recent (the past decade and a half) prospective studies of children of schizophrenic parents, with a focus on neurobehavioral (neurocognitive, neuromotor, and neurophysiological) variables that may reflect aspects of the genetic liability to schizophrenia and related disorders. The few neuroimaging studies on children of schizophrenic parents are also briefly mentioned. Because of space limitations, the overview is not intended as a comprehensive or detailed review of this area of high-risk research.

Cognitive and behavioral precursors of schizophrenia.

Attentional deficits are well-established characteristics of patients with schizophrenia and their at-risk offspring, suggesting a biological connection between attention and schizophrenia. The goal of this study is to clarify the developmental role of attention in the illness. Data has been collected from 87 subjects at high and low risk for schizophrenia who have participated in the New York High-Risk Project from 1977 to the present. Individuals are considered to be at high risk if either or both of their parents has schizophrenia. Analyses of attention and global behaviors, measured at intervals from about 12 to 26 years of age, indicate (a) attentional deficits can be reliably detected in high-risk children who will develop future schizophrenia-spectrum disorders (the prespectrum [PSP] group); (b) these deficits are stable, enduring over time, and appear to reflect a compromised attentional capacity; (c) attention is not affected by the onset of illness in the PSP group; (d) for all subjects, attention and global behaviors follow independent developmental pathways; and (e) behavioral difficulties, but not attention deficits, appear to be highly sensitive to environmental factors, especially rearing by a mentally ill parent. It is concluded that in PSP individuals impaired attention probably results from prenatal developmental abnormalities (possibly on the cellular level) and is likely to be a marker of a biological vulnerability to schizophrenia. In addition, attentional deficits, as opposed to early behavioral difficulties, are concluded to be a useful first step in screening for youngsters in need of early intervention.

Relationship between childhood behavioral disturbance and later schizophrenia in the New York High-Risk Project.

OBJECTIVE: An association between childhood behavioral disturbance and adulthood schizophrenia has been seen previously in retrospective or follow-back studies and in prospective studies. The authors examined the relationship between childhood behavioral problems and adulthood schizophrenia-related psychoses. Because a high rate of childhood behavioral problems is known to be associated with adult substance abuse, these analyses controlled for substance abuse. METHOD: The subjects of this investigation (N = 185) were offspring of parents with schizophrenia or affective disorder and of normal parents from the New York High-Risk Project (sample A). Data on childhood behavioral problems were obtained in a parent interview at initial assessment in 1971-1972. Adulthood outcomes (schizophrenia-related psychoses, affective disorders, anxiety disorders, substance abuse) were based on lifetime axis I diagnoses according to the Research Diagnostic Criteria. RESULTS: Substance abuse had a significant interaction with the clinical outcome groups. In subjects without substance abuse, those with schizophrenia-related psychoses had exhibited significantly more behavioral problems as children than had adult offspring with affective or anxiety disorder or with substance abuse only or no disorder. CONCLUSIONS: These results support the view that schizophrenia-related psychoses can be followed back to early behavioral disturbances. The confounding effects of substance abuse should be statistically controlled in studies of longitudinal associations between childhood behavioral disturbance and axis I outcomes.

The New York High-Risk Project: attention, anhedonia and social outcome.

In the New York High-Risk Project we have followed two samples of subjects (Sample A and Sample B) at risk for schizophrenic or affective disorders and low-risk controls from childhood to adulthood, in an attempt to identify early predictors of later psychopathology. We administered a large number of cognitive, psychometric and other types of measures to both samples as possible psychopathology predictors, including an index of attentional deviance assessed in childhood, the Physical Anhedonia Scale in adolescence, and three measures of social outcome in adulthood ('Suspicious Solitude', 'Social Insecurity', and 'Lack of Empathy'), derived from the Personality Disorders Examination. In the analysis of the combined samples, parental diagnostic group, gender, attentional deviance in childhood, and physical anhedonia in adolescence were used to predict three measures of social outcome in adulthood. While only physical anhedonia was directly related to all three social outcome measures, with the strongest relationship to Suspicious Solitude, attention deviance successfully predicted two of the three outcomes. Subjects at risk for affective disorder did not show increased levels of attention deviance, physical anhedonia, or social dysfunction, relative to the normal control subjects. Attention deviance appears to be a key neurobiological indicator and physical anhedonia appears to be a potentiating factor mediating the relationship between risk for schizophrenia and later social dysfunction.

The New York High-Risk Project: social and general intelligence in children at risk for schizophrenia.

UNLABELLED: Social deficits, as well as low performance on intelligence tests, are known early symptoms of schizophrenia. We studied whether impairment of social intelligence can be detected before the outbreak of the disorder. In the New York High-Risk Project, children at risk for schizophrenia (HRSz) or affective disorder (HRAff) and a normal control group (NC) were studied over the past 26 years. The children are now in mid-adulthood, with known psychiatric outcomes. Developmental and clinical data from childhood can now be related to adulthood diagnoses. We compared mean WISC (or WISC-R) and WAIS (or WAIS-R) scores from childhood and adolescence, and change of IQ, between the risk groups, as well as between the adulthood outcomes. We were specifically interested in the development of social intelligence (the Picture Arrangement and Comprehension subtests). We used logistic regression analyses to generate a model predicting adulthood schizophrenia. RESULTS: IQ at age 9,7 was lower in children with HRSz than with HRAff. Adulthood schizophrenia, compared with major depressive disorder and no psychiatric diagnosis could not be related conclusively to low IQ. This may be a result of the study design, since children with IQ below 70 or behavioral problems were not eligible as study subjects. There was no evidence of lower scores or more decline in social intelligence related to age or group membership (risk or outcome). Subtest-Scatter, a nondirectional measure of the differences between all subtests and Vocabulary, reflecting a lesser difference between crystallized and fluid intelligence, was identified as a significant predictor of adulthood schizophrenia, in the whole group as well as in the HRSz group alone.

The New York High-Risk Project. Prevalence and comorbidity of axis I disorders in offspring of schizophrenic parents at 25-year follow-up.

BACKGROUND: The New York High-Risk Project is a study of offspring of patients with schizophrenia (HRSz group) or affective illness (HRAff group) and psychiatrically normal parents (NC group) observed prospectively from childhood to adulthood. We herein present lifetime prevalence and comorbidity rates of Axis I disorders in subjects and their siblings from sample A of the project. METHODS: Schedule for Affective Disorders and Schizophrenia-Lifetime Version interviews conducted with the offspring in adulthood were used to obtain diagnoses of Axis I disorders. RESULTS: Schizophrenia and unspecified psychoses occurred only in the HRSz group. However, schizoaffective and psychotic affective disorders occurred equally in the HRSz and HRAff groups. Total rates of psychosis in these groups were significantly higher than in the NC group. All groups had similar rates of nonpsychotic affective and substance abuse disorders. The HRAff group, however, had significantly more total affective illness than the NC group and tended to have more anxiety disorders than the other groups. Comorbidity rates in the HRSz and HRAff groups were nearly twice those of the NC group. CONCLUSIONS: The familial liabilities to schizophrenia and affective disorders show specificities and commonalities, differing markedly from each other in their expression of some disorders and sharing others. Patterns of comorbidity are generally, although not entirely, similar to these liabilities.

Negative and positive dimensions of schizotypal personality disorder.

The positive (perceptual-cognitive) and negative (social-interpersonal) dimensions of schizotypal personality traits were examined in biological relatives of individuals with Axis I disorder. The subjects were young adult offspring from three contrasting parental groups, including schizophrenic disorder, affective disorder, and normal controls. Cognitive correlates, including digit span (presumed to assess working memory) and P3 amplitudes, were also examined. Preliminary results showed that positive and negative dimensions were distinguished by different prevalence patterns in the offspring subjects, and by a different pattern of correlations with cognitive measures. Negative dimensions were more frequent in offspring from the schizophrenic parental group than in the offspring from affective disorder and normal control parental groups. Digits forward and backward, and P3 amplitude decrements, characterized a subset of offspring with negative features from the schizophrenic parental group. Positive dimensions did not differ between the psychiatric parental groups, and did not covary with digit span or P3 amplitude assessments. These results support the view that positive and negative dimensions may reflect separable pathophysiologic processes.