Effects of deep brain stimulation on dopamine D2 receptor binding in patients with treatment-refractory depression.

BACKGROUND: Depression is a chronic psychiatric disorder related to diminished dopaminergic neurotransmission. Deep brain stimulation (DBS) has shown effectiveness in treating patients with treatment-refractory depression (TRD). This study aimed to evaluate the effect of DBS on dopamine D2 receptor binding in patients with TRD. METHODS: Six patients with TRD were treated with bed nucleus of the stria terminalis (BNST)-nucleus accumbens (NAc) DBS were recruited. Ultra-high sensitivity [11C]raclopride dynamic total-body positron emission tomography (PET) imaging was used to assess the brain D2 receptor binding. Each patient underwent a [11C]raclopride PET scan for 60-min under DBS OFF and DBS ON, respectively. A simplified reference tissue model was used to generate parametric images of binding potential (BPND) with the cerebellum as reference tissue. RESULTS: Depression and anxiety symptoms improved after 3-6 months of DBS treatment. Compared with two-day-nonstimulated conditions, one-day BNST-NAc DBS decreased [11C]raclopride BPND in the amygdala (15.9 %, p < 0.01), caudate nucleus (15.4 %, p < 0.0001) and substantia nigra (10.8 %, p < 0.01). LIMITATIONS: This study was limited to the small sample size and lack of a healthy control group. CONCLUSIONS: Chronic BNST-NAc DBS improved depression and anxiety symptoms, and short-term stimulation decreased D2 receptor binding in the amygdala, caudate nucleus, and substantia nigra. The findings suggest that DBS relieves depression and anxiety symptoms possibly by regulating the dopaminergic system.

Clinical Characteristics and Outcomes of Acute Ischemic Stroke in Patients with Type 2 Diabetes: A Single-Center, Retrospective Study in Southern China.

OBJECTIVE: To explore the associations between type 2 diabetes mellitus (DM) and stroke by evaluating the clinical risk factors, characteristics, and outcomes of acute ischemic stroke (AIS) patients with and without type 2 DM. METHODS: A total of 1,156 AIS patients (including 410 with type 2 DM (AIS-DM group)) and 746 without type 2 DM (AIS-NDM group)) were included. Patients' demographics, auxiliary examinations, clinical manifestations, and treatment outcomes were recorded and analyzed. RESULTS: Among the included AIS patients, 35.46% had type 2 DM. The AIS-DM group had less males (59.76% versus 70.64%), less smokers (33.90% versus 41.96%), more patients with hypertension (72.93% versus 63.94%; p=0.002), higher triglyceride levels (42.93% versus 25.08%; p ≤ 0.01), and lower total cholesterol (147.06 mg/dl versus 175.31 mg/dl) than the AIS-NDM group. The proportion of patients with large artery atherosclerosis (LAA) in the AIS-DM group was lower (77.56% versus 85.92%; p < 0.05) than that in the AIS-NDM group, and the proportion of patients with small arterial occlusions (SAO) in the AIS-DM group was higher (27.07% versus 13.67%; p < 0.05) than that in the AIS-NDM group. The mean National Institutes of Health Stroke Scale (NIHSS) score at admission in the AIS-DM group was lower than that in the AIS-NDM group (4.39 versus 5.00; p=0.008), but there was no significant difference in the NIHSS score or the modified Rankin Scale score between the two groups at discharge. A total of 85 AIS patients underwent intravenous thrombolysis treatment with recombinant tissue plasminogen activator (rtPA). The door-to-needle time (DNT) did not differ significantly between the groups (49.39 ± 30.40 min versus 44.25 ± 15.24 min; p=0.433). In addition, there were no significant differences in the baseline NIHSS score, 7-day NIHSS score, and mRS score at discharge between the groups. After intravenous thrombolysis with rtPA, the AIS-NDM group had better recovery (44.30% versus 29.20%; p=0.017) and a higher ratio of good treatment outcome at discharge (65.60% versus 54.20%; p=0.762). CONCLUSIONS: Type 2 DM is associated with AIS and its risk factors, such as dyslipidemia and hypertension. Patients in the AIS-DM group had less LAA and smaller arterial occlusions, and DM could exacerbate the short-term clinical outcomes in AIS patients.

Lithium ameliorates open-field and elevated plus maze behaviors, and brain phospho-glycogen synthase kinase 3-beta expression in fragile X syndrome model mice.

OBJECTIVE: To investigate whether lithium modifies open-field and elevated plus maze behavior, and brain phospho-glycogen synthase kinase 3 (P-GSK3beta) expression in Fmr1 knockout mice. METHODS: One hundred and eighty FVB mice, including knockout and wild type, with an age of 30 days were used. An open-field and elevated plus maze was utilized to test behavior, while western blot was used to measure the P-GSK3beta expression. Six groups were formed: control (saline), lithium chloride 30, 60, 90, 120, and 200 mg/kg. The experiments were carried out in the Institute of Neuroscience, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China between January and June 2012. RESULTS: Lithium significantly decreased total distance, crossing, central area time, and center entry in the open-field test (p<0.05), and significantly reduced open-arm tracking, open-arm entry, and open-arm time in the elevated plus maze (p<0.05) in knockout mice. In wild type mice, significant changes were observed in both behavior tests in some treatment groups. Lithium ameliorated P-GSK3beta expression in the hippocampus of all the treatment groups in knockout mice (p<0.05). However, lithium did not modify either GSK3beta expression in tissues of knockout mice, or P-GSK3beta or GSK3beta expression in tissues of wild type mice. CONCLUSION: Lithium ameliorated open-field and elevated plus maze behaviors of Fmr1 knockout mice. This effect may be related to its enhancement of P-GSK3beta expression. Our findings suggest that lithium might have a therapeutic effect in fragile X syndrome.