Prefrontal mechanisms of comorbidity from a transdiagnostic and ontogenic perspective.

Accumulating behavioral and genetic research suggests that most forms of psychopathology share common genetic and neural vulnerabilities and are manifestations of a relatively few core underlying processes. These findings support the view that comorbidity mostly arises, not from true co-occurrence of distinct disorders, but from the behavioral expression of shared vulnerability processes across the life span. The purpose of this review is to examine the role of the prefrontal cortex (PFC) in the shared vulnerability mechanisms underlying the clinical phenomena of comorbidity from a transdiagnostic and ontogenic perspective. In adopting this perspective, we suggest complex transactions between neurobiologically rooted vulnerabilities inherent in PFC circuitry and environmental factors (e.g., parenting, peers, stress, and substance use) across development converge on three key PFC-mediated processes: executive functioning, emotion regulation, and reward processing. We propose that individual differences and impairments in these PFC-mediated functions provide intermediate mechanisms for transdiagnostic symptoms and underlie behavioral tendencies that evoke and interact with environmental risk factors to further potentiate vulnerability.

The development of psychotic disorders in adolescence: a potential role for hormones.

This article is part of a Special Issue "Puberty and Adolescence". The notion that adolescence is characterized by dramatic changes in behavior, and often by emotional upheaval, is widespread and longstanding in popular western culture. In recent decades, this notion has gained increasing support from empirical research showing that the peri- and post-pubertal developmental stages are associated with a significant rise in the rate of psychiatric symptoms and syndromes. As a result, interest in adolescent development has burgeoned among researchers focused on the origins of schizophrenia and other psychotic disorders. Two factors have fueled this trend: 1) increasing evidence from longitudinal research that adolescence is the modal period for the emergence of "prodromal" manifestations, or precursors of psychotic symptoms, and 2) the rapidly accumulating scientific findings on brain structural and functional changes occurring during adolescence and young adulthood. Further, gonadal and adrenal hormones are beginning to play a more prominent role in conceptualizations of adolescent brain development, as well as in the origins of psychiatric symptoms during this period (Walker and Bollini, 2002; Walker et al., 2008). In this paper, we begin by providing an overview of the nature and course of psychotic disorders during adolescence/young adulthood. We then turn to the role of hormones in modulating normal brain development, and the potential role they might play in the abnormal brain changes that characterize youth at clinical high-risk (CHR) for psychosis. The activational and organizational effects of hormones are explored, with a focus on how hormone-induced changes might be linked with neuropathological processes in the emergence of psychosis.

The prodrome and clinical risk for psychotic disorders.

The psychosis prodrome offers great promise for identifying neural mechanisms involved in psychotic disorders and offers an opportunity to implement empirical interventions to delay, and ultimately ameliorate, illness onset. This article summarizes the literature on individuals in the putatively prodromal phase of psychosis/deemed at clinical high risk (CHR) for psychosis onset. Standardized measurement and manifestation of the CHR syndromes are discussed, followed by empirical findings that highlight the psychological deficits and biological abnormalities seen in CHR syndromes and psychotic disorders. Current controversies surrounding the diagnosis of CHR syndromes and issues related to the treatment of CHR individuals are also presented.