Developmental mechanisms in the prodrome to psychosis

Abstract

Psychotic disorders continue to be among the most disabling and scientifically challenging of all mental illnesses. Accumulating research findings suggest that the etiologic processes underlying the development of these disorders are more complex than had previously been assumed. At the same time, this complexity has revealed a wider range of potential options for preventive intervention, both psychosocial and biological. In part, these opportunities result from our increased understanding of the dynamic and multifaceted nature of the neurodevelopmental mechanisms involved in the disease process, as well as the evidence that many of these entail processes that are malleable. In this article, we review the burgeoning research literature on the prodrome to psychosis, based on studies of individuals who meet clinical high risk criteria. This literature has examined a range of factors, including cognitive, genetic, psychosocial, and neurobiological. We then turn to a discussion of some contemporary models of the etiology of psychosis that emphasize the prodromal period. These models encompass the origins of vulnerability in fetal development, as well as postnatal stress, the immune response, and neuromaturational processes in adolescent brain development that appear to go awry during the prodrome to psychosis. Then, informed by these neurodevelopmental models of etiology, we turn to the application of new research paradigms that will address critical issues in future investigations. It is expected that these studies will play a major role in setting the stage for clinical trials aimed at preventive intervention.

HPA-axis function and grey matter volume reductions: imaging the diathesis-stress model in individuals at ultra-high risk of psychosis

“…Larger samples can be recruited through multicentre studies. 51 The significantly attenuated CAR observed in subjects who subsequently progressed to an established psychotic illness needs therefore to be considered with caution due to the small number of UHR subjects who transitioned. A greater severity of anxiety and depression symptoms in the UHR participants also needs to be acknowledged, especially considering that a blunted CAR is not a finding specific to psychosis.…”

The neural diathesis-stress model of schizophrenia revisited: An update on recent findings considering illness stage and neurobiological and methodological complexities

“…In particular, there are pronounced normative increases in cortisol secretion with the transition into adolescence (Shirtcliff et al, 2012, Holtzman et al, 2013. Further, in healthy subjects, basal cortisol secretion continues to increase with age through adolescence and young adulthood (Walker et al, 2013a). Thus HPA axis function is influenced not only by exogenous stressors, but also by endogenous developmental processes.…”

Early-Life Stress Affects Stress-Related Prefrontal Dopamine Activity in Healthy Adults, but Not in Individuals with Psychotic Disorder

“…Various lines of evidence suggest that psychosis is associated with critical alterations in central stress-regulatory mechanisms affecting neural and endocrine stress systems [ 8 – 10 ], and manifested through maladaptive affective and psychotic reactivity to stress [ 11 , 12 ]. Resilience to psychosis, on the other hand, appears to be promoted by advantageous neuroadaptive changes in the stress-modulatory network, through which early life stress likely exerts a hormetic effect on stress susceptibility later in life [ 13 ].…”