Activity-dependent Decay of Early LTP Revealed by Dual EPSP Recording in Hippocampal Slices from Young Rats

The early maintenance of long-term potentiation (LTP) was studied in the CA1 region of hippocampal slices from 12- to 18-day-old rats in a low-magnesium solution (0.1 mM). The α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptor-mediated components of the field excitatory postsynaptic potential were estimated in parallel using early and late measurements of the composite potential. At the normal test stimulus frequency of 0.1 Hz, LTP was seen initially as a predominant increase in the AMPA component, but converted, via a substantial decay of this component and a gradual growth of the NMDA component, into nearly equal changes of the two components. Interrupting the test stimulation for 10 min, changing the test stimulus frequency to 1/60 Hz after LTP induction, or using a test stimulus frequency of 1/60 Hz during the entire experiment significantly reduced the decay of the potentiation of the AMPA component while enhancing the potentiation of the NMDA one. The ratio between the magnitudes of the two excitatory postsynaptic potential (EPSP) components showed a decaying time course that was independent of the manipulations used. Application of the NMDA antagonist D(-)-2-amino-5-phosphonopentanoic acid (50μM) after LTP induction stabilized the LTP of the AMPA component until washout was started. On the other hand, the phosphatase inhibitor okadaic acid (1 μM) resulted in decay of the potentiation of both EPSP components back to around baseline and altered the time course of the ratio between the components. Our results show that the early maintenance of LTP is controlled in an activity-dependent and NMDA-dependent manner. This process accelerates the decay of LTP of both AMPA and NMDA components in parallel, suggesting that it is similar to homosynaptic long-term depression, although it operates at the normal test stimulus frequency. The data support a scenario in which LTP ensues as a selective AMPA receptor modification and subsequently converts to another modification, possibly a presynaptic one.     

Differences between urban and rural suicides

As part of a nation-wide psychological autopsy we examined the differences in DSM-III-R mental disorders, recent life events and other characteristics between urban (n=143) and rural (n=85) completed suicides in a random sample of 229 cases from the National Suicide Prevention Project in Finland for the period 1987-1988. Psychoactive substance use disorders (48% vs. 34%), cluster B personality disorders (24% vs. 9%) and psychiatric comorbidity (66% vs. 42%) were found more commonly among urban than rural suicides. Urban suicides were also more often reported to be preceded by a recent separation (25% vs. 8%), whereas rural suicide victims tended to have lacked a close companion of the opposite sex (36% vs. 18%) and to have had physical disorders (56% vs. 40%). Overall, urban and rural suicides may vary with regard to the prevalence of some mental disorders, their comorbidity, and physical disorders, as well as the preceding life situation. This variation may also imply the need for differences in strategies for suicide prevention in each setting.     

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。     

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.     

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.     

Dysphoric Rumination Impairs Concentration on Academic Tasks

Three studies investigated the effects of dysphoric rumination on concentration during 3 academic tasks—reading a passage from the GRE (Study 1), watching a videotaped lecture (Study 2), and proofreading written text (Study 3). Before performing these tasks, dysphoric and nondysphoric students were induced either to ruminate about themselves or to distract themselves by focusing on neutral images (all three studies) or by planning an event (Study 1). The results supported our hypothesis that dysphoric rumination, relative to distraction, would impair students' concentration. In all 3 studies, dysphoric ruminators reported difficulty concentrating, as well as interfering thoughts, during the relevant academic tasks. Furthermore, dysphoric ruminators were slower than dysphoric distractors in completing the tasks—specifically, reading the GRE passage (Study 1) and answering lecture comprehension questions (Study 2). In addition, dysphoric participants who ruminated showed impaired reading strategies (Study 1), reduced comprehension of academic material (Study 2), and poor proofreading performance (Study 3). These findings suggest that, in addition to its documented adverse effects on mood, thinking, and problem-solving, self-focused rumination interferes with instrumental behavior. Implications for social relationships and job performance are discussed.     

Antidepressant-associated maniform states in acute treatment of patients with bipolar-I depression

Medical records of 158 patients with bipolar depression were analysed for the incidence of a switch from depression to maniform states (mania and hypomania). Relation to psychopharmacological treatment was investigated. Thirty-nine (25%) patients of the total sample had switched to a maniform state during the treatment period in the hospital. Among that group the phenomenon occurred in 23 patients (15%) as a hypomania and in 16 patients (10%) as a mania. Patients with a switch were significantly more often treated with tricyclic antidepressants (TCA) than patients without switch (79.5% vs 51.3%). Mood stabilising medication might reduce the risk for switching, especially in patients treated with TCA; however, it seems not totally sufficient, since 59% of the switched patients received mood stabilisers. The switch phenomenon was not associated with sociodemographic or clinical data. Received: 23 September 1998 / Accepted: 28 September 1998