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

Abstract

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 relations of age and pubertal development with cortisol and daily stress in youth at clinical risk for psychosis

“…It has been proposed that the adverse effects of stress exposure on vulnerable individuals are partially mediated by the consequent increase in activation of the hypothalamic pituitary-adrenal (HPA) axis and elevated cortisol secretion (Walker et al, 2008). In addition, independent of stress, there is evidence that normal neuromaturational processes augment stress and cortisol levels during adolescence, and it has been suggested that these processes increase risk for onset of the prodrome to serious mental disorders, including psychosis (Trotman et al, 2013; Walker et al, 2008). Specifically, the risk for psychosis onset rises dramatically following age 13, and increases with each year of age through adolescence (de Girolamo et al, 2012; Thorup at al., 2007).…”

“…Also, independent of stress exposure, the normative rise in cortisol during adolescence may increase susceptibility to psychiatric disorders in vulnerable individuals (Quevedo et al, 2009; Sontag-Padilla et al, 2012). It has been suggested that increased HPA activation following the onset of puberty may increase susceptibility for a range of psychiatric syndromes, including psychosis (Trotman et al, 2013). …”

“…Some have proposed that the clinical expression of the prodrome to psychosis typically arises in adolescence because it is triggered by abnormalities in the timing and/or magnitude of postpubertal neuromaturational processes (Keshavan et al, 2014; Trotman et al, 2013). It is possible that, when compared to HCs, CHR adolescents manifest a more pronounced increase and/or an earlier onset of rising stress indices with the progression of puberty, and that this contributes to risk for psychosis.…”

Genetic Influences on Pubertal Development and Links to Behavior Problems

“…1 Pubertal hormones play a significant role in psychological change in adolescence: Extreme variations in the onset (timing) of pubertal development are linked to risks for depression and externalizing behavior problems (for reviews, see Ge and Natsuaki 2009; Graber 2013; Negriff and Susman 2011); attainment of midpubertal status appears to increase normative changes in risky behavior and to trigger psychopathology in vulnerable individuals (e.g., Gunnar et al 2009; Trotman et al 2013). These changes are hypothesized to reflect effects of social responses to youths’ changing bodies, and sex hormones and social experiences acting on the developing brain and stress systems.…”

Modeling pubertal timing and tempo and examining links to behavior problems.

“…There is a long-standing interest in psychological consequences of variations in pubertal development, particularly elevated risks of early maturation in girls for depression and externalizing behavior problems (e.g., delinquency, substance use, early sexual activity; for reviews, see Ge & Natsuaki, 2009; Graber, 2013; Negriff & Susman, 2011). Recent work has highlighted the role of puberty in normative adolescent development (e.g., increased risk taking), and in triggering psychopathology in vulnerable individuals; these changes are hypothesized to reflect effects of sex hormones and social experiences acting on the developing brain and stress systems (e.g., Gunnar, Wewerka, Frenn, Long, & Griggs, 2009; Trotman et al, 2013). …”