Intellectual functioning and the long-term course of schizophrenia-spectrum illness.

BACKGROUND: Recent neurodevelopmental models of schizophrenia, together with substantial evidence of neurocognitive dysfunction among people with schizophrenia, have led to a widespread view that general cognitive deficits are a central aspect of schizophrenic pathology. However, the temporal relationships between intellectual functioning and schizophrenia-spectrum illness remain unclear. METHOD: Longitudinal data from the Copenhagen High-Risk Project (CHRP) were used to evaluate the importance of intellectual functioning in the prediction of diagnostic and functional outcomes associated with the schizophrenia spectrum. The effect of spectrum illness on intellectual and educational performance was also evaluated. The sample consisted of 311 Danish participants: 99 at low risk, 155 at high risk, and 57 at super-high risk for schizophrenia. Participants were given intellectual [Weschler's Intelligence Scale for Children (WISC)/Weschler's Adult Intelligence Scale (WAIS)] assessments at mean ages of 15 and 24 years, and diagnostic and functional assessments at mean ages 24 and 42 years. RESULTS: Intellectual functioning was found to have no predictive relationship to later psychosis or spectrum personality, and minimal to no direct relationship to later measures of work/independent living, psychiatric treatment, and overall severity. No decline in intellectual functioning was associated with either psychosis or spectrum personality. CONCLUSIONS: These largely negative findings are discussed in the light of strong predictive relationships existing between genetic risk, diagnosis and functional outcomes. The pattern of predictive relationships suggests that overall cognitive functioning may play less of a role in schizophrenia-spectrum pathology than is widely believed, at least among populations with an evident family history of schizophrenia.

Early maternal and paternal bonding, childhood physical abuse and adult psychopathic personality.

BACKGROUND: A significant gap in the literature on risk factors for psychopathy is the relative lack of research on parental bonding.MethodThis study examines the cross-sectional relationship between maternal and paternal bonding, childhood physical abuse and psychopathic personality at age 28 years in a community sample of 333 males and females. It also assesses prospectively whether children separated from their parents in the first 3 years of life are more likely to have a psychopathic-like personality 25 years later. RESULTS: Hierarchical regression analyses indicated that: (1) poor parental bonding (lack of maternal care and low paternal overprotection) and childhood physical abuse were both associated with a psychopathic personality; (2) parental bonding was significantly associated with psychopathic personality after taking into account sex, social adversity, ethnicity and abuse; (3) those separated from parents in the first 3 years of life were particularly characterized by low parental bonding and a psychopathic personality in adulthood; and (4) the deviant behavior factor of psychopathy was more related to lack of maternal care whereas the emotional detachment factor was related to both lack of maternal care and paternal overprotection. CONCLUSIONS: Findings draw attention to the importance of different components of early bonding in relation to adult psychopathy, and may have potential implications for early intervention and prevention of psychopathy.

Genetic influences in criminal convictions: evidence from an adoption cohort.

The possibility that genetic factors are among the causes of criminal behavior was tested by comparing court convictions of 14,427 adoptees with those of their biological and adoptive parents. A statistically significant correlation was found between the adoptees and their biological parents for convictions of property crimes. This was not true with respect to violent crimes. There was no statistically significant correlation between adoptee and adoptive parent court convictions. Siblings adopted separately into different homes tended to be concordant for convictions, especially if the shared biological father also had a record of criminal behavior.

High social class and suicide in persons at risk for schizophrenia.

OBJECTIVE: The relationship between suicide and social class has been equivocal. While some authors have reported that higher social class is related to higher rates of suicide, most other studies report that lower social class is associated with higher rates of suicide. Our study attempted to resolve these inconsistencies by using a High Risk for schizophrenia method. METHOD: Children of women with severe schizophrenia were assessed in 1962. In 2005, when subjects were a mean age of 58 years, we identified those who had committed suicide. RESULTS: A higher rate of suicide was associated with risk for schizophrenia in the High-Risk sample. Higher social class origin was associated with suicide in persons at risk for mental illness. CONCLUSION: Higher social class origin was associated with suicide in subjects at genetic risk for schizophrenia (but not those without risk).

Polyvagal theory, neurodevelopment and psychiatric disorders.

Neurodevelopment is an area of psychiatry which has attracted huge interest in the last few decades. There is substantial evidence that perinatal events can contribute to later development of mental disorder. In the current perspective article we propose a novel polyvagal theory which attempts to link prenatal events with neurodevelopment and the later onset of psychiatric disorder.

Rhesus incompatibility as a risk factor for schizophrenia in male adults.

BACKGROUND: Rhesus (Rh) incompatibility is a cause of hemolytic disease of the fetus and newborn. Hemolytic disease results from the transplacentally transmitted maternal antibodies against Rh factor D and can cause permanent neurological damage in the affected newborn. This study examines the hypothesis that Rh incompatibility may be a risk factor for schizophrenia. METHODS: A sample of 1867 male subjects was divided into two groups, 535 Rh incompatible and 1332 Rh compatible, and compared on rate of schizophrenia. RESULTS: The rate of schizophrenia was significantly higher in the Rh-incompatible group (2.1%) compared with the Rh-compatible group (0.8%) (P < .03). In addition, since the risk for Rh hemolytic disease increases with second and later Rh incompatible pregnancies, it is noteworthy that the second- and later-born incompatible offspring exhibited a significantly higher rate of schizophrenia than second- and later-born compatible offspring (P < .05). Also, as predicted, the rate of schizophrenia among firstborn incompatible subjects was not significantly different from that of firstborn compatible subjects (1.1% vs 0.7%). CONCLUSION: Rh incompatibility may be a risk factor for schizophrenia.

Birth complications combined with early maternal rejection at age 1 year predispose to violent crime at age 18 years.

BACKGROUND: This study tests the bisocial interaction hypothesis that birth complications when combined with early maternal rejection of the infant predispose to adult violent crime. METHODS: This hypothesis was tested using a cohort of 4269 consecutive live male births on whom measures of birth complications (age 0), early maternal rejection (age 1 year), and violent crime (age 18 years) were collected. RESULTS: A significant interaction (P < .0001) between birth complications and early maternal rejection indicated that those who suffered both birth complications and early child rejection were most likely to become violent offenders in adulthood. While only 4.5% of the subjects had both risk factors, this small group accounted for 18% of all violent crimes. The effect was specific to violence and was not observed for nonviolent criminal offending. CONCLUSIONS: To our knowledge, this is the first study to show that birth complications in combination with early child rejection predispose to violent crime. The findings illustrate the critical importance of integrating biological with social measures to fully understand how violence develops and also suggest that prenatal, perinatal, and early postnatal health care interventions could significantly reduce violence.

Major mental disorders and criminal violence in a Danish birth cohort.

BACKGROUND: This epidemiological investigation was designed to examine the relationships between each of the major mental disorders and criminal violence. Specifically, we assessed whether a significant relationship exists between violence and hospitalization for a major mental disorder, and whether this relationship differs for schizophrenia, affective psychoses, and organic brain syndromes. METHODS: Subjects were drawn from a birth cohort of all individuals born between January 1, 1944, and December 31, 1947, in Denmark (N = 358 180). Because of the existence of accurate and complete national registers, data were available on all arrests for violence and all hospitalizations for mental illness that occurred for individuals in this cohort through the age of 44 years. RESULTS: There was a significant positive relationship between the major mental disorders that led to hospitalization and criminal violence (odds ratios 2.0-8.8 for men and 3.9-23.2 for women). Persons hospitalized for a major mental disorder were responsible for a disproportionate percentage of violence committed by the members of the birth cohort. Men with organic psychoses and both men and women with schizophrenia were significantly more likely to be arrested for criminal violence than were persons who had never been hospitalized, even when controlling for demographic factors, substance abuse, and personality disorders. CONCLUSIONS: Individuals hospitalized for schizophrenia and men hospitalized with organic psychosis have higher rates of arrests for violence than those never hospitalized. This relationship cannot be fully explained by demographic factors or comorbid substance abuse.

The children of psychiatrically disturbed parents: differences as a function of the sex of the sick parent.

To examine the effects of the sex of psychiatrically disturbed parent on the offspring, we compared children of a schizophrenic parent, a psychiatrically disturbed but not schizophrenic parent, and a normal parent using behavioral, attentional, and neurological indices. Results of a discriminant analysis indicate that children of psychiatrically disturbed mothers have an increased sensitivity to tactile stimulation, possibly reflecting more labile autonomic nervous system functioning. In addition, children with a schizophrenic parent of either sex show evidence of neurological motor dysfunction.

Antecedents of predominantly negative- and predominantly positive-symptom schizophrenia in a high-risk population.

We reanalyzed the Copenhagen schizophrenia high-risk project data set to test recently developed models of the antecedents of predominantly negative and predominantly positive forms of schizophrenia. Among a group of 138 high-risk individuals, those at elevated genetic risk who suffered severe delivery complications and who were autonomic nonresponders during adolescence were significantly more likely than those without this pattern to evidence outcomes of schizophrenia with predominantly negative symptoms (86% vs 0.8%, respectively). Among a group of 160 high-risk subjects, those who escaped delivery complications, who evidenced a high degree of autonomic responsiveness in adolescence, and who experienced severe disruption of the early family rearing environment were significantly more likely than those without this pattern to evidence outcomes of schizophrenia with predominantly positive symptoms (40% vs 1.2%, respectively). In late childhood and early adolescence, predominantly negative-symptom schizophrenics were rated by their teachers as passive, socially isolated, and unresponsive to praise; predominantly positive-symptom schizophrenics were rated as overactive, irritable, distractible, and aggressive. The study is limited by the fact that the hypotheses were based in part on previous analyses of the same data set, by the small number of schizophrenic subjects of each subtype, and by the use of simplified theoretical and statistical models that do not address the multidetermination of negative and positive symptoms.

Genetic and perinatal determinants of structural brain deficits in schizophrenia.

Using a subsample from the Copenhagen schizophrenia high-risk project, we examined the contributions of schizophrenic genetic liability and perinatal complications to computed tomographic (CT) measurements of ventricular enlargement and cortical and cerebellar abnormalities. A factor analysis of six CT measurements yielded two significant factors. One factor reflected multisite neural deficits as evidenced by abnormality of the cerebellar vermis and widening of the sylvian and interhemispheric fissures and cortical sulci. The other factor reflected periventricular damage as evidenced by enlargement of the third and lateral ventricles. Because all of the subjects had schizophrenic mothers, the major source of genetic variation is contributed by the diagnostic status of their fathers. In a stepwise multiple-regression analysis, it was determined that the multisite neural deficits factor was significantly related to genetic risk for schizophrenia (as measured by schizophrenia spectrum illness in the subjects' fathers) but was unrelated to pregnancy or delivery complications or to weight at birth. Periventricular damage was highly and significantly correlated with the number of complications suffered at delivery, but only among subjects with an elevated genetic risk. Although limited by a small sample size, these results suggest that the two types of CT abnormalities in schizophrenia may reflect partially independent processes based on different combinations of genetic and perinatal influences.

Impaired autonomic nervous system-habituation in those at genetic risk for schizophrenia.

BACKGROUND: Schizophrenia has been associated with habituation of skin conductance activity. Skin conductance data from the Copenhagen High Risk Project were analyzed. We hypothesized that genetic risk for schizophrenia and development of schizophrenia later in life are related to impaired habituation of autonomic nervous system activity. METHODS: Data were collected in 1962, when subjects averaged 15 years of age and had not yet qualified for a psychiatric diagnosis. Nonspecific fluctuations in electrodermal activity were monitored during a rest period free of sensory stimulation. RESULTS: We found that an increasing level of genetic risk for schizophrenia was related to impaired habituation of autonomic nervous system activity over time. Individuals with two schizophrenia-spectrum parent evidenced no habituation, those with one spectrum parent evidence some habituation, and those with normal parents evidenced rapid habituation. Subjects who developed schizophrenia in adulthood evidenced significant deficits in habitation in adolescence. CONCLUSIONS: These results suggest that impaired habituation of spontaneous autonomic nervous system activity may represent a behavioral marker of the genetic predisposition to schizophrenia.

Adult schizophrenia following prenatal exposure to an influenza epidemic.

In the context of a Finnish birth cohort, we tested the hypothesis that viral infection during the latter two thirds of fetal development would increase the risk of adult schizophrenic outcome. Psychiatric hospital diagnoses were recorded for all individuals in greater Helsinki who were fetuses during the 1957 type A2 influenza epidemic. Those exposed to the viral epidemic during their second trimester of fetal development were at elevated risk of being admitted to a psychiatric hospital with a diagnosis of schizophrenia. This was true for both males and females and independently in several psychiatric hospitals. The second-trimester effect was seen in the elevated proportion of schizophrenics among those admitted to a psychiatric hospital and also in higher rates of schizophrenia per 1000 live births in the city of Helsinki. The study has several limitations: (1) We have no direct evidence that the subjects actually suffered a viral infection. (2) The psychiatric data were obtained only for subjects up to the age of 26 years, 56 days. (3) The findings are based on hospital diagnoses. (4) The determination of stage of gestation at time of exposure to the epidemic is based on date of birth. The viral infection might have occurred outside the official epidemic window; the infant may have had a preterm or postterm delivery. These sources of error, however, should not serve to enhance the findings. The observed viral effect is interpreted as being one of many potential perturbations of gestation. We suggest that it is less the type than the timing of the disturbance during fetal neural development that is critical in determining risk for schizophrenia.

Adult major affective disorder after prenatal exposure to an influenza epidemic.

BACKGROUND: We have previously reported an increase in schizophrenia diagnoses in a population exposed during the second trimester to the 1957 influenza epidemic. These basic findings together with a fair number of replications have been interpreted as supporting a neurodevelopmental contribution to the origins of schizophrenia. Recent neuroimaging findings suggest that affective illness may also have a neurodevelopmental origin. We examined the hypothesis that exposure to an influenza epidemic during the second trimester would increase the risk for adult major affective disorder. METHODS: The subjects had been exposed as fetuses to the type A2/Singapore influenza epidemic in greater Helsinki, Finland. Control subjects were born in the 6 years before the epidemic. RESULTS: We found a significant (P < .001) increase in the proportion of hospital diagnoses for major affective disorder for individuals exposed to the influenza epidemic during their second trimester of fetal development compared with control subjects (13% vs 2%). This second-trimester effect seems somewhat stronger in men (16% vs 2%) (P < .001), although the rates of major affective disorder in women (8% vs 3%) (P > .05) were similar. The second-trimester effect remained when we estimated population-based rates (2.1 vs 0.6 per 1000) (P < .05) of major affective disorder. Additional analyses revealed that the increase of major affective disorder among subjects in the index group who were exposed during the second trimester was due to a significant (P < .002) elevation of unipolar forms, although a similar though not significant (P > .05) elevation was observed for the bipolar forms of major affective disorder. CONCLUSIONS: These data are consistent with the hypothesis concerning the possible neurodevelopmental contribution to the origins of some forms of major affective disorder, especially unipolar depressive disorder. These encouraging findings, if replicated, may suggest that some mental disorders may stem, in part, from a disturbance in the development of the fetal brain during the second trimester.

Maternal smoking during pregnancy and adult male criminal outcomes.

BACKGROUND: Perinatal risk factors are related to persistent and violent criminal outcomes. Prenatal maternal smoking may represent an additional perinatal risk factor for adult criminal outcomes. Our study examines maternal smoking during pregnancy as a predictor of offspring crime in the context of a prospective, longitudinal design. METHODS: Subjects were a birth cohort of 4169 males born between September 1959 and December 1961 in Copenhagen, Denmark. During the third trimester of pregnancy, mothers self-reported the number of cigarettes smoked daily. When the male offspring were 34 years of age, their arrest histories were checked in the Danish National Criminal Register. Additional data were collected concerning maternal rejection, socioeconomic status, maternal age, pregnancy and delivery complications, use of drugs during pregnancy, paternal criminal history, and parental psychiatric hospitalization. RESULTS: Results indicate a dose-response relationship between amount of maternal prenatal smoking and arrests for nonviolent and violent crimes. Maternal prenatal smoking was particularly related to persistent criminal behavior rather than to arrests confined to adolescence. These relationships remained significant after potential demographic, parental, and perinatal risk confounds were controlled for. CONCLUSIONS: Maternal prenatal smoking predicts persistent criminal outcome in male offspring. This relationship has not been accounted for by related parental characteristics or perinatal problems. Potential physiologic or central nervous system mediators between maternal smoking during pregnancy and offspring criminal outcomes need further study.

High rates of violence, crime, academic problems, and behavioral problems in males with both early neuromotor deficits and unstable family environments.

BACKGROUND: It is commonly assumed that individuals with both biological and psychosocial deficits are more likely to become criminal, but there is surprisingly little empirical support for this assumption. We test the hypothesis that a group with biosocial risk factors are more likely to develop behavioral and academic problems in adolescence and violent criminal offending in adult-hood compared with groups with only biological or only social risk factors. METHODS: Hypotheses were tested on a sample of 397 male subjects, using obstetric and early neuromotor measures collected in the first year of life; family, social, demographic, and behavioral measures at age 17 to 19 years; and criminal data at 20 to 22 years of age. RESULTS: Cluster analysis of the risk factors indicated a group with obstetric risk factors only, a group with poverty risk factors only, and a biosocial group with both early neuromotor deficits and unstable family environments. The biosocial group had more than double the adult violence, theft, and total crime rates of the other 2 groups and had significantly more behavioral and academic problems in adolescence. CONCLUSIONS: When early neuromotor deficits and negative family factors cluster together, individuals are particularly likely to become criminal and violent compared with those with only poverty or only obstetric risk factors. Because this biosocial group accounted for 70.2% of all crimes committed in the entire sample, early interventions that tackle these deficits might significantly reduce violence.

Exposure to influenza epidemics during gestation and adult schizophrenia. A 40-year study.

We attempted to replicate earlier findings of an association between exposure to influenza in the second trimester of gestation and adult schizophrenia. The number of live births, of births of future schizophrenics, and of cases of influenza reported to the Ministry of Health in Denmark was ascertained by month from 1911 to 1950. The relationship between fetal exposure to influenza and adult schizophrenia was examined. It is possible that unknown factors produce excesses of both influenza and schizophrenia in the winter, creating an artifactual association. To control for this coincidence, the effects of season were removed from the monthly influenza and schizophrenic birth-rates by several methods. Using the residual scores, it was found that influenza rates higher than seasonally expected, occurring in the sixth month of gestation, were associated with rates of births of schizophrenics greater than seasonally expected. This association was not attributable to some winter-related, third factor or to climatic variables.

Developmental brain abnormalities in the offspring of schizophrenic mothers. II. Structural brain characteristics of schizophrenia and schizotypal personality disorder.

BACKGROUND: We examined differences in ventricular and sulcal cerebrospinal fluid-to-brain ratios as a function of lifetime psychiatric diagnosis in the offspring of schizophrenic mothers (high-risk sample) and in the offspring of normal parents (low-risk sample). METHODS: We used a cohort analytic study of 17 high-risk individuals with schizophrenia, 31 high-risk individuals with schizotypal personality disorder, 33 high-risk individuals with nonschizophrenia-spectrum psychiatric disorders, 45 high-risk individuals with no disorders, 31 low-risk individuals with psychiatric disorders of all types, and 46 low-risk individuals with no disorders, evaluated initially in 1962 when they were a mean age of 15 years, and reexamined from 1986 through 1989 with psychiatric interviews and computed tomographic scans of the brain. RESULTS: High-risk individuals with schizophrenia and schizotypal personality disorder evidenced an equivalent degree of cortical sulcal enlargement, and both groups evidenced significantly greater sulcal enlargement than did high-risk individuals with nonschizophrenia-spectrum disorders and no disorders and low-risk individuals with psychiatric disorders and no disorders. High-risk individuals with schizophrenia evidenced significantly greater ventricular enlargement than did high-risk and low-risk subjects with other disorders and no disorders, including those with schizotypal personality disorder. These differences were independent of age, gender, history of substance dependence, and history of organic brain syndromes and head injuries. CONCLUSIONS: Among the offspring of schizophrenic parents, cortical abnormalities are expressed equally across the range of syndromes in the schizophrenia spectrum. Subcortical abnormalities (ie, ventricular enlargement) are more pronounced in the more severe syndrome (ie, schizophrenia).

Developmental brain abnormalities in the offspring of schizophrenic mothers. I. Contributions of genetic and perinatal factors.

OBJECTIVE: We examined the contributions of genetic risk for schizophrenia and obstetric complications to brain morphological abnormalities in the offspring of schizophrenic and normal patents. METHODS: We used a cohort analytic study of 60, 72, and 25 individuals with neither, one, or two parents, respectively, who were affected with schizophrenia spectrum disorders, evaluated initially in 1962 when they were on average 15 years old, and reexamined from 1986 through 1989 with psychiatric interviews and computed tomographic scans of the brain. RESULTS: After controlling for the effects of age, gender, substance abuse, and history of organic brain syndromes and head injuries, there were significant stepwise, linear increases in cortical and ventricular cerebrospinal fluid-brain ratios with increasing level of genetic risk for schizophrenia. Genetic risk for schizophrenia also interacted with prospectively assessed birth complications in predicting selectively to enlargement of the ventricular system; ie, the effect of birth complications on ventricular enlargement was greater among those with two affected parents compared with those with one affected parent, and greater among those with one affected parent compared with those with normal parents. Perinatal exposure to ether anesthesia was associated with a generalized increase in brain abnormality, which varied in severity according to level of genetic risk for schizophrenia. CONCLUSIONS: The type and degree of brain abnormalities shown by adult offspring of schizophrenic and normal parents are strongly predicted by the independent and interacting influences of genetic risk for schizophrenia and obstetric complications. The findings further substantiate the hypothesis that structural brain abnormalities in schizophrenia are at least in part neurodevelopmental in origin.

Lifetime DSM-III-R diagnostic outcomes in the offspring of schizophrenic mothers. Results from the Copenhagen High-Risk Study.

OBJECTIVES: To perform a long-term prospective follow-up of children at high risk for schizophrenia to identify risk factors for the development of this disorder. DESIGN: Prospective follow-up population study of children of schizophrenic mothers and their matched controls from age 15 years to age 42 years, with multiple diagnostic assessments performed by senior clinicians using structured interviews blindly with respect to the group membership of the subject. PARTICIPANTS: Two hundred seven offspring of schizophrenic mothers and 104 control children without schizophrenic parents matched to the index group on age, sex, paternal socioeconomic status, urban/rural residence, and the amount of time spent during childhood in institutional rearing. MAIN OUTCOME MEASURE: The prevalence of the DSM-III-R disorders during the subjects lifetime. RESULTS: A significant aggregation of schizophrenia (16.2%) and other nonaffective, nonorganic psychosis (4.6%), and Cluster A personality disorders (21.3%) occurred among the offspring of schizophrenic mothers compared with the controls (1.9%, 0.9%, and 5%, respectively). No evidence of increased aggregation of (psychotic and nonpsychotic) affective disorders was noted among the offspring of schizophrenics. CONCLUSION: These results coincide with the results of other family studies in demonstrating a significant and specific familial aggregation of schizophrenia and nonpsychotic schizophrenia spectrum disorders among the biological relatives of schizophrenics.