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Eur Arch Psychiatry Clin Neurosci. 2018 Oct;268(7):641-651. doi: 10.1007/s00406-017-0851-5. Epub 2017 Nov 11.

Neural substrate of unrelenting negative symptoms in schizophrenia: a longitudinal resting-state fMRI study.

Li M1,2, Deng W1,2, Das T3,4,5, Li Y1,2, Zhao L1,2, Ma X1,2, Wang Y1,2, Yu H1,2, Li X1,2, Meng YJ1,2, Wang Q1,2, Palaniyappan L6,7,8,9, Li T10,11.

Author information

1
Mental Health Center and Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
2
West China Brain Research Center, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
3
Robarts Research Institute and The Brain and Mind Institute, University of Western Ontario, London, ON, Canada.
4
Department of Psychiatry, University of Western Ontario, London, ON, Canada.
5
Lawson Health Research Institute, London, ON, Canada.
6
Robarts Research Institute and The Brain and Mind Institute, University of Western Ontario, London, ON, Canada. lpalaniy@uwo.ca.
7
Department of Psychiatry, University of Western Ontario, London, ON, Canada. lpalaniy@uwo.ca.
8
Lawson Health Research Institute, London, ON, Canada. lpalaniy@uwo.ca.
9
Prevention and Early Intervention Program for Psychoses (PEPP), A2-636, LHSC-VH, 800 Commissioners Road, London, ON, N6A 5W9, Canada. lpalaniy@uwo.ca.
10
Mental Health Center and Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China. litaohx@scu.edu.cn.
11
West China Brain Research Center, West China Hospital, Sichuan University, Chengdu, People's Republic of China. litaohx@scu.edu.cn.

Abstract

Developing a mechanistic insight into the specific brain processes that underpin improvement in negative symptoms can help us design novel chemical and physical treatments against these unrelenting symptoms. The aim of the present study is to explore the longitudinal changes in the brain's regional functional efficiency that accompany improvement in negative symptoms seen in first-episode patients with schizophrenia when treated with antipsychotic for 1 year. Forty-seven first-episode patients with schizophrenia were scanned at a drug-naive baseline state and followed up for 1 year to identify negative symptom responders (Rn) and non-responders (NRn). Fractional amplitude of low-frequency fluctuations (fALFF) and Granger analysis of effective connectivity (EC) were used to examine the different patterns of regional function and connectivity between Rn and NRn during the 1 year follow-up. Increase of fALFF in the left superior temporal gyrus (STG) and increase of EC from the left STG to the dorsolateral prefrontal cortex (DLPFC) was found in Rn compared to NRn. We further validated that the identified changes in fALFF/EC of STG occur specifically in relation to negative symptoms only (i.e., not pseudo-specific in relation to positive, extrapyramidal or depressive symptoms), and occur irrespective of arbitrary clinical categorization of treatment response. An increase in fALFF in the precuneus and the inferior parietal lobule, and a decrease in EC from the left STG to the occipital cortex, were also found at the 1 year follow-up irrespective of improvement in negative symptoms. Interventions that improve the functional efficiency of left STG and its prefrontal connectivity may show efficacy in alleviating negative symptoms in first-episode schizophrenia.

KEYWORDS:

Left superior temporal gyrus; Longitudinal study; Negative symptoms; Outcome; Schizophrenia

PMID:
29128871
DOI:
10.1007/s00406-017-0851-5

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