White Matter Microstructure in Individuals at Clinical High Risk of Psychosis: A Whole-Brain Diffusion Tensor Imaging Study

Abstract

Background:The study of individuals at clinical high risk (CHR) for psychosis provides an important opportunity for unraveling pathological mechanisms underlying schizophrenia and related disorders. A small number of diffusion tensor magnetic resonance imaging (DTI) studies in CHR samples have yielded anatomically inconsistent results. The present study is the first to apply tract-based spatial statistics (TBSS) to perform a whole-brain DTI analysis in CHR subjects. Methods: A total of 28 individuals meeting CHR criteria and 34 healthy controls underwent DTI. TBSS was used for a group comparison of fractional anisotropy (FA), as well as axial, radial, and mean diffusivity (AD, RD, and MD). Conversion to psychosis was monitored during a mean follow-up period of 12.3 months. Results: The rate of conversion to psychosis was relatively low (4%). TBSS revealed increased MD in several clusters in the right hemisphere, most notably in the superior longitudinal fasciculus (SLF), posterior corona radiata, and corpus callosum (splenium and body). Increased RD was restricted to a smaller area in the posterior parietal lobe. Conclusion: We present further evidence that white matter microstructure is abnormal in CHR individuals, even in a sample in which the vast majority do not transition to psychosis over the following year. In accord with previous studies on CHR individuals and patients with early-onset schizophrenia, our findings suggest an important pathological role for the parietal lobe and especially the SLF. The latter is known to undergo particularly dynamic microstructural changes during adolescence and early adulthood, a critical phase for the development of psychotic illness.

White matter tractography in early psychosis: clinical and neurocognitive associations

“…The forceps major communicates somatosensory information be tween the parietal and occipital lobes via the splenium, a struc ture shown to be impaired in individuals at early and later stages of psychosis 1 as well as ultrahigh risk individuals. 53 A re port by Waltz and colleagues 54 demonstrated that individuals with schizophrenia showed a selective deficit in the ability to learn from positive outcomes but no deficits in learning from negative outcomes. This motivational deficit correlated with negative symptoms but not with neuropsychological measures of working memory, suggesting that the observation was not a neuropsychological deficit.…”

Differential Time Course of Microstructural White Matter in Patients With Psychotic Disorder and Individuals at Risk: A 3-Year Follow-up Study

“…6 Both a neurodevelopmental model, 7,8 implying that WM alterations are present before disease onset and a postonset progression model, indicating that structural brain abnormalities progress over time after disease onset, have been proposed. 9,10 In support of the neurodevelopmental model, several cross-sectional DTI studies have revealed microstructural WM alterations in frontotemporal and -parietal connections in first-degree relatives without symptoms, 11,12 in clinical high-risk populations before onset, 13,14 and in patients with early onset psychosis. 15 Indeed, the lifetime trajectory of WM alterations in schizophrenia suggests higher percentages of WM loss in the first years of the illness, implicating altered neurodevelopment.…”

Altered Thalamo-Cortical White Matter Connectivity: Probabilistic Tractography Study in Clinical-High Risk for Psychosis and First-Episode Psychosis

“…40 However, their method involved hypothesisfree whole brain white matter group comparisons, and, therefore, might not have been sufficiently sensitive to detect subtle changes in the thalamo-cortical white matter connections.…”