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irritability, apathy or changes in behavior including as in mood and psychotic disorders. In addition, in
agitation/restlessness alternating with episodes of autoimmune diseases, the mechanisms of control may
somnolence. temporarily restore the antigenic tolerance, leading to
a cyclical pattern of exacerbation and remission of the
A case of anti‑NMDAR encephalitis mimicking disease. These general pathophysiological mechanisms
bipolar disorder has been described. [52] More of autoimmunity lead to common clinical features,
recently Steiner et al. [53] examined patients with including familial occurrence, progression from
schizophrenia (n = 121), major depressive disorder subclinical to the clinical level of the symptomatology,
(n = 70), and borderline personality disorder (n = 38) and the exacerbation‑remission periodic course.
and found that 9.9% of the patients diagnosed with Interestingly, both affective and nonaffective psychosis
schizophrenia had NMDAR‑R antibodies in their serum have been definitively shown to possess all these
compared with 2.8% of the depressed patients and 0% clinical features.
of the borderline personality disorder. Interestingly,
[61]
patients with schizophrenia, who were seropositive, had In a recent study by our group, on a clinical sample of
immunoglobulin G antibodies not only directed against 347 BD patients, we found a very high prevalence (48.1%)
the NR1a subunit of the NMDAR but also against the of AAD. The result is particularly interesting for two
NR1a/NR2b subunit again raising the question about the reasons: first, for the disproportion with the prevalence
level of involvement the immune system might have in observed in the general population (in our country the
the pathogenesis of some forms of psychotic disorders. estimated prevalence in general population is about
3.2% for autoimmune diseases and about 20‑30%
Perceptual disturbances are also common, including for allergic conditions); [62,63] second, for the lack of a
misinterpretations, illusions or hallucinations (visual difference in gender distribution, because AAD are
and auditory) and delusions (often pertaining to usually more represented in women.
hallucinations). During the unresponsive phase,
patients have been referred to as catatonic with The association between AAD and BD has rarely been
features involving purposeless motor activity, extreme systematically investigated in clinical samples. An
negativism, bizarre posturing, grimacing, mutism, increased prevalence of mood symptoms has been
echolalia, and echopraxia. found in a variety of inflammatory conditions, including
auto‑immune diseases, cardiovascular diseases,
It has been hypothesized that in a proportion of diabetes, obesity, and metabolic syndrome, as well as in
patients diagnosed as bipolar or psychotic disorders, more benign inflammatory conditions such as asthma
autoantibodies may be present during an earlier and allergies. [64] A large Danish cohort study showed
developmental period resulting in a gradual and chronic that a history of Guillain‑Barre syndrome, Crohn’s
exposure to NMDA‑R hypofunction. [54] Because of the disease, and autoimmune hepatitis was associated
similarities in symptom presentation, the possible role with raised risk of BD. [56] The authors concluded
of autoimmunity in bipolar‑ and psychotic‑spectrum that autoimmune processes precede the onset of BD.
disorders seems to represent a promising direction for A subsequent study, based on Danish hospital data,
future research. reported that a broad range of autoimmune diseases and
infections requiring hospitalization increase the risk of
AUTOIMMUNE DISEASES AND PSYCHOTIC AND developing schizophrenia and mood disorders. [65] The
NON PSYCHOTIC MOOD DISORDERS observed associations support a possible immunological
contribution in subgroups of patients with severe
Many evidences suggest a role of inflammatory mediators mental disorders, such as bipolar and other psychotic
and immune dysregulations in the pathogenesis of disorders. However, whether it is a causal relationship
psychiatric disorders such as BD, [7,55,56] schizophrenia, or an epiphenomenon due to other environmental
[8]
depression, [57] and Alzheimer’s disease. [58] factors or common genetic vulnerability remains to
be clarified and deserve further research. Genetically
Autoimmune diseases, as well as BD and schizophrenia, vulnerable individuals might be at a particular risk
are multifactorial disorders related to an interaction of developing mood disorders as a consequence of
between gene and environment. A familial occurrence autoimmune reactions and inflammation affecting
[59]
is commonly found. [60] Moreover, autoimmune the brain.
reactions often advance much more slowly than
immune reactions to pathogens, suggesting that control Inflammatory mechanisms can affect the brain through
mechanisms can continue to work until a threshold many different pathways that are not necessarily
has been exceeded leading to a progression from mutually exclusive. [66‑68] Peripheral inflammation
subclinical to clinically significant symptomatology can affect the brain without passing the blood‑CNS

232 Neuroimmunol Neuroinflammation | Volume 2 | Issue 4 | October 15, 2015