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Brain Impairment in Chronic Schizophrenia Patients with Depressive Symptoms Differs from Brain Impairment in Chronic Depression Patients with Psychotic Symptoms.

Byline: Feng. Ji, Ce. Chen, Min. Chen, Li-Na. Wang, Jie. Li, Chuan-Jun. Zhuo

Numerous studies have identified many specific structural alterations in the brains of patients with schizophrenia and depression. Schizophrenia is associated with gray matter volume (GMV) impairment in certain key brain regions, which progresses in the first 2-3 years after the first episode of schizophrenic symptoms.[1] Schizophrenia has also been shown to be associated with concurrent white matter (WM) alterations. The fasciculus uncinatus and arcuate fasciculus have been proposed to be a part of the quality index for schizophrenia.[2] Similar to schizophrenia, major depressive disorder (MDD) is associated with a GMV reduction and aberrant WM. GMV reductions in the bilateral middle temporal gyrus left ventral medial prefrontal gyrus, left lingual gyrus, and dorsal medial prefrontal gyrus have been correlated with the severity of the depressive symptoms. Schizophrenic and depressive symptoms usually coexist in schizophrenia and MDD. In this pilot study, we compared the GMV and WM differences in the brains of chronic schizophrenia patients with depressive symptoms with those of chronic depression patients with psychotic symptoms.[1],[2]

In this pilot study, we selected 20 chronic schizophrenia patients with moderate-to-severe depressive symptoms (mean age was 34.0 [+ or -] 3.5 years, 8 female individuals, 12 male individuals, mean eductational level was 12.3 [+ or -] 2.7 years, mean illness duration was 4.1 [+ or -] 1.6 years, mean score of positive and negative syndrome scale was 148.1 [+ or -] 15.7, mean score of calgary depression rating scale was 15.3 [+ or -] 3.1) and 20 chronic depression patients with moderate-to-severe psychotic symptoms (mean age was 35.3 [+ or -] 3.7 years, 9 female individuals, 11 male individuals, mean eductational level was 11.5 [+ or -] 2.0 years, mean illness duration was 4.8 [+ or -] 1.2 years, mean score of positive and negative syndrome scale was 136.2 [+ or -] 20.5, mean score of calgary depression rating scale was 20.1 [+ or -] 2.3). The mean antipsychotic dosage (chlorpromazine equivalents) in the chronic schizophrenia patients was 621.0 [+ or -] 70.6 mg/d, and it was 298.5 [+ or -] 90.5 mg/d in the chronic depression patients. The Tianjin Mental Health Center-affiliated Medical Research Ethics Committee approved our study.

SPM8 ( was used to preprocess and process the raw MRI data. A voxel-based analysis method was used to calculate alterations in GMV, and the tract-based spatial statistics method was used to calculate alterations in WM. We found that compared to chronic depression patients with moderate-to-severe psychotic symptoms, GMV was significantly decreased in the left operculum cortex in chronic schizophrenia patients with moderate-to-severe depressive symptoms. The WM was also reduced in the left frontal lobe of the chronic schizophrenia patients with moderate-to-severe depressive symptoms [Figure 1]a and [Figure 1]b. All significant differences were corrected using the family-wise error method.[3]{Figure 1}

The left superior temporal gyrus is a component of the second sensory cortex. Impairment of the superior temporal gyrus disturbs the individual's sensory information processing, which may contribute to the sensory disturbances experienced by chronic schizophrenia patients with moderate-to-severe depressive symptoms.[1],[2],[4],[5] Sensory disturbances have been confirmed to play a role in the development of psychotic and depressive symptoms. Secondary sensory processing disturbances have also been confirmed to influence emotional processing, and emotional processing disturbances play a key role in mood disorders, which may explain the association between chronic schizophrenia and moderate-to-severe depressive symptoms. Although secondary sensory processing disturbances are also involved in depressive symptoms, the effects of secondary sensory processing disturbances have been reported to be related to the core symptoms of schizophrenia, which include emotional blunting, emotional withdrawal, abnormal sensation, and hallucinations.[1],[2],[4],[5] The frontal lobe cortex is a key brain region that contains the pivotal components of the central executive control network. Forceps minor is a component of the frontal lobe. Frontal lobe impairment leads to a reduction in cognitive ability, control ability, attention ability, and certain behavioral disturbances. Cognitive impairment has been confirmed to be one of the core symptoms of schizophrenia. Simultaneously, cognitive, executive, and attention ability impairments can also cause disturbances in thought processing, which is a feature of schizophrenia. The fiber tract in the left frontal lobe plays a key role in information transmission within the frontal lobe and between the frontal lobe and other brain regions, such as the temporal lobe. Fiber tract impairment in the left frontal lobe impacts information transmission within and without the frontal lobe, subsequently causing cognitive, executive, and attentional information transmission processing disturbances. This disturbance leads to processing disturbances, thereby inducing psychotic symptoms.[1],[2],[4],[5]

Our findings support the hypothesis that GMV reduction in schizophrenics is approximately 2%, and it demonstrates a progressive pattern during the first 2 years following the first episode, while WM reduction is approximately 1% and does not demonstrate a progressive pattern.[1],[2],[4],[5]

Although many flaws (such as lack healthy controls group) exist in the present study and further work is required to clarify our findings, we compared structural differences in the brains of patients with chronic schizophrenia with moderate-to-severe depressive symptoms and those with chronic depression with moderate-to-severe psychotic symptoms, and provide a clue for future study. We suggest that GMV reduction in superior temporal gyrus and WM impairment in the forceps minor may play a key role in chronic schizophrenia patients with moderate-to-severe depressive symptoms. Overall, our findings suggest that the pathologic features of schizophrenia ultimately differ from those of depression, even though many symptoms of these two diseases highly overlap. Nevertheless, we must acknowledge that our conclusions are not solid based on the current findings, and we must conduct a well-designed, high-quality study to solve the aforementioned scientific obstacles.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s)/patient's guardians has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the article. The patients/patient's guardians understand that their names and initials will not be published and due efforts will be made to conceal the identity of the patient, although anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


1. Haijma SV, Van Haren N, Cahn W, Koolschijn PC, Hulshoff Pol HE, Kahn RS, et al. Brain volumes in schizophrenia: A meta-analysis in over 18 000 subjects. Schizophr Bull 2013;39:1129-38. doi: 10.1093/schbul/sbs118.

2. Dong D, Wang Y, Chang X, Chen X, Chang X, Luo C, et al. Common and diagnosis-specific fractional anisotropy of white matter in schizophrenia, bipolar disorder, and major depressive disorder: Evidence from comparative voxel-based meta-analysis. Schizophr Res 2017. pii: S0920-9964(17)30404-8. doi: 10.1016/j.schres.2017.07.003.

3. Dietsche B, Kircher T, Falkenberg I. Structural brain changes in schizophrenia at different stages of the illness: A selective review of longitudinal magnetic resonance imaging studies. Aust N Z J Psychiatry 2017;51:500-8. doi: 10.1177/0004867417699473.

4. Smith SM, Jenkinson M, Woolrich MW, Beckmann CF, Behrens TE, Johansen-Berg H, et al. Advances in functional and structural MR image analysis and implementation as FSL. Neuroimage 2004;23 Suppl 1:S208-19.

5. Suzuki M, Zhou SY, Takahashi T, Hagino H, Kawasaki Y, Niu L, et al . Differential contributions of prefrontal and temporolimbic pathology to mechanisms of psychosis. Brain 2005;128(Pt 9):2109-22. Epub 2005 Jun 1.
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Article Details
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Title Annotation:Clinical Observation
Author:Ji, Feng; Chen, Ce; Chen, Min; Wang, Li-Na; Li, Jie; Zhuo, Chuan-Jun
Publication:Chinese Medical Journal
Article Type:Report
Date:Mar 18, 2018
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