Major depressive disorder (MDD) is a common psychiatric disorder effecting approximately 121 million people worldwide and recent reports from the World Health Organization (WHO) suggest that it will be the leading contributor to the global burden of diseases. At present the most commonly used treatment strategies are still based on the monoamine hypothesis that has been the predominant theory in the last 60 years. Clinical observations that only a subset of depressed patients exhibits full remission when treated with classical monoamine-based antidepressants together with the fact that patients exhibit multiple symptoms suggest that the pathophysiology leading to mood disorders may differ between patients. Accumulating evidence indicates that depression is a neural circuit disorder and that onset of depression may be located at different regions of the brain involving different transmitter systems and molecular mechanisms. This review synthesizes findings from rodent studies from which emerges a role for different, yet interconnected, molecular systems and associated neural circuits to the etiology of depression.

ObjectivesTo examine the association of living arrangements with functional disability among older persons and explore the mediation of impact factors on the relationship.DesignCross-sectional analysis using data from Healthy Aging study in Zhejiang Province.ParticipantsAnalyzed sample was drawn from a representative rural population of older persons in Wuyi County, Zhejiang Province, including 1542 participants aged 60 and over in the second wave of the study.MeasurementsLiving arrangements, background, functional disability, self-rated health, number of diseases, along with contemporaneous circumstances including income, social support (physical assistance and emotional support). Instrument was Activities of Daily Living (ADL) scale, including Basic Activities Daily Living (BADL) and Instrumental Activities of Daily Living (IADL).ResultsLiving arrangements were significantly associated with BADL, IADL and ADL disability. Married persons living with or without children were more advantaged on all three dimensions of functional disability. Unmarried older adults living with children only had the worst functional status, even after controlling for background, social support, income and health status variables (compared with the unmarried living alone, ß for BADL: −1.262, ß for IADL: −2.112, ß for ADL: −3.388; compared with the married living with children only, ß for BADL: −1.166, ß for IADL: −2.723, ß for ADL: −3.902). In addition, older adults without difficulty in receiving emotional support, in excellent health and with advanced age had significantly better BADL, IADL and ADL function. However, a statistically significant association between physical assistance and functional disability was not found.ConclusionFunctional disabilities vary by living arrangements with different patterns and other factors. Our results highlight the association of unmarried elders living with children only and functioning decline comparing with other types. Our study implies policy makers should pay closer attention to unmarried elders living with children in community. Community service especially emotional support such as psychological counseling is important social support and should be improved.

BackgroundDexmedetomidine (DEX) has been used under perioperative settings as an adjuvant to enhance the analgesic property of local anesthetics by some anesthesiologists. However, the analgesic mechanisms and neurotoxicity of DEX were poorly understood. This study examined the effect of DEX alone on inflammatory pain, and it also examined the underlying molecular mechanisms of DEX in the spinal cord. Furthermore, in vivo and in vitro experiments were performed to investigate the neurotoxicity of DEX on the spinal cord and cortical neurons.MethodsThis study used adult, male Kunming mice. In the acute inflammatory model, the left hind-paws of mice were intradermally injected with pH 5.0 PBS while chronic constrictive injury (CCI) of the sciatic nerve was used to duplicate the neuropathic pain condition. Thermal paw withdrawal latency and mechanical paw withdrawal threshold were tested with a radiant heat test and the Von Frey method, respectively. Locomotor activity and motor coordination were evaluated using the inverted mesh test. Western blotting examined spinal ERK1/2, p-ERK1/2, caspase-3 and β-actin expressions, while spinal c-Fos protein expression was realized with immunohistochemical staining. Hematoxylin eosin (HE) staining was used to examine the pathological impacts of intrathecal DEX on the spinal cord. DAPI (4′,6-diamidino-2-phenylindole) staining was used to observe cell death under an immunofluorescence microscope.ResultsIntra-plantar pH 5.0 PBS-induced acute pain required spinal ERK1/2 activation. Inhibition of spinal ERK1/2 signaling by intrathecal injection of DEX displayed a robust analgesia, via a α2-receptor dependent manner. The analgesic properties of DEX were validated in CCI mice. In vivo studies showed that intrathecal DEX has no significant pathological impacts on the spinal cord, and in vitro experiments indicated that DEX has potential protective effects of lidocaine-induced neural cell death.ConclusionIntrathecal injection of DEX alone or as an adjuvant might be potential for pain relief.