PALS advocates a life course approach to the study of allostatis to advance our understanind of the pathways leading from risk to disease as part of the foundation for preventive interventions.  


Epidemiological studies have identified multiple risk factors for mental disorders. Risk factors are characteristics or exposures that increase the likelihood of psychopathology in affected individuals compared to the general population.  Risk factors may reside within the individual (e.g., genetics), within the social environment (e.g., family adversity), or within the physical environment (e.g., lead). Across diagnostic categories, key risk factors include low socioeconomic status, familial psychopathology, stressful life events or trauma, family dysfunction, and substance use.  For many of these factors, the timing of exposure plays an important role in determining their effect on the risk for disease1. It is implicitly understood that risk factors trigger or cause alterations in the function or structure of biological systems relevant to mental health.  The concept of “allostasis and allostatic load/overload”  has been proposed to describe the interplay over time between risk factors, biological systems, and mental health outcomes2.


Importantly, the allostatic load model has been most widely applied to depression3. It provides a useful integrative framework that enables a translational and a reverse translational approach to the specification of the pathways leading to depression onset, progression, and remission and the interactions among systemic as well as neural mediators. 


1Papachristou E, Frangou S, Reichenberg A. Expanding conceptual frameworks: life course risk modelling for mental disorders. Psychiatry Res. 2013;206(2-3):140-5.  2McEwen BS1, Stellar E. Stress and the individual. Mechanisms leading to disease. Arch Intern Med. 1993;153(18):2093-101. 3Rasgon NL, McEwen BS. Insulin resistance-a missing link no more. Mol Psychiatry. 2016;21(12):1648-1652.  

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