Types Of Antidepressants Research Articles

Prevalence and clinical correlates of impaired fasting blood glucose in children and adolescents with depressive disorder and relationship with triglyceride and high-density lipoprotein ratio

Depressive disorder is a significant public health problem worldwide, which adversely affects children and adolescents’ health. Impaired fasting blood glucose (IFG) is more common in depressive disorder, which becomes a clinical problem that needs to be focused on. The study purposed to determine the prevalence and related factors of IFG in Chinese children and adolescents with depressive disorder and the relationship between triglyceride and high-density lipoprotein cholesterol (TG/HDL-C) ratio and IFG. This research encompassed 756 individuals aged 8 to 18 with major depressive disorders, all diagnosed under DSM-5 criteria at the Third People’s Hospital of Fuyang from January 2020 to December 2021. We detected fasting blood glucose (FBG) and lipid levels and assessed the suicidal behaviors and depressive symptoms severity of each participant. The sociodemographic and included study variables were collected and analyzed. Our study employed multiple logistic regression to discern independent factors affecting IFG in conjunction with depressive disorders among children and adolescents. The prevalence of IFG was 6.5% (49/756). IFG was positively correlated with FBG, BMI, TG, TG/HDL-C, and was negatively correlated with gender and the type of antidepressant drug taken. Binary logistic analysis showed that male (OR = 2.57, 95% CI: 1.43–4.63, P = 0.002) and higher levels of TG (OR = 1.63, 95% CI: 1.11–2.38, P = 0.013) were independently associated with IFG in children and adolescents with depressive disorder. The incidence of IFG in children and adolescents with depressive disorder was high and was positively related to the TG/HDL-C ratio. The evaluation and management of IFG in pediatric depression should extend beyond pharmacological interventions. Comprehensive strategies in both assessment and management of IFG are essential to address this condition effectively in young patients facing depressive disorders.

Ketamine as a treatment of stress-induced maternal depression in mice: effects on offspring behaviour

Maternal depression during pregnancy adversely affects offspring neurodevelopment and behaviour. Typical antide-pressants like selective serotonin reuptake inhibitors have limitations due to risks of crossing the placenta. Ketamine has emerged as a promising alternative treatment. This research examined ketamine's effects on offspring of mater¬nally stressed mice. Dams were divided into control, maternal adversity, fluoxetine, and ketamine groups. Open field, sucrose preference, elevated plus maze, and forced swim tests assessed offspring anxiety, anhedonia, and despair. Maternal adversity increased anxiety-like behaviours and ketamine or fluoxetine reversed some effects. However, fluoxetine more effectively mitigated despair in forced swim tests. Ketamine moderately alleviated anhedonia versus controls. Further research on dose-response and timing is needed to optimize ketamine treatment. Mitigating maternal depression is crucial for preventing maladaptive offspring neurobehavioral trajectories.

Integrated physio-biochemical and transcriptomic analysis reveals the joint toxicity mechanisms of two typical antidepressants fluoxetine and sertraline on Microcystis aeruginosa

Selective serotonin reuptake inhibitor (SSRI) antidepressants are of increasing concern worldwide due to their ubiquitous occurrence and detrimental effects on aquatic organisms. However, little is known regarding their effects on the dominant bloom-forming cyanobacterium, Microcystis aeruginosa. Here, we investigated the individual and joint effects of two typical SSRIs fluoxetine (FLX) and sertraline (SER) on M. aeruginosa at physio-biochemical and molecular levels. Results showed that FLX and SER had strong growth inhibitory effects on M. aeruginosa with the 96-h median effect concentrations (EC50s) of 362 and 225 μg/L, respectively. Besides, the mixtures showed an additive effect on microalgal growth. Meanwhile, both individual SSRIs and their mixtures can inhibit photosynthetic pigment synthesis, cause oxidative damage, destroy cell membrane, and promote microcystin−leucine−arginine (MC-LR) synthesis and release. Moreover, the mixtures enhanced the damage to photosynthesis, antioxidant system, and cell membrane and facilitated MC-LR synthesis and release compared to individuals. Furthermore, transcriptomic analysis revealed that the dysregulation of the key genes related to transport, photosystem, protein synthesis, and non-ribosomal peptide structures was the fundamental molecular mechanism underlying the physio-biochemical responses of M. aeruginosa. These findings provide a better understanding of the toxicity mechanisms of SSRIs to microalgae and their risks to aquatic ecosystems.

Receptor specific mechanisms underlying psychedelic effects on affective behaviors

AbstractBackgroundAlzheimer’s Disease (AD) patients experience affective symptoms. Conventional therapies to address affective symptoms have limited efficacy in AD, alternative options, like psychedelics, have received interest. Psychedelics work through serotonergic pathways ‐ a neuromodulatory system with dysfunction in AD ‐mechanisms underlying behavioral changes and potential efficacy of their use are unknown. Evaluation of mechanisms underlying behavioral effects is needed to determine their potential as interventions. Psychedelics act through serotonin receptors, not serotonin re‐uptake inhibition characteristic of typical antidepressants. We investigate psychedelics’ mechanism of action as a potential effector of hedonic tone to assess its potential use for affective symptoms in AD.MethodWT mice were subject to one of three paradigms: (1) a 10‐day social defeat stress (SDS); (2) an injection of 2,5‐Dimethoxy‐4‐iodoamphetamine (DOI); or (3) SDS with DOI. SDS was used instead of an AD proteinopathy model to induce effects like anhedonia. Afterwards, mice underwent behavioral tests to evaluate compulsivity and affect. An additional group will receive DOI +serotonin receptor antagonistsResultFirst, SDS increased time spent in closed arms of the elevated plus maze (EPM; p = 0.0068) indicating an increase in anxiety. It also increased nest shredding (NST; p = 0.206), indicating an increase in compulsivity.Secondly, an injection of DOI decreased time spent in closed arms (p = 0.0151) indicating decrease in anxiety, and decreased nest shredding (p = 0.0325) indicating a decrease in compulsivity.Lastly, we expect that DOI will decrease anxiety and compulsivity. We expect to find the inverse to be true in mice that receive DOI +antagonist.ConclusionWe are showing that a traumatic stressor, like that a human might experience pre‐AD, induces potentially maladaptive affective behavioral changes. Here, we’ve demonstrated that psychedelics can act to recover affective dysfunction by activation of serotonin receptors. Because of degeneration of key serotonergic nuclei in AD, the use of serotonin reuptake inhibitors has limited efficacy for addressing symptoms like depression. Psychedelics may offer improved outcomes for AD patients in this regard due to its alternative mechanism of action. Further work to evaluate the efficacy of psychedelics in animal models more closely approximating AD‐type changes in serotonergic systems will help refine this understanding and guide potential clinical applications.

Impact of sertraline on biohydrogen production from alkaline anaerobic fermentation of waste activated sludge: Focusing on microbial community and metabolism

Nowadays, antidepressants are massively consumed worldwide, inevitably bringing about the concern for their latent hazard to the natural environment. This research focused on exploring the effect of sertraline (SET, a typical antidepressant) on hydrogen yields from alkaline anaerobic fermentation of waste activated sludge (WAS). The hydrogen accumulation reached the peak of 14.73 mL/g VSS (volatile suspended solids) at a SET dosage of 50 mg/kg TSS (total suspended solids), i.e., 1.90 times of that in the control fermenter. The data of Illumina high-throughput sequencing demonstrated that SET promoted the expression of genes regulating the membrane transport. Microbial community analysis suggested that some species that could degrade refractory substances were enriched after SET exposure. Finally, metabolic pathways of hydrogen production and consumption were found to be significantly affected with SET addition. This study would deepen the concept of typical antidepressants influencing energy recovery from WAS.

Bupropion Mediated Effects on Depression, Attention Deficit Hyperactivity Disorder, and Smoking Cessation.

Bupropion had been in use since the late 1980s as an unconventional treatment for depression. Unlike other antidepressants, bupropion has no serotonergic activity and inhibits the reuptake of norepinephrine and dopamine. The drug has been used to treat depression, Attention Deficit Hyperactivity Disorder (ADHD), and smoking cessation. This investigation reviews the pharmacokinetic and pharmacodynamic effects of bupropion and its mechanisms of action and interactions with other drugs. We evaluated the efficacy of major on and off-label uses of bupropion, focusing on the indications, benefits, and adverse effects. Our review demonstrates that bupropion is superior to placebo and non-inferior to SSRIs such as escitalopram in treating major depressive disorder. More research is needed to determine positive patient-centered outcomes such as increases in quality of life. In the case of ADHD, the evidence for efficacy is mixed with poorly conducted randomized clinical trials, small sample sizes, and a lack of long-term assessments. The same is true in the case of bipolar disorder in which there is still limited and controversial data available on bupropion's safety and efficacy. In the case of smoking cessation, bupropion is found to be an effective anti-smoking drug with synergistic benefits when used as a combination therapy. We conclude that bupropion has the potential to provide benefit for a subset of patients who do not tolerate other typical antidepressants or anti-smoking therapies or for those whose treatment goals align with bupropion's unique side effect profile, such as smokers who wish to quit and lose weight. Additional research is needed to determine the drug's full clinical potential, particularly in the areas of adolescent depression and combination therapy with varenicline or dextromethorphan. Clinicians should use this review to understand the varied uses of the drug and identify the situations and patient populations in which bupropion can lend its greatest benefit.

Development of electrospun nanofibers based on Poly (vinyl alcohol) for thin film solid-phase microextraction of antidepressant drugs in biological samples

Today, antidepressants are widely used and it is important to determine their trace amounts due to harmful consequences. Here, a new nano sorbent was reported for the simultaneous extraction and determination of three types of antidepressant drugs (Clomipramine (CLO), Clozapine (CLZ), and Trimipramine (TRP) by the thin-film solid-phase micro-extraction (TFME-μSPE) method followed by the Gas Chromatography-flame ionization detector (GC-FID) analysis. So, the compound poly (vinyl alcohol) (PVA)/citric acid(CA)/β-cyclodextrin/Bi2S3@g-C3N4 nano sorbent was constructed by electrospinning technique. Then, nano sorbent was studied to optimize the many parameters impacting the extraction performance. Electrospun nanofiber has a large surface area, high porosity, and homogeneous morphology with a uniform bead-free structure. In optimal conditions, the limits of detection and quantification were calculated to be 0.15–0.03 ng mL−1 and 0.5–0.1 ng mL−1, respectively. The dynamic linear range (DLR) was in the range of 0.1 to 1000 ng mL−1 for CLO and CLZ, and 0.5 to 1000 ng mL−1 for TRP with correlation coefficients (R2) of 0.999. The relative standard deviations (RSDs) were achieved in the range of 4.9–6.8% (intra-day, n = 4) and 5.4–7.9% (inter-day, n = 3) in the period of 3 days. Finally, the capability of the method was evaluated to simultaneously measure trace amounts of antidepressants aqueous sample with desirable extraction efficiency (78 to 95%).

Antidepressants and Suicide: 7,829 Inquests in England and Wales, 2003–2020

Background:Antidepressant (AD) medications increase suicidality for some, or all, age groups. Some, or all, types of ADs, are frequently used in suicides involving overdoses.Methods:The article examines a previously unanalyzed data set summarizing 7,829 media reports of Coroners’ inquests in England and Wales that mention ADs, between 2003 and 2020.Results:The most frequently cited ADs were SSRIs (48.9%) and tricyclics (24.6%). The specific drugs cited most often were the SSRI drug citalopram (19.8%) and the tricyclic drug amitriptyline (17.5%). Of 2,329 cases of death by overdose, 933 (40.1%) were overdoses of ADs, 512 of which (54.9%) did not involve other substances. The ADs most frequently named were amitriptyline (186), and citalopram (86). A further 929 were overdoses of unnamed medicines, a proportion of which may have been ADs.Limitations:The data set, which relies primarily on archives of local newspapers, is incomplete and therefore underestimates the total numbers involved. The accuracy of coroners’ verdicts is not perfect.Conclusions:If preventing suicide is a primary reason for prescribing ADs, this data set includes several thousand people for whom the drugs clearly did not work. Furthermore, about 1,000 people used the drugs that were supposed to alleviate their depression to kill themselves. Systematic analyses of all inquests would be more informative. Meanwhile, reducing the overprescribing of these relatively ineffective and, for some, lethally dangerous substances is suggested, to reduce suicides.

In utero antidepressant exposure not associated with ADHD in the offspring: A case control sibling design.

Recent studies have reported an association between antidepressant (AD) use during pregnancy and the risk to develop attention-deficit/hyperactivity disorder (ADHD) in the offspring. However, the association might be confounded by risk factors in the pregnant parent. To control for unmeasured factors between pregnancies carried by the same parent, we set up a case-control sibling study using the University of Groningen prescription database IADB.nl. Children receiving medication for ADHD (cases) before the age of 16 years were matched to siblings not receiving such medication (controls). Exposure was defined as at least two prescriptions for any AD during pregnancy, i.e., the period of 39weeks before the birth date of the offspring. Secondary analyses were performed to assess the effects of the degree of exposure (the amount of Defined Daily Doses) and the type of AD exposed to. Univariate and multivariate logistic regression was used to estimate odds ratios (ORs) with corresponding 95% confidence intervals (CI). In total, 2,833 children (1,304 cases and 1,529 controls) were included in the analysis. Exposure rate to ADs among cases and controls was 2.2% and 2.4%, respectively. After adjusting for the birth date of the child (as a proxy for the date of pregnancy), age of the pregnant parent at birth, use of psychostimulants, opioids, and antiepileptic drugs by the pregnant parent in the 15 months before birth of the child, an adjusted OR of 1.11 (95% CI 0.67-1.83) was found for the risk of ADHD in the offspring when exposed in utero to ADs. This indicates no increased risk of ADHD in offspring following in utero exposure to ADs. The secondary analyses revealed no statistically significant associations either. The present study provides further evidence that an association between in utero AD exposure and ADHD in offspring might not exist. This perceived association may be caused (at least partially) by confounding by indication. The extent to which depression in the pregnant parent could cause mental disorders such as ADHD in offspring, and the mechanisms involved, should be investigated in further studies.

Ultraviolet oxidative degradation of typical antidepressants: Pathway, product toxicity, and DFT theoretical calculation

The ubiquity of antidepressants in the environment has posed a potential threat to eco-systematic safety. In this study, six kinds of antidepressants including fluoxetine (FLU), paroxetine (PAR), sertraline (SER), fluvoxamine (FLX), citalopram (CTP), and venlafaxine (VEN) were selected to explore their degrading kinetics, transformation pathways, and the acute toxicity of the reaction solution during UV oxidation. The results showed that the order of the photodegradation rate was FLU > PAR > SER > CTP > FLX > VEN. The calculation results of density functional theory (DFT) and molecular orbital theory showed that it was positively correlated with the frontier electron density of drugs and negatively correlated with the HOMO-LUMO gap, respectively. Intermediates were identified with UHPLC-Q-TOF/MS/MS to propose the possible degradation pathways of the drugs and the most likely directions of the reactions were determined by the single point energy calculation. The results of toxicity tests indicated that the acute toxicity of the reaction solution of PAR did not change significantly. The photolysates toxicity of FLU, SER, and FLX decreased at the end of the reaction, while that of CTP and VEN was increased by 1.5 and 1.3 times compared with the parent compound, respectively. Toxicity predictions by the quantitative structure activity relationship (QSAR) model showed that except FLU-162, FLX-174, and VEN-230, other degradation products have developmental toxicity. The results revealed the transformation pathways of these drugs under the UV disinfection process in wastewater treatment plants, especially the formation of toxic by-products during the disinfection process.

Effects of escitalopram therapy on functional brain controllability in major depressive disorder

Antidepressant drugs are the mainstay of treatment for patients with major depressive disorders (MDD). Given the critical role of the underlying neural control mechanism in the physiopathology of depression, this study aims to investigate the effects of escitalopram, a type of antidepressant drug, on the changes of functional brain controllability throughout the escitalopram treatment for MDD. We collected resting-state functional magnetic resonance imaging data from 20 unmedicated major depressive patients at baseline (visit 1, pre-treatment), one week (visit 2, 1-week after the onset of the treatment) and six weeks (visit 3, after the 6-week escitalopram treatment). Our results revealed that the global average and modal controllability of MDD patients were significantly larger and smaller, respectively, compared to healthy subjects (P < 0.01). Furthermore, the modal controllability rank of the frontoparietal network in depression patients was also significantly smaller than the healthy subjects (P < 0.01). However, throughout the escitalopram treatment, the global average and modal controllability, and the controllability of the default mode network and frontoparietal network of MDD patients were consistently changed to the healthy subjects' level. Our results also showed that the changes of global average and modal controllability measures can predict the improvements of clinical scores of the MDD patients as the escitalopram treatment advanced (P < 0.05). In conclusion, this study reveals promising brain controllability-based biomarkers to mechanistically understand and predict the effects of the escitalopram treatment for depression and maybe extended to predict and understand the effects of other interventions for other neurological and psychiatric diseases.

Behavioural Disorders in Dogs and Cats: A Review

Psychiatry is a specialized branch of medicine that studies behavioural disorders in humans and animals. In dogs and cats, behavioural problems are analogous to human psychiatric diseases, with the most common psychopathologies addressed being generalized anxiety disorder, obsessive compulsive disorder, separation anxiety and post-traumatic stress disorder. The level of bizarre behaviours displayed by the pets varies due to a variety of factors such as hereditary, prenatal dam modification and events during their neonatal and socializing phase. The behavioural changes recorded in dogs and cats include trembling, vocalizing, urinating, soiling, defecating, salivating, hiding, destructiveness, aggression, fear and obsessive behaviours. It is critical to remember that other medical complications, that can produce similar behavioural changes, must be addressed for the animal’s specific therapy. For the treatment of behavioural disorders in pets, different therapeutic agents (like Tricyclic antidepressants, selective serotonin reuptake inhibitors, benzodiazepines and a typical antidepressants) are used together with the behavioural modification strategies.

Tianeptine, but not fluoxetine, decreases avoidant behavior in a mouse model of early developmental exposure to fluoxetine

Depression and anxiety, two of the most common mental health disorders, share common symptoms and treatments. Most pharmacological agents available to treat these disorders target monoamine systems. Currently, finding the most effective treatment for an individual is a process of trial and error. To better understand how disease etiology may predict treatment response, we studied mice exposed developmentally to the selective serotonin reuptake inhibitor (SSRI) fluoxetine (FLX). These mice show the murine equivalent of anxiety- and depression-like symptoms in adulthood and here we report that these mice are also behaviorally resistant to the antidepressant-like effects of adult SSRI administration. We investigated whether tianeptine (TIA), which exerts its therapeutic effects through agonism of the mu-opioid receptor instead of targeting monoaminergic systems, would be more effective in this model. We found that C57BL/6J pups exposed to FLX from postnatal day 2 to 11 (PNFLX, the mouse equivalent in terms of brain development to the human third trimester) showed increased avoidant behaviors as adults that failed to improve, or were even exacerbated, by chronic SSRI treatment. By contrast, avoidant behaviors in these same mice were drastically improved following chronic treatment with TIA. Overall, this demonstrates that TIA may be a promising alternative treatment for patients that fail to respond to typical antidepressants, especially in patients whose serotonergic system has been altered by in utero exposure to SSRIs.

Study protocol for SKIPMDD: subcutaneous ketamine infusion in palliative care patients with advanced life limiting illnesses for major depressive disorder (phase II pilot feasibility study)

IntroductionMajor depressive disorder (MDD) in people with advanced life-limiting illnesses can have significant impact on the quality-of-life of those affected. The management of MDD in the palliative care setting can...

Fast-Trk(B)ing the mechanism of antidepressants

The mechanism by which antidepressants elicit clinical improvements has proven elusive. In a recent publication in Cell, Casarotto etal. (2021) reveal a surprising direct interaction between antidepressants and TrkB. This link provides an important mechanistic insight into synaptic remodeling that may assist in the design of improved antidepressant therapeutics.

Antidepressant drugs act by directly binding to TRKB neurotrophin receptors

SummaryIt is unclear how binding of antidepressant drugs to their targets gives rise to the clinical antidepressant effect. We discovered that the transmembrane domain of tyrosine kinase receptor 2 (TRKB), the brain-derived neurotrophic factor (BDNF) receptor that promotes neuronal plasticity and antidepressant responses, has a cholesterol-sensing function that mediates synaptic effects of cholesterol. We then found that both typical and fast-acting antidepressants directly bind to TRKB, thereby facilitating synaptic localization of TRKB and its activation by BDNF. Extensive computational approaches including atomistic molecular dynamics simulations revealed a binding site at the transmembrane region of TRKB dimers. Mutation of the TRKB antidepressant-binding motif impaired cellular, behavioral, and plasticity-promoting responses to antidepressants in vitro and in vivo. We suggest that binding to TRKB and allosteric facilitation of BDNF signaling is the common mechanism for antidepressant action, which may explain why typical antidepressants act slowly and how molecular effects of antidepressants are translated into clinical mood recovery.

Creation of a gene expression portrait of depression and its application for identifying potential treatments

Depression is a complex mental health disorder and the goal here was to identify a consistent underlying portrait of expression that ranks all genes from most to least dysregulated and indicates direction of change relative to controls. Using large-scale neural gene expression depression datasets, a combined portrait (for men and women) was created along with one for men and one for women only. The depressed brain was characterized by a “hypo” state, that included downregulation of activity-related genes, including EGR1, FOS, and ARC, and indications of a lower brain temperature and sleep-like state. MAP kinase and BDNF pathways were enriched with overlapping genes. Expression patterns suggested decreased signaling for GABA and for neuropeptides, CRH, SST, and CCK. GWAS depression genes were among depression portrait genes and common genes of interest included SPRY2 and PSEN2. The portraits were used with the drug repurposing approach of signature matching to identify treatments that could reverse depression gene expression patterns. Exercise was identified as the top treatment for depression for the combined and male portraits. Other non-traditional treatments that scored well were: curcumin, creatine, and albiflorin. Fluoxetine scored best among typical antidepressants. The creation of the portraits of depression provides new insights into the complex landscape of depression and a novel platform for evaluating and identifying potential new treatments.

Predictors of quetiapine extended-release formulation add-on in older patients exposed to antidepressant drugs: A Danish register-based cohort study.

This study investigated which comorbidities or comedications increased the probability of receiving quetiapine extended-release formulation (quetiapine XR) as an add-on treatment. Danish administrative registers were used as data sources. The study period was from 01 January 2011 to 01 July 2017. New users of selective serotonin reuptake inhibitors (SSRI), serotonin and norepinephrine reuptake inhibitors (SNRI), atypical antidepressants (AAD), and tricyclic antidepressants (TCA) aged ≥65 years were included in the study population. A multivariable Cox regression model was used to find predictors for receiving quetiapine XR add-on within the first year of antidepressant therapy. A total of 123 655 new users of SSRI, SNRI, TCA, and AAD were eligible. The study population was composed of 57.7% females and the mean age was 77.2 years (SD 7.9 years). SSRI users comprised 49.6% of the study population. Among users of antidepressants, 171 (0.14%) patients received quetiapine XR as add-on treatment. In the adjusted analyses, female patients (HR 0.70; 95%CI 0.52-0.95) and glucocorticoid users (HR 0.41; 95%CI 0.21-0.80) had a significantly lower hazard of receiving quetiapine XR. Patients with dementia (HR 2.43; 95%CI 1.52-3.87) had a significantly higher hazard of receiving quetiapine XR than patients without this condition. When compared with SSRI users, AAD (HR 1.80; 95%CI 1.31-2.46) and TCA users (HR 0.18; 95%CI 0.06-0.49) had an increased/reduced hazard of receiving quetiapine XR, respectively. This study suggests that the choice of prescribing quetiapine add-on is driven by patient's differences in comorbidities, comedications and the type of antidepressant drug.

Putative Inflammatory Sensitive Mechanisms Underlying Risk or Resilience to Social Stress

It has been well recognized that exposure to stress can lead to the onset of psychosocial disorders such as depression. While there are a number of antidepressant therapies currently available and despite producing immediate neurochemical alterations, they require weeks of continuous use in order to exhibit antidepressant efficacy. Moreover, up to 30% of patients do not respond to typical antidepressants, suggesting that our understanding of the pathophysiology underlying stress-induced depression is still limited. In recent years inflammation has become a major focus in the study of depression as several clinical and preclinical studies have demonstrated that peripheral and central inflammatory mediators, including interleukin (IL)-1β, are elevated in depressed patients. Moreover, it has been suggested that inflammation and particularly neuroinflammation may be a direct and immediate link in the emergence of stress-induced depression due to the broad neural and glial effects that are elicited by proinflammatory cytokines. Importantly, individual differences in inflammatory reactivity may further explain why certain individuals exhibit differing susceptibility to the consequences of stress. In this review article, we discuss sources of individual differences such as age, sex and coping mechanisms that are likely sources of distinct changes in stress-induced neuroimmune factors and highlight putative sources of exaggerated neuroinflammation in susceptible individuals. Furthermore, we review the current literature of specific neural and glial mechanisms that are regulated by stress and inflammation including mitochondrial function, oxidative stress and mechanisms of glutamate excitotoxicity. Taken together, the impetus for this review is to move towards a better understanding of mechanisms regulated by inflammatory cytokines and chemokines that are capable of contributing to the emergence of depressive-like behaviors in susceptible individuals.

The functional variant rs334558 of GSK3B is associated with remission in patients with depressive disorders.

PurposeGSK3B and AKT1 genes have been implicated in the pathogenesis of a number of psychiatric and neurological disorders. Furthermore, their genetic variants are associated with response to antidepressant pharmacotherapy. As the evidence is still incomplete and inconsistent, continuing efforts to investigate the role of these two genes in the pathogenesis and treatment of brain disorders is necessary. The aim of our study was thus to evaluate the association of variants of these two genes with depressive disorders and drug treatment response.Patients and methodsIn the present study, 222 patients with a depressive disorder who underwent pharmacological antidepressant treatment were divided into remitters and non-remitters following a 28-day course of pharmacotherapy. The association of a depressive disorder and remission rates with polymorphisms rs334558 in the GSK3B gene and rs1130214 and rs3730358 in the AKT1 gene was evaluated with a chi-square test.ResultsNeither of the studied genetic variants was associated with a depressive disorder. Furthermore, frequencies of alleles and genotypes for rs1130214 and rs3730358 were not different in the groups of remitters and non-remitters. However, the activating allele T of the functional polymorphism rs334558 was significantly associated with remission, when all types of antidepressant drugs were included. This association continued as a trend when only patients taking selective serotonin reuptake inhibitors were considered.ConclusionThe present study provides support that the functional polymorphism rs334558 of GSK3B may play a role as a useful genetic and pharmacogenetic biomarker in the framework of personalized medicine approach.