Approaches for adolescents with an affected family member with schizophrenia

Abstract

Prospective studies of adolescents at risk for schizophrenia (high-risk studies) can shed light on the possible premorbid precursors of schizophrenia. Recent studies have provided evidence of neurobehavioral, brain structural, physiologic, and neurochemical deficits in adolescent nonpsychotic high-risk relatives that may date back to childhood or earlier. These results are collectively providing a critical window into the inter-relationships between genetic predisposition, neurodevelopment, and premorbid indicators of risk in schizophrenia. Convergent approaches are inherently powerful in mutually informing each other in enriching the knowledge of the risk factors that predict the eventual onset of schizophrenia. Defining such reliable predictors of the onset of schizophrenia may provide us with the tools to better understand the etiology and pathophysiology of the illness, and may pave the way for innovative methods of treatment and possibly prevention. The authors review the relevant literature in this promising field of inquiry and summarize recent findings from high-risk studies.

Dysfunction and Dysconnection in Cortical–Striatal Networks during Sustained Attention: Genetic Risk for Schizophrenia or Bipolar Disorder and its Impact on Brain Network Function

“…As indicated previously, HGR constitute a unique risk group, distinct from prodromal or clinical high-risk samples ( 94 – 97 ). Studying HGR in the medication naïve state can provide interesting insights into the intersection of genetic risk and abnormal neurodevelopment ( 98 , 99 ). By focusing on a profile of cumulative genetic risk , rather than on individual genes , such approaches are important given the polygenic and non-specific genetic bases of psychiatric disorders ( 100 , 101 ).…”

Cortical surface characteristics among offspring of schizophrenia subjects

“…In majority of cases, it is proposed that the pathophysiological processes may begin much before the clinical manifestation, possibly in the prenatal life (Murray and Lewis 1987; Weinberger 1987). Examining the first-degree relatives of schizophrenia probands before the illness onset could potentially provide neurobiological data that may be relatively less affected by the clinical phenotype (Diwadkar et al 2004; Gottesman and Shields 1973; Gottesman 1991). Such data could prove valuable to identify reliable intermediate phenotypes because first degree relatives have approximately 10 times higher risk for developing schizophrenia compared to the general population.…”

Fronto-parietal hypo-activation during working memory independent of structural abnormalities: Conjoint fMRI and sMRI analyses in adolescent offspring of schizophrenia patients

“…Adolescent offspring of schizophrenia patients are at increased risk for schizophrenia and psychiatric disorders, and therefore provide an interesting and important group in whom to assess vulnerabilities in developmentally mediated brain dysfunction and structure (Diwadkar et al, 2004). Whereas documented conversion rates to psychosis are relatively low, the incidence of psychopathology (Keshavan et al, 2008), cognitive and affective impairments and in vivo imaging related abnormalities (Diwadkar et al, 2006; Keshavan et al, 2002a) is relatively high or significantly different from controls (with no immediate family history of the disorder).…”