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barrier by proinflammatory cytokines activating the and alcohol) than the general population, results
tryptophan‑kynurenine pathway, regulating serotonin of several population‑based studies indicate that
production together with NMDA and glutamate patients with schizophrenia have a lower risk of
receptor activity and may also indirectly affect prostate, colorectal cancers, and melanoma but a
dopamine regulation. [69] The increased inflammation higher risk of breast and lung cancer. The increased
in autoimmune diseases may also influence the brain risk for certain tumors could be associated with
through increased permeability of the blood‑CNS diverse and non mutually exclusive factors such as
barriers, making the brain vulnerable to immune drug side‑effects, unhealthy lifestyle, poor access to
components, such as cytokines and auto‑antibodies. health care and differences in socioeconomic status.
Furthermore, brain‑reactive antibodies can induce a On the other hand, the reduced risk of other types of
range of psychiatric and neurological symptoms, as cancer may be explained by genetic factors, such as
observed in association with antibody‑induced LE. [12] the increased expression of various candidate tumor
suppressor genes, or the decreased expression of
More controversial and less explored by the literature some oncogenes in genomic regions implicated in
is the association we found between AAD comorbidity, schizophrenia or BD susceptibility. [77,78] An alternative
generalized anxiety, and cyclothymic‑anxious explanation may be related to the possibility of
temperament. [61] This finding suggests a possible an increased immune reactivity in patients with
intriguing relationship between autoimmune‑mediated BD and/or other mental disorders. During the
[7]
inflammatory process, trait emotional reactivity, and process of carcinogenesis, in fact, naturally occurring
stress vulnerability. antibody responses to tumor antigens were found to
be associated with improved survival and protection
Although the link between stress and mood disorders against the spread of cancer. [79] In recent trials,
is well‑recognized, [70] there are no specific studies on cancer immunotherapy, clinically significant
examining the role of stress, immune dysregulation, antitumor responses were often associated with the
and autoimmunity in BD. Retrospective studies in induction of autoimmune toxicity. [80] This finding
autoimmune diseases have found that up to 80% of suggests that the same immune mechanisms that
patients report uncommon emotional stress before elicit autoimmunity may also contribute to the
disease onset, and it has been suggested that immune destruction of tumors.
[71]
system activation may vary across affective states
in BD patients. [72] In a more theoretical perspective, CONCLUSION
it is possible to hypothesize a “constitutional”
reinforcing loop between emotional/mood reactivity Neuroinflammation and peripheral immune
and autoimmune/allergic reactivity that characterizes dysregulation may play a role in the pathophysiology
the “usual” self of these individuals and influence the of severe mood and psychotic disorders. Recent research
entire span of their existence. on autoimmune disorders provides additional links
between systemic and CNS pathophysiology. This
[7]
Interestingly, in our sample, the lifetime prevalence involves a complex interaction between immune cells
of cancer and neoplastic diseases was very low, of the CNS and periphery resulting in cellular damage
involving less than 1% of the patients. Recent data through mechanisms involving excitotoxicity, oxidative
suggested an association between certain diagnosis stress, and mitochondrial dysfunction. These pathways
[7]
and a lower‑than‑expected probability (negative are possibly shared between comorbid medical disorders
comorbidity) of developing other disorders. [73] and severe mood and psychotic disorders and may
It has been recently suggested that the immune reflect common underlying vulnerabilities.
system and other regulatory systems, particularly,
the peripheral nervous system, convey signals Some of the strongest evidence for the potential of
from tumor cells to the brain that might play a autoimmunity and immune components to cause
part in tumor progression and metastases, through psychiatric symptoms comes from the identification of
sympathetic and parasympathetic nerves, and by the antibody‑induced LE, where psychiatric symptoms are
modulation of the hypothalamic‑pituitary‑adrenal often dominant in the initial and the remission phase of
axis and adrenal medulla activity. [74] The majority of the disorder in up to 70% of the cases, [12,34] and which
studies have focused on cancer and schizophrenia; [75] has been demonstrated to be treatable with immune
there are few data regarding patients with BD. [76] therapies. [81] The prevalently psychiatric presentation
Although individuals with Schizophrenia and BD of some of these autoimmune limbic encephalitis
are exposed to more environmental noxious agents often leads patients to early psychiatric evaluation.
that contribute to tumor development (e.g. tobacco For this reason, it is very important to increase the

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