Effective Treatment For Major Depression Research Articles

Cortical excitation/inhibition ratios in patients with major depression treated with electroconvulsive therapy: an EEG analysis

Electroconvulsive therapy (ECT) is an effective treatment for major depression, but its working mechanisms are poorly understood. Modulation of excitation/inhibition (E/I) ratios may be a driving factor. Here, we estimate cortical E/I ratios in depressed patients and study whether these ratios change over the course of ECT in relation to clinical effectiveness. Five-minute resting-state electroencephalography (EEG) recordings of 28 depressed patients were recorded before and after their ECT course. Using a novel method based on critical dynamics, functional E/I (fE/I) ratios in the frequency range of 0.5–30 Hz were estimated in frequency bins of 1 Hz for the whole brain and for pre-defined brain regions. Change in Hamilton Depression Rating Scale (HDRS) score was used to estimate clinical effectiveness. To account for test–retest variability, repeated EEG recordings from an independent sample of 31 healthy controls (HC) were included. At baseline, no differences in whole brain and regional fE/I ratios were found between patients and HC. At group level, whole brain and regional fE/I ratios did not change over the ECT course. However, in responders, frontal fE/I ratios in the frequencies 12–28 Hz increased significantly (pFDR < 0.05 [FDR = false discovery rate]) over the ECT course. In non-responders and HC, no changes occurred over time. In this sample, frontal fE/I ratios increased over the ECT course in relation to treatment response. Modulation of frontal fE/I ratios may be an important mechanism of action of ECT.

Literature study on the Efficacy of antidepressants with CBT in the treatment of depression

Introduction: Depression is of global concern to clinicians, researchers and governments. This study seeks to review the benefits of including cognitive behavioural therapy (CBT) as an adjunctive treatment with antidepressants and to explore the role that physical exercise can offer as a treatment for depression. There is considerable literature available on the use of antidepressants with and without CBT. Various neurological studies have identified new roles which suggest the effectiveness of physical exercise as a supportive treatment against depressive symptoms. The production of endorphins can lead to the development of new neuronal growth which may be helpful in the restructuring of neurocognition and thereby protecting against depressive symptoms. Purpose: Current review study aims at scoping the efficacy of antidepressants with CBT and insightful neurocognitive views on the way physical exercise can restructure the cognition of depressive patients which would make the treatment more effective. Method: This literature review study engine proceeds by scoping 72 articles from the previous literature studies and medical news using electronic databases such as PubMed, Medical news, both clinical and the theoretical implications of these findings are discussed. The study also referred to other journals including Psych-INFO, NCBI, and CINAH from 2010 to 2022 which are analysed to draw insightful information concerning the use of antidepressants with CBT and physical exercises to increase the effective treatment for major depression. Conclusion: the current literature study evidences the enhanced efficacy of treatment for depression with CBT in the treatment of depression, its role in reducing relapse episodes of depression and residual symptoms and the efficacy of physical exercises in the treatment of depression. The implication of the study to place these findings in the larger context of treatment selection in managing residual symptoms, reducing the risk of relapse and neurocognitive changes through physical exercise in major depressive disorder (MDD).

Left intermittent theta burst stimulation combined with right low-frequency rTMS as an additional treatment for major depression: A retrospective study.

Background:Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for major depression (MD). We retrospectively analyzed the efficacy of intermittent theta burst stimulation (iTBS) on the left dorsolateral prefrontal cortex (DLPFC) combined with low-frequency rTMS (LF-rTMS) on the right DLPFC as an additional therapy to standard medication treatment.Materials and Methods:The study included 54 patients with MD who completed 10 courses (5 days per week) of rTMS as an add-on therapy. Thirty patients were treated in the combination group (120% resting motor threshold; left DLPFC, iTBS, 600 stimuli + right DLPFC, 1-Hz rTMS, 600 stimuli), while 24 patients were in the high-frequency rTMS (HF-rTMS) group (120% resting motor threshold; left DLPFC, 10-Hz rTMS, 3000 stimuli). The outcome was assessed based on the changes in scores of 24-item Hamilton Depression Scale (HAMD-24) and 14-item Hamilton Anxiety Scale (HAMA-14).Results:Both depression and anxiety were significantly improved after 2 weeks of treatment by rTMS combined with medication. The combination of iTBS and LF-rTMS was significantly superior to HF-rTMS in improving the scores of HAMD-24 (P = 0.041) and HAMA-14 (P = 0.0095), and the response rate (P = 0.027).Conclusion:The pilot study showed that the combination of iTBS and LF-rTMS may hold promise as a potentially effective alternative therapy for MD due to its efficacy and time-saving benefit. The preliminary results shed light on the study of the efficacy and acceptability of the combination of iTBS and LF-rTMS for MD.

ECT practice in England from 2012/13 to 2018/19: a retrospective analysis

AimsThe purpose of this study was to look longitudinally at ECT practice in England over the past 7 years: namely over the following key time periods; 2012/13, 2014/15, 2016/17, 2017/18, and 2018/19. A previous study by Chaplin et al, published in 2016, found that there had been a striking decline observed in the number of courses of ECT prescribed to patients from 2006 to two time points i.e. 2012/13 and 2014/15.In this study we investigated whether or not this trend had continued. Hence we looked at the change in frequency of ECT use, the length of ECT courses, patient demographics and clinical outcomes; between 2012/13 and 2018/19.BackgroundElectroconvulsive therapy (ECT) is an effective treatment for Major Depression, Treatment-Resistant Depression, Catatonia, and Clozapine-resistant psychosis. There have been regular improvements in the administration of ECT, over the past two decades. Increases in the volume of the hippocampus and the amygdala have consistently been observed in ECT studies. Stigma has been the major barrier to patients receiving ECT in a timely fashion. The Royal College of Psychiatrists (RCPsych) Centre for Quality Improvement (CCQI) established the ECT Accreditation Service (ECTAS) back in 2006. ECTAS had the aim of standardising ECT practice through the production of evidence-based standards that all member ECT Clinics could use to support their practice.MethodWe looked at the minimum dataset of information collected from ECTAS Members within England for the following years; 2012/13, 2014/15, 2016/17, 2017/18, 2018/19. In 2012/13, 2325 adjusted courses of ECT treatment were given to patients in England. In 2014/15 it was 2302.ResultBetween 2012/13 and 2018/19; two thirds of ECT patients continue to be female. The modal age of patients has also remained the same at 70 years. The number of patients detained under the Mental Health Act 1983 receiving ECT has gone up by 12%; suggesting that the patients receiving ECT were more clinically unwell. After treatment, CGI scale scores (i.e. the very much improved and much improved scores) slightly reduced by 6% from 2012/3 to 2018/19.ConclusionThe use of ECT in England notably declined from 2006 to 2012/13 and 2014/15. However, from 2012/13 to 2018/19, ECT use has remained relatively stable; suggesting that it is currently being used appropriately on patients, who are amongst the most severely unwell. The clinical effectiveness of ECT remains high however, it has slightly dipped by 6%.

Hormonal Treatments for Major Depressive Disorder: State of the Art.

Major depressive disorder is a common psychiatric disorder associated with marked suffering, morbidity, mortality, and cost. The World Health Organization projects that by 2030, major depression will be the leading cause of disease burden worldwide. While numerous treatments for major depression exist, many patients do not respond adequately to traditional antidepressants. Thus, more effective treatments for major depression are needed, and targeting certain hormonal systems is a conceptually based approach that has shown promise in the treatment of this disorder. A number of hormones and hormone-manipulating compounds have been evaluated as monotherapies or adjunctive treatments for major depression, with therapeutic actions attributable not only to the modulation of endocrine systems in the periphery but also to the CNS effects of hormones on non-endocrine brain circuitry. The authors describe the physiology of the hypothalamic-pituitary-adrenal (HPA), hypothalamic-pituitary thyroid (HPT), and hypothalamic-pituitary-gonadal (HPG) axes and review the evidence for selected hormone-based interventions for the treatment of depression in order to provide an update on the state of this field for clinicians and researchers. The review focuses on the HPA axis-based interventions of corticotropin-releasing factor antagonists and the glucocorticoid receptor antagonist mifepristone, the HPT axis-based treatments of thyroid hormones (T3 and T4), and the HPG axis-based treatments of estrogen replacement therapy, the progesterone derivative allopregnanolone, and testosterone. While some treatments have largely failed to translate from preclinical studies, others have shown promising initial results and represent active fields of study in the search for novel effective treatments for major depression.

Electroconvulsive therapy decreases striatal dopamine transporter binding in patients with depression: A positron emission tomography study with [18F]FE-PE2I

Electroconvulsive therapy (ECT) is an effective treatment for major depression. Previous studies suggested that dopaminergic neurotransmission plays a crucial role in the mechanism of the action of ECT. Since dopamine transporters (DAT) regulate extracellular dopamine concentration, DAT represents an interesting target for the study of the mechanism of action of ECT. Eight inpatients (7 patients with major depressive disorder and 1 patient with bipolar disorder with a DSM-IV diagnosis) received a series of 7–15(11.3±5.2) bilateral ECT sessions.The severity of symptoms was assessed using the 21-item Hamilton Depression Rating Scale (HDRS) and Clinical Global Impression-Severity (CGI-S). All patients were examined with [18F]FE-PE2I positron emission tomography (PET) at pre-ECT, after the 10th ECT, and at post-ECT. Striatal DAT-binding potential (BPND) of all patients was reduced, with an average change ratio of DAT-BPND of -13.1±5.6%. In the 2 cases with 15 ECT sessions, the ratio change of DAT-BPND after the 15th ECT was larger than that after the 10th ECT. Also, HDRS and CGI-S were reduced. These results indicate that the dopamine nervous system is part of themechanism of action of ECT.

Role of autobiographical memory in patient response to cognitive behavioural therapies for depression: protocol of an individual patient data meta-analysis

IntroductionCognitive behavioural therapies (CBTs) are one of the most effective treatments for major depression. However, ~50% of individuals do not adequately respond to intervention and of those who do remit...

The effect of electroconvulsive therapy (ECT) on serum tryptophan metabolites

BackgroundPrior studies suggest that activation of the tryptophan catabolism via the kynurenine pathway by proinflammatory cytokines may be involved in the pathophysiology of depression. Electroconvulsive therapy (ECT) is an effective treatment for major depression (MD) with immunomodulation as one of the proposed modes of action. ObjectiveThe aim of this study was to investigate serum concentrations of tryptophan and kynurenine pathway metabolites in MD patients and healthy controls, and to explore the effect of ECT on components of the kynurenine pathway. MethodsThe study included 27 moderately to severely depressed patients referred to ECT. Blood samples were collected prior to treatment and after the completed ECT-series. Baseline samples were also collected from 14 healthy, age- and sex-matched controls. Serum concentrations of tryptophan, kynurenine, 3-hydroxykynurenine (HK), kynurenic acid (KA), xanthurenic acid (XA), anthranilic acid (AA), 3-hydroxyanthranilic acid (HAA), quinolinic acid (QA), picolinic acid (Pic), pyridoxal 5′-phosphat (PLP), riboflavin, neopterin and cotinine were measured. ResultsPatients with MD had lower levels of neuroprotective kynurenine-pathway metabolites (KA, XA and Pic) and lower metabolite ratios (KA/Kyn and KA/QA) reflecting reduced neuroprotection compared to controls. The concentration of the inflammatory marker neopterin was increased after ECT, along with Pic and the redox active and immunosuppressive metabolite HAA. ConclusionIn this pilot study, we found increased concentrations of inflammatory marker neopterin and putative neuroprotective kynurenine metabolites HAA and Pic in MD patients after ECT. Further research in larger cohorts is required to conclude whether ECT exerts its therapeutic effects via changes in the kynurenine pathway.

An Electrophysiological Biomarker That May Predict Treatment Response to ECT.

Electroconvulsive therapy (ECT) is the most effective treatment for major depression but also carries risk of cognitive side effects. The ability to predict whether treatment will be effective before initiation of treatment could significantly improve quality of care, reduce suffering, and diminish costs. We sought to carry out a comprehensive and definitive study of the relationship between the background electroencephalography (EEG) and therapeutic response to ECT. Twenty-one channel resting EEG was collected pre-ECT and 2 to 3 days after ECT course from 2 separate data sets, one to develop an EEG model of therapeutic response (n = 30) and a second to test this model (n = 40). A 3-way principal components analysis was applied and coherence and spectral amplitude across 6 frequency bands were examined. The primary outcome measure was the Montgomery-Asberg Rating Scale (MADRS). Four patterns of amplitude and coherence along with baseline MADRS score accounted for 85% of the variance in posttreatment course MADRS score in study 1 (R = 0.85, F = 11.7, P < 0.0002) and 53% of the variance in MADRS score in study 2 (R = 0.53, F = 5.5, P < 0.003). Greater pre-ECT course anterior delta coherence accounted for the majority of variance in therapeutic response (study 1: R = 0.44, P = 0.01; study 2: R = 0.16, P = 0.008). These results suggest a putative electrophysiological biomarker that can predict therapeutic response before a course of ECT. Greater baseline anterior delta coherence is significantly associated with a better subsequent therapeutic response and could be indicative of intact circuitry allowing for improved seizure propagation.

Efficacy of vestibular stimulation treatment in the depressive phase of bipolar disorder: study protocol for a randomized, double-blind, controlled trial

Background and objectives: Bipolar disorder (BD) is a neuropsychiatric disorder characterized by the oscillation of mood states between hypoactive/pessimistic (depressive phase) and hyperactive/optimistic states (manic/hypomanic phase). Previous studies evidenced that a particular technique of neuro-vestibular stimulation is an effective treatment for major depression. This study will investigate the efficacy of the said vestibular stimulation technique in the depressive phase of BD, and will compare it with sham vestibular stimulation. Design: A double-blind, randomized controlled study. Methods: One hundred and twenty patients with bipolar type I or II, currently undergoing a depressive phase, will be randomized into the experimental group (n = 60) or control group (n = 60), receiving three sessions of real/sham vestibular stimulation. Outcome measures: The primary outcome is the change in Montgomery Asberg Depression Rating Scale scores from baseline to post 4 and 12 weeks. The secondary outcome is the vestibular activity assessed at baseline, post 4 and 2 weeks. Discussion: Currently, no treatment has proved efficacy for bipolar depression. Studies have demonstrated that lateralized neuro-vestibular stimulation is an effective treatment for mayor depression but has not been studied in the depressive phase of bipolar disorder. This investigation will give the first evidence supporting or denying the use of vestibular stimulation treatment in BD depression. Ethics and dissemination: This study protocol was approved by the Ethics Committee of SSMO (Servicio de Salud Metropolitano Oriente) in Santiago, Chile (approval No. 08032016) on March 8, 2016. The results of the study will be published in scientific journals and other media. Trial registration: ClinicalTrials.gov Identifier: NCT02778256.

A Further Decrease in the Rates of Administration of Electroconvulsive Therapy in England.

Electroconvulsive therapy (ECT) is an effective treatment of major depression, and there have been consistent improvements in the administration of ECT in the past decade. However, studies have reported a steady decline in the rates of use of ECT in the United Kingdom and Ireland. Despite this, there has been no consistent record of how much ECT is being given or to whom it is given, for more than 20 years. The purpose of this study is to estimate the change in frequency of ECT use, the length of courses, patient demographics, and clinical outcomes between 2006 and 2 periods of 2012/2013 and 2014/2015. In 2012/2013, clinics were asked to complete an online survey giving details of every patient who started a course of ECT between April 1, 2012, and March 31, 2013. This was repeated for the same period in 2014/2015. There continues to be a striking decline in the number of courses of ECT prescribed. Course length has increased. Women are twice as likely to be prescribed ECT as men. Modal age is 60 to 80 years, and the most common diagnosis is depression. Most courses were rated as clinically effective, especially for people with severe illnesses. Maintenance ECT is used at half the clinics surveyed. The use of ECT in England continues to decline. The reasons for this are unclear and need investigation.

Ten month outcome of cognitive behavioural therapy v. interpersonal psychotherapy in patients with major depression: a randomised trial of acute and maintenance psychotherapy.

Cognitive behaviour therapy (CBT) and interpersonal psychotherapy (IPT) are the most studied psychotherapies for treatment of depression, but they are rarely directly compared particularly over the longer term. This study compares the outcomes of patients treated with CBT and IPT over 10 months and tests whether there are differential or general predictors of outcome. A single centre randomised controlled trial (RCT) of depressed outpatients treated with weekly CBT or IPT sessions for 16 weeks and then 24 weeks of maintenance CBT or IPT. The principle outcome was depression severity measured using the MADRS. Pre-specified predictors of response were in four domains: demographic depression, characteristics, comorbidity and personality. Data were analysed over 16 weeks and 40 weeks using general linear mixed effects regression models. CBT was significantly more effective than IPT in reducing depressive symptoms over the 10 month study largely because it appeared to work more quickly. There were no differential predictors of response to CBT v. IPT at 16 weeks or 40 weeks. Personality variables were most strongly associated with overall outcome at both 16 weeks and 40 weeks. The number of personality disorder symptoms and lower self-directness and reward dependence scores were associated with poorer outcome for both CBT and IPT at 40 weeks. CBT and IPT are effective treatments for major depression over the longer term. CBT may work more quickly. Personality variables are the most relevant predictors of outcome.

Anterograde Amnesia during Electroconvulsive Therapy: A Prospective Pilot-Study in Patients with Major Depressive Disorder.

Electroconvulsive therapy (ECT) is considered an effective treatment for major depression with melancholic features. However, neurocognitive side-effects such as anterograde amnesia still regularly occur. The present study aims to evaluate the severity and course of anterograde amnesia in severely depressed patients undergoing ECT. In a prospective naturalistic study, anterograde memory function was assessed among inpatients who underwent ECT (n = 11). Subjects met DSM-IV criteria for major depressive disorder. Recruitment took place between March 2010-March 2011 and March 2012-March 2013. Controls treated with antidepressants (n = 9) were matched for age, gender and depression severity. Primary outcome measure was immediate recall; secondary outcome measures were delayed recall, recognition, and visual association. Differences were tested using repeated measures ANOVA and paired t-tests. Correlations with hypothesized covariates were calculated. In patients with major depressive disorder, ECT had a significant effect on delayed memory function (p<0.01 with large effect sizes). Findings on immediate recall were less consistent. Four weeks after treatment discontinuation, these memory functions had recovered. Age was identified as a very important covariate. The main limitations of our study are its naturalistic design, possibly compromising internal validity, and its small sample size. However, if these findings can be reproduced in a more comprehensive study group, then the possible induction of anterograde amnesia is not a justifiable reason for clinicians to disregard ECT as a treatment option.

Considering Eligibility for Studies of Deep Brain Stimulation for Treatment-Resistant Depression: Insights From a Clinical Trial in Unipolar and Bipolar Depression.

While electroconvulsive therapy (ECT) is the most effective treatment for major depression (major depressive disorder [MDD]), deep brain stimulation (DBS) has shown efficacy in patients who have not received benefit from ECT. Studies of DBS are small, and a better understanding of which eligibility criteria lead to exclusion may help achieve a more appropriate balance between scientific rigor and generalizability in future trials. We assessed the rate and reasons for exclusion from a study of DBS for treatment-resistant MDD and bipolar type II (BPII) depression. One thousand ninety-eight adults were screened for a study of DBS for MDD or BPII. Reasons for exclusion were documented. Descriptive statistics were calculated for each reason for exclusion for the entire sample as well as the self-reported MDD and BPII subgroups. Ninety-eight percent (98%) of patients screened were excluded. Exclusion due to lack of interest or inability to relocate to the study site was high (41%). Following this, primary reasons for exclusion were lack of prior ECT and presence of psychiatric/general medical comorbidity. Patients with MDD were more likely to be excluded because of inadequate ECT, whereas patients with BPII depression were more likely to be excluded for comorbid psychiatric diagnoses and not meeting minimum severity criteria. A surprisingly high number of potential participants were excluded because of lack of adequate ECT. This suggests that many patients self-identifying as "treatment resistant" have not truly exhausted available, evidence-based treatments. Overall exclusion rate was high, with key differences in exclusion reasons between the MDD and BPII subgroups. These findings can inform design of future clinical trials for treatment-resistant unipolar and bipolar depression.Clinicaltrials.gov Identifier: NCT00367003.

Electroconvulsive Therapy May Be Effective Treatment for Major Depression

A long recovery from disorientation following electroconvulsive therapy seems to be a sign that the therapy has eff ectively treated an elderly patient who has major depression, suggests a longitudinal cohort study conducted in Norway. The study comprised 57 Norwegianspeaking inpatients, age 60–85, who had major depressive disorders. To enter the study, a patient needed to have a minimum baseline score of 18 on the 17-item Hamilton Rating Scale for Depression (HRSD17). Among the study’s exclusion criteria were a diagnosis of dementia, Parkinson’s disease, schizophrenia, or schizoaffective disorder, and any use of ECT during the previous 6 months. All study participants received the seizureinducing ECT twice a week. The intensity of therapy varied per patient and session, and age and sex of a patient were among the criteria used to determine the

Breathing exercise combined with cognitive behavioural intervention improves sleep quality and heart rate variability in major depression.

The aim of this study was to investigate the effects of a cognitive behavioural intervention combined with a breathing relaxation exercise on sleep quality and heart rate variability in patients with major depression. Depression is a long-lasting illness with significant effects not only in individuals themselves, but on their family, work and social relationships as well. Cognitive behavioural therapy is considered to be an effective treatment for major depression. Breathing relaxation may improve heart rate variability, but few studies have comprehensively examined the effect of a cognitive behavioural intervention combined with relaxing breathing on patients with major depression. An experimental research design with a repeated measure was used. Eighty-nine participants completed this study and entered data analysed. The experimental group (n=43) received the cognitive behavioural intervention combined with a breathing relaxation exercise for fourweeks, whereas the control group (n=46) did not. Sleep quality and heart rate variability were measured at baseline, posttest1, posttest2 and follow-up. Data were examined by chi-square tests, t-tests and generalised estimating equations. After adjusting for age, socioeconomic status, severity of disease and psychiatric history, the quality of sleep of the experimental group improved, with the results at posttest achieving significance. Heart rate variability parameters were also significantly improved. This study supported the hypothesis that the cognitive behavioural intervention combined with a breathing relaxation exercise could improve sleep quality and heart rate variability in patients with major depression, and the effectiveness was lasting. The cognitive behavioural intervention combined with a breathing relaxation exercise that included muscle relaxation, deep breathing and sleep hygiene could be provided with major depression during hospitalisation. Through group practice and experience sharing, participants could modulate their heart rate variability and share feeling about good sleep as well relaxation.

Epigenetic regulation of Dnmt3a and Arc gene expression after electroconvulsive stimulation in the rat

Electroconvulsive therapy (ECT) remains one of the most effective treatments of major depression. Unfortunately, some patients report side effects, of which the most prominent are memory deficits. The immediate early gene Arc plays a critical role in the maintenance phase of long-term potentiation and consolidation of memory in the rat brain. We recently observed increased methylation of the Arc promoter 24h after acute electroconvulsive stimulation (ECS) in rats, which could cause decreased Arc expression and provide an explanation for the observed memory deficits. In the present study we investigated the methylation and expression changes of Arc at 48h post-ECS and determined the role of de-novo methylation in that process. We initially measured expression of DNA methyltransferases (Dnmt1 and Dnmt3a) and Arc 1, 4, 8, 16, 24, and 48h after a single ECS. Arc expression increased approximately 10-fold at 1 and 4h after ECS, and subsequently decreased below sham levels. Four hours after ECS we also observed a significant increase in Dnmt3a expression, which was attenuated in a second experiment by the use of DNMT inhibitor decitabine (5-aza-2-deoxycytidine). We then investigated Arc gene expression and methylation changes at 48h post-ECS and we found a slightly reduced Arc expression in ECS-treated rats as compared to sham. In animals that received decitabine we observed a significant decrease in Dnmt3a expression and an increase of Arc expression in both ECS and sham groups. The same tendency for reduced Arc expression after ECS, as compared to sham was observed despite the blocking of DNA methylation with decitabine. The DNA methylation as measured by pyrosequencing is decreased 48h post-ECS both in the promoter and intragenic regions as a response to ECS regardless of the treatment with decitabine. Overall the results suggest that DNA methylation is involved in regulating Arc expression but is not the causal mechanism responsible for reducing Arc expression after ECS. We speculate that the decrease is caused by ECS-induced HDAC2 upregulation and decreased H3 acetylation at the Arc promoter.

Learned helplessness paradigm in P2xr7 wild type and knock out mice and its effect on synapses in the dentate gyrus

Although depression is one of the prevailing central nervous system disorders, there is still not enough knowledge about the exact alterations underlying its pathophysiology and the treatment is often inefficient. Our study aims at exploring a potential relationship between major depressive disorder and the purinergic P2X7 receptor (P2X7R), since in previous behavioural tests P2rx7 knock out mice displayed an antidepressant-like phenotype. Among many other known symptoms, the loss of hippocampal spine synapses is a revealing feature of the disorder. Therefore we wanted to measure the density of spine synapses in the molecular layer of the dentate gyrus in the learned helplessness paradigm and later see if genetic inhibition of P2X7R could have influence on this condition. Wild type C57Bl/6 and P2rx7 knock out male mice were exposed to inescapable footshocks (IES) in shuttle boxes during 2 training days and on the 3rd day learned helplessness was tested, where helpless animals usually failed to escape. Control animals were also placed in shuttle boxes but did not receive footshocks until testing. Escape failures and the latency to escape were measured to determine helpless behaviour. Electron microscopy analysis was performed to determine spine synapse density in the different groups. In wild type mice both average escape latency and the number of failed escapes were significantly higher in the IES treated group, however, we could not find such divergency in P2rx7 knock out mice. Electron microscopy analysis confirmed alterations in spine synapse density in the molecular layer of the dentate gyrus subsequent to learned helplessness experiments, as results indicated a significant decrease in spine synapse density in wild type mice, but not in knock out animals. These findings may lead to presume a role of the P2X7 receptor in this disorder and further experiments will hopefully help get a better understanding and thus more effective treatment of major depression.

Early effects of duloxetine on emotion recognition in healthy volunteers.

The serotonin-noradrenaline reuptake inhibitor (SNRI) duloxetine is an effective treatment for major depression and generalised anxiety disorder. Neuropsychological models of antidepressant drug action suggest therapeutic effects might be mediated by the early correction of maladaptive biases in emotion processing, including the recognition of emotional expressions. Sub-chronic administration of duloxetine (for two weeks) produces adaptive changes in neural circuitry implicated in emotion processing; however, its effects on emotional expression recognition are unknown. Forty healthy participants were randomised to receive either 14 days of duloxetine (60 mg/day, titrated from 30 mg after three days) or matched placebo (with sham titration) in a double-blind, between-groups, repeated-measures design. On day 0 and day 14 participants completed a computerised emotional expression recognition task that measured sensitivity to the six primary emotions. Thirty-eight participants (19 per group) completed their course of tablets and were included in the analysis. Results provide evidence that duloxetine, compared to placebo, may reduce the accurate recognition of sadness. Drug effects were driven by changes in participants’ ability to correctly detect subtle expressions of sadness, with greater change observed in the placebo relative to the duloxetine group. These effects occurred in the absence of changes in mood. Our preliminary findings require replication, but complement recent evidence that sadness recognition is a therapeutic target in major depression, and a mechanism through which SNRIs could resolve negative biases in emotion processing to achieve therapeutic effects.

A 5-HT3 receptor antagonist potentiates the behavioral, neurochemical and electrophysiological actions of an SSRI antidepressant

More effective treatments for major depression are needed. We studied if the selective 5-HT3 receptor antagonist ondansetron can potentiate the antidepressant potential of the selective serotonin (5-HT) reuptake inhibitor (SSRI) paroxetine using behavioral, neurochemical and electrophysiological methods. Flinders Sensitive Line (FSL) rats, treated with ondansetron, and/or a sub-effective dose of paroxetine, were assessed in the forced swim test. The effects of an acute intravenous administration of each compound alone and in combination were evaluated with respect to 5-HT neuronal firing rate in the dorsal raphe nucleus (DRN). Effects of s.c. administration of the compounds alone and in combination on extracellular levels of 5-HT were assessed in the ventral hippocampus of freely moving rats by microdialysis. The results showed that ondansetron enhanced the antidepressant activity of paroxetine in the forced swim test. It partially prevented the suppressant effect of paroxetine on DRN 5-HT neuronal firing and enhanced the paroxetine-induced increase of hippocampal extracellular 5-HT release. These findings indicate that 5-HT3 receptor blockade potentiates the antidepressant effects of SSRIs. Since both paroxetine and ondansetron are used clinically, it might be possible to validate this augmentation strategy in depressed patients.