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T D Cannon

Publications and source records attributed to T D Cannon.

47 records · Page 3Linked to original sources
PubMed1994

Structural brain abnormalities as indicators of vulnerability to schizophrenia.

The literature on structural brain abnormalities in schizophrenia is examined to determine whether these abnormalities represent viable candidate markers of vulnerability to the disorder. A majority of studies agree in finding that schizophrenia patients as a group have significantly larger ventricles and smaller limbic brain structures than normal control subjects, but about 50 percent of patients fall within the range of control subjects on these measures. This result has been interpreted to suggest that structural abnormalities characterize only a subgroup of patients. However, given the substantial degree of normal variability in brain structure between families, the use of biologically unrelated individuals as controls is misleading. Studies that have compared schizophrenia patients with their unaffected first-degree relatives have found a much higher sensitivity rate for ventricular enlargement and reduced limbic volumes (i.e., 70%-100%). This high within-family sensitivity, together with evidence from meta-analytic reviews of a substantial relationship between ventricular enlargement and severity of illness, argues in favor of a continuous distribution of the brain pathology in schizophrenia and against a model in which the pathology characterizes only a subgroup of patients. The structural abnormalities observed in both younger and older patients have been found to be highly correlated with familial risk for schizophrenia and obstetric complications, suggesting that some part of the deviance may be present in the premorbid state and that it may reflect both genetic and environmental etiologic processes. The evidence for specificity of the deficits to schizophrenia is equivocal, but no study has yet compared the within-family sensitivities of morphological measures among the major psychiatric conditions. Additional studies using first-degree relatives and well-defined neuroanatomical measurements are needed to determine which brain regions have the highest sensitivities as indicators of schizophrenia in families.

Brain↗
PubMed1994

Clinical subtypes of schizophrenia: differences in brain and CSF volume.

OBJECTIVE: Investigations of the relation of clinical features of schizophrenia to neuroanatomic measures have produced inconclusive results. The purpose of this study was to examine measures of whole-brain volume in men and women and relate them to clinical subtypes of schizophrenia. METHOD: Magnetic resonance imaging measures of cranial, brain, and ventricular and sulcal CSF volume were examined in 81 patients with schizophrenia (50 men and 31 women), divided into subgroups based on their symptom profiles, and 81 demographically matched healthy comparison subjects. RESULTS: The men had higher cranial and brain volumes than the women. The patients had smaller cranial and brain volumes than the comparison subjects; they also had higher ventricular CSF volumes and thus higher ventricle-brain ratios (VBRs). Ratio elevations were larger for the female than for the male schizophrenic patients. The patients with predominantly negative symptoms of schizophrenia had higher VBRs and sulcal CSF-brains ratios than the comparison subjects, although the component volumes did not differ. The patients with predominantly Schneiderian symptoms had higher VBRs than the comparison subjects but showed reduced cranial and brain volumes. The paranoid patients had normal VBRs, reduced sulcal CSF-brain ratios, and lower cranial and sulcal CSF volumes. CONCLUSIONS: The results suggest two patterns of neuroanatomic whole-brain abnormalities that differ in severity according to the relative prominence of negative, Schneiderian, and paranoid symptoms. These patterns may reflect differential involvement of dysgenic and atrophic pathophysiological processes. Sex moderates abnormalities in the neuroanatomic features of schizophrenia.

Adolescent↗
PubMed1993

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.

Adolescent↗
PubMed1993

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.

Adolescent↗
PubMed1993

The schizophrenia high-risk project in Copenhagen: three decades of progress.

We describe the design, theoretical approach and major recent findings of a prospective longitudinal study of the offspring of schizophrenic mothers and controls, initiated in 1962 by Sarnoff Mednick and Fini Schulsinger in Copenhagen, Denmark. Over 90% of the original 207 high-risk and 104 low-risk subjects have been successfully followed up since the initial assessment. At the time of the most recent assessment (1989), the subjects averaged 42 years of age and were nearly completely through the risk period for developing schizophrenia. By relating the lifetime psychiatric diagnoses of the subjects back to information on their premorbid experiences and functioning, we have identified several precursors of schizophrenia. This paper reviews our recent findings concerning whether outcomes of schizophrenia that differ in the relative prominence of negative versus positive symptoms represent discrete longitudinal syndromes. Predominantly negative and predominantly positive symptom schizophrenia were found to follow different patterns of symptom development from adolescence through the adult course of illness and were predicted by different combinations of genetic and environmental influences. Taken together, the findings suggest that the pathological processes underlying these two forms of schizophrenia are 1) partly independent of each other, 2) at least partly active during the premorbid state and 3) to some degree stable in the adult course of illness.

Adolescent↗
PubMed1992

Third ventricle enlargement and lower heart rate levels in a high-risk sample.

Heart rate activity and computed tomographic measures of structural brain abnormalities were evaluated in 32 individuals with a genetic risk for schizophrenia (offspring of schizophrenic mothers). Heart rate activity was assessed in 1962 when the subjects were a mean age of 15.1 years. Diagnostic and computed tomography assessments were conducted in 1980. Compared to individuals with normal third ventricles, individuals with enlarged third ventricles evidenced significantly lower heart rate levels overall and significantly lower heart rate during rest and during the periods preceding conditioning and test for conditioning stimulus trials. These effects were independent of age, psychiatric diagnosis, and abnormalities in other brain regions. Difficulties in interpretation posed by the index of brain abnormality employed and by the 18-year time interval between the heart rate and computed tomography assessments are discussed. Together with prior evidence of a relationship between third ventricle enlargement and reduced electrodermal responsiveness in the same subjects, these findings provide a preliminary indication that enlargement of the third ventricle may involve damage to diencephalic structures involved in autonomic nervous system activity.

Adolescent↗
PubMed1990

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.

Adolescent↗
PubMed1989

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.

Adolescent↗
PubMed1989

Fetal neural development and schizophrenia.

The conference on Fetal Neural Development and Schizophrenia which was held in Washington, DC, May 31-June 1, 1988, focused on factors of possible etiological significance in fetal development. Schizophrenia researchers joined experts in brain imaging, neuropathological, and neurochemical changes in brain development and investigators of potential genetic and neurobehavioral causes of psychosis. The combined evidence suggested dysfunction in frontal and parieto-occipital neocortex, basal ganglia, hippocampus, and amygdala. Dopamine transmission was implicated both in basal ganglia deficits and in widespread neocortical disturbances. Viral infection, or excessive stress, during the second trimester of pregnancy, as well as obstetrical complications, minor physical anomalies, and brain defects, correlated positively with incidence of adult schizophrenia. Autonomic nonresponding, birth complications, and ventricular enlargement were found to be closely related to negative symptom schizophrenia in high-risk populations. A dual factor model of schizophrenia was suggested, where genetic and environmental influences combine to produce psychosis.

Brain↗
PubMedDate not supplied

Ventricular enlargement and premorbid deficits in school-occupational attainment in a high risk sample.

Using a subsample of subjects from the Copenhagen schizophrenia high-risk project, this study examined the relationship between ventricular enlargement and prospectively assessed deficits in premorbid school/occupational adjustment. Subjects with enlarged ventricles evidenced poorer premorbid school-occupational adjustment across three times of measurement spanning a period of 10 years. This effect was independent of the age and sex of the subjects and remained significant after controlling for psychiatric diagnosis. The results provide prospective evidence for an association between ventricular enlargement and poor premorbid history.

Achievement↗