White Matter Abnormalities and Clinical Symptom Severity in Schizophrenia

BRAIN Initiative
BRAIN Initiative
New findings provide an insight about the association between white matter microstructure and the severity of schizophrenia clinical symptoms.

According to recent findings published in NeuroImage Clinical, aberrant white matter microstructure of motor tracts, as well as of the prefrontal and right temporal lobes, is associated with the severity of clinical symptoms such as abnormal psychomotor behavior and negative symptoms, respectively, among patients diagnosed with schizophrenia.

Extensive white matter abnormalities are known to exist in the brains of individuals diagnosed with schizophrenia, but until now, limited evidence has been provided to establish the direct association between brain structural changes and the observed, clinically significant behavior. Patients with schizophrenia often present with a combination of negative (apathy, low motivation, “flat affect”), positive (delusions, hallucinations), cognitive (learning, memory, attention, and executive dysfunction), and motor (abnormal involuntary movements, psychomotor slowing, neurological soft signs) symptoms.

It has previously been reported that white matter fiber abnormalities contribute to impaired function across various cognitive domains such as attention, memory, and language in patients diagnosed with this chronic, disabling neuropsychiatric illness. The available data also indicate that patients diagnosed with the ‘typical first negative symptoms schizophrenia‘ present with significantly lower fractional anisotropy values across numerous brain areas, including the prefrontal cortex, temporal lobe, inferior frontal gyrus, and the corpus callosum, as measured by diffusion-tensor MRI (DTI). In addition, these values are negatively correlated with the negative symptoms scale scores (ie, the PANSS scale).

In the current study, investigators used DTI to image the white matter tracts in 40 patients (15 women) diagnosed with schizophrenia (77.5%), schizophreniform disorder (17.5%), or schizoaffective disorder (5.0%). With this study, the investigators sought to examine the association between white matter microstructure and symptom severity of the five main DSM-5 dimensions (ie, delusions, hallucinations, disorganized speech, abnormal psychomotor behavior, and negative symptoms). Researchers included age, gender, and antipsychotic medication usage as covariates.

Data indicate that white matter microstructure is associated with 2 out of 5 DSM-5 schizophrenia symptom dimensions. More specifically, in line with previous findings, white matter brain structure of the prefrontal lobe and right temporal lobe is associated with the severity of negative symptoms. In addition, aberrant white matter microstructure in the motor tracts was found to be associated with the severity of abnormal psychomotor behavior.

With regard to the other 3 dimensions (ie, delusions, hallucinations, disorganized speech), investigators reported no significant association with white matter microstructure. “The constructs behind these 3 DSM-5 dimension ratings are too complex to be mapped on brain structure… and, [these 3] dimensions share less temporal stability compared to the motor and negative symptom dimensions,” the authors wrote.

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Viher PV, Stegmayer K, Giezendanner S, et al. Cerebral white matter structure is associated with DSM-5 schizophrenia symptom dimensions. Neuroimage Clin. 2016;12:93-99.