Prefrontal cortical dopamine deficit may cause impaired glucose metabolism in schizophrenia.

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.

Risk factors for osteoporosis in chronic schizophrenia on long-term treatment with antipsychotics: a cross-sectional study.

BACKGROUND: Little is known about the laboratory variable risks with bone mineral density (BMD) in patients with schizophrenia. This study was designed to fully investigate the related risk factors for decreased BMD in schizophrenia, as well as evaluate the gender difference of BMD. METHOD: The BMD of the forearm of 211 patients (males/females = 140/71) who met the diagnostic criteria for DSM-5 schizophrenia was measured by dual-energy X-ray absorptiometry. Basic demographic information, clinical assessments, and laboratory variables (regarding nutrition, hormones, metabolism, and inflammatory markers) were comprehensively collected. RESULTS: Among 211 subjects, seventy-four (35%) patients had low BMD. Males had a significantly lower BMD T-score than females (P = 0.002). Multiple regression analyses showed that the independent risks with low BMD were lower folate, glycosylated hemoglobin levels, higher age, serum ferritin, and follicle-stimulating hormone (FSH) levels. In female patients, the BMD was mainly associated with age and serum hormones (FSH and testosterone), while the BMD of male patients was primarily related to age, microelements (serum ferritin and 25-OH-VD), and parathyroid hormone. CONCLUSION: Our study found several meaningful correlations between osteoporosis and schizophrenia, especially regarding laboratory measures, which may provide new clues to identifying or preventing osteoporosis in clinical patients.

Diagnostic Stability in Psychiatric Patients From Hospital Admission to Discharge: A 10-Year Retrospective Study.

OBJECTIVE: This study aimed to evaluate the consistency or stability of mental disorders diagnosed in the psychiatry ward setting, investigate factors associated with consistency, and observe the disease distribution over the decade. METHODS: A total of 20,359 psychiatric inpatients were included in this retrospective study from June 2011 to December 2020. Diagnoses from the first admission to discharge were evaluated to determine the diagnostic consistency during hospitalization. Readmissions were selected as the subgroup, whose first and last discharge diagnoses were compared to analyze the relatively long-term diagnostic stability. Demographic and clinical characteristics were collected to identify predictors of diagnostic discrepancy. RESULTS: From 2011-2020, the hospitalization rate decreased from 42.7% to 20.7% for schizophrenia and grew from 13.3% to 23.8% for depression. Diagnoses were retained by 92.6% of patients at their first discharge diagnosis, ranging from 100% for disorders of psychological development to 16.3% for unspecified mental disorders. About 33.9% of diagnostic conversions were to bipolar disorder in patients having inconsistent diagnoses. However, among rehospitalizations, the diagnostic stability notably dropped to 71.3%. For rehospitalizations, mood disorders and schizophrenia spectrum disorders were relatively stable diagnoses categories, with 72.6% to 76.7% of patients receiving the same diagnosis, although results of specified diagnoses within these categories ranged from 5.9% to 91.0%. Except for mood disorders and schizophrenia spectrum disorders, the diagnoses of all other categories were below 70%. Long lengths of hospitalization and old age were associated with short-term diagnosis alterations. CONCLUSION: Longitudinal follow-up and integration of multiple aspects of information are essential for accurate diagnosis.

Relapse in patients with schizophrenia and amisulpride-induced hyperprolactinemia or olanzapine-induced metabolic disturbance after switching to other antipsychotics.

Hyperprolactinemia and metabolic disturbance are common side effects of antipsychotics that cause intolerance. Despite its potential influence on relapse, there are no established guidelines for antipsychotic switching. This naturalistic study explored the association between antipsychotic switching, baseline clinical status, metabolic changes, and relapse in patients with schizophrenia. In total, 177 patients with amisulpride-induced hyperprolactinemia and 274 with olanzapine-induced metabolic disturbance were enrolled. Relapse was determined by assessing changes in Positive and Negative Syndrome Scale (PANSS) total scores from baseline to 6 months (increased over 20% or 10% reaching 70). Metabolic indices were measured at baseline and 3 months. Patients with baseline PANSS >60 were more likely to relapse. Further, patients switching to aripiprazole had a higher risk of relapse regardless of their original medication. Participants who originally used amisulpride had reduced prolactin levels following medication change, while switching to olanzapine caused increased weight and blood glucose levels. In patients originally using olanzapine, only switching to aripiprazole reduced insulin resistance. Adverse effects on weight and lipid metabolism were observed in patients who switched to risperidone, while amisulpride improved lipid profiles. Changing schizophrenia treatment requires careful consideration of multiple variables, particularly the choice of substituted drug and the patient's baseline symptoms.