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Neurological diseases expose individuals to a higher risk of suicidal ideation and suicidal behavior, including completed suicides and suicide attempts. They also represent a paradigmatic arena to study the etiopathogenic mechanisms underlying suicidality because they are emblematic of the heterogeneity and complexity of mutual interrelationships characterizing this issue. On the one hand, neurological diseases imply strictly biological impairments that are postulated to be the basis of vulnerability to suicide or result in the need for treatments for which a suicidal risk has been hypothesized. On the other hand, they question some subjective experiences of neurological patients, up to near existential positions. Often, in fact, they are accompanied by severe hopelessness. The latter may originate in, particularly for the most severe neurological diseases, the absence of curative treatments, unpredictable disease progression that leads to acute relapses or chronicity, a decrease in autonomy or selfidentity, progressive social isolation, a sense of becoming useless, and perception of feeling stigmatized. This may ultimately cause a slip into experiencing an absurd condition. At the confluence of neurobiology and hopelessness, frequent psychiatric comorbidities may play a primary role. To conclude, neurological patients require special attention from clinicians in form of openly verbalizing and exploring the suicidal thematic, inquiring about protective and risk factors, and promptly initiating both a psychopharmacological treatment and, where possible, psychological support.

Neurotransmitters and hormones regulate major immune functions, including the selection of T helper (Th)1 or Th2 cytokine responses, related to cell-mediated and humoral immunity, respectively. A role of imbalance and dynamic switching of Th1/Th2 system has been proposed, with relative displacement of the immune reserve in relation to complex interaction between Th1/Th2 and neuro-hormonal balance fluctuations, in the pathogenesis of various chronic human diseases, probably also including psychiatric disorders. Components of the stress system such as norepinephrine (NE) and glucocorticoids appear to mediate a Th2 shift, while serotonin (5-HT) and melatonin might mediate a Th1 shift. Some antidepressants would occur affecting these systems, acting on neurotransmitter balance (especially the 5-HT/NE balance) and expression levels of receptor subtypes, which in turn affect cytokine production and relative Th1/Th2 balance. It could be therefore hypothesized that the antidepressant-related increase in NE tone enhances the Th2 response, while the decrease in NE tone or the increase in 5-HT tone enhances the Th1 response. However, the neurotransmitter and Th1/Th2 balance modulation could be relative, aiming to restore physiological levels a previous imbalance in receptor sensitivity and cytokine production. The considerations on neuro-immunomodulation could represent an additional aid in the study of pathophysiology of psychiatric disorders and in the choice of specific antidepressants in specific clusters of symptoms, especially in comorbidity with internal pathologies. Furthermore limited data, reviewed here, have shown the effectiveness of some antidepressants as pure immunomodulators. However, these considerations are tentative and require experimental confirmation or refutation by future studies.