Antidepressant Treatment Research Articles

Clustering and drivers of symptoms observed at week six after antidepressant treatment in depressed outpatients.

Depressive symptoms remaining after antidepressant treatment increase the risk of relapse and recurrence. We aimed to analyze the distribution and main drivers of remaining symptoms in patients with a major depressive episode. Two independent samples of 8,229 and 5,926 patients from two large naturalistic studies were retrospectively analyzed. DSM-IV criteria for major depressive episodes were assessed during two face-to-face visits with clinicians: before the prescription of a new antidepressant, and after 6weeks of treatment. The Hospital Anxiety and Depression Scale (HADS) was used to assess baseline severity of anxiety and depression. In both samples, two clusters of remaining symptoms were observed. The first cluster encompassed symptoms related to a negative emotional and cognitive bias and was specifically driven by the baseline severity of depression. The second cluster encompassed neurovegetative symptoms and was specifically driven by the baseline severity of anxiety. The baseline anxiety-depressive balance of patients could be considered to adapt the treatment, focusing on emotional and cognitive symptoms with patients with high baseline severity of depression, and neurovegetative symptoms with patients with high baseline anxiety severity.

A Scoping Review of Eosinophilic Pneumonia and Antidepressants: An Association Not to Be Overlooked

Background: Eosinophilic pneumonias denote a rare condition, wherein infiltrating eosinophilic granulocytes accumulate within the lung parenchyma. Although eosinophilic pneumonias may be idiopathic, they are also associated with secondary causes. More than 110 medications have been linked to eosinophilic pneumonia, including several antidepressants. This review presents an analysis of case reports of eosinophilic pneumonia correlated to antidepressants. Objectives: The objectives of this study are to provide a contemporary overview of the literature delineating eosinophilic pneumonia as a potential sequela of antidepressant medication treatment, and to discuss possible pathogenetic mechanisms linking antidepressants to eosinophilic pneumonia. Methods and Data Selection: A literature search was performed in PubMed and Scopus databases from 1963 to October 2024. The search strategy used the terms “eosinophilic pneumonia AND antidepressants”. Sources included in this review were screened for relevance, focusing on references discussing eosinophilic pneumonia associated with any class of antidepressants. Case reports meeting the diagnostic criteria for acute eosinophilic pneumonia (AEP) or chronic eosinophilic pneumonia (CEP) were included in the review. Clinical, epidemiological, laboratory, radiology and bronchoscopy data, implicated antidepressant and dosage, and therapeutic interventions were reported. Results: This study found that various types of antidepressants are associated with AEP and CEP. The clinical presentation ranges from mild symptoms to respiratory failure and intubation. Outcomes were favorable in most cases, with complete remission achieved after discontinuation of the causative drug and, in severe cases, a short course of corticosteroids. Conclusions: Although a rare cause, antidepressants may lead to eosinophilic pneumonia, and should be considered in the differential diagnosis of unexplained pulmonary infiltrates. Clinical suspicion must be aroused, as early recognition would prevent unnecessary work-up and navigation of the diagnosis.

Inclination of antidepressant medication continuation during pregnancy between 2012 and 2023 in Japan: A cohort study.

As multiple Japanese academic societies have recently issued treatment guidelines for perinatal antidepressant treatments, it is considered worthwhile to evaluate the latest trends and continuation of antidepressant medication during pregnancy to optimize antenatal prescriptions. The prevalence, trend, and continuation of antidepressant use during pregnancy in Japan from 2012 to 2023 were evaluated, using a large administrative claims database, in women whose pregnancies ended in live births. Annual changes were evaluated using a multivariate logistic regression model adjusted for maternal age at delivery. Of 179,797 women with a mean maternal age at delivery of 32.5 years, 1870 (1.04 %) were prescribed antidepressants during pregnancy. The prevalence significantly increased (P < 0.0001) from 0.63 % in 2012 to 1.67 % in 2023. Antidepressants were prescribed to 1730 women (0.96 %) during the first trimester. Of these, 670 (38.7 %) were antidepressant continuers throughout pregnancy, showing a significant increase (P < 0.0001) from 19.51 % in 2012 to 50.70 % in 2023. The most frequently prescribed class of antidepressants during pregnancy was serotonin reuptake inhibitors (0.74 %), especially sertraline (0.33 %) and escitalopram (0.23 %), with a significant increase in their annual prevalence. Prescriptions for women whose pregnancies ended in abortion or stillbirth could not be evaluated. Given that antidepressant use and its continuation during pregnancy have become more common, it is important to further disseminate knowledge of the guidelines to healthcare professionals and women of childbearing age, including the promotion of preconception care and shared decision-making.

Reconsidering remission in recurrent late-life depression: clinical presentation and phenotypic predictors of relapse following successful antidepressant treatment.

Late-life depression (LLD) is characterized by repeated recurrent depressive episodes even with maintenance treatment. It is unclear what clinical and cognitive phenotypic characteristics present during remission predict future recurrence. Participants (135 with remitted LLD and 69 comparison subjects across three institutions) completed baseline phenotyping, including psychiatric, medical, and social history, psychiatric symptom and personality trait assessment, and neuropsychological testing. Participants were clinically assessed every two months for two years while receiving standard antidepressant treatment. Analyses examined group differences in phenotypic measure using general linear models. Concurrent associations between phenotypic measures and diagnostic groups were examined using LASSO logistic regression. Sixty (44%) LLD participants experienced a relapse over the two-year period. Numerous phenotypic measures across all domains differed between remitted LLD and comparison participants. Only residual depressive symptom severity, rumination, medical comorbidity, and executive dysfunction significantly predicted LLD classification. Fewer measures differed between relapsing and sustained remission LLD subgroups, with the relapsing group exhibiting greater antidepressant treatment intensity, greater fatigue, rumination, and disability, higher systolic blood pressure, greater life stress and lower instrumental social support. Relapsing group classification was informed by antidepressant treatment intensity, lower instrumental social support, and greater life stress. A wide range of phenotypic factors differed between remitted LLD and comparison groups. Fewer measures differed between relapsing and sustained remission LLD subgroups, with less social support and greater stress informing vulnerability to subsequent relapse. This research suggests potential targets for relapse prevention and emphasizes the need for clinically translatable relapse biomarkers to inform care.

Investigating the role of GPR39 in treatment of stress-induced depression and anxiety.

Chronic stress is one of the leading causes of depression. Yet, knowledge of the pathomechanism of this process still eludes us. Chronic unpredictable mild stress (CUMS) model of depression enables researchers to look for a root cause of the disease in mice by mimicking a stressful human environment. Since zinc has already been shown to impact the treatment of depression, in our study we aimed to shed light on the role of the zinc receptor GPR39 in stress-induced depression. We also aimed to highlight the role of GPR39 activation in monoamine-based antidepressant treatment. Using large battery of behavioural tests, we provided a detailed description of CUMS-induced phenotype in both - CD-1 and GPR39 knock-out mice. Our experiments showed that combined treatment with TC-G 1008 (GPR39 agonist) and antidepressants produces stronger antidepressant-like effect of classic antidepressants. We also demonstrated the inter-strain differences in stress response and the greater stress susceptibility of GPR39 knock-out mice. The lack of GPR39 expression also either diminished or completely abolished the response to treatment with different antidepressants combined with TC-G 1008. The results show that GPR39 KO mice are more susceptible to chronic stress and that they are non-responsive to SSRI treatment. Utilizing various behavioural tests gave us much broader understanding not only of the role of GPR39 in depression treatment, but also of the importance of detailed behavioural description in a proper interpretation of the results. Further research with known selective agonists and antagonists of GPR39 will be necessary to understand the full potential of this receptor as a pharmacological target.

Antidepressants and Weight Gain: An Update on the Evidence and Clinical Implications.

To highlight recent research on antidepressant use and weight change and explore best clinical practices for reducing weight gain and obesity risk in individuals with depression. Research on antidepressant use and weight gain suggests that genetic and biological factors including metabolizer phenotypes and inflammation can help to predict an individual's threshold for weight change among specific agents. For individuals with increased susceptibility to metabolic complications, medications including bupropion, fluoxetine, and newer agents (e.g., gepirone) have shown to be efficacious in improving depressive symptoms while concurrently reducing metabolic risks. Additional areas of focus following antidepressant related weight gain include switching to a weight neutral drug alternative, integrated behavioral interventions, and/or pharmacotherapy including GLP-1 receptor agonists (e.g., metformin, liraglutide). Individuals experiencing depression are at heightened risk of metabolic disorders and weight gain, which may be further exacerbated by antidepressant treatment. The increased support of weight neutral antidepressant agents in addition to innovative lifestyle interventions, breakthroughs in drug mechanisms, anti-obesity medications and overall familiarity with the side effects of each antidepressant class will help clinicians make appropriate decisions when treating patients with depression.

Abnormal regional brain activity in patients with first-episode medication-naïve depressive disorder: a longitudinal fNIRS study

The potential relationship between abnormal brain activity and clinical symptoms in patients with major depressive disorder (MDD) is important for auxiliary diagnosis and prediction of the curative effect of treatments for MDD. Before antidepressant treatment (T1), 4 weeks after treatment (T2), and 8 weeks after treatment (T3), 33 patients with first-episode medication-naïve MDD and 30 healthy controls (HCs) were examined using functional near-infrared spectroscopy (fNIRS) to evaluate the cerebral hemodynamic response in the frontal and temporal cortex during the Verbal Fluency Task (VFT). Compared with HCs, VFT scores and activation levels of the frontal pole, inferior frontal gyrus, and dorsolateral prefrontal cortex were significantly decreased in the first-episode medication-naïve depressive disorder patients (FMD). Compared with T2, the activation levels of the superior temporal gyrus and inferior central gyrus were increased at T3 in the FMD. The low activation pattern of the frontal pole, inferior frontal gyrus, and dorsolateral prefrontal cortex in the FMD during VFT is helpful for clinical diagnosis of MDD. The superior temporal gyrus and inferior central gyrus may be sensitive brain regions that reflect the clinical effect of MDD in patients.

Agomelatine as Antidepressant Treatment in Elderly Patients With Previous Hyponatremia Due To SSRI Use: Case Series.

To evaluate agomelatine treatment in elderly patients with major depressive disorder (MDD) who developed hyponatremia while using selective serotonin receptor inhibitors (SSRIs). Patients (60years or older) with hyponatremia after SSRI treatment for MDD were changed to agomelatine 50mg/day during one month to observe sodium levels during the treatment and change in depressive symptoms. Montgomery-Asberg Depression Rating Scale (MADRS) and the Clinical Global Impression Scale (CGI) of severity were used before and after treatment with agomelatine. The mean age of our sample (five patients) was 75.3 (SD±7.8) years. Sodium levels while using SSRIs were reported with a mean of 122.54 (SD±10.8) mEq/L. Mean MADRS and CGI scores on SSRIs before treatment with agomelatine were 27.8 (SD±3.90) and 5 (SD±0.71) respectively. After 4weeks of treatment with agomelatine 50mg/day, mean scores of sodium were reported at 135.48 (SD±1.6) mEq/L, and mean MADRS and CGI scores were 13.6 (SD±8.35) and 2.4 (SD±1.5). The difference in means of the MADRS scale before and after treatment with agomelatine was found to be statistically significant (27.8 [3.89] versus 13.6 [8.35], p=<0.01). Our open observational study suggests that agomelatine represents a safe and effective treatment option for elderly patients with major depressive disorder and previous SSRIs-induced hyponatremia.

The bidirectional interaction between antidepressants and the gut microbiota: are there implications for treatment response?

This review synthesizes the evidence on associations between antidepressant use and gut microbiota composition and function, exploring the microbiota's possible role in modulating antidepressant treatment outcomes. Antidepressants exert an influence on measures of gut microbial diversity. The most consistently reported differences were in β-diversity between those exposed to antidepressants and those not exposed, with longitudinal studies supporting a potential causal association. Compositional alterations in antidepressant users include an increase in the Bacteroidetes phylum, Christensenellaceae family, and Bacteroides and Clostridium genera, while a decrease was found in the Firmicutes phylum, Ruminococcaceae family, and Ruminococcus genus. In addition, antidepressants attenuate gut microbial differences between depressed and healthy individuals, modulate microbial serotonin transport, and influence microbiota's metabolic functions. These include lyxose degradation, peptidoglycan maturation, membrane transport, and methylerythritol phosphate pathways, alongside gamma-aminobutyric acid metabolism. Importantly, baseline increased α-diversity and abundance of the Roseburia and Faecalibacterium genera, in the Firmicutes phylum, are associated with antidepressant response, emerging as promising biomarkers. This review highlights the potential for gut microbiota as a predictor of treatment response and emphasizes the need for further research to elucidate the mechanisms underlying antidepressant-microbiota interactions. More homogeneous studies and standardized techniques are required to confirm these initial findings.

Neurobiological mechanisms of antidepressant properties of psilocybin: A systematic review of blood biomarkers.

Psilocybin represents a novel therapeutic approach for individuals with major depressive disorder (MDD) who do not respond to conventional antidepressant treatment. Investigating the influence of psilocybin on the pathophysiological processes involved in MDD could enhance our neurobiological understanding of the presumed antidepressant action mechanism. This systematic review aims to summarize the results of human studies investigating changes in blood-based biomarkers of MDD to guide future research on potentially relevant analytes that could be monitored in clinical trials. A systematic search was performed in MEDLINE, Embase, and Web of Science to retrieve studies investigating changes in serum and plasma levels of neurotrophic, immunologic, neuroendocrine, and metabolic markers. Nine studies were included, describing findings on 15 biomarkers, exclusively in healthy participants. Studies consistently reported a decrease in interleukin-6, C-reactive protein, and eosinophils, and an increase in cortisol, prolactin, oxytocin, thyroid-stimulating hormone, adrenocorticotropic hormone, brain-derived neurotrophic factor, and free fatty acids following psilocybin administration. Less consistent effects were observed on interleukin-1β, interleukin-8, tumour necrosis factor-alpha, soluble urokinase plasminogen activator receptor, and growth hormone. The results are in line with preclinical studies and provide initial support from human studies that psilocybin potentially leads to beneficial effects on biomarkers of MDD. However, given the limited number of studies, findings should be approached with caution prior to replication. Further research should include larger samples, clinical populations, longer-term assessment, rigorous experimental designs, and account for the potential confounding of psychological stress related to the psychedelic experience.

Antidepressant Treatment Response Prediction With Early Assessment of Functional Near-Infrared Spectroscopy and Micro-RNA

Antidepressant Treatment Response Prediction With Early Assessment of Functional Near-Infrared Spectroscopy and Micro-RNA

Trajectories of antidepressant use and 6-year change in body weight: a prospective population-based cohort study.

Antidepressant drug treatment may be associated with weight gain, but long-term studies are lacking. We included 3,127 adults (1,701 women) from the REGICOR study, aged 55.6 (SD = 11.6) years on average in 2003-2006, living in the northeast of Spain. They had data at two time points (baseline and a median of 6.3 years later) on self-reported antidepressant use, body weight and height, and on baseline smoking, physical activity, diet quality, education, civil status, and depressive symptoms assessed with the Patient Health Questionnaire (PHQ-9) at follow-up. We defined four trajectories of antidepressant use as follows: never use, new use at follow-up, initial use discontinued, repeated use at both time points. We used multivariable linear models to estimate the association of these trajectories with the percentage of weight change. In people without obesity at baseline (n = 2,404), we also estimated the association with obesity incidence at follow-up. The average 6-year weight gain was 0.53kg (1.01% body weight), and 24.5% of the participants gained >5% of body weight. The majority (83.6%) of participants did not report any use of antidepressants, 6.2% initiated during follow-up, 5.1% discontinued it, and 5.1% reported their use at both time points. In multivariable analyses, compared to never users, all trajectories were associated with greater weight gain: +1.78% (0.57, 2.98) for initial use discontinued, +2.08% (0.97, 3.19) for new use at follow-up, and +1.98% (95% CI: 0.75, 3.20) for repeated use. In non-obese participants at baseline (n = 2,404), the odds ratio for becoming obese was 2.06 (1.03, 3.96) for repeated use and non-statistically significant for the other trajectories. In a population-based adult cohort, repeated use of antidepressants was strongly associated with weight gain. New and discontinued use was associated with weight gain, but non-significantly to obesity incidence. Given the global obesity epidemic and the widespread use of antidepressants, weight management and metabolic monitoring should be encouraged and integrated into depression follow-up guidelines alongside antidepressant prescriptions.

Genome-wide meta-analyses of non-response to antidepressants identify novel loci and potential drugs.

Antidepressants exhibit a considerable variation in efficacy, and increasing evidence suggests that individual genetics contribute to antidepressant treatment response. Here, we combined data on antidepressant non-response measured using rating scales for depressive symptoms, questionnaires of treatment effect, and data from electronic health records, to increase statistical power to detect genomic loci associated with non-response to antidepressants in a total sample of 135,471 individuals prescribed antidepressants (25,255 non-responders and 110,216 responders). We performed genome-wide association meta-analyses, genetic correlation analyses, leave-one-out polygenic prediction, and bioinformatics analyses for genetically informed drug prioritization. We identified two novel loci (rs1106260 and rs60847828) associated with non-response to antidepressants and showed significant polygenic prediction in independent samples. Genetic correlation analyses show positive associations between non-response to antidepressants and most psychiatric traits, and negative associations with cognitive traits and subjective well-being. In addition, we investigated drugs that target proteins likely involved in mechanisms underlying antidepressant non-response, and shortlisted drugs that warrant further replication and validation of their potential to reduce depressive symptoms in individuals who do not respond to first-line antidepressant medications. These results suggest that meta-analyses of GWAS utilizing real-world measures of treatment outcomes can increase sample sizes to improve the discovery of variants associated with non-response to antidepressants.

Cost-Effectiveness of rTMS as a Next Step in Antidepressant Non-Responders: A Randomized Comparison With Current Antidepressant Treatment Approaches.

Although repetitive transcranial magnetic stimulation (rTMS) is an effective and commonly used treatment option for treatment-resistant depression, its cost-effectiveness remains much less studied. In particular, the comparative cost-effectiveness of rTMS and other treatment options, such as antidepressant medication, has not been investigated. An economic evaluation with 12 months follow-up was conducted in the Dutch care setting as part of a pragmatic multicenter randomized controlled trial, in which patients with treatment-resistant depression were randomized to treatment with rTMS or treatment with the next pharmacological step according to the treatment algorithm. Missing data were handled with single imputations using predictive mean matching (PMM) nested in bootstraps. Incremental cost-effectiveness and cost-utility ratios (ICERs/ICURs) were calculated, as well as cost-effectiveness planes and cost-effectiveness acceptability curves (CEACs). Higher QALYs, response, and remission rates were found for lower costs when comparing the rTMS group to the medication group. After 12 months, QALYs were 0.618 in the rTMS group and 0.545 in the medication group. The response was 27.1% and 24.4% and remission was 25.0% and 17.1%, respectively. Incremental costs for rTMS were -€2.280, resulting in a dominant ICUR for QALYs and ICER for response and remission. rTMS appears to be a cost-effective treatment option for treatment-resistant depression when compared to the next pharmacological treatment step. The results support the implementation of rTMS as a step in the treatment algorithm for depression. The trial is registered within the Netherlands Trial Register (code: NL7628, date: March 29, 2019).

High Prevalence of Severe Depression in Mexican Patients Diagnosed with HIV Treated with Efavirenz and Atazanavir: Clinical Follow-Up at Four Weeks and Analysis of TPH2 SNPs.

Efavirenz (EFV) causes neuropsychiatric effects such as anxiety, depression, and suicidal thoughts in people with HIV (PWH). Depressive disorders have been associated with the Tryptophan hydroxylase type 2 (TPH2) gene. Objectives: This study determines the genotypes and allelic frequencies of three TPH2 single nucleotide polymorphisms (SNPs) in a Mexican cohort of HIV-1 treatment-naïve-patients and the severity of depressive symptoms at baseline and after a four-week clinical follow-up of antiretroviral treatment. Methods: In a pilot prospective study, eighty-one antiretroviral treatment-naïve patients were recruited from the Infectious Disease Hospital, National Medical Center "La Raza", in Mexico City. Of these, 39 were treated using a set-dose combination regimen of tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) plus EFV and 42 were treated with TDF/FTC plus atazanavir/ritonavir (ATV/r), and fifty-nine control volunteers. Genomic DNA was obtained from peripheral blood mononuclear cells. All DNA samples underwent qPCR utilizing TaqMan probes for the three TPH2 SNPs studied. All participants underwent evaluation utilizing the Beck Depression Inventory. Results: Of the three SNPs examined, none exhibited any notable differences in the distribution of the alleles between the groups; nevertheless, rs4570625 TT and rs1386493 GG presented a twofold and fivefold greater risk of severe depression in PWH, respectively, independently of the treatment. Among PWH, those treated with EFV experienced severe depression at a higher rate of 90.4% after four weeks, compared to 87.5% in those treated with ATV/r. Conclusions: High rates of severe depression were identified in PWH, who presented the rs4570625 TT and rs1386493 GG polymorphic variants. Depression increased after four weeks of treatment and was higher with EFV than ATV/r. It is crucial to emphasize the necessity of conducting psychiatric monitoring for every patient with HIV and administering prompt antidepressant treatment.

Effects of vagus nerve stimulation on daily function and quality of life in markedly treatment-resistant major depression: Findings from a one-year, randomized, sham-controlled trial.

Depression treatments aim to minimize symptom burden and optimize quality of life (QoL) and psychosocial function. Compare the effects of adjunctive versus sham vagus nerve stimulation (VNS) on QoL and function in markedly treatment-resistant depression (TRD). In this multicenter, double-blind, sham-controlled trial, 493 adults with TRD and ≥4 adequate but unsuccessful antidepressant treatment trials (current episode) were randomized to active (n=249) or sham (n=244) VNS (plus treatment as usual) over a 12-month observation period. Quarterly outcomes included QoL with the Q-LES-Q, Mini-Q-LES-Q, and EQ-5D-5L, and function with the WHODAS 2.0 and Work Productivity and Activity Impairment Questionnaire (WPAI) item 6. Differences between treatment groups in change in scores from baseline and percentage of time with a meaningful response in Q-LES-Q, Mini-Q-LES-Q, and WPAI item 6 scores were analyzed. Active VNS was superior to sham in mean change in scores from baseline in the Mini-Q-LES-Q (P=0.050) and WPAI item 6 (health condition's effect on regular activities [P=0.050]) used as continuous variables, with a similar trend for Q-LES-Q (P=0.061). Active VNS was superior to sham in time spent in clinically meaningful benefit (categorical analyses) using the Q-LES-Q (P=0.029), Mini-Q-LES-Q (P=0.011), and WPAI item 6 (P=0.039). The WHODAS 2.0 (P=0.304) and EQ-5D visual analog scale (P=0.125) failed to reveal between-group differences. Active VNS was superior to sham VNS in improving QoL and psychosocial function in patients with TRD. VNS has a broader therapeutic impact than symptom improvement alone in patients with marked psychosocial impairment.

Resistance to antidepressant treatment among patients with major depressive disorder: a nationwide study.

Treatment-resistant depression (TRD) has great clinical importance because it has the highest disability burden of all depressive conditions. We investigated the prevalence of TRD and identified the risk and protective factors associated with antidepressant resistance among adult patients with major depressive disorder (MDD). A total of 176 132 adult patients with MDD were selected from the Taiwan National Health Insurance Research Database between 2001 and 2010 and followed for 1 year. TRD was defined as nonresponse to at least two antidepressants, and treatment-resistant tendency was defined as nonresponse to at least the first antidepressant. General physical condition measured by the Charlson Comorbidity Index (CCI), psychiatric comorbidities, and economic status were assessed. Only 2.6% ( n = 4608) of the adults with MDD met the TRD criteria, but 26.4% ( n = 46 491) were classified as having treatment-resistant tendency. The following psychiatric comorbidities were related to TRD: anxiety disorders [odds ratio (OR): 1.88], substance use disorders (OR: 1.73), alcohol use disorders (OR: 1.27), and personality disorders (OR: 2.12). In addition, a more severe physical condition (higher CCI) increased the likelihood of TRD (OR: 1.12). Psychiatric comorbidities and poor general physical condition may increase the likelihood of antidepressant treatment failure.

MicroRNA Expression Profile Is Altered by Short-Term and Chronic Lithium Treatment in a Rat Model of Depression.

Depression is a common disease that affects 3.8% of the global population. Despite various antidepressant treatments, one-third of patients do not respond to antidepressants, therefore augmentation with mood stabilizers such as lithium may be required in this group. One of the suggested pathomechanisms of depression is the dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and recent reports showed that microRNAs (miRNA) can impact its activity by epigenetic regulation. We aimed to explore the miRNA expression profile in the depression model and its changes upon short-term and chronic lithium treatment in the rat brain (pituitary, hypothalamus, and hippocampus). We used a chronic mild stress rat model of depression and short- and long-term lithium treatment. The behavior was assessed by an open-field test. The miRNA expression profile in the pituitary was estimated by sequencing and validated in the hypothalamus and hippocampus with qPCR. We found several miRNAs in the pituitary that were significantly altered between CMS-exposed and control rats as well as after short- and long-term lithium treatment. MicroRNAs chosen for validation in the hypothalamus and hippocampus (rno-miR-146a-5p, rno-miR-127-3p) showed no significant changes in expression. We performed in silico analysis and estimated potential pathways involved in lithium action for miRNAs differentially expressed in the pituitary at different time points. Specific microRNA subsets showed altered expression in the pituitary in depression model upon short- and long-term lithium treatment. We identified that biological pathways of target genes for these altered miRNAs differ, with the Foxo pathway potentially involved in disease development.

Neuroplasticity in Depressive Disorders: The Role of BDNF in Linking Pharmacotherapy and Physical Activity

Introduction: Depressive disorders are among the most prevalent mental health conditions globally, affecting millions of people. Despite extensive research, the exact pathophysiology of depression remains unclear. Recent evidence suggests that neuroplasticity, particularly the role of brain-derived neurotrophic factor (BDNF), plays a crucial role in both the onset and treatment of depressive disorders. Aim of Study: This review explores the relationship between neuroplasticity and depression, focusing on BDNF as a central biomarker and potential therapeutic target. It also examines how antidepressant therapies and physical activity influence neuroplasticity and BDNF levels, offering insights into novel approaches for treating depressive disorders. Material and Methods: A literature review was conducted using PubMed and Google Scholar databases, focusing on peer-reviewed articles with the keywords: "neuroplasticity", "BDNF", "depression", "antidepressants" and "physical activity". Conclusions: Neuroplasticity, particularly through BDNF signaling, plays a critical role in the pathogenesis and treatment of depression. Elevated BDNF levels promote synaptic plasticity, neurogenesis, and recovery of brain function. Antidepressant treatments enhance neuroplasticity by increasing BDNF levels. Antidepressants and physical activity both influence neuroplastic processes, with BDNF serving as a key mediator.

Placebo effect in the treatment with antidepressants : Implications for the scientific evaluation and clinical use of pharmaceutical treatments of depression

Blinded placebo treatment arms in clinical trials often achieve up to 80% of the clinical improvements of the verum groups. Apparently, the majority of the effects found in the antidepressant groups in clinical trials are due to factors that are not specific to antidepressant treatment. This article reviews the factors that contribute to the high effectiveness of placebo interventions for antidepressants. Anarrative literature review is presented with particular emphasis on placebo effects in antidepressant clinical trials. There is aparticularly strong placebo effect in depression compared to other mental disorders. The magnitude of this effect can be modulated by helpful versus nonhelpful instructions, by patient participation in the decision-making process but also by personal attention, especially if the clinician is perceived as competent and warmhearted. The occurrence of subtle side effects can also reinforce placebo effects. Placebo effects are not only reflected in subjective patient-reported outcome variables but are also evident in neurochemical changes in the body. Clinicians essentially contribute to the effectiveness of antidepressant treatment through their own behavior. At the same time, the relatively small overall difference between verum and placebo treatments for depression leads to the necessity of acritical evaluation of the cost-benefit ratio, adapted to the individual case. Study designs for the evaluation of antidepressants are required that better reflect the complex interactions between the genuine drug effects and placebo effects.