Winter birth and biological family history in adopted schizophrenics.

To investigate relationships between birth season and biological family history in schizophrenia, this study used a sample of schizophrenics that had the advantages of (a) particularly thorough diagnostic assessments of schizophrenics' relatives, including information from direct interviews as well as chart reviews, and (b) schizophrenic probands who were adopted at early age, mitigating the usual confounding of genetic and postnatal environmental influences of the family. Adopted schizophrenics with no biological family history of schizophrenia-spectrum disorders were significantly more likely to be born in winter months than were either (a) their own biological relatives, including their sibs and half-sibs, (b) schizophrenics with a positive family history for schizophrenia-spectrum disorders, or (c) people in the general population. Family-history-positive schizophrenics and their schizophrenic relatives were, in turn, significantly less likely than their own non-schizophrenic biological relatives to be born in the winter; schizophrenics in these families tended to be born in the milder-weather seasons, particularly the spring and fall. Results suggest that environmental factors associated with winter birth may be etiologically important in schizophrenia, particularly for cases in which familial liability factors are weak. By contrast, a familial, probably genetic, liability factor may be especially important in schizophrenics born in mild weather.

Perinatal complications and abnormal proton metabolite concentrations in frontal cortex of adolescents seen on magnetic resonance spectroscopy.

OBJECTIVE: The relation of perinatal complications to metabolism of orbitofrontal cortex was studied in 12 normal adolescents aged 13 to 17 years. BACKGROUND: Perinatal complications are associated with both (a) behavioral signs of frontal lobe dysfunction and (b) increased risk for mood disorders and schizophrenia. Perinatal complications are not usually sufficient to produce these disorders, however, suggesting an etiologic model in which perinatal complications interact with a second, familial, liability factor. The present study tested a key prediction of this "two-factor" model, namely, that perinatal complications will be associated with physiologic signs of frontal dysfunction, even in persons who have no personal or family history of these psychiatric disorders. METHODS: Subjects were screened by structured interviews with the Kiddie Schedule for Affective Disorders and Schizophrenia and had no personal or family history of psychiatric disorder. Ratios of choline and N-acetyl aspartate to creatine in orbitofrontal cortex were measured using proton magnetic resonance spectroscopy. Perinatal complications were scored with the examiners blinded to magnetic resonance spectroscopy data, applying published scales to hospital records on subjects' gestations and births. RESULTS: Perinatal complications were significantly correlated with reduced concentrations of choline and N-acetyl aspartate. CONCLUSIONS: Our results complement earlier findings of significant relations between perinatal complications and signs of frontal lobe dysfunction, as well as elevated rates of these two types of variables in mood disorders and schizophrenia.

Eye-tracking dysfunction and birth-month weather in schizophrenia.

The prevalence of eye-tracking dysfunction (ETD) is significantly elevated in individuals with a diagnosis of schizophrenia and in their nonschizophrenic relatives, suggesting that ETD marks a familial (most likely genetic) risk factor for schizophrenia. Birth in a season with intemperate weather is also a widely reported risk factor for schizophrenia and is particularly marked for the subgroup with no family history of the disorder. This study examined how these two risk factors covaried in 78 patients with a Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev.; American Psychiatric Association, 1987) diagnosis of schizophrenia. Eye tracking and birth-month weather were independently assessed. As hypothesized, patients without ETD were significantly more likely to be born in months with intemperate weather (both hot and cold) than either patients with ETD or people in the general population. Etiologic factors associated with severe weather near birth may be important sources of nonfamilial schizophrenia.

Neurologic signs of cerebellar and cortical sensory dysfunction in schizophrenics and their relatives.

Previous research has found that both schizophrenics and their relatives have significantly elevated rates of clinical neurologic signs--including 'hard' signs screened to exclude artifacts. The present study examined whether hard signs that indicate relatively localized dysfunction in particular brain regions significantly distinguish schizophrenics and/or their non-schizophrenic relatives from psychiatrically normal controls and patients with other disorders. All patients were diagnosed with DSM-III or DSM-IIIR criteria, using information from structured interviews, supplemented by chart review and family informants. Subjects were administered clinical neurologic examinations by a neurologist blind to diagnosis. The proband sample, composed of 54 schizophrenic or schizoaffective subjects, had a significantly greater proportion of subjects with signs of cerebellar dysfunction than any of the comparison samples, which included: 44 control subjects, 24 patients with substance abuse, 37 patients with bipolar disorder, and 73 of the probands' non-schizophrenic parents and adult siblings. Proportions of both probands and their relatives with signs of dysfunction of sensory cortex were significantly higher than for other groups. Cerebellar and sensory cortical dysfunctions may distinguish different subgroups of schizophrenics and may tend to reflect, respectively, non-familial and familial neuropathological factors.

Pre- and perinatal complications and risk for bipolar disorder: a retrospective study.

BACKGROUND: Many studies have reported that obstetric complications are risk factors for schizophrenia, but few studies have examined whether complications increase risk for bipolar disorder. METHODS: Bipolar-disorder probands and their adult siblings were diagnosed using DSM-III-R criteria. Obstetrical data from maternal reports were scored, blind to diagnosis, applying published scales that take into account number and severity of complications. RESULTS: Obstetric complication scores were significantly worse in probands than siblings without mood disorders. LIMITATIONS: Probands had relatively severe symptoms; research using more heterogeneous samples is needed. CONCLUSION: Results suggest obstetric complications are etiologically significant in bipolar disorder.

Inverse relationship of perinatal complications and eye tracking dysfunction in relatives of patients with schizophrenia: evidence for a two-factor model.

OBJECTIVE: Because both smooth pursuit eye tracking dysfunction and obstetrical complications are significant risk factors for schizophrenia, the authors tested the predictions of a two-factor model of how eye tracking dysfunction and obstetrical complications covary in patients with schizophrenia, their siblings, and comparison subjects. METHOD: Psychiatric diagnoses, eye tracking dysfunction, and obstetrical complications noted in birth records were independently assessed in 18 patients with schizophrenia, 16 of their siblings without schizophrenia, and 49 comparison subjects with neither personal nor family histories of schizophrenia. RESULTS: As hypothesized, 1) the combination of eye tracking dysfunction and perinatal obstetrical complications discriminated patients with schizophrenia significantly from subjects without schizophrenia, including siblings of patients with schizophrenia, and 2) eye tracking dysfunction and perinatal obstetrical complications manifested a significant inverse association in the nonschizophrenic siblings of patients with schizophrenia. CONCLUSIONS: These results support a two-factor model in which obstetrical complications often interact with genetic liability, indicated by eye tracking dysfunction, to produce schizophrenia.

Thought disorder in schizophrenic and control adoptees and their relatives.

BACKGROUND: Previous research showed significantly elevated levels of thought disorder in the relatives of persons with schizophrenia, as well as in the persons with schizophrenia themselves. Comparisons of schizophrenic and control adoptees and their respective relatives provide a method for minimizing the confounding of genetic and environmental sources of familial resemblance and for elucidating whether the elevated levels of thought disorder in persons with schizophrenia and their relatives reflect the influence of shared genetic factors, shared environmental factors, or both. The present study provides the first such adoption-sample data on an operationally defined measure of thought disorder. METHODS: Speech samples elicited by standard interview questions from schizophrenic and control adoptees and their respective biological and adoptive relatives were tape-recorded. Verbatim transcripts of these speech samples were scored, while unaware of the personal or family diagnoses of the subjects, using the Thought Disorder Index (TDI). RESULTS: The mean TDI scores were significantly higher in schizophrenic than in control adoptees and in biological relatives of the schizophrenic adoptees than in the biological relatives of the control adoptees, whereas the respective groups of adoptive relatives did not differ significantly. The differences were most marked for the samples of biological sibs and half sibs, which were larger and more representative than the samples of parents. CONCLUSION: Results suggest that the elevated TDI scores in the relatives of persons with schizophrenia that have been found in other studies reflect the operation of genes increasing the liability for schizophrenia, rather than the rearing experiences that were shared in common with schizophrenic probands.

Season of birth and obstetrical complications in schizophrenics.

Many studies indicate that both obstetrical complications (OCs) and birth in winter or early spring are risk factors for schizophrenia, but few studies have examined how these risk factors covary in the same subjects. We assessed pre- and perinatal OCs, while blind to diagnosis, using medical data recorded at the time of subjects' births, in 29 probands with DSM-III schizophrenia or schizoaffective disorder and 39 of their unaffected adult sibs. Pre- and perinatal OCs were both significantly more common in probands than sibs. Schizophrenics not born during the winter or early spring had significantly more total and perinatal OCs than schizophrenics born in other months, but did not differ for prenatal OCs. Results indicate that OCs increase risk for schizophrenia, but also suggest the possibility that the impact of OCs on this risk may be affected by season of birth.

Mental illness in the biological and adoptive relatives of schizophrenic adoptees. Replication of the Copenhagen Study in the rest of Denmark.

BACKGROUND: Our previous investigation of the prevalence of mental illness among the biological and adoptive relatives of schizophrenic adoptees in Copenhagen, Denmark, showed a significant concentration of chronic schizophrenia (5.6%) and what Bleuler called "latent schizophrenia" (14.8%) in the biological relatives of chronic schizophrenic adoptees, indicating the operation of heritable factors in the liability for schizophrenic illness. METHODS: We now report the results of a replication of that study in the rest of Denmark (the "Provincial Sample"). RESULTS: In this sample, the corresponding prevalences were 4.7% and 8.2%. In the combined "National Sample" of adoptees with chronic schizophrenia, that disorder was found exclusively in their biological relatives and its prevalence overall was 10 times greater than that in the biological relatives of controls. CONCLUSIONS: This study and its confirmation of previous results in the Copenhagen Study speak for a syndrome that can be reliably recognized in which genetic factors play a significant etiologic role. These findings provide important and necessary support for the assumption often made in family studies: observed familial clustering in schizophrenia is an expression of shared genetic factors.

Independent diagnoses of adoptees and relatives as defined by DSM-III in the provincial and national samples of the Danish Adoption Study of Schizophrenia.

BACKGROUND: This report describes the independent application of DSM-III criteria to the adoptees and relatives in the Provincial sample of the Danish Adoption Study of Schizophrenia of Kety and colleagues. We report these results and combine them with those reported previously for the Copenhagen sample to form the National sample. METHODS: Personal interviews and institutional record summaries of adoptees and biological and adoptive relatives were "blindly" diagnosed using DSM-III criteria. "Schizophrenia spectrum" was a priori defined as schizophrenia; schizoaffective disorder, mainly schizophrenic subtype; and schizotypal and paranoid personality disorders. RESULTS AND CONCLUSION: In the Provincial sample, the prevalence of "spectrum" disorders was significantly greater in biological relatives of schizophrenia spectrum vs control adoptees. The results were also consistent with the genetic transmission of individual diagnoses within the spectrum. When combined into the National sample, the results provided strong evidence for (1) the genetic transmission of DSM-III schizophrenia; (2) a genetic relationship between DSM-III schizophrenia, mainly schizophrenic schizoaffective disorder, and schizotypal personality disorder; and (3) the absence of a significant genetic relationship between the schizophrenia spectrum and either psychotic nonspectrum disorders, major depression, or anxiety disorders. We found no evidence for the familial environment transmission of schizophrenia spectrum disorders. These results are consistent with the findings reported by Kety and coworkers from their diagnostic review.

Obstetrical complications and trail making deficits discriminate schizophrenics from unaffected siblings and controls.

Numerous studies have reported that both obstetrical complications (OCs) and deficits on the Trail Making Test show elevated prevalences in schizophrenics. Trail Making deficits have also been reported to be more common in schizophrenics' relatives than in controls, suggesting poor Trail Making performance may be a behavioral indicator of a familial risk factor for schizophrenia. Few studies, however, have investigated how these two variables co-vary in samples of schizophrenics and non-schizophrenics. In this study, DSM-III-R diagnoses, OCs noted in birth records, and Trail Making performance were independently assessed in 30 subjects: 9 schizophrenics, 8 of their non-schizophrenic siblings, and 13 comparison subjects with neither a personal nor a family history of schizophrenia. Results supported two key predictions of a two-factor etiologic model of schizophrenia: (a) the combination of perinatal OCs and poor Trail Making performance discriminated schizophrenics extremely well from non-schizophrenics, including their own non-schizophrenic sibs, and (b) perinatal OCs and Trail Making errors manifested a significant inverse association among schizophrenics' non-schizophrenic sibs, but not among other subjects.

Obstetrical complications in patients with bipolar disorder and their siblings.

Although indirect evidence suggests that obstetric complications are risk factors for bipolar disorder, few studies have directly addressed this question. Probands with bipolar disorder and their adult siblings were diagnosed according to DSM-III-R criteria by clinicians who had no knowledge of the subjects' obstetrical histories. Hospital records on gestations and births of 16 probands and 20 of their siblings without major mood disorders were scored for obstetric complications without knowledge of diagnosis. The assessment of obstetrical history was based on rating scales that have proved reliable and that reflect the number and severity of complications. Overall complication scores were significantly more severe in probands than siblings. Differences were most marked for perinatal complications.

Patterns of neuropsychological deficits that discriminate schizophrenic individuals from siblings and control subjects.

Previous research on persons with schizophrenia and their relatives suggests two independent etiologic factors may combine to produce schizophrenia, and these factors may be indexed respectively by independent neuropsychological tests. Two neurocognitive measures, the Trail Making and Wisconsin Card Sorting (WCST) tests, were administered to 28 schizophrenic subjects, 15 nonschizophrenic siblings, and 35 control subjects by investigators blind to DSM-III-R diagnoses. Results support key predictions of a two-factor model: 1) having poor scores on both tests discriminated schizophrenic individuals from both siblings and control subjects, and 2) poor Trail Making and WCST performance were inversely associated among schizophrenic individuals' non-schizophrenic siblings.

The therapist as muse: greater roles for clinicians in fostering innovation.

Recent research on psychological and social factors that facilitate creativity indicates that clinicians can play important roles in fostering innovations crucial for national economic and social well-being. New research evidence indicates that individuals who carry increased liability for certain psychiatric illnesses, such as bipolar disorder (and possibly other disorders such as schizophrenia, as well) may tend to have unusual potential for creative accomplishment--particularly if they do not themselves have severe symptoms. Clinicians' professional skills give them special opportunities to nurture unusual creative potential in such individuals by using various approaches, ranging from more sensitive use of medication to creating special occupational niches in which unusually talented but psychologically vulnerable individuals can flourish. Clinicians are also needed to catalyze interdisciplinary reforms of occupational and educational institutions to remove authoritarian and harshly competitive conditions that discourage creativity and replace them with new social settings that actively foster innovation. Therapists, therefore, have important cultural roles to play in fostering creativity, not only through traditional professional roles, such as treating patients referred to them, but also through more "practice" ones, such as matching individuals with creative temperaments to optimal social settings, or inventing new social organizations. To fill these roles properly, therapists will themselves have to become more innovative in recasting their own professional identifies and responsibilities.

Neurologic signs in patients with paranoid and nonparanoid schizophrenia.

Previous research found that both persons with schizophrenia and their unaffected relatives had significantly more neurologic signs than normal controls. As hypothesized, in this study neurologic signs were significantly greater in patients with nonparanoid than paranoid schizophrenia; the difference was greatest for "hard" signs.

Hard neurologic signs and psychopathology in relatives of schizophrenic patients.

Previous research found more hard neurologic signs (i.e., signs that have localizing significance and exclude likely artifacts) in the nonschizophrenic relatives of schizophrenic patients than in control subjects, and in the psychiatrically normal relatives of schizophrenic patients compared with their ill relatives. Using interview-based DSM-III-R diagnoses and standard clinical neurological examinations on new samples, we found a trend to more hard signs in the 52 nonschizophrenic relatives of schizophrenic patients than in 20 control subjects, and significantly more signs in psychiatrically normal relatives than in ill ones. When pooled with previous data, signs were significantly higher in (1) relatives vs. controls and (2) normal vs. ill relatives, suggesting neurologic signs reflect an etiologic factor that often runs in families of schizophrenic patients.

Neurological "hard" signs and family history of psychosis in schizophrenia.

Previous research found schizophrenics to have significantly more neurological signs than normal controls, even when signs were screened to exclude possible artifacts, and limited to "hard" signs of localizing significance. Schizophrenics with a family history of psychosis also tended to have more neurological signs than those without such a history. The present study examined whether these findings could be confirmed in new samples of schizophrenics and controls, using interview-based DSM-III and DSM-III-R diagnoses. Schizophrenics had significantly more hard signs than controls, and schizophrenics with a family history for psychosis again had more signs than those without this history. When present study data were analyzed alone, as well as when pooled with data from previous research using similar methods, hard signs were significantly greater in both (a) schizophrenics versus controls and (b) schizophrenics with versus without a family history of psychosis, supporting the hypothesis that neurological signs reflect a significant etiologic factor in schizophrenia.