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Multisystem stress response biotypes: a precision psychiatry approach to identifying and treating multidimensional risk factors for anhedonia in adolescence

Neuropsychopharmacology (2024)Cite this article

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Developmental changes in neurobiological and psychological systems render adolescence a vulnerable period for the emergence of risk factors associated with psychopathology. Anhedonia (i.e., the reduced ability to anticipate or experience pleasure) is a core characteristic of multiple psychopathologies that increase during adolescence. Aberrant stress responsivity and recovery across multiple physiological systems may contribute to anhedonia [1], however current research is limited in its focus on singular biological systems (i.e., neural or physiological). Examining the additive and interactive activity across multiple systems offers a more nuanced approach, which may uncover individualized treatments for anhedonia (i.e., “precision psychiatry”).

Evidence implicates disruptions of fronto-striatal and fronto-limbic circuits that are involved in the anticipation, expectation, and consumption of pleasurable experiences. Prefrontal cortical regions and their connectivity, which mature through adolescence, are involved in executive functioning, decision-making, and impulse control. An immature prefrontal cortex can impair the ability to regulate emotions and stress responses. The limbic system, including the amygdala and the hippocampus, also becomes more reactive to stress during adolescence. Disruptions in the maturation of neural circuits can contribute to aberrant stress responses and long-term risk for anhedonia.

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Fig. 1: Conceptual Model of Multisystem Stress Response Biotypes: acute stress activates neural and physiological systems critical for the onset and regulation of adaptive stress responses.

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Funding

AB is supported by NIMH R01DA048627; NICHD P50HD13573; NIMH U01MH124639; NIDA R01DA057312; FOH Seed Grant. DR is supported by Brain and Behavior Foundation (grant number 24820) and K23MH113709.

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  1. Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA

    Danielle S. Roubinov & Aysenil Belger

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  1. Danielle S. Roubinov
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  2. Aysenil Belger
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AB and DR wrote the manuscript and prepared the figure.

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Correspondence to Danielle S. Roubinov or Aysenil Belger.

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The authors declare no competing interests.

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Roubinov, D.S., Belger, A. Multisystem stress response biotypes: a precision psychiatry approach to identifying and treating multidimensional risk factors for anhedonia in adolescence. Neuropsychopharmacol. (2024). https://doi.org/10.1038/s41386-024-01953-9

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  • DOI: https://doi.org/10.1038/s41386-024-01953-9

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