Yin Cui

Chronic social defeat stress increases dopamine D2 receptor dimerization in the prefrontal cortex of adult mice.

The present study aimed to examine the effects of chronic social defeat stress on the dopamine receptors and proteins involved in post-endocytic trafficking pathways. Adult mice were divided into susceptible and unsusceptible groups after 10 days of social defeat stress. Western blot analysis was used to measure the protein expression levels of dopamine D2 receptors (D2Rs), a short (D2S) and a long form (D2L) and, D2R monomers and dimers, dopamine D1 receptors (D1Rs), neuronal calcium sensor-1 (NCS-1) and G protein-coupled receptor-associated sorting protein-1 (GASP-1), and reverse transcription-polymerase chain reaction (RT-PCR) was used to measure the mRNA expression levels of D2S, D2L, D2R monomers and dimers, and D1Rs in different brain areas. We observed increased expression of D2S, D2L and D2Rs dimers in the prefrontal cortex (PFC) of susceptible and/or unsusceptible mice compared with controls. The only significant findings with regard to mRNA expression levels were lower expression of D2S mRNA in the amygdala (AMYG) of susceptible and unsusceptible mice compared with controls. The present study demonstrated that chronic social defeat stress induced increased expression of D2S, D2L, and D2R dimers in the PFC of susceptible and/or unsusceptible mice.

The mRNA Expression Status of Dopamine Receptor D2, Dopamine Receptor D3 and DARPP-32 in T Lymphocytes of Patients with Early Psychosis

Peripheral blood lymphocytes are an attractive tool because there is accumulating evidence indicating that lymphocytes may be utilized as a biomarker in the field of psychiatric study as they could reveal the condition of cells distributed in the brain. Here, we measured the mRNA expression status of dopamine receptor D2 (DRD2), DRD3, and dopamine and cyclic adenosine 3′,5′-monophosphate regulated phosphoprotein-32 (DARPP-32) in T lymphocytes of patients with early psychosis by quantitative real-time polymerase chain reaction (q-PCR) and explored the relationships between their mRNA levels and the psychopathological status of patients. The present study demonstrated that the mRNA expression levels of DRD3 in T lymphocytes were significantly different among controls, and in patients with psychotic disorder not otherwise specified (NOS) and schizophrenia/schizophreniform disorder. However, no significant differences in mRNA expression levels of DRD2 and DARPP-32 were found among the three groups. We found a significant positive correlation between the DRD2 mRNA level and the score of the excited factor of the Positive and Negative Syndrome Scale (PANSS) in patients with schizophrenia/schizophreniform disorder. These findings suggest that DRD3 mRNA levels may serve as a potential diagnostic biomarker differentiating patients with early psychosis from controls.

Bilateral Repetitive Transcranial Magnetic Stimulation for Auditory Hallucinations in Patients with Schizophrenia: A Randomized Controlled, Cross-over Study

Objective A randomized double-blind cross-over trial was conducted in patients with persistent auditory hallucinations (AHs) to investigate whether bilateral repetitive transcranial magnetic stimulation (rTMS) at the temporoparietal area or Brocas area is more effective at high- or low-frequencies compared to a sham condition. Methods Twenty three patients with persistent AHs who remained stable on the same medication for 2 months were enrolled. They were randomized to one of four conditions: low-frequency (1 Hz)-rTMS to the temporoparietal area (L-TP), high-frequency (20 Hz)-rTMS to the temporoparietal area (H-TP), high-frequency (20 Hz)-rTMS to Brocas area (H-B), or sham. Results All the four rTMS conditions resulted in significant decrease in the scores under the auditory hallucination rating scale and hallucination change scale over time. However, there were no significant treatment effects or interaction between time and treatment, suggesting no superior effects of the new paradigms over the sham condition. Conclusion Our findings suggest that bilateral rTMS at the temporoparietal area or Brocas area with high- or low-frequency does not produce superior effects in reducing AHs compared to sham stimulation.

Associations of fatty acids with cognition, psychopathology, and brain-derived neurotrophic factor levels in patients with first-episode schizophrenia and related disorders treated with paliperidone extended release

This study assessed fatty acid and brain-derived neurotrophic factor levels in patients with first-episode schizophrenia and related disorders. The levels of erythrocyte fatty acids and plasma brain-derived neurotrophic factor were measured at baseline and week 8 after treatment with paliperidone extended release. Cognitive function was evaluated using the Cognitive Assessment Interview and the cognition subscale of the Neuroleptic-Induced Deficit Syndrome Scale. There were significant decreases in stearic acid and nervonic acid levels and a significant increase in eicosapentaenoic acid levels after eight weeks. At week 8, cognition was positively associated with dihomo-γ-linolenic acid, linoleic acid, and eicosapentaenoic acid levels, and negatively associated with nervonic acid levels. Psychopathology was positively correlated with polyunsaturated fatty acid levels, and negatively correlated with saturated fatty acid levels at week 8. At both baseline and week 8, brain-derived neurotrophic factor level had a negative association with polyunsaturated fatty acids and a positive association with saturated fatty acids and monounsaturated fatty acids. The present study demonstrated that fatty acids have significant associations with cognition and psychopathology at week 8, and with brain-derived neurotrophic factor levels at both baseline and week 8.

Longer Telomere Length of T lymphocytes in Patients with Early and Chronic Psychosis

Objective To investigate pathological conditions that act as sources of pro-inflammatory cytokines and cytotoxic substances to examine telomere length (TL) in patients with either early (duration of illness [DI] ≤5 years) or chronic (DI >5 years) psychosis using T lymphocytes. Methods Based on these factors and the important role that T lymphocytes play in inflammation, the present study measured the TL of T lymphocytes in patients with either early or chronic psychosis. Additionally, smoking, metabolic syndrome, depression, and cognitive functioning were assessed to control for confounding effects. Results TL was significantly longer in patients with early and chronic psychosis than in healthy control subjects and, moreover, the significance of these findings remained after controlling for age, smoking, metabolic syndrome, DI, chlorpromazine-equivalent dose, and cognitive functioning (F=9.57, degree of freedom=2, p<0.001). Additionally, the DI, chlorpromazine-equivalent doses, and the five-factor scores of the Positive and Negative Syndrome Scale were not significantly correlated with the TL of T lymphocytes in either all patients or each psychosis group. Conclusion Possible mechanisms underlying the effects of antipsychotic medications on telomerase are discussed in the present study, but further studies measuring both telomerase activity and TL using a prospective design will be required.

Acceptance rate of long-acting injection after short information: a survey in patients with first- and multiple-episode psychoses and their caregivers.

The aim of this study was to investigate the acceptance rates of long‐acting injection (LAI) in patients with first‐ and multiple‐episode psychoses before and after providing concise information about LAI to the patients and their caregivers. Additionally, predictors of choosing LAI and the reasons for reluctance to accept LAI were also evaluated.

Early predictors of a clinical response at 8 weeks in patients with first-episode psychosis treated with paliperidone ER

Identification of early clinical markers that predict later treatment outcomes in first-episode psychosis is highly valuable. The present study was conducted to determine the best time at which to predict the late treatment response in first-episode psychosis patients treated with paliperidone extended release (ER), the factors predicting early treatment responses (at Week 2 and Week 3) and the relationships between the paliperidone ER plasma concentrations at Week 2 and Week 3, and the treatment responses at Week 2, Week 3 and Week 8. Various criteria for assessing treatment response were employed. We determined the plasma paliperidone concentrations at Week 2 and Week 3, using validated high-performance liquid chromatography/tandem mass spectrometry (HPLC-MS/MS). The treatment response at Week 3 optimally predicted the later (Week 8) response, in terms of negative predictive value (NPV). Independent predictors for good treatment responses at Week 2 and Week 3 were: Female gender, a higher educational level, a higher Positive and Negative Syndrome Scale (PANSS) excited score, and/or a shorter duration of untreated psychosis (DUP). The plasma paliperidone concentration at Week 3, but not Week 2, was a significant predictor of the late treatment response at Week 8. These results may help appropriate clinical decision-making for early non-responders after having their first episode of psychosis.

Neural Signature for Auditory Hallucinations in Schizophrenia: A High-Resolution Positron Emission Tomography Study with Fludeoxyglucose ( 18 F)

Objective Auditory hallucinations (AHs) are a core symptom of schizophrenia. We investigated the neural signature of AHs by comparing hallucinating patients with schizophrenia with non-hallucinating patients with schizophrenia. Methods We recruited hallucinating patients with schizophrenia meeting the criteria for persistent, prominent, and predominant AHs (n=10) and non-hallucinating patients with schizophrenia (n=12). Various clinical assessments were performed incluing Psychotic Symptom Rating Scale for Auditory Hallucinations. Using fludeoxyglucose (18F) positron emission tomography, regional differences in neural activity between the groups were analyzed. Results The regions of interest analysis showed significantly lower standardized uptake value ratio (SUVR) in the superior, middle, and inferior frontal gyri, and higher SUVR in the putamen in patients with AHs versus patients without AHs. These findings were confirmed in the voxel-wise analysis. Conclusion Our findings indicate that hypoactivity in the frontal and cingulate gyri, coupled with hyperactivity in the temporal gyrus and putamen, may contribute to the pathophysiology of AHs.

Effects of Community Mental Health Service in Subjects with Early Psychosis: One-Year Prospective Follow Up.

The use of a multidisciplinary team approach is essential for increasing the likelihood of recovery among individuals with early psychosis. The aim of the present study was to investigate the effects of community-based mental health services on the symptoms and socio-occupational functioning of subjects with early psychosis. The study included participants who were referred to our Mental Health Promotion Center and who agreed to participate in diverse individual and group programs. During the 1-year follow-up, the medication adherence rate remained high, the recovery rate substantially increased, and the scores on the Positive and Negative Syndrome Scale, Psychotic Symptom Rating Scale-Delusion and Auditory Hallucinations subscales, Global Assessment of Functioning, Interpersonal Sensitivity Measure, and Social Functioning Questionnaire significantly improved over time. The findings suggest that the 1-year outcome of subjects with early psychosis can be improved by diverse community-based psychosocial interventions.