{Reference Type}: Journal Article {Title}: Minor physical anomalies in schizophrenia and first-degree relatives in comparison to healthy controls: A systematic review and meta-analysis. {Author}: Sut E;Akgül Ö;Bora E; {Journal}: Eur Neuropsychopharmacol {Volume}: 86 {Issue}: 0 {Year}: 2024 Jun 28 {Factor}: 5.415 {DOI}: 10.1016/j.euroneuro.2024.05.007 {Abstract}: Minor physical anomalies (MPAs) are anatomical variations that are markers of aberrant early neurodevelopment. Schizophrenia is associated with increased MPA frequency, however, the frequency and distribution of MPAs exhibit substantial heterogeneity in schizophrenia and are not exclusive to this disorder. MPAs at different localizations might represent different developmental origins and might be related to latent genetic predisposition or vulnerability to develop full-blown psychosis. Therefore, we conducted a thorough review of minor physical anomalies (MPAs) in schizophrenia (Sch) and first-degree relatives (SchRel). Analyzing 52 studies published from January 1980 to October 2023, the meta-analysis compared MPA scores between 3780 schizophrenia patients and 3871 controls, as well as 1415 SchRel and 1569 controls. The total MPA score was significantly increased in schizophrenia compared to controls (g = 0.78 [0.63-0.93], p<0.001). In regional MPA meta-analyses, effect sizes ranged from 0.56 to 0.78. The difference between SchRel and controls was moderate (g = 0.44 [0.28-0.61], p<0.001). When individual MPA items were analyzed separately, fine electric hair, malformed ear, asymmetrical ear, curved 5th finger were anomalies that were shared between both schizophrenia and SchRel. Also, direct comparisons of the frequency of MPAs in schizophrenia and their relatives were conducted. Additionally, the early age of onset of schizophrenia was associated with mouth anomalies (Z=-2.13, p = 0.03), and ear anomalies were associated with a higher percentage of males in the schizophrenia group (Z = 2.64, p = 0.008). These findings support the notion that different MPAs might be associated with genetic susceptibility as well as vulnerability to developing full-blown psychosis. Studies investigating clinical and neurobiological correlates of MPAs in schizophrenia might be helpful in characterizing subtypes of psychoses that are associated with different developmental processes.