THE INTERPLAY BETWEEN BRAIN NEUROTRANSMITTERS AND OPIOID SYSTEMS IN MAJOR DEPRESSION (MD) AND COMORBID MD AND GENERALIZED ANXIETY
Authors: Trofimova *Irina N 
Published: February 2025

Abstract

Background
Mu-opioid receptors (MOR) are known to have entangled regulation with dopamine and serotonin. The roles of brain neurotransmitters (NT) and and opioid receptor (OR) systems in the regulation of specific dynamical properties of behaviour were earlier summarised within the 12 components of the neurochemical framework Functional Ensemble of Temperament (FET). The FET framework allows having a neurochemistry-based structure of a taxonomy that can classify both, healthy bio-psychological traits and symptoms of psychopathology, with depression taken as an example for this study.
Aims and objectives of this study were to investigate the predictions of the FET framework regarding the correspondence between the FET components and the Major Depression (MD) symptoms and comorbid MD and Generalized Anxiety (GAD) symptoms.

Method
FET-structured temperament profiles of patients and clients of private practice were collected for four groups: MD, GAD, comorbid MD-GAD and control (no mental illness), matched by age and sex.

Results
The FET- structured profiles showed a good convergence with the classic criteria of MD and GAD and showed a good differentiating power for the comorbid MD-GAD. Each symptom was presented in the framework of the interaction between the NT and OR and analysed in terms of differentiation between the symptoms recorded in four studied groups.

Discussion & Conclusion
Multi-systems neurochemical interaction of studied disorders is presented in the FET in terms of differentiation between the universal aspects of behaviour, such as orientation, integration and energetic maintenance analysed separately for physical, social and mental aspects of activity, plus three emotionality-related aspects. Each of 12 FET aspects is linked to a specific NT-OR team. Our results confirmed the expectations of the FET that MD is a result of a compromised serotonin-MOR interaction with dopamine, not affecting orientational aspects of behaviour but having a negative impact on energetic maintenance and integration of actions, as well as influencing dispositional moods. In contrast to MD, GAD involves more kappa-opioid and noradrenalinergic systems, inducing loss of focus, agitation and chronic anxiety but not necessarily a low dispositional mood, fatigue or lack of interest, as in MD. Finally, comorbid MD-GAD is the most serious condition out of three studied diagnoses, negatively impacting the cortical functioning, including probabilistic processing of environmental information (that involves brain acetylcholine, kappa-opioid receptors and glutaminergic systems). Structuring the contributions of multiple neurochemical systems in major diagnoses in line with the functional constructivism approach employed in the FET is a step forward to a systematic linking of these neurochemical biomarkers to specific consistent behavioural patterns, including symptoms of psychopathology.

References
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