Relatives of people with bipolar disorder may show attenuated signs of the illness, such as physical features commonly identified with the disorder. These may include structural and/or functional anomalies as well as sleep disturbances.

What is the evidence for physical anomalies in relatives?

Moderate quality evidence suggests relatives of people with bipolar disorder show increased grey matter volume in the right inferior frontal gyrus, the left supramarginal gyrus, and the left superior temporal gyrus compared to controls. Decreased grey matter volume was found in relatives in the right lingual gyrus, the right cerebellum, and the right superior frontal gyrus. There were decreases in white matter integrity in relatives compared to controls in the right corpus callosum body, left corpus callosum splenium, and the left corticospinal tract.

Across all functioning tasks, relatives showed increased brain activation in the ventral anterior cingulate, right amygdala, and parahippocampal gyrus, and decreased activation in the right inferior parietal gyrus, left postcentral gyrus, and left superior parietal gyrus. During cognitive tasks, relatives showed increased activation in the frontal lobe, right caudate, right inferior frontal gyrus, dorsal anterior cingulate, and left middle temporal gyrus/superior temporal gyrus and decreased activation in the parietal lobe. During emotion processing, relatives showed increased activation in the right amygdala, right parahippocampal gyrus, and right middle occipital gyrus. During reward processing, relatives showed increased activation in the anterior and medio-orbital parts of the prefrontal cortex.

Relatives showed a large increase in the P50 ratio compared to controls. The P50 ratio is measured with EEG and increases are indicative of reduced cortical inhibition. There was also higher relative amplitude of the sleep-wake cycle in relatives compared to people with bipolar disorder.

March 2022

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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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