How does cognitive therapy prevent relapse in residual depression? Evidence from a controlled trial.

This study examined the cognitive mediation of relapse prevention by cognitive therapy (CT) in a trial of 158 patients with residual depression. Scores based on agreement with item content of 5 questionnaires of depression-related cognition provided no evidence for cognitive mediation. A measure of the form of response to those questionnaires, the number of times patients used extreme response categories ("totally agree" and "totally disagree"), showed significant and substantial prediction of relapse, differential response to CT, and conformity to mediational criteria. CT reduced relapse through reductions in absolutist, dichotomous thinking style. CT may prevent relapse by training patients to change the way that they process depression-related material rather than by changing belief in depressive thought content. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Electrochemical properties of self-assembled monolayer based on mono-(6-deoxy-6-mercapto)-β-cyclodextrin toward controlled molecular recognition

The present work describes the construction of nanoporous assemblies based on single self-assembled monolayer (SAM) of mono-(6-deoxy-6-mercapto)-β-cyclodextrin (βCDSH) and two-component monolayers of βCDSH and 11-mercaptoundecanoic acid. An investigation of its supramolecular properties toward the tricyclic antidepressants drugs chlorprothixene and imipramine is also presented. The adsorption process was investigated by using surface plasmon resonance and the selectivity of the SAM was verified by using electroactive species permeable and not permeable into the cyclodextrin SAM, such as ferrocenemonocarboxylic acid, hexacyanoferrate, methylene blue and hexamineruthenium (II). The redox probe was chosen based on its capability to permeate the grafted cyclodextrin molecules and its electrochemical characteristics. It was applied to imipramine and chlorprothixene competitive assay by the mono-(6-deoxy-6-mercapto)-β-cyclodextrin self-assembled cavity. Finally, the pK_a of the surface and its effects on thee host-guest interaction properties were also investigated.     

Prediction of Long-Term Treatment Response to Selective Serotonin Reuptake Inhibitors (SSRIs) Using Scalp and Source Loudness Dependence of Auditory Evoked Potentials (LDAEP) Analysis in Patients with Major Depressive Disorder

Background: Animal and clinical studies have demonstrated that the loudness dependence of auditory evoked potentials (LDAEP) is inversely related to central serotonergic activity, with a high LDAEP reflecting weak serotonergic neurotransmission and vice versa, though the findings in humans have been less consistent. In addition, a high pretreatment LDAEP appears to predict a favorable response to antidepressant treatments that augment the actions of serotonin. The aim of this study was to test whether the baseline LDAEP is correlated with response to long-term maintenance treatment in patients with major depressive disorder (MDD). Methods: Scalp N1, P2 and N1/P2 LDAEP and standardized low resolution brain electromagnetic tomography-localized N1, P2, and N1/P2 LDAEP were evaluated in 41 MDD patients before and after they received antidepressant treatment (escitalopram (n = 32, 10.0 ± 4.0 mg/day), sertraline (n = 7, 78.6 ± 26.7 mg/day), and paroxetine controlled-release formulation (n = 2, 18.8 ± 8.8 mg/day)) for more than 12 weeks. A treatment response was defined as a reduction in the Beck Depression Inventory (BDI) score of >50% between baseline and follow-up. Results: The responders had higher baseline scalp P2 and N1/P2 LDAEP than nonresponders (p = 0.017; p = 0.036). In addition, changes in total BDI score between baseline and follow-up were larger in subjects with a high baseline N1/P2 LDAEP than those with a low baseline N1/P2 LDAEP (p = 0.009). There were significantly more responders in the high-LDAEP group than in the low-LDAEP group (p = 0.041). Conclusions: The findings of this study reveal that a high baseline LDAEP is associated with a clinical response to long-term antidepressant treatment.     

Molecular Consequences of Depression Treatment: A Potential In Vitro Mechanism for Antidepressants-Induced Reprotoxic Side Effects

The incidence of depression among humans is growing worldwide, and so is the use of antidepressants. However, our fundamental understanding regarding the mechanisms by which these drugs function and their off-target effects against human sexuality remains poorly defined. The present study aimed to determine their differential toxicity on mouse spermatogenic cells and provide mechanistic data of cell-specific response to antidepressant and neuroleptic drug treatment. To directly test reprotoxicity, the spermatogenic cells (GC-1 spg and GC-2 spd cells) were incubated for 48 and 96 h with amitriptyline (hydrochloride) (AMI), escitalopram (ESC), fluoxetine (hydrochloride) (FLU), imipramine (hydrochloride) (IMI), mirtazapine (MIR), olanzapine (OLZ), reboxetine (mesylate) (REB), and venlafaxine (hydrochloride) (VEN), and several cellular and biochemical features were assessed. Obtained results reveal that all investigated substances showed considerable reprotoxic potency leading to micronuclei formation, which, in turn, resulted in upregulation of telomeric binding factor (TRF1/TRF2) protein expression. The TRF-based response was strictly dependent on p53/p21 signaling and was followed by irreversible G2/M cell cycle arrest and finally initiation of apoptotic cell death. In conclusion, our findings suggest that antidepressants promote a telomere-focused DNA damage response in germ cell lines, which broadens the established view of antidepressants’ and neuroleptic drugs’ toxicity and points to the need for further research in this topic with the use of in vivo models and human samples.     

Enhanced sensitivity of the MRL/MpJ mouse to the neuroplastic and behavioral effects of acute and chronic antidepressant treatments.

Adult hippocampal neurogenesis has been implicated in the pathophysiology of depression and in the therapeutic effects of antidepressant drugs. Current immunohistochemical methods that study neurogenesis are time consuming and labor intensive. Therefore, a significantly more rapid flow cytometric method was characterized to measure neurogenesis in the adult mouse brain. The sensitivity of mice to the effects of antidepressant treatments is dependent on genetic background. Thus, studies were conducted comparing the responsiveness of 2 inbred mouse strains, MRL/MpJ and C57BL/6J, to the acute and chronic effects of antidepressants on neurochemistry and behavior. Acutely, MRL/MpJ mice displayed more robust behavioral and neurochemical responses to pharmacologically distinct antidepressants than C57BL/6J mice. Chronic administration of the antidepressant drugs fluoxetine and desipramine produced robust elevations in hippocampal cell proliferation and brain-derived neurotrophic factor (BDNF) protein levels in MRL/MpJ mice. C57BL/6J mice treated similarly with antidepressant drugs were mainly unresponsive on these measures. Mice were tested in the novelty-induced hypophagia (NIH) paradigm to examine a behavioral response associated with chronic, but not acute, antidepressant treatment. Only MRL/MpJ mice were behaviorally responsive to chronic antidepressant administration in the NIH paradigm. The positive effects of chronic antidepressants on hippocampal cell proliferation and BDNF paralleled the ability of these drugs to produce changes in NIH behavior. These studies highlight the advantages of using flow cytometry to study hippocampal neurogenesis and identify the MRL/MpJ mouse as a strain with superior response to antidepressant drug treatments that may lead to a better understanding of the genetics behind antidepressant efficacy and sensitivity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Multiple Organolithium Generation in the Continuous Flow Synthesis of Amitriptyline

A continuous flow protocol for the preparation of the tricyclic antidepressant (TCA) amitriptyline is reported. The advantages of flow chemistry when handling organometallic agents as well as when performing reaction with gases are demonstrated. Continuous multilithiation combined with carboxylation and the Parham cyclization, a Grignard addition and thermolytic water elimination by inductive heating are key features of the multistep protocol.

     

Genetic Background Underlying 5-HT1A Receptor Functioning Affects the Response to Fluoxetine

The influence of genetic background on sensitivity to drugs represents a topical problem of personalized medicine. Here, we investigated the effect of chronic (20 mg/kg, 14 days, i.p.) antidepressant fluoxetine treatment on recombinant B6-M76C mice, differed from control B6-M76B mice by CBA-derived 102.73–110.56 Mbp fragment of chromosome 13 and characterized by altered sensitivity of 5-HT_1A receptors to chronic 8-OH-DPAT administration and higher 5-HT_1A receptor mRNA levels in the frontal cortex and hippocampus. Significant changes in the effects of fluoxetine treatment on behavior and brain 5-HT system in recombinant B6-M76C mice were revealed. In contrast to B6-M76B mice, in B6-M76C mice, fluoxetine produced pro-depressive effects, assessed in a forced swim test. Fluoxetine decreased 5-HT_1A receptor mRNA levels in the cortex and hippocampus, reduced 5-HT_1A receptor protein levels and increased receptor silencer Freud-1 protein levels in the hippocampus of B6-M76C mice. Fluoxetine increased mRNA levels of the gene encoding key enzyme for 5-HT synthesis in the brain, tryptophan hydroxylase-2, but decreased tryptophan hydroxylase-2 protein levels in the midbrain of B6-M76B mice. These changes were accompanied by increased expression of the 5-HT transporter gene. Fluoxetine reduced 5-HT and 5-HIAA levels in cortex, hippocampus and midbrain of B6-M76B and in cortex and midbrain of B6-M76C; mice. These data demonstrate that changes in genetic background may have a dramatic effect on sensitivity to classic antidepressants from the Selective Serotonin Reuptake Inhibitors family. Additionally, the results provide new evidence confirming our idea on the disrupted functioning of 5-HT_1A autoreceptors in the brains of B6-M76C mice, suggesting these mice as a model of antidepressant resistance.     

Prescriptive authority in the face of research revelations.

Fox and his colleagues (May–June 2009) listed three occurrences beginning in the 1980s that have dampened psychologists’ desires to procure the right to prescribe psychotropic medications. That research review highlighted the fact that antidepressants produce a very modest effect at best when compared with placebos. I briefly summarize here some of the important findings that emerged from our original survey and two more recent reviews (Greenberg & Davis Goldman, 2009; Greenberg & Fisher, 1997). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

快眼动睡眠调节机制及影响药物

探究快眼动（rapid eye movement,REM）睡眠调节机制及影响药物。本文从调控REM睡眠的神经环路出发，总结了脑桥、延髓、下丘脑中调控REM睡眠的相关核团，并且归纳了各类影响REM睡眠的药物，例如：选择性去甲肾上腺素再摄取抑制剂和选择性5-羟色胺（5-hydroxytryptamine,5-HT）再摄取抑制剂等，其作用机制可归纳为减少突触部位去甲肾上腺素、5-HT的降解，延长神经递质的作用时间；减少突触前膜再摄取，使突触间隙中递质作用时间延长, 相对提高去甲肾上腺素、5-HT神经元的兴奋性。