Dopamine-beta-hydroxylase activity and homovanillic acid in spinal fluid of schizophrenics with brain atrophy.

Schizophrenic patients with high ventricle brain ratios and cortical brain atrophy, as shown by computerized tomography, had decreased spinal fluid concentrations of homovanillic acid and dopamine-beta-hydroxylase activity. These decreased cerebral spinal fluid concentrations in patients with brain atrophy support the proposal of disturbed noradrenaline and dopamine neurotransmission in a subgroup of schizophrenic patients.

Genetic strategies in biological psychiatry.

Studies of the etiology of schizophrenia and other psychiatric illnesses may be executed by using a genetic framework in the experimental design. This article describes research strategies for identifying the genetic factors that produce a vulnerability to a psychiatric illness. The proposed strategies evaluate the role of a given genetic factor by comparing the transmission of this factor within pedigrees to the transmission of that illness. In a biologically heterogeneous disorder, these strategies can be used to identify homogeneous subgroups. This report also describes a strategy for identification of the environmental events that promote the development of a psychiatric illness, either independently or in conjunction with the genetic diathesis.

Biologic heterogeneity and psychiatrict research. Platelet MAO activity as a case study.

This article examines current research strategies in biological psychiatry and the possible effects of biological heterogeneity on these strategies. First, the limited power of t test comparisons of measurements obtained from groups of patients and controls is demonstrated through a computer simulation. Second, we examine statistically the data from 14 recent platelet MAO studies to see if the heterogeneity in results of these studies could relate to an underlying biological heterogeneity. Finally, we suggest research methods we believe may be more useful than the current standard paradigm for elucidating the biological etiologies of psychiatric syndromes.

Offspring of schizophrenics. III. Hyperactivity and neurological soft signs.

Twenty-nine male offspring of "continuous schizophrenics" (chronic, borderline, and chronic schizoaffective schizophrenics), plus controls, were given neurological and psychological examinations at age 7. Eight of the 29 were found to have high ratings on a factor score that was termed "hyperactive" (increased activity, impulsivity, distractibility, and emotional lability), and three of these boys had high ratings for neurological signs as well. These frequencies were significantly greater than the control values. Mild incoordination, such as awkwardness in performing rapidly alternating movements, was the neurological soft sign most elevated in the index group. Fifteen female offspring of schizophrenics were not found to differ from their controls on these measures. Previous studies of the childhood of male schizophrenics have found behavior patterns similar to the behavior of the boys who scored high on our hyperactive factors. It is thus likely that the "hyperactive cases" in this sample are even more at risk for developing schizophrenia in later life than the other offspring of schizophrenic parents.

The offspring of schizophrenics. II. Perinatal factors and IQ.

Within a sample of 60 children of schizophrenic parents, IQ and the correlates of IQ were examined. The Wechsler Intelligence Scale for Children was administered at age 7. The offspring of parents with schizophrenia were found to have a slightly lower IQ than their matched controls. This deficit could be attributed entirely to the male offspring. Using a second comparison group numbering several thousand, we computed correlations for various perinatal and socioeconomic factors with seven-year IQ. These correlations were also computed for the children of schizophrenics, and the difference in correlations was examined. IQs for the offspring of "continuous schizophrenics" (chronic, borderline, and chronic schizo-affective schizophrenics) were found to have lower correlations with socioeconomic indices and higher correlations, in a negative direction, with certain perinatal events. The findings were found to a lesser, nonsignificant degree among the small sample of offspring of acute schizophrenics. If these perinatal events are more negatively correlated with IQ because the children of continuous schizophrenics are specifically susceptible to them, it is possible that these factors are also influential in the later development of schizophrenia.

The offspring of schizophrenics. Fetal and neonatal deaths.

This is the first report in a projected series on neurological development among the offspring of schizophernics. An increased incidence of fetal and neonatal deaths is noted among offspring of schizophrenics when compared to a closely matched control group, using data collected prospectively. In many cases, no apparent reason for death was determined; in some cases, major neurological malformations were found. It is necessary to consider three possible explantions for these findings--genotype of the child, adverse intrauterine environment, and medication toxicity.

Parent-child relationships and psychopathological disorder in the child.

This report uses naturally occurring adoptions to tease apart the effects of heredity and rearing on the development of psychopathological disorder in the child. The quality of relationship between the child and his adoptive parents was assessed in four groups of subjects, and the degree of illness in the child was correlated with the quality of parent-child relationship. Quality of rearing and hereditary input both affect the development of psychopathological disorder, but the amount of variance explained by rearing tends to be low.

Computed tomographic scans in patients with schizophrenia, schizoaffective, and bipolar affective disorder.

Computed tomographic (CT) scans of 28 chronic schizophrenic patients, 15 chronic schizoaffective patients, and 19 patients with bipolar affective disorder were compared on three measures: ventricular size, sulcal prominence (cortical atrophy), and cerebellar atrophy. Because the patients with bipolar disorder were older, measures were adjusted by controlling for age statistically or excluding patients over age 50 years. After age correction, there were no significant differences across diagnostic groups. Each group contained some subjects with enlarged ventricles, sulcal prominence, and/or cerebellar atrophy. The similarity of CT scan results across the three groups argues against ascribing these abnormalities to any one psychiatric disorder or to a specific drug effect. Sampling effects and the possibility of differential causes of the findings in the different diagnostic groups must be considered. Examination of the correlations of these three CT scan measures found them to be significantly related to each other. Age correlated with all measures when patients over age 50 years were included in the analysis, but not for patients aged 50 years and younger.

Extreme MMPI scores and the Research Diagnostic Criteria. Screening college men for psychopathology.

This study compares psychiatric evaluations made with the Minnesota Multiphasic Personality inventory (MMPI) to evaluations with a standard clinical interview and the Research Diagnostic Criteria (RDC). The purpose was to generate a nonhospitalized, previously undiagnosed sample of persons who had psychiatric difficulties or symptoms. Of 385 college male volunteers, 56 with scores at least 3 SD above the mean on at least one MMPI scale were chosen as an index group, and 27, with all MMPI scores within normal limits, as a control group. In the index group, 82% met the RDC for at least one diagnosis, whereas only 22% of the control sample met the RDC for any diagnosis. One index subject met the RDC for schizophrenia; 15 met the RDC for a major affective disorder. Some correspondence between specific MMPI profile code types and RDC diagnoses was evident. Thus, researchers can identify a range of psychopathology meeting the RDC by using MMPI screening in a nonhospital setting. Such a research sample, free from the possible artifacts of hospitalization, drug treatment, and diagnostic labeling, can be useful particularly in testing hypotheses concerning the biological correlates of psychopathology.

A review of sexual behavior in the United States.

OBJECTIVE: Knowledge of sexual behavior in the United States is necessary for 1) directing risk-reduction interventions aimed at preventing transmission of human immunodeficiency virus (HIV) and other sexually transmitted pathogens and 2) appreciating the current normative patterns of sexual behavior. METHODS: The authors reviewed American surveys that included measures of sexual behavior and analyzed the 1988-1990 General Social Surveys. RESULTS: Most American males have intercourse by 16-17 years of age, and females do so by 17-18 years of age. The majority of young adults aged 18-24 have multiple, serial sex partners. Among adults 25-59 years old, relative monogamy appears to be the norm: 80% of heterosexually active men and 90% of heterosexually active women in this age group report having had only one sex partner in the preceding year. The average frequency of intercourse among such monogamous individuals is one to three times per week. Approximately 25% of adults have had heterosexual anal intercourse. Up to 20% of adult men report that they have had a homosexual experience; 1%-6% report such an experience during the preceding year. CONCLUSIONS: Through accumulated studies, data are now available on normative sexual behavior across the life cycle. Such data should assist in psychiatric diagnosis and in the development of treatment goals that rely on assumptions regarding normative behavior. A large proportion of young heterosexual persons are at considerable risk for sexually transmitted disease. Sexual history taking and risk-reduction counseling should be integral components of psychiatric care.

The factor structure of self-report DSM-III axis II symptoms and their relationship to clinicians' ratings.

A factor analysis of the entire item set of the DSM-III criteria was conducted to determine the extent to which the factors that emerged corresponded to the 11 personality disorders and three clusters included in DSM-III. Data were obtained from 552 patients who completed a self-report personality questionnaire and from 287 psychiatrists who rated their patients. Eleven questionnaire factors emerged that had eigenvalues greater than one, and at least three items emerged with factor loadings greater than 0.40. A correlational and multiple regression analysis of the questionnaire factors and clinicians' ratings showed few strong relationships between the factors and the 11 personality disorders but good correspondence with the three clusters.

Neuropsychological deterioration and CT scan findings in chronic schizophrenia.

Structural abnormalities of the brain, particularly ventricular enlargement and prominence of cortical sulci, have been documented reliably in CT scan investigations of chronic schizophrenic patients. Although the clinical significance of these findings is still obscure, neuropsychological (NP) deficits have emerged as relatively robust correlates of the structural anomalies. Unfortunately, it remains unknown whether the previous findings of NP impairment in association with CT scan abnormalities reflect poor premorbid abilities or deterioration from previously higher levels. This study involved administration of an extensive NP battery and CT scans in a chronic schizophrenic sample. In addition to global and specific scales of NP functions, indices of premorbid ability and deterioration were also employed. The results are consistent with the hypothesis that CT scan findings are associated more with deterioration of functioning than with global measures of NP dysfunction or poor premorbid ability. Conversely, the findings suggest that in patients with normal scans, NP morbidity may be a consequence of failure in the acquisition of a normal cognitive repertoire.

Borderline schizophrenia: evidence of its validity.

Borderline schizophrenia is held to be a valid entity that should be included in the DSM-III. It is a chronic illness that may be associated with many other symptoms but is best characterized by perceptual-cognitive abnormalities. It has a familial distribution and a genetic relationship with schizophrenia. The term schizotypal personality is an acceptable alternative to borderline schizophrenia, but given the apparent genetic relationship with schizophrenia, and given that we are dealing with a vulnerability to episodic symptoms more than personality traits, we prefer the older term.

Symptomatic and neuropsychological components of defect states.

The distinction between positive and negative symptoms has gained prominence in schizophrenia research, but the construct has not been unequivocally validated. The authors report preliminary findings of investigations in which symptomatic and neuropsychological assessments were conducted in a sample of 32 chronic schizophrenic inpatients. Three distinct clusters of symptoms were identified in correlative analyses. One cluster of symptoms (alogia, attentional impairment, positive formal though disorder, and bizarre behavior) appeared to reflect primarily a disorganization of though independent of current definitions of the positive/negative symptom construct. A second cluster of symptoms (affective flattening, avolition/apathy, and anhedonia) appeared to reflect predominantly blunting of affect and volition. A third cluster (delusions, hallucinations, and "breadth of psychosis") seemed to represent only the florid psychotic features. The first and (to a lesser extent) second clusters of symptoms were selectively associated with neuropsychological impairment. The patterns of neuropsychological deficits correlated with the first cluster of symptoms appeared to be consistent with a process characterized by failure in the development of a normal repertoire of cognitive abilities. It is suggested that the "defect state" may not be a monothetic construct, and that within the domain of "type II" schizophrenia, disturbances of thought may be distinguished from those of affect and motivation.

The relationship of prenatal and perinatal complications to cognitive functioning at age 7 in the New England Cohorts of the National Collaborative Perinatal Project.

Previous literature shows that children who later develop schizophrenia have elevated rates of prenatal and perinatal complications (PPCs) and neuropsychological deficits in childhood. However, little is known about the relationship of these risk factors to each other. We evaluated the relationship between PPCs and neuropsychological functioning at age 7 in a large epidemiological study of pregnancy, birth, and development: the National Collaborative Perinatal Project (NCPP). Thirteen standardized measures of cognitive abilities were acquired on 11,889 children at approximately age 7. Principal components analysis was used to create three neuropsychological measures: academic achievement skills, verbal-conceptual abilities, and perceptual-motor abilities. We measured the relationship between these factors and three measures of PPCs: low birth weight (LBW), probable hypoxicischemic complications, and chronic hypoxia. All three measures of PPCs were significantly associated with lower neuropsychological performance, after controlling for various confounders. LBW had the strongest association with neuropsychological performance, followed by an index of presumed hypoxic insults. The effect sizes between PPCs and cognitive factors at age 7 were consistently largest with perceptual-motor abilities, followed by academic achievement skills and verbal-conceptual abilities. Future studies will evaluate the effects of specific PPCs and genetic risk factors for psychosis on cognitive functioning in childhood.

Impact of genetic vulnerability and hypoxia on overall intelligence by age 7 in offspring at high risk for schizophrenia compared with affective psychoses.

Risk factors for schizophrenia, such as genetic vulnerability and obstetric complications, have been associated with cognitive deficits in schizophrenia. We tested the association of these risk factors with general intellectual ability in offspring at high risk for psychoses and normal control subjects. Offspring of 182 parents with DSM-IV schizophrenia or affective psychoses were recruited and diagnosed from the Boston and Providence cohorts of the National Collaborative Perinatal Project (NCPP). Control subjects from the NCPP were selected to be comparable with affected parents based on the parent's age, ethnicity, study site, number of offspring enrolled in the NCPP, and payment status, and on the offspring's age, sex, and history of obstetric complications. Based on data prospectively acquired from pregnancy and events of gestation, labor, delivery, and the neonatal period, we derived a measure of probable hypoxic-ischemic insult. We also report on standardized measures of general intelligence (intelligence quotient [IQ]) collected at age 7. General linear mixed models were used to test for the simultaneous effects of genetic vulnerability, defined as parental diagnosis, and probable hypoxic insult on age 7 IQ. Specificity of the effects for schizophrenia compared with affective psychoses and sex effects were also tested. Low IQ at age 7 was significantly associated with genetic vulnerability to psychoses, in particular with schizophrenia.

The multisite field trial of the consultation-liaison psychiatry assessment instrument.

A multisite field trial was conducted at 11 institutions to test the clinical reliability of a 29-item consultation-liaison (C-L) psychiatry assessment instrument. Twenty-five raters viewed videotapes of two "trainees" conducting clinical interviews with a simulated patient. One trainee was a medical student, the other was a fellow in psychiatry. Raters completed the 29-item assessment instrument for each trainee. The mean value scores reflected the skill of each trainee. The medical student had a mean score of 1.93, whereas the C-L fellow had a mean score of 3.13 which parallels the expected level of skill for the two interviewers. Eighty-six percent of the items (25/29) had a standard deviation (SD) of less than 1.0. Each of the remaining four items (14%) had a SD minimally greater than 1.0. These results reflect clear wording of items with measurable parameters defined for assessing trainees' skills. The authors present different uses for the assessment instrument, including giving feedback to trainees regarding interviewing techniques and skills; setting "gold" and "lead" standards for clinical C-L interviewing skills; and training supervisors in evaluation using a standardized assessment instrument.

Sulcal prominence in young chronic schizophrenic patients: CT scan findings associated with impairment on neuropsychological tests.

Four of 17 chronic schizophrenic (or chronic schizoaffective) patients between the ages of 20 and 35, in partial remission, and living in the community were found to have mildly or moderately prominent sulci, as disclosed by computerized tomography (CT scan). These four patients were matched for sex and age with four chronic schizophrenic (or schizoaffective) patients without sulcal prominence. The Halstead-Reitan battery (HRB) of neuropsychological tests, including the Wechsler Adult Intelligence Scale (WAIS), was administered to these eight patients with the examiner blind to results of the CT scan. Each of the four patients with sulcal prominence considerably exceeded an established cutoff score for brain impairment on the HRB, whereas only one of the control schizophrenics performed in the impaired range, and that just beyond the cutoff. The WAIS Verbal IQ, mneasured concurrently, was in the normal range for all subjects and similar for the two groups. These findings suggest that mild or moderate sulcal prominence on CT scans among young chronic schizophrenics is associated with impaired neuropsychological functioning.