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Published on: September 8, 2021
Altered subicular MAP2 immunoreactivity in schizophrenia
Gorazd Rosoklija1, John G Keilp, Glen Toomayan
1Department of Neuroscience, New York State Psychiatric Institute, New York, NY 10032, USA. gbr2@columbia.edu
Abstract:
We wished to test independently a previously reported loss of subicular microtubule-associated protein 2 (MAP2) in the brains of deceased individuals who had suffered from schizophrenia, and to determine whether there were any clinical characteristics attached to such a loss. Immunohistochemistry for MAP2 was examined in the hippocampal region from 94 psychiatric patients: 64 with a primary diagnosis of schizophrenia or schizoaffective disorder, 12 with a primary diagnosis of major depressive or bipolar disorders, and 18 with a primary diagnosis of dementia; and from 17 individuals without psychiatric disease. Lifelong symptomatology was evaluated with the modified Diagnostic Evaluation After Death. Subicular MAP2 immunoreactivity was prominently depressed in 20% of schizophrenia cases, 8% of mood disorder cases, 22% of dementia cases, and in no nonpsychiatric cases. Among dementia cases, those with loss of subicular MAP2 immunoreactivity displayed more subicular gliosis, while among the schizophrenia cases, there was no such association. Among schizophrenia subjects, loss of subicular MAP2 immunoreactivity was associated with fewer positive and negative symptoms over the course of the illness. Subicular MAP2 immunoreactivity is markedly diminished in a significant proportion of individuals chronically institutionalized for schizophrenia, and this does not represent a generalized destruction of subicular neurons. In contrast, among individuals institutionalized for dementia, loss of subicular MAP2 immunoreactivity is accompanied by gliosis. The loss of MAP2 immunoreactivity is associated with fewer clinical symptoms, suggesting that it may represent an adaptive response to schizophrenia. The chemical or structural abnormalities underlying decreased MAP2 immunoreactivity in schizophrenia remain to be determined.
Insights
Reduced microtubule-associated protein 2 (MAP2) in the subiculum was observed in some schizophrenia patients, correlating with fewer symptoms. This MAP2 loss may be an adaptive response in schizophrenia, unlike in dementia where it indicates neuronal damage.
Area of Science:
- Neuroscience
- Psychiatry
- Cell Biology
Background:
- Microtubule-associated protein 2 (MAP2) is crucial for neuronal structure and function.
- Previous studies suggested reduced MAP2 in the subiculum of schizophrenia patients.
Purpose of the Study:
- To independently verify the loss of subicular MAP2 in schizophrenia.
- To investigate clinical associations with subicular MAP2 loss in psychiatric disorders.
Main Methods:
- Immunohistochemistry for MAP2 in the hippocampus of 94 psychiatric patients and 17 controls.
- Evaluation of lifelong symptomatology using the modified Diagnostic Evaluation After Death.
Main Results:
- Subicular MAP2 immunoreactivity was reduced in 20% of schizophrenia, 8% of mood disorder, and 22% of dementia cases, but not in controls.
- In schizophrenia, MAP2 loss correlated with fewer positive and negative symptoms.
- In dementia, MAP2 loss was associated with subicular gliosis; this was not observed in schizophrenia.
Conclusions:
- Reduced subicular MAP2 is present in a subset of schizophrenia patients and may represent an adaptive response.
- MAP2 loss in schizophrenia differs from dementia, where it is linked to neuronal damage (gliosis).
- Further research is needed to determine the underlying causes of decreased MAP2 in schizophrenia.
