Immune Associated Mental Illnesses in Adolescents and Young Adults: Pathophysiological Role and Therapeutic Perspectives

There is an increasing recognition of the pathophysiological role of neuroinflammation and neuronal autoantibodies across neurological, paediatric and mental – in particular atypical mood and psychotic – illnesses. The leading example has been the clinicopathological profile associated with antibodies to the N-methyl-D-aspartate receptor (NMDAR), resulting in an acute or subacute encephalitis-like syndrome. While this was thought to be restricted to acute neurologic-like presentations with delirium, seizures and a malignant course, it has become increasingly clear that NMDAR antibodies (NMDAR-Abs) are associated with a much broader and often sub-acute clinical picture. Symptoms are transdiagnostic in type, and include psychotic phenomena, catatonia, mood disturbance as well as aggression. Psychosis is seen in 46% percent of the cases of NMDAR-Abs encephalitis-like syndromes, and over one quarter of the cases never developed psychotic symptoms. Although the better understanding of NMDAR-Abs encephalitis-like syndrome has led to more frequent autoantibody screening, current data indicate that focusing on psychosis alone is a too narrow approach. A more promising approach is to screen population-based groups who are likely to contain subjects with higher rates of the broad phenotype of interest (possible cases of immune associated mood and psychotic syndromes).

Meanwhile, a range of other neuronal autoantibodies have now been identified that mimic the clinical course first ascribed to NMDAR-Abs. These related conditions appear to be more likely to present with marked behavioral disturbance, and cognitive impairment, rather than frank neurological features such as seizures or delirium. Importantly, these other neuronal autoantibodies occur in association with either psychotic or mood syndromes, along with emotional instability, major depression, sleep disturbances, anxiety, and panic attacks. Besides neuronal autoantibodies, other CNS and systemic non-CNS autoantibodies have been found to be associated with psychiatric manifestations. Furthermore, also a more general immune dysregulation (including increased levels of circulating pro-inflammatory cytokines, granulocytes, and monocytes, and concomitant activation of microglia) can lead to psychiatric symptoms.

With regards to the developmental course, there has been increasing interest in the ways in which earlier antenatal or childhood infective or antigenic stimuli may predispose adolescents or young people to the acute or sub-acute onset of immune-associated mood or psychotic disorders. Broader immune screening in young people may also provide new evidence that other immune factors can trigger adolescent-onset of major mood or psychotic syndromes.

This Research Topic is intended to bridge the gap between the numerous publications that deal with the panoply of immune system responses in adolescents and young adults with mental health presentations and the urgent need to provide clinicians and carers with a more systematic approach to recognising and adequately capturing those immune system responses at the earliest illness stages.

The Research Topic welcomes work in all animal species, including humans, that contribute to (1) unraveling the pathophysiological role of neuroinflammation and autoantibodies in adolescents and young adults presenting with mental illnesses, and; (2) elucidating therapeutic perspectives of immune-associated mental health disorders. Articles focusing on screening, characterisation, treatment or special needs of children, adolescents, and young people presenting with immune associated mental illnesses are of special interest.