Oral and Gut Microbiota in Individuals With Autism Spectrum Disorder: A Pilot Case-Control Study.

On average, people diagnosed with bipolar disorder (BD), schizophrenia or other non-affective psychotic disorders (SZ) show widespread white matter microstructure abnormalities, including lower fractional anisotropy (FA). In large-scale studies, effects are strongest in the corpus callosum and cingulum for BD [], and in the corpus callosum and anterior corona radiata for SZ [], with effect sizes for overall average FA at d = 0.26 for BD and 0.42 for SZ. Even so, case-control studies cannot inform us about the origins of these deviations in white matter structure. They could be a cause of the illness (and therefore be present at illness onset or prior to the emergence of psychiatric symptoms), or a consequence of the illness or of its treatment, or a combination of both cause and consequence. Indeed, effects of medication use have been reported []. In this regard, familial high-risk designs (i.e., studies of patients’ relatives) can be informative, because of the heightened risk for illness in relatives of established cases, without the confounds of illness duration or medication. Considering the overlap in white matter microstructural abnormalities across the disorders [] as well as a partially overlapping genetic liability for these disorders [], genetic liability for SZ or BD might influence white matter microstructure. Twin studies have shown that global FA shares genetic variance with SZ liability []. A meta-analysis found lower FA in the genu and splenium of the corpus callosum in relatives of individuals with SZ compared to controls, and lower FA in the inferior longitudinal fasciculus in BD relatives compared to controls []. This was a post-hoc meta-analysis, though, with only previously published data and with varying analysis pipelines and varying strictness of thresholding, and with no direct comparisons to the white matter microstructure deficits seen in people with SZ/BD. Besides genetic liability, childhood traumatic experiences are a risk factor for many forms of psychopathology [], including BD and SZ, and have been associated with lower FA in the corpus callosum and other tracts []. Animal research has shown that psychosocial stress can result in apoptosis of oligodendrocytes and disrupted myelination [, ]. Since most myelination takes place during development, this demonstrates a potential mechanism through which childhood traumatic experiences can impact white matter. By examining how childhood traumatic experiences are related to white matter microstructure in relatives and controls, we can evaluate to what extent the association of this environmental risk factor with white matter structure is specific to those who are psychiatrically ill or a broader mechanism affecting the general population. Examining how familial risk and childhood traumatic experiences contribute to white matter abnormalities as seen in individuals with SZ and BD, can lead to a better understanding of the mechanisms behind these illnesses and their outcomes, and provide support for preventive interventions.