PATHOPHYSIOLOGY OF DEPRESSION: DO WE HAVE ANY SOLID EVIDENCE OF INTEREST TO CLINICIANS?

Due to the clinical and etiological heterogeneity of major depressive disorder, it has been difficult to elucidate its pathophysiology. Current neurobiological theories with the most valid empirical foundation and the highest clinical relevance are reviewed with respect to their strengths and weaknesses. The selected theories are based on studies investigating psychosocial stress and stress hormones, neurotransmitters such as serotonin, norepinephrine, dopamine, glutamate and gamma-aminobutyric acid (GABA), neurocircuitry, neurotrophic factors, and circadian rhythms. Because all theories of depression apply to only some types of depressed patients but not others, and because depressive pathophysiology may vary considerably across the course of illness, the current extant knowledge argues against a unified hypothesis of depression. As a consequence, antidepressant treatments, including psychological and biological approaches, should be tailored for individual patients and disease states. Individual depression hypotheses based on neurobiological knowledge are discussed in terms of their interest to both clinicians in daily practice and clinical researchers developing novel therapies.     

Ketamine modulates TRH and TRH-like peptide turnover in brain and peripheral tissues of male rats

Major depression is the largest single healthcare burden with treatments of slow onset and often limited efficacy. Ketamine, a NMDA antagonist used extensively as a pediatric and veterinary anesthetic, has recently been shown to be a rapid acting antidepressant, making it a potential lifesaver for suicidal patients. Side effects and risk of abuse limit the chronic use of ketamine. More complete understanding of the neurobiochemical mechanisms of ketamine should lead to safer alternatives. Some of the physiological and pharmacological actions of ketamine are consistent with increased synthesis and release of TRH (pGlu-His-Pro-NH₂), and TRH-like peptides (pGlu-X-Pro-NH₂) where “X” can be any amino acid residue. Moreover, TRH-like peptides are themselves potential therapeutic agents for the treatment of major depression, anxiety, bipolar disorder, epilepsy, Alzheimer's and Parkinson's diseases. For these reasons, male Sprague–Dawley rats were anesthetized with 162 mg/kg ip ketamine and then infused intranasally with 20 μl of sterile saline containing either 0 or 5 mg/ml Glu-TRH. One, 2 or 4 h later, the brain levels of TRH and TRH-like peptides were measured in various brain regions and peripheral tissues. At 1 h in brain following ketamine only, the levels of TRH and TRH-like peptides were significantly increased in 52 instances (due to increased biosynthesis and/or decreased release) or decreased in five instances. These changes, listed by brain region in order of decreasing number of significant increases (↑) and/or decreases (↓), were: hypothalamus (9↑); piriform cortex (8↑); entorhinal cortex (7↑); nucleus accumbens (7↑); posterior cingulate (5↑); striatum (4↑); frontal cortex (2↑,3↓); amygdala (3↑); medulla oblongata (1↑,2↓); cerebellum (2↑); hippocampus (2↑); anterior cingulate (2↑). The corresponding changes in peripheral tissues were: adrenals (8↑); epididymis (4↑); testis (1↑,3↓); pancreas (1↑); prostate (1↑). We conclude that TRH and TRH-like peptides may be downstream mediators of the rapid antidepressant actions of ketamine.     

Improving psychometric assessment of the Beck Depression Inventory using Multidimensional Item Response Theory

We studied the latent factor structure of the Beck Depression Inventory (BDI) under the light of Multidimensional Item Response Theory models. Under a Bayesian Markov chain Monte Carlo setting, we chose the most adequate model, estimated its parameters and verified its fit to the data. An evaluation of the inventory in terms of the assumed dimensions seems to agree with previous investigations in the factor structure of the BDI present in the literature. Cognitive and somatic‐affective latent traits were identified in the analysis making possible the interpretation of symptom evolution along these dimensions, in terms of probability of their appearance.     

Phase-Synchronization of Daily Motor Activities Can Reveal Differential Circadian Patterns

A patient diagnosed with seasonal affective disorder (SAD) carried out prospective ratings of depression weekly for nearly a decade. A winter peak of depression and benzodiazepine intake was documented. However, over the years, the depressive episodes shifted toward spring in an apparent free-running circannual rhythm (periodogram peaks at 53 and 55 weeks). This patient may have an underlying seasonal propensity to depression no longer precisely entrained to environmental cues. (Chronobiology International, 18(2), 309–313, 2001)     

Effects of Insulin and Streptozotocin-Induced Diabetes on Brain Norepinephrine Metabolism in Rats

Administration of insulin (2 IU/kg, i.p.) produced a significant decrease (18%) in forebrain norepinephrine and a significant increase in the major metabolite of norepinephrine, 3-methoxy-4-hydroxyphenylglycol-sulfate (MOPEG-SO4, +19%) in rats. Streptozotocin-induced diabetes produced the opposite effects, resulting in an increase in forebrain norepinephrine (+17%) and a decrease in MOPEG-SO4 (-26%). In addition, insulin increased (+143%) and diabetes decreased (-41%) the turnover rate of norepinephrine, as measured by the rate of decrease of norepinephrine following inhibition of tyrosine hydroxylase by alpha-methyl-p-tyrosine. All of these effects in diabetic rats were reversed by insulin replacement therapy. These data are discussed within the context of mood disorders characteristic of diabetic patients.     

Design,synthesis and biological evaluation of novel serotonin and dopamine receptor ligands being 6-bromohexyl saccharine derivatives

Due to numerous side effects of current antidepressants, the search for new, safer bioactive compounds is still a valid research topic in medical chemistry. In our research we decided to synthesize and determine SAR for new hexyl arylpiperazines (LACPs) derivated with saccharin moiety. High biological activity has been explained using molecular modelling methods. The compounds obtained show high affinity for the 5-HT_1A (compound 18, K_i = 4 nM – antagonist mode) and D₂ (compound 15, K_i = 7 nM – antagonist mode) receptor, and in some cases also 5-HT₇ receptor (compound 17, K_i = 20 nM). A preliminary ADME analysis showed that the compounds exhibit CNS drugability properties. We have proved that carbon-chain lengthening may have a beneficial effect on increasing the activity towards serotonin and dopamine receptors.     

Culpa por percibirse como una carga. Una variable relevante asociada al malestar psicológico de las personas mayores

AimsTo analyze the relationship between guilt for perceiving oneself as a burden and negative self-perceptions of aging, perceived control and anxious and depressive symptomatology in older people without cognitive or functional limitations.MethodsParticipants were 351 community-dwelling people over 60 years without explicit cognitive or functional limitation. Indirect effet analysis were conducted that examined the indirect effect of negative self-perceptions of aging through 1) perceived control and anxious symptomatology and 2) perceived control and depressive symptomatology in guilt for perceiving oneself as a burden.ResultsBoth models showed an indirect relationship between negative self-perceptions of aging and guilt for perceiving oneself as a burden through 1) perceived control and anxious symptomatology and 2) perceived control and depressive symptomatology, explaining 26.37% of anxious symptomatology, 48.51% of depressive symptomatology and 13.73% and 14.44% of guilt for perceiving oneself as a burden, respectively.DiscussionThe results obtained suggest that higher negative self-perceptions of aging is associated with a lower perception of control and greater psychological distress (anxiety and depression), and this process increases the feeling of guilt for perceiving oneself as burden to family members in older people without functional or cognitive limitations.     

运动疗法对慢性阻塞性肺疾病患者抑郁状态的效果观察

目的:探讨运动疗法对慢性阻塞性肺疾病(COPD)患者抑郁状态的临床效果。方法:选取52例COPD患者,随机分为试验组和对照组,各26例。对照组给予支气管扩张、健康教育、氧疗,试验组在对照组的基础上实施运动疗法,采用焦虑自评量表(SAS)、抑郁自评量表(SDS)、ADL生活质量量表对两组患者治疗前后进行评估。结果:对照组患者SAS、SDS评分治疗前后无明显变化,试验患者SAS、SDS评分均明显低于治疗前(P0.05),两组治疗后组间比较,差异亦有统计学意义(P0.05);试验组生活质量的改善优于对照组(P0.05)。结论:运动疗法能有效的改善COPD患者焦虑、抑郁负性情绪,提高患者的生存质量。     

当归抗抑郁作用及配伍应用

旨在探讨当归在抑郁症治疗中发挥的作用。通过分析相关文献,结合当归的临床功效和抑郁症的疾病特点,概括当归抗抑郁作用规律。当归在抑郁症治疗中具有补血以养肝体、活血以通心脉、通便以利肠腑的作用,以其为主药的抗抑郁复方临床应用广泛。当归的抗抑郁作用值得进一步深入研究。     

渤海海域渤东凹陷沙河街组四段古生物组合的发现及其意义

渤海海域渤东凹陷沙河街组四段内发现了丰富的孢粉、藻类和轮藻类化石组合,孢粉组合与渤海湾沿岸地区沙河街组四段的E phedri pites-Ulmoidei pites tricostatus-Pterisis porites组合特征一致,沟鞭藻类见有Luxadinium elongatum,Cangaianella e...