Brain structure changes differ between schizophrenia symptoms

By Eleanor McDermid, Senior medwireNews Reporter

The specific areas of the brain with reduced grey matter in patients with schizophrenia differ according to whether they have predominant positive, negative or disorganised symptoms, research suggests.

Tianhao Zhang (University of Pennsylvania, Philadelphia, USA) and study co-authors used factor analysis to categorise 163 schizophrenia patients according to their predominant symptoms; 57 had predominant positive symptoms, 55 negative symptoms and 51 disorganised symptoms.

All three groups had significant grey matter reductions relative to 163 matched controls, largely affecting the prefrontal and perisylvian regions. However, patients with predominant positive or negative symptoms had widespread regions with significant reductions, whereas only small areas were significantly affected in those with disorganised symptoms.

The researchers used Optimally-Discriminative Voxel-Based Analysis to compare grey matter between the patient and control groups. They say this involves “a spatially adaptive analysis scheme, which accounts for the interrelatedness of spatial information in the brain” and thus is more sensitive and specific than conventional voxel-based morphometry.

When comparing the three patient groups, the negative symptom group had significant reductions in the right cerebellum relative to the positive symptom group and in the left inferior orbitofrontal cortex and right thalamus compared with the disorganised symptom group.

Patients with positive symptoms had the largest number of affected areas, including bilateral reductions in the inferior orbitofrontal cortex versus both the negative and disorganised symptom groups. There were also reductions in the right middle occipital gyrus versus the negative symptom group and in the right temporal pole relative to the disorganised symptom group.

“The pattern of [grey matter] reductions revealed by our analysis is strikingly consistent with the topography of the dopaminergic pathways in the brain, and in particular of the mesolimbic and mesocortical pathways, which include projections from the ventral tegmental area to the limbic, frontal, and insular cortices”, write the researchers in Schizophrenia Bulletin.

They highlight the reductions in the cerebellum in the negative symptom group, and the marked impact on areas comprising the ventromedial prefrontal cortex in patients with positive symptoms, and, also in this group, the reductions in occipitotemporal brain regions, which they say have been little reported in the past.

“Besides adding to our knowledge of the biological underpinnings of schizophrenia, these patterns of structural differences between subgroups may serve in the future as early biomarkers of disease subtypes, hence for biomarker-based patient stratification in clinical psychiatry”, the team concludes.

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