A trend toward smaller optical angles and medial‐ocular distance in schizophrenia spectrum, but not in bipolar and major depressive disorders

Abstract

Minor physical anomalies (MPAs) are subtle signs of fetal developmental abnormalities that have been considered to be among the most replicated risk markers for schizophrenia-spectrum disorders. However, quantitative approaches are needed to measure craniofacial MPAs. The present study adopted an imaging-based quantitative approach to examine craniofacial MPAs across the spectrum of schizophrenia and affective disorders, to address their sensitivity and specificity. We sampled 31 patients with schizophrenia, 30 of their unaffected relatives, and 30 individuals with schizotypal personality traits, as well as 37 non-schizotypal controls. We also examined 17 patients with bipolar disorder and 19 patients with major depressive disorder. Five craniofacial MPAs were measured on anterior-posterior commissure-aligned T1-weighted images of an individual's native brain space: medial-ocular distance, lateral-ocular distance, optical angle, maximum skull length, and skull-base width. Compared to non-schizotypal controls, patients with schizophrenia and their relatives showed a trend toward having smaller optical angles and medial-ocular distance, while no difference was found in patients with bipolar or major depressive disorders, suggesting some degree of specificity to schizophrenia. Our approach may benefit future research on craniofacial MPAs as risk markers for schizophrenia-spectrum disorders, and may eventually be useful in strategies to enhance risk stratification using multiple risk markers.

Development and validation of a web-based prediction tool on minor physical anomalies for schizophrenia

“…This finding is consistent with those of most studies 3 , 4 , 21 , 40 , but failed to agree with those presented in a paper published in 2016; that study reported that patients with schizophrenia have a significantly wider palate 26 . The inclusion of the high palate and furrowed tongue in both the models shows that our results are consistent with the findings that palate and tongue anomalies represent the highest prevalence of MPAs in the mouth region of patients with schizophrenia 8 , 25 , 41 , 42 . Our results revealed that patients with schizophrenia have a greater skull height and nasal width, and smaller mouth width and palate width.…”

“…Furthermore, a study measuring the quantitative characteristics of the eyes showed that patients with schizophrenia tended to have smaller optical angles and inner canthal distance. These results were supported by another study measuring the eye and skull regions 8 .…”

“…Minor physical anomalies (MPAs) are subtle morphological alterations in the head, eyes, ears, mouth, hands, and feet that do not have significant cosmetic or clinical effects 1 . Data from past research have proven that MPAs arise during the first or early second trimester and can be considered as indicators of altered brain development during early neurodevelopment due to schizophrenia 2 – 8 . Qualitative minor malformations represent defects of embryogenesis during the process of organogenesis, and the phenogenetic variation of final morphogenesis can be seen through quantitative defects 9 .…”

Ectodermal disturbance in development shared by anorexia and schizophrenia may reflect neurodevelopmental abnormalities

“…As aforementioned, MPA were not only observed in psychotic patients. Nevertheless, the association between MPA, schizophrenia and its increased genetic burden was confirmed (Hajnal et al., 2016 ; Wang et al., 2016 ). Similar profile of MPA found in HC and SSD groups is also in line with continuum model of psychosis.…”

“…High rates of MPA were also associated with a family history of schizophrenia, obstetric complications, lower number of siblings, later position in birth order and male gender (O'Callaghan et al., 1991 ). Anomalies in the craniofacial regions were also more common in patients’ unaffected relatives than in controls (Hajnal et al., 2016 ; Wang et al., 2016 ). Early onset schizophrenia (EOS) was associated with more MPA in different subsamples than in adult‐onset schizophrenia (AOS) (Green et al., 1987 ; Hata et al., 2003 ) and was in this sample linked with brain morphology abnormalities (Hata et al., 2003 ); in keeping with the notion suggesting a greater biological burden in EAO compared to AOS.…”