Psychiatric manifestations of autoimmune encephalitis

A transcriptome-wide Mendelian randomization study in isolated human immune cells highlights risk genes involved in viral infections and potential drug repurposing opportunities for schizophrenia

“…Notably, MAD1L1 was associated with B cell lymphoma and mosaic variegated aneuploidy syndrome 7 with inflammation and tumour predisposition, both of which are characterized by immune dysfunction. Furthermore, IRF3 was associated with herpes simplex virus-1 (HSV-1)-induced encephalitis 45, 46 , which is characterized by acute inflammation in the brain and can present with psychotic symptoms 12, 47 . Not only does this indicate a clear link between IRF3 and inflammation, but it also hints at a mechanism by which IRF3 may contribute towards SCZ-related symptoms.…”

“…However, following initial infection, HSV-1 is capable of travelling afferently along sensory neurons from the skin into the brain and has been shown to specifically infect parts of the limbic system 61 . This results in central inflammation to maintain HSV-1 latency 62 and in extreme cases can cause encephalitis, which can present with psychotic symptoms 12, 47 . Thus, chronic low-grade or acute intermittent bouts of inflammation in response to infection within the limbic system, for example, may play a role in triggering or aggravating SCZ symptoms in some patients.…”

“…For example, some people with SCZ have abnormalities in the levels of circulating immune markers 8, 9 and autoantibodies 10 . People with SCZ also have an increased risk of comorbid immune-mediated diseases, particularly autoimmune diseases 11 ; while inflammation of the brain – or encephalitis – can often present with psychiatric symptoms such as psychosis 12 . Although the relationship between the immune system and SCZ is highly complex and likely confounded by several lifestyle factors (e.g., smoking) and medication effects (e.g., antipsychotics), findings from Mendelian randomization (MR) studies, which are robust to such confounds, suggest that several circulating immune markers may be causally associated with SCZ risk 13–15 .…”

Improving Early Recognition of Treatment‐Responsive Causes of Rapidly Progressive Dementia: The STAM3P Score

“…Importantly, AE mimics (eg, Creutzfeldt–Jakob disease, glioma) can present with these findings and should remain on the differential until excluded through further workup 7,37 . Mania may be observed at presentation in AE, especially in patients with anti‐NMDA‐receptor encephalitis; 43 however, the detection of mania in RPD should suggest a broader differential, including primary psychiatric disease (eg, bipolar affective disorder), toxicity associated with medications/substance use, and neurosyphilis 44 . Movement abnormalities are often seen in AE, including faciobrachial dystonic seizures in LGI1 antibody‐associated encephalitis, and choreoathetosis, catatonia, and orofacial dyskinesias in anti‐NMDA‐receptor encephalitis 8,24 .…”

A Near-Fatal Encounter with Acute Suicidal Behavior in Anti-N-methyl-D-aspartate Autoimmune Encephalitis

“…Despite its overall rarity, the cumulative incidence is approximately 3–12 per million person-years. AE is increasingly considered, particularly in patients with acute psychiatric symptoms or unusual progression of new-onset epilepsy, as it is potentially treatable with immunotherapy [ 1 , 2 , 3 ]. Patients with AE often exhibit unusual seizure frequencies or atypical polymorphic psychosis, highlighting the importance of neurologists considering the probable etiology of immune disorders.…”