“The mission of the Clinical Neuroscience Lab and Affiliated Research Centers is to improve the quality of life for individuals at risk for, and those suffering from, thought disorders such as schizophrenia and bipolar disorder, by discovering and sharing knowledge to advance prevention strategies and treatment methods. We pursue this mission through innovative, responsible research; excellence in patient care; educating students, mental health professionals, families, clients, and our community; and bridging the gap between research and clinical practice.”

The primary aims of the CNS Lab are to discover the causes of schizophrenia and to develop effective treatment and prevention strategies based on an understanding of the genetic and neural mechanisms that give rise to the disorder. Family, twin, and adoption studies have demonstrated that schizophrenia is substantially heritable, but the genetic basis of schizophrenia is complex, involving many different genes and probably also interactions between particular genes and particular kinds of environmental factors. Unfortunately, despite suggestive evidence from genetic linkage studies of a number of different chromosomal regions that are likely to harbor susceptibility genes for schizophrenia, thus far we have not been able to identify any specific gene that participates in causing this illness. Progress on this front has been hindered in part by the fact that genes predisposing to schizophrenia may be present in some family members who do not manifest the disorder phenotypically. Our strategy has focused on elucidating the consequences of genetic predisposition to schizophrenia in the nervous system, consequences that would be expected to appear (to some degree) in unaffected carriers of the predisposing genes. These neural traits can then be used as phenotypic indicators in linkage studies, greatly improving the precision and sensitivity of genetic linkage analyses in identifying particular susceptibility genes. Our search for the neural consequences of genetic predisposition to schizophrenia has focussed on structures in the frontal and temporal lobes as well as in subcortical areas, and the interconnections between these cortical and subcortical areas, since deficits in these systems are relatively prominent against a background of generalized cerebral dysfunction in schizophrenic patients, and since individuals with acquired lesions in these areas show many of the symptoms characteristic of schizophrenia. We have conducted a number of studies of offspring, siblings, and co-twins of schizophrenic patients. These studies have demonstrated that abnormalities in the frontal region of the brain are present in schizophrenic patients as well as some of their non-schizophrenic relatives, varying in a dose-dependent fashion with degree of genetic loading, while other deficits (i.e., subcortical and temporal lobe changes) are specific to those who manifest the clinical phenotype and are predicted primarily by non-genetic etiologic influences (i.e., obstetric complications associated with fetal oxygen deprivation). These findings suggest that different neural circuits are most affected by genetic and non-genetic sources of liability and provide an indication of the configuration of neural system deficits that might be necessary for symptom expression.

Work currently in progress includes:

a) a multi-modal brain-imaging study (assessing regional cerebral blood flow, electrical activity, and neuroreceptor distribution) of schizophrenic patients, their unaffected monozygotic and dizygotic co-twins, and normal comparison twins, aimed at further specifying the neural disturbances inherited in association with schizophrenia;

b) collaborative genetic linkage studies in families with a high density of schizophrenia to isolate genes that confer susceptibility to the neural system dysfunctions associated with the disorder;

c) brain-imaging studies of schizophrenic patients at first admission and later follow-up, aimed at identifying neural changes associated with symptom relief following anti-psychotic medication treatment;

d) prospective, longitudinal studies of birth cohorts and high-risk samples aimed at elucidating the roles of genetic and non-genetic factors in the etiology of schizophrenia and developing strategies for primary prevention.