Not All Hallucinations Are Alike: The Brain Tells Us So


Can schizophrenia be distinguished from bipolar disorder via gray matter volume?


Despite differences observed by the astute clinician, hallucinatory and delusional symptoms of schizophrenia and bipolar disorder can be very similar, rendering a differential diagnosis based on clinical symptoms inadequate. When describing hallucinations, affect can be flatter among patients with schizophrenia than patients with bipolar disorder, whose hallucinations also tend to be less severe, more visual, less auditory, and often accompanied by persecutory delusions.

A team of researchers recently illustrated gray-matter volume differences in patients with schizophrenia and bipolar disorder with delusions/hallucinations.1 Their aim was to not only show that the frontal cortex is commonly affected in these patients-as previous research has shown-but to finely illustrate gray-matter volume abnormalities that distinguish schizophrenia from bipolar disorder. They found that gray-matter volume deficits are more diffuse in schizophrenia than bipolar disorder and that hallucination symptoms originate from distinct areas of the brain.

To conduct the study, Song and colleagues followed 93 patients with schizophrenia and 75 patients with bipolar disorder (all outpatients) who had undergone magnetic resonance imaging (MRI) of the brain while experiencing psychotic symptoms. All were medication-free for at least a month before the MRI scan. In addition to MRI, other diagnostic assessments included the Structured Clinical Interview for DSM-IV Axis I Disorders, the Positive and Negative Syndrome Scale, the Young Mania Rating Scale (YMRS), and the Edinburgh Inventory (to assess handedness). The patients were then followed for 3 years to confirm that their initial diagnoses were accurate. Brain scans of healthy controls also were acquired for comparison.

The final study cohort consisted of 71 patients with schizophrenia and 44 patients with bipolar disorder. After controlling for whole gray-matter volume, age, sex, YMRS score, and duration of medication, the researchers found that, compared with the brains of healthy controls, the brains of patients with schizophrenia had decreased gray-matter volume in the left frontal precentral gyrus, left extra nucleus, left caudate body, left cerebellum, right frontal precentral gyrus, right lentiform nucleus, and right caudate body. The brains of patients with bipolar disorder had decreased gray-matter volume in the left middle frontal gyrus, left temporal fusiform gyrus, and right parietal postcentral gyrus.

When schizophrenic and bipolar brains were compared, the researchers found that a distinguishing feature of the former was decreased gray-matter volume in the left cerebellum, right temporal lobe, right lentiform nucleus, and putamen. These findings diverge somewhat from earlier studies that describe more widespread cortical thinning in the schizophrenic brain compared with the bipolar brain, characterized by localized thinning in small regions within the frontal and temporal cortices.

Although delusion symptoms were negatively correlated with gray-matter volume in the bilateral frontal cortex in both schizophrenia and bipolar disorder, the bilateral temporal and parietal cortices were affected as well in schizophrenia. Whereas hallucination symptoms were negatively correlated with gray matter volume in the temporal lobe in the schizophrenic brain, they were negatively correlated with the insular cortex in the bipolar brain.

These findings confirm previous studies that provide a basis for differences in hallucination and delusion symptoms between patients with schizophrenia and bipolar disorder and show that brain imaging during hallucinatory or delusional episodes can be diagnostic. The researchers called for future studies that compare longitudinal changes in gray matter in association with delusions and hallucinations in these 2 patients groups.


1. Song J, Han DH, Kim SM, et al. Differences in gray matter volume corresponding to delusion and hallucination in patients with schizophrenia compared with patients who have bipolar disorder. Neuropsychiatr Dis Treat. 2015;11:1211-1219.

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