| First Author | Wu Q | Year | 2024 |
| Journal | Transl Psychiatry | Volume | 14 |
| Issue | 1 | Pages | 79 |
| PubMed ID | 38320995 | Mgi Jnum | J:352329 |
| Mgi Id | MGI:7581595 | Doi | 10.1038/s41398-024-02800-7 |
| Citation | Wu Q, et al. (2024) Prefrontal cortical dopamine deficit may cause impaired glucose metabolism in schizophrenia. Transl Psychiatry 14(1):79 |
| abstractText | The brain neurotramsmitter dopamine may play an important role in modulating systemic glucose homeostasis. In seven hundred and four drug- naive 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 Disc1(tr) exhibited depressive-like symptoms, impaired glucose homeostasis, and compared to wild type littermates reduced D2R expression in prefrontal cortex. |
