2. Academic Validation
  3. Prefrontal cortical dopamine deficit may cause impaired glucose metabolism in schizophrenia

Prefrontal cortical dopamine deficit may cause impaired glucose metabolism in schizophrenia

  • Transl Psychiatry. 2024 Feb 6;14(1):79. doi: 10.1038/s41398-024-02800-7.
Qiongqiong Wu # 1 2,  Yujun Long # 1,  Xingjie Peng 1,  Chuhan Song 1,  Jingmei Xiao 1,  Xiaoyi Wang 1,  Furu Liu 1,  Peng Xie 1,  Jinqing Yang 1,  Zhe Shi 3,  Zhonghua Hu 4,  Colin McCaig 5,  David St Clair 5,  Bing Lang 1,  Renrong Wu 6
Affiliations

Affiliations

  • 1 National Clinical Research Center for Mental Disorders, and Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China.
  • 2 Affiliated Mental Health Centre & Hangzhou Seventh People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310013, China.
  • 3 Key Laboratory for Quality Evaluation of Bulk Herbs of Hunan Province, Hunan University of Chinese Medicine, Changsha, Hunan, China.
  • 4 Hunan Key Laboratory of Molecular Precision Medicine, Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
  • 5 School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK.
  • 6 National Clinical Research Center for Mental Disorders, and Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China. wurenrong@csu.edu.cn.
  • # Contributed equally.
PMID: 38320995 DOI: 10.1038/s41398-024-02800-7
Abstract

The brain neurotramsmitter dopamine may play an important role in modulating systemic glucose homeostasis. In seven hundred and four drug- naïve patients with first-episode schizophrenia, we provide robust evidence of positive associations between negative symptoms of schizophrenia and high fasting blood glucose. We then show that glucose metabolism and negative symptoms are improved when intermittent theta burst stimulation (iTBS) on prefrontal cortex (PFC) is performed in patients with predominantly negative symptoms of schizophrenia. These findings led us to hypothesize that the prefrontal cortical dopamine deficit, which is known to be associated with negative symptoms, may be responsible for abnormal glucose metabolism in schizophrenia. To explore this, we optogenetically and chemogenetically inhibited the ventral tegmental area (VTA)-medial prefrontal cortex (mPFC) dopamine projection in mice and found both procedures caused glucose intolerance. Moreover, microinjection of dopamine two receptor (D2R) neuron antagonists into mPFC in mice significantly impaired glucose tolerance. Finally, a transgenic mouse model of psychosis named Disc1tr exhibited depressive-like symptoms, impaired glucose homeostasis, and compared to wild type littermates reduced D2R expression in prefrontal cortex.

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