Immunometabolic patterns in psychiatric disease

Abstract: Many forms of immune system dysregulation are linked to psychiatric disorders. This thesis examines specific types of immune dysregulation in broad cohorts with psychiatric disease. The first section focuses on adipokines and other immunometabolic biomarkers and their interaction with state vs. trait symptoms. Direct-acting autoantibodies are an increasingly recognized mechanism for causing psychosis and obsessive-compulsive disorder, but it is unclear how prevalent this patient group is. To identify which patients to investigate more extensively, superior methods are needed. Therefore, the second section addresses the value of clinical red flags in predicting elevated central nervous system (CNS) damage biomarkers and other CNS pathology.In paper I-III, a psychiatric cohort of young adults was examined for plasma immunometabolic biomarkers, depressive symptom severity, bulimia nervosa and neurotic traits. Psychiatric diagnoses were based on diagnostic interviews while depressive symptom severity was assessed with the self-rating version of the Montgomery-Åsberg Depression Rating Scale. Personality traits were evaluated using the Swedish universities Scales of Personality. Young adults with higher leptin levels self-reported more severe depressive symptoms (paper I) and leptin levels were independently linked to neuroticism (paper III). Neuroticism was also linked to other immunometabolic alterations. Women with bulimia nervosa had elevated plasma adiponectin levels that remained stable over time (paper II), suggesting long-term metabolic changes.In paper IV, a psychiatric patient cohort enriched for clinical signs of suspected autoimmune psychiatric disease was investigated for psychiatric symptoms, neurological findings and signs of CNS pathology in radiological, neurophysiological, blood and CSF analyses. In this cohort, 27% had CSF signs of CNS tissue damage and 21% had CSF signs of neuroinflammation or blood-brain barrier dysfunction. Six percent had known anti-neuronal autoantibodies in serum and 2% in CSF. CNS damage biomarkers in CSF were also linked to red flags and specific psychiatric features.In summary, the thesis confirms different patterns of immunometabolic biomarkers and associations with trait and state symptoms in a psychiatric patient cohort that may have important implications for the future health of young adults with psychiatric morbidity. The final study supports clinical red flags in previous guidelines, indicating that a more comprehensive inclusion of patients with diverse psychiatric symptoms (not restricted to purely psychosis) is necessary to find all psychiatric patients requiring further investigation for immune system involvement.