Does Anhedonia Presage Increased Risk of Posttraumatic Stress Disorder?

Abstract

Anhedonia, the reduced ability to experience pleasure, is a dimensional entity linked to multiple neuropsychiatric disorders, where it is associated with diminished treatment response, reduced global function, and increased suicidality. It has been suggested that anhedonia and the related disruption in reward processing may be critical precursors to development of psychiatric symptoms later in life. Here, we examine cross-species evidence supporting the hypothesis that early life experiences modulate development of reward processing, which if disrupted, result in anhedonia. Importantly, we find that anhedonia may confer risk for later neuropsychiatric disorders, especially posttraumatic stress disorder (PTSD). Whereas childhood trauma has long been associated with increased anhedonia and increased subsequent risk for trauma-related disorders in adulthood, here we focus on an additional novel, emerging direct contributor to anhedonia in rodents and humans: fragmented, chaotic environmental signals ("FRAG") during critical periods of development. In rodents, recent data suggest that adolescent anhedonia may derive from aberrant pleasure/reward circuit maturation. In humans, recent longitudinal studies support that FRAG is associated with increased anhedonia in adolescence. Both human and rodent FRAG exposure also leads to aberrant hippocampal function. Prospective studies are underway to examine if anhedonia is also a marker of PTSD risk. These preliminary cross-species studies provide a critical construct for future examination of the etiology of trauma-related symptoms in adults and for and development of prophylactic and therapeutic interventions. In addition, longitudinal studies of reward circuit development with and without FRAG will be critical to test the mechanistic hypothesis that early life FRAG modifies reward circuitry with subsequent consequences for adolescent-emergent anhedonia and contributes to risk and resilience to trauma and stress in adulthood.

Rethinking Concepts and Categories for Understanding the Neurodevelopmental Effects of Childhood Adversity

“…There is growing recognition that critical features of the early environment such as predictability and contingent responding of caregivers (or, alternatively, chaos and lack of stability) have an important role in shaping young children’s experience and development (Glynn & Baram, 2019; Risbrough et al, 2018; Wismer Fries & Pollak, 2017). Predictability refers to the degree to which accurate predictions can be made about future events on the basis of current ones.…”

“…Evidence from nonhuman animals also indicates that parental responsivity and sensitivity plays an important role in shaping learning processes, particularly social learning (Baram et al, 2012; Risbrough et al, 2018; Zajac, Raby, & Dozier, 2019). For example, monkeys reared in isolation demonstrate disruptions in social and reward learning (F.…”

Influences of early‐life stress on frontolimbic circuitry: Harnessing a dimensional approach to elucidate the effects of heterogeneity in stress exposure

“…Rodents exposed to unpredictable care show greater c‐Fos expression in the basolateral amygdala, relative to animals raised in typical conditions (Malter Cohen et al, 2013). Altered frontolimbic interactions also appear to underlie anhedonia following unpredictable care (Bolton, Molet, et al, 2018; Bolton, Ruiz, et al, 2018; Molet et al, 2016; Risbrough et al, 2018). Among rodents previously exposed to unpredictable care, social play is associated with increased corticotropin‐releasing hormone expression in the amygdala and increased structural connectivity between the amygdala and mPFC (Bolton, Molet, et al, 2018).…”

The Developmental Origins of Opioid Use Disorder and Its Comorbidities

“…Many of these are common across several mental illnesses and may share common biological substrates. Anhedonia defined broadly as an inability to experience pleasure is a feature of substance use disorder in some individuals (Ahmed and Koob, 1998;Koob and Moal, 2001;Janiri et al, 2005;Hatzigiakoumis et al, 2011;Sussman and Leventhal, 2014;Kiluk et al, 2019;Brenner et al, 2020) and of other psychiatric diagnoses that are comorbid with addiction (Gorwood, 2008), such as depression (Loas, 1996;Blanchard et al, 2001;Pizzagalli et al, 2008;Martinotti et al, 2012), schizophrenia and psychosis (Andreasen and Olsen, 1982;Blanchard et al, 2001;Martinotti et al, 2012), PTSD (Risbrough et al, 2018), eating disorders (Davis and Woodside, 2002;Halmi, 2009), and other ''high-risk'' behaviors (Franken et al, 2006).…”