Synaptic Plasticity in an In Vitro Slice Preparation of the Rat Nucleus Accumbens

Extra- and intracellular recordings in slices were used to examine what types of synaptic plasticity can be found in the core of the nucleus accumbens, and how these forms of plasticity may be modulated by dopamine. Stimulus electrodes were placed at the rostral border of the nucleus accumbens in order to excite primarily infralimbic and prelimbic afferents, as was confirmed by injections of the retrograde tracer fluoro-gold. In extracellular recordings, tetanization induced long-term potentiation (LTP) of the population spike in 20 out of 53 slices. The presynaptic compound action potential did not change following LTP induction. For the intracellularly recorded excitatory postsynaptic potential, three types of synaptic plasticity were noted: long-term potentiation (16 out of 54 cells), decremental potentiation (eight cells) and long-term depression (LTD; six cells). No correlation was found between the occurrence of potentiation or depression and various parameters of the tetanic depolarization (e.g. peak voltage, integral under the curve). The N -methyl- d -aspartate receptor antagonist d (–)-2-amino-5-phosphonopentanoic acid (50 μM; d -AP5) reduced, but did not completely prevent, the induction of LTP. The incidence of LTD was not markedly affected by d -AP5. No difference in LTP was found when comparing slices bathed in dopamine (10 μM) and controls. Likewise, slices treated with a mixture of the D1 receptor antagonist Sch 23390 (1 μM) and the D2 antagonist S (–)-sulpiride (1 μM) generated a similar amount of LTP as controls. In conclusion, both LTP and LTD can be induced in a key structure of the limbic-innervated basal ganglia. LTP in the nucleus accumbens strongly depends on N -methyl- d -aspartate receptor activity, but is not significantly affected by dopamine.     

Deprivation of parenting disrupts development of homeostatic and reward systems in marmoset monkey offspring.

BACKGROUND: Early environment is a major determinant of long-term mental health, evidenced by the relationship between early-life neglect or abuse and chronically increased vulnerability to developmental psychopathology, including major depressive disorder (MDD). Animal studies can increase understanding of environmentally mediated causal risk processes. We describe how daily deprivation of biological parenting in primate infants disrupts development of homeostatic and reward systems central to MDD. METHODS: Nine breeding pairs of marmoset monkeys provided control twins (CON) and early-deprived twins (ED); the latter were socially isolated for 30-120 min/day on days 2-28. During the first year of life, basal urinary norepinephrine (NE) titers and cardiophysiologic activity were measured. At the end of year 1 (adolescence), automated neuropsychologic tests were conducted to measure responsiveness to changes in stimulus-reward association (simple/reversed visual discrimination learning) and to reward per se (progressive ratio [PR] reinforcement schedule). RESULTS: The ED monkeys exhibited increased basal urinary NE titers and increased systolic blood pressure relative to CON siblings. The ED monkeys required more sessions to reinstate stimulus-oriented behavior following reversal, suggesting increased vulnerability to perceived loss of environmental control; ED monkeys also performed less PR operant responses, indicating that reward was less of an incentive and that they were mildly anhedonic relative to CON. CONCLUSIONS: In marmoset monkeys, neglect-like manipulation of ED leads to chronic changes in homeostatic systems, similar to those in children and adolescents exposed to early-life adversity and in MDD, and to responses to environmental stimuli similar to those that characterize MDD.     

抑郁障碍对血液透析患者的影响

目的 探讨尿毒症患者产生抑郁障碍的可能因素及其对血液透析的影响，并尝试药物治疗，改善患者的生活质量。方法 选择无精神病史的规律性血透患者51例，进行汉密尔顿抑郁量表(HAMD，24项版本)评分，并分为抑郁组和非抑郁组；在组间进行性别、年龄、文化程度和经济状况的比较，观察患者透析充分性、营养、就业率及顺应性在组间的差异。选择重度抑郁状态者予博乐欣(75-150mg/d)抗抑郁治疗，观察疗效。结果 (1)35．3％的患者存在抑郁障碍；(2)两组的年龄、性别、文化程度和婚姻障碍情况均无显著差异；(3)两组间在医疗付费方式、透前规律性肾科门诊及顺应性、充分性、营养状态方面存在显著差异；(4)在18例中选7例抗抑郁治疗，1个月后HAMD评分均有不同程度下降。结论 抑郁障碍在血透患者中是常见的。它可造成血透患者的顺应性下降、营养不良、透析不充分等。抗抑郁的药物治疗可望改善患者的抑郁状态。     

兔孤束核区微量注射γ-氨基丁酸的降压效应

在53只乌拉坦麻醉家兔身上,观察到延髓孤束核(NTS)区注射γ-氨基丁酸(GABA)使血压显著下降,安定(DZ)有相似的降压效应,荷包牡丹碱(BIC)和印防己毒素(PIC)则使血压升高;促甲状腺素释放激素(TRH)和甲硫脑啡肽(MTP)对血压无明显影响;延髓的另一些区域应用GABA等药物后血压变化不明显;提示GABA能神经递质系统参与心血管活动的抑制性中枢调节,NTS区是其作用部位之一。     

Prefrontal cortex dysfunction and depression in atypical parkinsonian syndromes.

Depressive symptoms are common in patients with neurodegenerative disorders. Imaging studies suggest that a disruption of frontal-subcortical pathways may underlie depression associated with basal ganglia disease. This pilot study tested the hypothesis that frontal dysfunction contributes to depression associated with multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). Depressed patients with MSA (n = 11), PSP (n = 9), and age-matched controls (n = 25) underwent measures of cerebral glucose metabolism applying positron emission tomography with (18)F-fluorodeoxyglucose. Regional metabolism in the patient groups was compared to the normal subjects using the voxel-based statistical parametric mapping. Depressive symptom severity (Hamilton Depression Rating) and degree of locomotor disability (Hoehn & Yahr) were assessed in the patient groups. The association between prefrontal metabolism and the occurrence of depressive symptoms and the degree of locomotor disability was investigated. When compared to controls, MSA patients revealed significant metabolic decreases in bilateral frontal, parietal, and cerebellar cortex and in the left putamen. In PSP patients, significant hypometabolism was demonstrated in bilateral frontal cortex, right thalamus, and midbrain. Depression severity but not the patients' functional condition was significantly associated with dorsolateral prefrontal glucose metabolism in both patient groups. The findings of this pilot study support the hypothesis that depressive symptoms in MSA and PSP are associated with prefrontal dysfunction.     

住院抑郁症患者糖尿病患病率调查

目的:调查抑郁症患者糖尿病的患病率,分析与2型糖尿病患病率有关的危险因素。方法:以2003年内的抑郁症出院病例为研究对象,以世界卫生组织关于糖尿病的诊断标准(1997年)观察血糖和血脂的动态变化,了解抑郁症患者中糖尿病的患病率;用Logistic回归分析影响糖尿病发生的相关因素。结果:248例抑郁症患者中糖尿病患者为27例,抑郁症患者中糖尿病的患病率为10.9%;进入单因素非条件Logistic回归方程的有性别、年龄、文化程度、高脂血症、伴发躯体疾病数目和抑郁症发病诱因;选入多因素非条件Logistic回归方程的有高脂血症、伴发躯体疾病数目和抑郁症发病诱因。结论:抑郁症患者中糖尿病的患病率为10.9%,高脂血症、伴发躯体疾病数目和发病诱因是抑郁症合并糖尿病的独立危险因素。     

Screening for major depression in persons with HIV infection: the concurrent predictive validity of the Profile of Mood States Depression‐Dejection Scale

Major Depressive Disorder (MDD) is among the most prevalent but underdiagnosed psychiatric disorders in persons with HIV infection. Given the known adverse impact of comorbid MDD on HIV disease progression and health‐related quality of life, it is important both for research and for efficient, effective clinical care, to validate existing screening measures that may discriminate between MDD and the somatic symptoms of HIV (such as fatigue). In the current study, we evaluated the concurrent predictive validity of the Profile of Mood States (POMS) Depression‐Dejection scale in detecting current MDD in 310 persons with HIV infection. The Structured Clinical Interview for DSM‐IV (SCID) diagnosis of MDD and the Cognitive‐Affective scale from the Beck Depression Inventory (BDI‐CA) served as comparative diagnostic and severity measures of depression, respectively. Results demonstrated that the POMS Depression‐Dejection scale accurately classified persons with and without MDD SCID diagnoses, with an overall hit rate of 80%, sensitivity of 55%, specificity of 84%, and negative predictive power of 91% using a recommended cutpoint of 1.5 standard deviations above the normative mean. Moreover, the POMS performed comparably to the BDI‐CA in classifying MDD. Findings support the predictive validity of the POMS Depression‐Dejection scale as a screening instrument for MDD in persons with HIV disease. Copyright © 2006 John Wiley & Sons, Ltd.     

抑郁症病机及临证治疗思路

抑郁症的发病率呈上升趋势,引起全社会的重视。中医药治疗该病具有独到的优势,认为病位在脑,病机为气痰郁结、阴血不足、精髓不足、阴虚内热,据此提出抑郁症分为3期,初期为肝郁,中期为心脾两虚,后期为肾虚。     

A neurotrophic model for stress-related mood disorders.

There is a growing body of evidence demonstrating that stress decreases the expression of brain-derived neurotrophic factor (BDNF) in limbic structures that control mood and that antidepressant treatment reverses or blocks the effects of stress. Decreased levels of BDNF, as well as other neurotrophic factors, could contribute to the atrophy of certain limbic structures, including the hippocampus and prefrontal cortex that has been observed in depressed subjects. Conversely, the neurotrophic actions of antidepressants could reverse neuronal atrophy and cell loss and thereby contribute to the therapeutic actions of these treatments. This review provides a critical examination of the neurotrophic hypothesis of depression that has evolved from this work, including analysis of preclinical cellular (adult neurogenesis) and behavioral models of depression and antidepressant actions, as well as clinical neuroimaging and postmortem studies. Although there are some limitations, the results of these studies are consistent with the hypothesis that decreased expression of BDNF and possibly other growth factors contributes to depression and that upregulation of BDNF plays a role in the actions of antidepressant treatment.