NEUROPSICOBIOLOGIA DEI DISTURBI DELL’UMORE: CONNESSIONI TRA PROCESSI AFFETTIVI E VIE MOLECOLARI

Background: Bipolar Disorder (BD) and Major Depressive Disorder (MDD) are chronic, recurrent mood disorders marked by clinical and biological heterogeneity, diagnostic uncertainty, and progressive neurobiological impairment. Contemporary research highlights their systemic nature, where mood dysregulation arises from interconnected processes involving mitochondrial dysfunction, immune imbalance, and altered neuroplasticity. Methods: A multimodal design was implemented to assess three biological domains: Systemic inflammation, quantified using composite indices (NLR, SIRI, AISI, SII); Neurotrophic activity, measured by plasma levels of Brain-Derived Neurotrophic Factor (BDNF); Mitochondrial function, evaluated through circulating Humanin and MOTS-c peptides. Results: Patients exhibited a marked elevation in inflammatory indices relative to controls, together with decreased MOTS-c concentrations and a phase-dependent modulation of BDNF (decreased in MDD, increased in BD). Multivariate modeling identified a mitochondrial–inflammatory axis as the major biological discriminator between affective subtypes. Conclusions: The findings support a system-level model in which chronic low-grade inflammation drives mitochondrial impairment and oxidative stress, ultimately disrupting neurotrophic signaling. This integrated biological framework underlies neuronal vulnerability and neuroprogression in mood disorders. The proposed multimodal strategy—combining inflammatory, mitochondrial, and neurotrophic markers—offers a promising pathway toward peripheral biosignatures capable of improving differential diagnosis, monitoring treatment response, and advancing precision psychiatry. Keywords: Mood disorders; Bipolar disorder; Mitochondrial dysfunction; BDNF; MOTS-c; Humanin; Systemic inflammation; Precision psychiatry.