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Physical anomalies in first-degree relatives

How are physical abnormalities relevant to families of people with schizophrenia? 

Relatives of people with schizophrenia may show attenuated signs of the illness, such as physical features that are commonly identified with the disorder. Identifying these signs can help determine how genetics may contribute to the risk of schizophrenia.

What is the evidence for physical abnormalities in family members?

Moderate to high quality evidence found increases in pituitary and left thalamus volume of relatives compared to controls. There were decreases in total grey matter volume, and decreases in the hippocampus, third ventricle, bilateral anterior cingulate gyrus, right insula, left amygdala, left subcallosal gyrus, left inferior frontal gyrus, left middle temporal gyrus, and right cerebellum of relatives.

There was also abnormal brain activation in relatives compared to controls during cognitive tasks. Relatives show abnormalities in closed loop gain during smooth pursuit eye movement tasks. There was increased intrusive anticipatory saccades, impairment in fixational stability, and increased error rate in visual and memory guided saccades. EEG studies also show abnormalities, with large effects of increased P50 ratio and reduced P50 suppression, a medium-sized effect of reduced P300 amplitude, a small to medium-sized effect of longer latency, and a small trend effect of reduced mismatch negativity amplitude in relatives.

Moderate quality evidence found biochemical alterations in relatives compared to controls. There were small effects of increased thalamic glutamate + glutamine concentrations and reduced variability of striatal D2/D3 receptor availability. There was reduced glutamate/glutamine ratio in the dorsolateral prefrontal cortex, and reduced N-Acetylaspartate/creatine ratio in the anterior cingulate cortex and hippocampus of relatives.

There were large increases in rates of neurological soft signs (mild motor or sensory anomalies), and small increases in rates of movement disorders (dyskinesia or parkinsonism) in relatives compared to controls.

March 2022

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Last updated at: 2:10 pm, 31st March 2022
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