Antidepressant Treatment Research Articles

The Potential Role of Dopamine Pathways in the Pathophysiology of Depression: Current Advances and Future Aspects.

Depression is a serious mental health disorder that impacts more than 350 million individuals globally. While the roles of serotonin and norepinephrine in depression have been extensively studied, the importance of dopaminergic pathways-essential for mood, cognition, motor control, and endocrine function-often gets overlooked. This review focuses on four major dopamine (DA) circuits: the mesolimbic (MLP), mesocortical (MCP), nigrostriatal (NSP), and thalamictuberoinfundibular pathways (TTFP), and their roles in depression. The MLP, which is key to reward processing, is linked to anhedonia, a primary depression symptom. The MCP, projecting to the prefrontal cortex, affects cognitive issues like impaired attention and decision-making. The NSP, mainly responsible for motor control, is related to psychomotor retardation in depression, while the TTFP manages neuroendocrine responses, which are often disrupted in stress-related depressive conditions. Current antidepressant treatments mainly target serotonin and norepinephrine systems but tend to be less effective for patients with DArgic dysfunction, leading to treatment resistance. This review underscores emerging evidence that suggests targeting DArgic pathways could improve treatment outcomes, especially for symptoms like anhedonia and cognitive deficits that conventional therapies often fail to address. Future research should aim to combine advancements in neuroimaging, optogenetics, and genetic studies to better map DArgic pathways and create personalized treatment plans. This review highlights the potential for new therapies that focus on DA systems, which could pave the way for more effective and tailored approaches to treating depression.

A case report of mental disorder caused by shunt blockage after hydrocephalus surgery

IntroductionHydrocephalus is a form of communication hydrocephalus syndrome characterized by ventricular enlargement and normal intraventricular pressure. The primary clinical manifestations include gait disturbances, cognitive dysfunction, urinary incontinence, and either elevated or normal intracranial pressure. This paper presents a case of a mental disorder resulting from inadequate drainage following a ventriculoperitoneal shunt procedure for hydrocephalus. The case report aims to enhance clinicians’ understanding of such organic brain lesions, which are prone to misdiagnosis and inappropriate treatment, thereby improving differential diagnostic skills.Case presentationThis case report describes a 34-year-old male with a 16-year history of depressive disorder, previously managed with 150 mg of venlafaxine daily, 7.5 mg of zopiclone every night, and 2.4 g of piracetam every day. The patient underwent a ventriculoperitoneal shunt procedure for hydrocephalus, leading to the development of a mental disorder attributable to poor drainage from the shunt tube. Initial symptoms consisted of low mood, decreased interest, and cognitive impairment. Despite psychiatric consultation and antidepressant treatment, there was no improvement in his condition. The final diagnosis was an organic mental disorder. Following an increase in shunt drainage and the administration of a low dose of olanzapine, the patient’s psychiatric symptoms showed significant improvement.ConclusionReporting this case seeks to enhance clinicians’ awareness of the psychiatric manifestations of organic brain lesions, expand the differential diagnostic approach for psychiatrists, and improve diagnostic accuracy. Additionally, it emphasizes the need for cautious use of psychiatric medications, appropriate symptomatic management, and timely referral when necessary.

Documentary Analysis of Hypericum perforatum (St. John’s Wort) and Its Effect on Depressive Disorders

Hypericum perforatum, also known as St. John’s Wort, pericon, or yellow grass, is known for its antidepressant potential. It could represent a natural alternative to current pharmacological antidepressant treatments, which have a high incidence of side effects in patients and therefore lead to early dropouts. Through a bibliographic revision of clinical trials and information collected from scientific articles during the first period of 2020, we aimed to evaluate whether its administration could be beneficial in the treatment of mild-to-moderate depression, with fewer side effects compared to synthetic drugs. Among the main components, hypericin and hyperforin have been related to the observed antidepressant activity; therefore, their possible mechanism of action was reviewed and highlighted. Furthermore, patients receiving Hypericum extracts were less likely to withdraw from studies because of adverse effects compared to those receiving older standard antidepressants. This review aims to provide suggestions for an alternative treatment of mild-to-moderate depression disorder under the supervision of a medical doctor, since, although it appears to be a potentially efficient treatment with a low presence of adverse effects in comparison to synthetic antidepressants, it might also interact with other medications and lead to therapeutic failures if misused for self-medication.

Chronic citalopram effects on the brain neurochemical profile and perfusion in a rat model of depression detected by the NMR techniques – spectroscopy and perfusion

BackgroundMajor depressive disorder (MDD) is a mental illness with a high worldwide prevalence and suboptimal pharmacological treatment, which necessitates the development of novel, more efficacious MDD medication. Nuclear magnetic resonance (NMR) can non-invasively provide insight into the neurochemical state of the brain using proton magnetic resonance spectroscopy (1H MRS), and an assessment of regional cerebral blood flow (rCBF) by perfusion imaging. These methods may provide valuable in vivo markers of the pathological processes underlying MDD. MethodsThis study examined the effects of the chronic antidepressant medication, citalopram, in a well-validated MDD model induced by bilateral olfactory bulbectomy (OB) in rats. 1H MRS was utilized to assess key metabolite ratios in the dorsal hippocampus and sensorimotor cortex bilaterally, and arterial spin labelling was employed to estimate rCBF in several additional brain regions. ResultsThe 1H MRS data results suggest lower hippocampal Cho/tCr and lower cortical NAA/tCr levels as a characteristic of the OB phenotype. Spectroscopy revealed lower hippocampal Tau/tCr in citalopram-treated rats, indicating a potentially deleterious effect of the drug. However, the significant OB model–citalopram treatment interaction was observed using 1H MRS in hippocampal mI/tCr, Glx/tCr and Gln/tCr, indicating differential treatment effects in the OB and control groups. The perfusion data revealed higher rCBF in the whole brain, hippocampus and thalamus in the OB rats, while citalopram appeared to normalise it without affecting the control group. ConclusionCollectively, 1H MRS and rCBF approaches demonstrated their capacity to capture an OB-induced phenotype and chronic antidepressant treatment effect in multiple brain regions.

The association between gait speed and depressive disorders – A cross-sectional analysis of very old adults in the 21st century

Objectives To investigate the association between gait speed and depressive disorders among very old adults (≥85 years). Method This study utilized the GERDA-database, which encompasses a representative sample of those aged 85, 90, and 95+ years residing in northern Sweden and western Finland. From four data collections between 2000 and 2017, this study included 1794 participants. Self-paced gait speed was measured over 2.4-m and depressive disorders was evaluated by a specialist in geriatric medicine according to the DSM-IV-TR criteria. T-tests and multivariable logistic regressions were used to explore differences and associations between gait speed and depressive disorders. Results Gait speed was independently associated with depressive disorders among very old adults (p < .001). The results showed significantly different mean gait speeds (m/s) between individuals with/without a depressive disorder (0.34 ± 0.24/0.52 ± 0.26, p < .001), between individuals with a depressive disorder with/without antidepressant treatment (0.35 ± 0.24/0.44 ± 0.24, p < .001) and between non-responders/responders to antidepressants (0.36 ± 0.21/0.42 ± 0.22, p = .020). Conclusion This is the first study focusing on very old adults that has shown an independent association between gait speed and depressive disorders. Responders to antidepressant medication had a higher mean gait speed than non-responders, which may imply shifts in function upon successful treatment.

Longitudinal trajectories of symptom change during antidepressant treatment among managed care patients with depression and anxiety

Despite the high correlation between anxiety and depression, little remains known about the course of each condition when presenting concurrently. This study aimed to identify longitudinal patterns during antidepressant treatment in patients with depression and anxiety, and evaluate related factors associated with these patterns. By analyzing longitudinal self-report Patient Health Questionnaire-9 (PHQ-9) and General Anxiety Disorder-7 (GAD-7) scores that tracked courses of depression and anxiety over a three-month window among the 577 adult participants, six depression and six anxiety trajectory subgroups were computationally derived using group-based trajectory modeling. Three depression subgroups showed symptom improvement, while three showed nonresponses. Similar patterns were observed in the six anxiety subgroups. Multinomial regression was used to associate patient characteristics with trajectory subgroup membership. Compared to patients in the remission group, factors associated with depressive symptom nonresponse included older age and lower depression severity.

TMS in the Kingdom of Denmark: an overview of current clinical practice

Purpose Repetitive TMS (rTMS) has been demonstrated to be an effective treatment of several neuropsychiatric disorders. Its safety and efficacy are well established, and multiple rTMS devices have been approved by both Conformitè Europëenne Mark and U.S. Food and Drug Administration. We aimed to survey TMS practice in Psychiatry in the Kingdom of Denmark and compare it with the international state of the art. Methods A survey of rTMS clinical practice in 2023 was sent to all general adult psychiatry departments practicing TMS in the Danish Realm (Denmark = 10, Faroe Islands = 0, Greenland = 0). Results Response rate was 100%. rTMS was available in 37% of psychiatric departments and 3 out of 5 Danish Regions. Admission criteria required a diagnosis of unipolar depression with a degree of treatment-resistance or unacceptable side-effects to antidepressant treatment. Common contraindications included: cochlear implants (100%), pacemaker and neurostimulators (80%), other ferromagnetic/implanted devices in head, neck, or thorax (70%), active substance misuse (60%), and electrolytic disturbances (50%). Three rTMS protocols were identified: 10 Hz rTMS delivered over the L-DLPFC, iTBS delivered over the L-DLPFC and 1 Hz rTMS delivered over the right-DLPFC. 383 patients were treated with TMS. Conclusions rTMS is unequally available in the public healthcare of the Kingdom of Denmark. Existing strategies for solving inequalities could address such issues. Unipolar depression was the only psychiatric disorder treated with rTMS in 2023. rTMS practice in the Danish Realm considers the use of evidence-based protocols and is consistent with recommendations from international expert guidelines.

The effect of antidepressant treatment on viral suppression among people with HIV diagnosed with depression in an urban clinic, 2012-2023.

To estimate the effect of antidepressant initiation on viral non-suppression among people with HIV (PWH) with clinically recognized, untreated depression. Retrospective, observational cohort study. We included clinical diagnoses of depression from January 2012-June 2022 among PWH in the Johns Hopkins HIV Clinical Cohort without another serious psychiatric illness who had initiated antiretroviral therapy. We excluded diagnoses less than 90 days from a prior diagnosis, antidepressant prescription, or >1 mental health visits. We estimated the association between initiating an antidepressant within 1 month of the index depression diagnosis and viral load non-suppression (>200 copies/mL) on the first viral load 3-12 months subsequent. We adjusted for a comprehensive set of demographic and clinical confounders. We included 2,346 depression diagnoses among 946 patients; patients initiated an antidepressant following 16%. The risk of viral non-suppression in the absence of antidepressant treatment was 15.6% (95% confidence interval [CI]: 13.1, 18.4). Antidepressant initiation was not associated with viral non-suppression (risk difference: 0.5%; 95% CI: -3.7, 4.8) or secondary outcomes: improvement or resolution of depressive symptoms or adherence to scheduled clinic visits. In this sample of patients with as-yet-untreated depression, in a setting with co-located, low-barrier psychiatric services, antidepressant treatment was not associated with improved viral suppression. Pharmacologic management of depression has documented benefits in other studies. However, there may be a subset of PWH with depression who have been previously unsuccessfully treated with antidepressants who are less likely to respond to approved pharmacologic options and who require different interventions to improve their viral suppression.

Changes in hippocampal volume, 5-HT4 receptor binding, and verbal memory over the course of antidepressant treatment in major depressive disorder

Serotonin reuptake inhibitors have been reported to increase hippocampal volume and improve memory function in patients with Major depressive disorder (MDD). The postsynaptic 5-HT4 receptor (5-HT4R) is involved in hippocampal development, familial risk for depression and depressive pathology. In an open-label trial with 91 patients (72% female, mean 27.2 years) with MDD, we investigated the relation between changes in hippocampal volume, 5-HT4R, and verbal memory during 12 weeks treatment with 10–20 mg escitalopram. Depression severity, verbal memory, MRI-determined hippocampus volume and PET-determined 5-HT4R were measured pretreatment. Forty-three patients were rescanned at week 8. HAMD17 was reassessed at week 8 and together with verbal memory at week 12. We used mixed-effects models and linear regressions. We estimated a 27 mm3 (p = 0.086) reduction in mean hippocampus volume over the course of eight weeks. In patients clinically responding to treatment, we estimated a 45 mm3 reduction (p = 0.019), 8 mm3 increase in non-responders (p = 0.78), and a 52 mm3 group difference (p = 0.12). Hippocampal 5-HT4 receptor binding before treatment and at week eight was negatively associated with hippocampal volume in females, regardless of treatment response (p-values≤0.006). However, no clear evidence for an association in males or sex interaction could be established (p-values≥0.16). Although the hippocampus volume did not increase with treatment, we found a decrease in clinically responsive patients. Our findings suggest an association between 5-HT4R signalling and changes in hippocampal volume in females with MDD during antidepressant treatment, highlighting the need for further investigation into the role of serotonergic mechanisms in hippocampal plasticity.

Glycosylation changes of vWF in circulating extracellular vesicles to predict depression

The clinical diagnosis of major depressive disorder (MDD) still depends on subjective information in terms of various symptoms regarding mood. Detecting the characterization of extracellular vesicles (EVs) in blood may result in finding a diagnostic biomarker that reflects the depressive stage of patients with MDD. Here, we report the results on the glycosylation pattern of enriched plasma EVs from patients with MDD. We compared glycosylation patterns by lectin blotting expressed in EVs isolated from the plasma of both patients with MDD and age-matched healthy control participants (HCs) using size-exclusion chromatography. The levels of Wheat germ agglutinin (WGA), N-acetyl glucosamine (GlcNAc), and N-Acetylneuraminic acid (Neu5Ac, sialic acid) - binding lectin, were significantly decreased in patients with MDD in the depressive state compared to HCs and in remission state. Furthermore, proteome analysis revealed that the von Willebrand factor (vWF) was a significant factor recognized by WGA. WGA-binding vWF antigen differentiated patients with MDD versus HCs and the same patients with MDD in a depressive versus remission state. In this study, the change patterns in the glycoproteins contained in plasma EVs support the usability of testing to identify patients who are at increased risk of depression during antidepressant treatment.

'The effect of neuropeptide Y1 receptor agonist on hypothalamic neurogenesis in rat experimental depression model'.

Depression is responsible for neuropathies such as decreased neurogenesis and increased dendritic atrophy. There is information that antidepressant treatments have an effect by increasing hippocampal neurogenesis and neurotrophic factor expression. The neuropeptide Y1 (NPY1R) receptor agonist has been suggested to have anxiolytic effects. Based on this information, it was aimed to investigate the effect of NPY1R agonist on depression in rats with depression using the CMS model and to determine how depression affects cell proliferation in the hypothalamus and hypothalamic peptide levels. Forty-eight adult, male Wistar albino rats were divided into groups as Control, Depression (D), Depression + NPY1R and NPY1R. Various stressors were applied to D for 30 days. An open field test (OFT) and forced swim test (FST) were performed to check whether the animals were depressed. On the 16th day, an osmotic mini pump was placed under the skin and NPY1R (130 ul/kg/day) was applied for 15 days. Behavioral tests were performed, hypothalamic peptide gene expression levels were analyzed by quantitative RT-PCR and statistical evaluations were made using ANOVA. A decrease in the percentage of movement in the D and control groups were noted in the OFT, an increase in the immobility time in the D group in the FST, and an increase in swimming behavior in the DNPY1R group. The animals did not display any anxiety behavior based on the elevated plus maze test results. It caused a decrease in IGF1R, FGF2, POMC, NPY and GLUT2 gene expression in the hypothalamus of depression group animals, and an increase in NPY gene expression in NPY1R treatment. This study compellingly demonstrated that exposure to chronic mild stress simultaneously downregulates gene expression in the hypothalamus; we observed that NPY receptor NPY1R treatment increased the effect of NPY. Therefore, adjunctive treatments with appropriate molecules such as NPY, Y1 receptor agonists or pharmacological derivatives may have significant potential in the treatment of depression.

Abnormal choroid plexus, hippocampus, and lateral ventricles volumes as markers of treatment-resistant major depressive disorder.

One-third of patients with major depressive disorder (MDD) do not achieve full remission and have high relapse rates even after treatment, leading to increased medical costs and reduced quality of life and health status. The possible specificity of treatment-resistant depression (TRD) neurobiology is still under investigation, with risk factors such as higher inflammatory markers being identified. Given recent findings on the role of choroid plexus (ChP) in neuroinflammation and hippocampus in treatment response, the aim of the present study was to evaluate inflammatory- and trophic-related differences in these regions along with ventricular volumes among patients with treatment-sensitive depression (TSD), TRD, and healthy controls (HCs). ChP, hippocampal, and ventricular volumes were assessed in 197 patients with MDD and 58 age- and sex-matched HCs. Volumes were estimated using FreeSurfer 7.2. Treatment resistance status was defined as failure to respond to at least two separate antidepressant treatments. Region of interest volumes were then compared among groups. We found higher ChP volumes in patients with TRD compared with patients with TSD and HCs. Our results also showed lower hippocampal volumes and higher lateral ventricular volumes in TRD compared with both patients without TRD and HCs. These findings corroborate the link between TRD and neuroinflammation, as ChP volume could be considered a putative marker of central immune activity. The lack of significant differences in all of the region of interest volumes between patients with TSD and HCs may highlight the specificity of these features to TRD, possibly providing new insights into the specific neurobiological underpinnings of this condition.

Structural neural plasticity evoked by rapid-acting antidepressant interventions.

A feature in the pathophysiology of major depressive disorder(MDD), a mood disorder, is the impairment of excitatory synapses in the prefrontal cortex. Intriguingly, different types of treatment with fairly rapid antidepressant effects (within days or a few weeks), such as ketamine, electroconvulsive therapy and non-invasive neurostimulation, seem to converge on enhancement of neural plasticity. However, the forms and mechanisms of plasticity that link antidepressant interventions to the restoration of excitatory synaptic function are still unknown. In this Review, we highlight preclinical research from the past 15 years showing that ketamine and psychedelic drugs can trigger the growth of dendritic spines in cortical pyramidal neurons. We compare the longitudinal effects of various psychoactive drugs on neuronal rewiring, and we highlight rapid onset and sustained time course as notable characteristics for putative rapid-acting antidepressant drugs. Furthermore, we consider gaps in the current understanding of drug-evoked in vivo structural plasticity. We also discuss the prospects of using synaptic remodelling to understand other antidepressant interventions, such as repetitive transcranial magnetic stimulation. Finally, we conclude that structural neural plasticity can provide unique insights into the neurobiological actions of psychoactive drugs and antidepressant interventions.

Oral Manifestations in Patients in Treatment with Antidepressants: A Systematic Review.

Background/Objectives: The rising use of antidepressants is linked to oral health risks, including xerostomia, caries, and periodontal disease. Recognizing these risks is essential for improving patient care. To systematically review oral manifestations in patients undergoing antidepressant treatment. Methods: This review follows the PRISMA guidelines and includes observational studies published in the last 21 years. A PICO-based question was developed to select relevant studies, which were assessed for quality using a modified STROBE checklist. Results: A total of 11 studies were analyzed, revealing a consistent association between antidepressant use and the increased risk of xerostomia, caries, and periodontal disease. Additional findings included taste dysfunction and oral bleeding complications. Among the antidepressants, selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) were most commonly associated with xerostomia and caries. However, no significant impact was observed on the chemical composition of saliva or on hemostasis in invasive dental procedures. Conclusions: Antidepressant use may lead to significant oral health issues, notably xerostomia and caries. Further studies are recommended to clarify the influence of specific antidepressants and confounding factors, such as treatment duration, dosage, and hygiene habits, on oral health outcomes.

Selective Serotonin Reuptake Inhibitors for Cessation of Betel Quid Use in Patients with Major Depressive Disorder in Taiwan.

Background/Objectives: Major depressive disorder (MDD) frequently co-occurs with substance use disorders such as alcohol and nicotine use disorders. Comorbid substance use disorders worsen the clinical symptoms of MDD and exacerbate addictive behaviors and presentations. However, the relationship between MDD and betel quid use disorder (BUD) in Taiwan has not been extensively investigated. Methods: We performed this cross-sectional study investigated associations between betel quid use, BUD, and MDD specifically in the Taiwanese population. Long-term betel quid use is a major public health concern, contributing significantly to the high incidence of oral cancers, which rank fifth among the top ten most common cancers in Taiwan. Results: Among patients with MDD, the current BUD prevalence rate was 7.32%, and the lifetime BUD prevalence rate was 15.45%. Patients with comorbid BUD were more likely to have severe alcohol and nicotine dependence disorders and required longer antidepressant treatment. Conclusions: Notably, 16.98% of patients with comorbid BUD who received selective serotonin reuptake inhibitor treatment achieved abstinence. BUD has a detrimental effect on health outcomes in patients with MDD, and selective serotonin reuptake inhibitor treatment may be required to be prolonged for betel quid abstinence therapy to be effective. Additional studies should investigate medication therapies for betel quid addiction disorders.

Dispositional optimism predicts antidepressant treatment response in major depressive disorder: potential relevance for positive psychology interventions

ABSTRACT Positive psychology interventions have demonstrated efficacy in treating Major Depressive Disorder (MDD), but the relationship between dispositional optimism and antidepressant treatment response remains unclear. In this study, optimism (Revised Life Orientation Test, LOT-R) and depression severity (Hamilton Depression Rating Scale, HDRS) were assessed in healthy unmedicated MDD participants (N = 86) and healthy controls (N = 65). Treatment response (≥50% reduction in HDRS) was measured in 46 of these MDD participants after 8 weeks of open-label selective serotonin reuptake inhibitor (SSRI) treatment. MDD participants reported significantly lower pre-treatment optimism than healthy controls. Higher pre-treatment optimism, as well as greater increase in optimism (pre-treatment to 8 weeks), were associated with greater likelihood of being an SSRI responder versus non-responder (β = 0.21, p = 0.013; β = 0.32, p = 0.01, respectively), even when ratings of optimism/pessimism were excluded from depression severity/response ratings. The findings are consistent with the importance of aspects of positive psychology in treatment response. Possible mechanisms are discussed.

The relation between cerebral morphological abnormalities in major depressive disorder and antidepressant treatment

Abstract. The cerebral morphological abnormalities caused by Major Depressive Disorder (MDD) are markedly different from those of many other cerebral parts in non-patients. This brain disorder may be coordinated by antidepressant treatment. This paper investigates the links between antidepressant medication and morphological features in MDD using a literature review method. The paper finds that there is a positive response and feedback on these neurobiological alterations. The relationship between morphological features and treatment may make it easier to objectively observe the effects of antidepressants on MDD patients. The review emphasizes the importance of understanding the cerebral morphological changes associated with MDD, as well as how antidepressant therapy can potentially modulate these alterations. By exploring the relationship between pharmacological interventions and structural brain changes, the paper provides insights into the neurobiological mechanisms underlying the therapeutic effects of antidepressants. This knowledge can enhance the advancement of more focused and efficient therapy approaches for patients with Major Depressive Disorder.

Trajectories of antidepressant use after tamoxifen initiation among young and middle-aged women with breast cancer.

Antidepressant treatment patterns may change after women with breast cancer (BC) initiate tamoxifen, potentially impacting health outcomes. We characterized trajectories of antidepressant use after initiating tamoxifen among young and middle-aged women with BC, identifying risk factors for trajectory group membership. A retrospective cohort included women 18-64years-old with BC and antidepressant treatment history who received a new tamoxifen dispensing (index date). We measured longitudinal antidepressant use post-index date as 12, monthly, proportion of days covered (PDC) measurements in a 25% random sample of IQVIA PharMetrics® Plus for Academics US claims, 2006-2022. Group-based trajectory models identified latent subgroups of antidepressant use by testing 2-6-group representations; the best model fit determined by the lowest Bayesian Information Criterion, clinical interpretability, and each subgroup comprising ≥ 5% of the cohort. Using multinomial logistic regression, baseline covariates including demographics, depression status and the CYP2D6-inhibitory strength of antidepressants were evaluated as risk factors for the trajectory of antidepressant use after tamoxifen initiation. Our sample of 851 women followed four distinct antidepressant adherence trajectories after tamoxifen initiation: 12% exhibited immediately decreasing use [mean PDC (sd) 8% (± 7)]; 7% exhibited delayed decreasing use [41% (± 14)]; 20% exhibited dynamic-moderate use [54% (± 15)]; and 60% exhibited consistently high use [91% (+ 7)]. Age, depression, and treatment with non CYP2D6-inhibiting antidepressants were associated with women's trajectory of antidepressant use after initiating tamoxifen. Nearly 40% of women were nonadherent to antidepressants after tamoxifen initiation. Future research should explore cancer-related and mental health implications of this nonadherence.

ABC Family Gene Polymorphisms and Cognitive Functions Interact to Influence Antidepressant Efficacy.

The importance of identifying relevant indicators of antidepressant efficacy is highlighted by the low response rates to antidepressant treatment for depression. The ABC gene family, encoding ATP-dependent transport proteins facilitating the transport of psychotropic drugs, has drawn attention. This study delved into the relationship between antidepressant efficacy and seven single nucleotide polymorphisms of ABCB1 and ABCB6 genes. A total of 549 depressed patients participated in the study, and all completed a 6-week course of antidepressant treatment. Cognitive function was assessed at baseline and post-treatment. Patients were categorized based on post-treatment HAMD-17 scores (with HAMD≤7 indicating remission), and comparisons were made between different groups in terms of allelic gene frequencies and genotypes. Logistic regression was used to explore the interaction between cognitive function and genotype on efficacy. Dual-luciferase reporter assays were performed to compare the regulatory effects of rs1109866 allele variants on the ABCB6 promoter. There were no notable differences in allelic gene frequencies and genotypes between the remission and non-remission groups. Nonetheless, a significant interaction was identified between the rs1109866 genotype and language fluency-related indicators concerning efficacy (p=0.029) before correction. The dual-luciferase reporter assays demonstrated markedly higher fluorescence intensity of rs1109866-C compared to that of rs1109866-T (p<0.001). Relying solely on genetic polymorphisms of ABC family genes as predictors of antidepressant treatment response may not be sufficient. However, the interaction between the rs1109866 and cognition plays a pivotal role. The potentially enhanced transcriptional activity of rs1109866-C might offer insight into its impact on antidepressant efficacy.

Microglia Sing the Prelude of Neuroinflammation-Associated Depression.

Major depressive disorder (MDD) is a psychiatric condition characterized by sadness and anhedonia and is closely linked to chronic low-grade neuroinflammation, which is primarily induced by microglia. Nonetheless, the mechanisms by which microglia elicit depressive symptoms remain uncertain. This review focuses on the mechanism linking microglia and depression encompassing the breakdown of the blood-brain barrier, the hypothalamic-pituitary-adrenal axis, the gut-brain axis, the vagus and sympathetic nervous systems, and the susceptibility influenced by epigenetic modifications on microglia. These pathways may lead to the alterations of microglia in cytokine levels, as well as increased oxidative stress. Simultaneously, many antidepressant treatments can alter the immune phenotype of microglia, while anti-inflammatory treatments can also have antidepressant effects. This framework linking microglia, neuroinflammation, and depression could serve as a reference for targeting microglia to treat depression.