Effect of cognitive behavioral group therapy on rehabilitation of community patients with schizophrenia: A short-term randomized control trial.

BACKGROUND: The efficacy of cognitive behavioral group therapy (CBGT) for cognitive dys-function and negative symptoms of schizophrenia is established, but more evidence is required. AIM: To assess the effectiveness of CBGT combined with mental health education as a treatment for schizophrenia compared with mental health education alone. METHODS: In all, 120 schizophrenia out-patients were randomized into CBGT combined with mental health education or single mental health education. The primary outcomes were positive and negative symptoms, cognitive function, excitatory factor, anxiety and depression symptom improvements on the positive and negative syndrome scale score. Secondary outcome measures included social function and drug compliance. RESULTS: There were significant differences between CBGT combined with mental health education and single mental health education on measures of positive and negative symptoms, cognitive functions, excitatory factor, anxiety and depression symptoms, and social functions. No other significant difference in outcomes was observed. CONCLUSION: CBGT combined with mental health education may be relevant beneficial treatment method in reducing symptoms, cognitive and social functions of patients with schizophrenia.

Historical Dynamics of Semi-Humid Evergreen Forests in the Southeast Himalaya Biodiversity Hotspot: A Case Study of the Quercus franchetii Complex (Fagaceae).

The Oligocene and Miocene are key periods in the formation of the modern topography and flora of East Asian and Indo-China. However, it is unclear how geological and climatic factors contributed to the high endemism and species richness of this region. The Quercus franchetii complex is widespread in the southeast Himalaya fringe and northern Indo-China with a long evolutionary history. It provides a unique proxy for studying the diversity pattern of evergreen woody lineages in this region since the Oligocene. In this study, we combined chloroplast (cpDNA) sequences, nuclear microsatellite loci (nSSRs), and species distribution modeling (SDM) to investigate the impacts of geological events on genetic diversity of the Q. franchetii complex. The results showed that the initial cpDNA haplotype divergence was estimated to occur during the middle Oligocene (30.7 Ma), which might have been raised by the tectonic activity at this episode to the Miocene. The nSSR results revealed two major groups of populations, the central Yunnan-Guizhou plateau (YGP) group and the peripheral distribution group when K = 2, in responding to the rapid YGP uplift during the late Miocene, which restricted gene flow between the populations in core and marginal areas. SDM analysis indicated that the distribution ranges of the Q. franchetii complex expanded northwards after the last glacial maximum, but the core distribution range in YGP was stable. Our results showed that the divergence of Q. franchetii complex is rooted in the mid-Oligocene. The early geological events during the Oligocene, and the late Miocene may play key roles to restrict seed-mediated gene flow among regions, but the pollen-mediated gene flow was less impacted. The uplifts of the YGP and the climate since LGM subsequently boosted the divergence of the populations in core and marginal areas.

Facile Preparation of Modifying Layered Double Hydroxide Nanoparticles for Drug Delivery.

Mg-Al-NO3 hydrotalcite (p-LDH) was employed as a carrier for the controlled release of 5-Fluorouracil (5-FU). The p-LDH was pretreated by acid-pretreatment to gain a more stable material (a-LDH) in acid medium for oral administration. It demonstrated that the a-LDH had smaller crystal size, particle sizes and higher permanent charge density (σp) compared with that of the p-LDH by means of XRD, SEM, FT-IR, UV-vis DRS, TG-DSC, BET/BJH and other techniques. The FU/a-LDH and FU/p-LDH delivery systems were obtained using anion-exchange method. The in vitro 5-FU drug release studies showed that no burst release phenomenon was observed at the beginning of release tests. The in vitro 5-FU release behaviors of the delivery systems at initial pH 4.6 and 7.5 were studied which could be described by first-order and Bhaskas models. Combined with the XRD and FT-IR analyses of the solid residues of the FU/a-LDH and FU/p-LDH after the release, it was found that the dissolution mechanism was mainly responsible for the release behavior of the FU/p-LDH at initial 4.6, while the anion-exchange between intercalated 5-FU and phosphate anions mechanism was responsible for the FU/a-LDH at pH 4.6 and 7.5 as well as FU/p-LDH at pH 7.5. It is concluded that the hydrotalcites could be used as the basis of a tunable drug delivery carrier for 5-FU.

Monocarboxylate transporter 1 and the vulnerability of oligodendrocyte lineage cells to metabolic stresses.

AIMS: Oligodendrocytes, especially oligodendrocyte precursor cells, are known to be sensitive to hypoxic and metabolic stresses. Vulnerability of oligodendrocytes is considered a contributing factor to white matter dysfunction. However, little is known about the energy processing characteristics of oligodendrocyte lineage cells under basal and metabolic stress conditions. The aim of this study was to identify the energy requirements and cellular responses of oligodendrocytes at different developmental stages. METHODS: We compared the metabolic stress responses between myelinating oligodendrocytes (OLs) and oligodendrocyte precursor cells (OPCs). Differential regulation of cellular response was also investigated. RESULTS: We found that, following cerebral ischemia, monocarboxylate transporter 1 (MCT1) expression was upregulated in the peri-infarct striatum but not in the cortex of the brain. In vitro ischemia models were used to induce oligodendrocyte stress as well. An increase in MCT1 expression was detected in OPCs after a mild oxygen-glucose deprivation. Double-labeled immunohistochemical analysis revealed that OPCs and OLs responded differently to metabolic stresses and that the susceptibility to metabolic stresses of OPCs and OLs was associated with their distinct expression profiles of MCT1. CONCLUSION: Taken together, this study shows that MCT1 plays a role in the responses of OPCs and OLs to metabolic and ischemic stresses and suggests that redistribution of energy substrates is a determinant in white matter injury.

The influence of dizocilpine on the reserpine-induced behavioral and neurobiological changes in rats.

Clinical studies have demonstrated that a single dose of ketamine produces complete remission within 24h in some depression patients. The ability of ketamine to produce fast-acting antidepressant-like effects in animal models depends on rapid synthesis of brain-derived neurotrophic factor (BDNF). Here we examined effects of a single dose dizocilpine, a non-competitive NMDA receptor antagonist, on the behavioral and neurobiological changes in rats treated with a single high dose reserpine, which is a monoamine re-uptake blocker and depletes monoamines in the brain with the outcome of depression-like symptoms in animals. A single high dose reserpine (4.0mg/kg) was given to rats intraperitoneally. Forty-eight hours later, the rats showed depressive symptoms as evidenced by decreased locomotor activity in the open field and increased immobility time in the forced swim test. Meanwhile, the treatment decreased BDNF levels and neurogenesis in the hippocampus. Pretreatment of a single dose dizocilpine (0.30mg/kg), however, prevented all the reserpine-induced changes, except for GluN1 subunit. These results are suggestive of the involvement of neurogenesis and BDNF in the rapid-acting antidepressant-like behavioral effects of the NMDA receptor antagonists in the reserpinized rats.

Changes in proinflammatory cytokines and white matter in chronically stressed rats.

Although the pathogenesis of depression, an incapacitating psychiatric ailment, remains largely unknown, previous human and animal studies have suggested that both proinflammatory cytokines and altered oligodendrocytes play important roles in the condition. This study examined these two factors in the brains of rats following unpredictable chronic mild stress for 4 weeks, with the hypothesis that chronic stress may affect oligodendrocytes and elevate proinflammatory cytokines in the brain. After suffering unpredictable stressors for 4 weeks, the rats showed depression-like behaviors, including decreased locomotion in the open field, increased immobility time in the forced swim test, and decreased sucrose consumption and less sucrose preference when compared with controls. Immunohistochemical staining of brain sections showed higher immunoreactivity of proinflammatory cytokines in certain brain regions of stressed rats compared with controls; lower immunoreactivity of myelin basic protein and fewer mature oligodendrocytes were seen in the prefrontal cortex, but no demyelination was detected. These results are interpreted and discussed in the context of recent findings from human and animal studies.

Chronic social isolation decreases glutamate and glutamine levels and induces oxidative stress in the rat hippocampus.

Social isolation (SI) rearing of rodents is a developmental manipulation, which is commonly compared with the psychological stressors in humans as it produces several behavioral outcomes similar to those observed in humans with early life stress. To explain the SI-induced behavioral outcomes, animal studies have been performed to examine the dopaminergic and glutamatergic systems in the brain. In this study, we measured possible changes in levels of glutamate and glutamine of SI-rats using proton magnetic resonance spectroscopy. We also assessed the oxidative stress parameters in certain brain regions to see if glutamate and/or glutamine changes, if any, are associated with oxidative stress. SI rearing for 8 weeks decreased the activities of antioxidant enzymes catalase, glutathione peroxidase, superoxide dismutase, and the total antioxidant capacity, but increased levels of hydrogen peroxide, in certain brain regions, of which prefrontal cortex and hippocampus were most vulnerable. It also decreased levels of glutamate, glutamine, N-acetyl-l-aspartate (NAA), and phosphocreatine in the dorsal hippocampus, but not in the cerebral cortex. Decreased phosphocreatine and NAA indicate energy metabolism deficit in brain cells; the latter also suggests the neuronal viability was inhibited. Decreased glutamate and glutamine may suggest the neuron-glial integrity was implicated by chronic SI. These neurochemical and biochemical changes may contribute to the SI-induced behavioral abnormalities including a high level of anxiety, social interaction deficit, and impaired spatial working memory shown in this study.

The effect of 3-hydroxybutyrate methyl ester on learning and memory in mice.

Learning and memory requires energy-demanding cellular processes and can be enhanced when the brain is supplemented with metabolic substrates. In this study, we found that neuroglial cell metabolic activity was significantly elevated when cultured in the presence of polyhydroxybutyrate (PHB) degradation product 3-hydroxybutyrate (3-HB) and derivatives. We demonstrated that the receptor for 3-HB, namely, protein upregulated in macrophages by IFN-gamma (PUMA-G), was expressed in brain and upregulated in mice treated with 3-hydroxybutyrate methyl ester (3-HBME). We also affirmed increased expression of connexin 36 protein and phosphorylated ERK2 (extracellular signal-regulated kinase 2) in brain tissues following 3-HBME treatment, although these differences were not statistically significant. Mice treated with 3-HBME performed significantly (p<0.05) better in the Morris water maze than either the negative controls (no treatment) or positive controls (acetyl-l-carnitine treatment). Moreover, we found that 3-HBME enhanced gap junctional intercellular communication between neurons. Thus, 3-HB and derivatives enhance learning and memory, possibly through a signaling pathway requiring PUMA-G that increases protein synthesis and gap junctional intercellular communication.

Brain IL-1 beta was involved in reserpine-induced behavioral depression in rats.

AIM: To investigate the mechanism of brain interleukin-1 beta (IL-1 beta) in reserpine-induced behavioral depression in rats. METHODS: Porsult swim test was used in the measurement of depressive behavior and ELISA was used in measurement of brain IL-1 beta. RESULTS: Intraperitoneal injection of reserpine (0, 4, 6, and 8 mg/kg, ip) increased floating time in the Porsult swim test in a dose-and time-dependent manner in rats. Intracerebroventricular injection (icv) of IL-1 beta receptor antagonist (IL-1ra, 6 mg/kg) blocked the increment of floating time in Porsult swim test at 48 and 72 h after reserpine injection, but not at 1 and 24 h after injection. Brain IL-1 beta increased after reserpine treatment in posterior cortex, hippocampus, and hypothalamus. The increase of IL-1 beta concentration starts at 24 hours after injection of reserpine and reached the peak at 48 h. CONCLUSION: Reserpine induced behavioral depression partially via brain interleukin-1 beta generation.