Abstract
BackgroundFamily, twin, adoption and candidate gene studies all support a genetic component for psychotic disorders. A considerable evidence suggests that the thalamus is abnormal in schizophrenia. The thalamus has a heterogeneous structure with its nucleus having distinct inputs and outputs. Disrupted thalamo-cortical connectivity, in particular, is considered as a core psychopathology in patients with schizophrenia. The disruption is also observed in subjects at clinical-high risk for psychosis. However, using the conventional magnetic resonance imaging methods, it had been difficult to investigate the subtle structural changes that may be present in the thalamus. Furthermore, despite the numerous reports of thalamic abnormalities in schizophrenia, the genetic aspect of the thalamic microstructure has not been thoroughly investigated.MethodsTo examine the microstructure of the thalamus, a total of 34 unaffected relatives of schizophrenia (UR) and 33 healthy control subjects underwent diffusion-weighted and diffusion kurtosis magnetic resonance imaging. Using the probabilistic tractography the projections from the thalamus to the lateral and medial prefrontal cortices, lateral and medial temporal cortices, occipital cortex, somatosensory cortex, parietal cortex and orbitofrontal cortex were analyzed. Then, the thalamus was segmented by the projections and the microstructures of those segmented regions were compared between the groups. The mean kurtosis values of the segmented regions were analyzed by analysis of covariance with age and sex as covariates and the results were adjusted with Bonferroni correction.ResultsThere was no statistical difference in the mean kurtosis values of the left and right thalamic regions projecting to any of the investigated regions between the UR and healthy controls.DiscussionOur findings, via diffusion kurtosis imaging, show preserved microstructural integrity of the thalamus in UR and that this imaging technique may be less well suited to detect thalamic abnormalities in them.
Highlights
Recent Magnetic Resonance Imaging (MRI) studies on schizophrenia suggest that auditory verbal hallucinations (AVH) might be caused by alterations in connectivity of frontal and temporoparietal language-related areas.[3] as well as in connectivity of the default mode network (DMN).[1]
Tract-based spatial statistics (TBSS) allows voxel-wise analysis of multi-subject diffusion data based on fractional anisotropy (FA), assessing microstructural properties of white matter tracts
This study investigates brain white matter tracts in 85 schizophrenia patients and 111 healthy, matched controls using TBSS analysis
Summary
CNS disorders are lagging behind other indications such as oncology in implementing genotype-dependent treatment algorithms for personalized medicine This is due to the limited knowledge about the interaction of the relevant biology and the drug’s pharmacology Methods: We applied a mechanism-based computer model of a cortico-striatal-thalamocortical loop of the dorsal motor circuit that has been calibrated with clinical data on antipsychotic treatment in schizophrenia patients (Spiros, Roberts et al 2017). The D2DRTaq1A allele interacts in a complex way with the COMT genotype with haloperidol, aripiprazole and risperidone and with the 5-HTLLPR genotype for haloperidol, aripiprazole, risperidone and paliperidone. These effects are anticipated to be detectable in clinical settings
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