Treatment Of Mood Disorders Research Articles

A replication study using the World Health Organization pharmacovigilance database (VigiBase®) to evaluate whether an association between ketamine and esketamine and alcohol and substance misuse exists

Background and objectivesKetamine and esketamine are increasingly prescribed in the treatment of resistant mood disorders and persons at risk of suicide. Ketamine is a drug of misuse with increasing non-therapeutic use in the general population. Herein, our aim was to determine whether ketamine and/or esketamine are disproportionately associated with reports of substance and/or alcohol misuse. MethodsReplicating a similar analysis recently conducted using the Food and Drug Administration Adverse Event Reporting System (FAERS) database, we identified cases of “alcohol problem, alcoholism, alcohol abuse, substance dependence, substance use disorder (SUD), substance abuse, drug dependence, drug use disorder and drug abuse” in association with ketamine and esketamine reported to the World Health Organization Pharmacovigilance Database (WHO VigiBase). We searched the database from inception to January 2024. The reporting odds ratio (ROR) of each of the aforementioned parameters was calculated; acetaminophen was used as the control. The numerator of the equation represents the number of cases (n) and the denominator represents the total cases of psychiatric disorders (N). Significance was obtained when the lower limit of the 95 % confidence (CI) > 1.0. ResultsThe RORs for ketamine was increased for most parameters (i.e., alcohol abuse (3.24), substance dependence (12.48), substance use disorder (170.44), substance abuse (2.94), drug dependence (2.88), drug use disorder (11.54) and drug abuse (2.85), respectively). With respect to esketamine, the RORs were observed to be different from ketamine insofar as we observed a reduction in the RORs for three parameters (i.e., substance abuse (0.41), drug dependence (0.083) and drug abuse (0.052), respectively). The IC025 values were significant for ketamine in cases of alcohol abuse (0.35), substance dependence (0.50), substance use disorder (2.77), substance abuse (0.83), drug dependence (0.97), drug use disorder (1.95) and drug abuse (0.94). Additionally, oxycontin showed significant IC025 values for substance use disorder (0.0014), substance abuse (0.042), and drug dependence (0.17). ConclusionEsketamine was not associated with an increased ROR for any parameter of alcohol and/or substance use disorder. Mixed results were observed with ketamine with some RORs increased and others decreased. Estimating RORs using a pharmacovigilance database does not establish causation in the case of elevated RORs and cannot be assumed to be a therapeutic effect when lower RORs were observed.

Neural correlates of approach–avoidance behavior in healthy subjects: Effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) over the right dorsolateral prefrontal cortex

The dorsolateral prefrontal cortex (dlPFC) is implicated in top-down regulation of emotion, but the detailed network mechanisms require further elucidation. To investigate network-level functions of the dlPFC in emotion regulation, this study measured changes in task-based activation, resting-state and task-based functional connectivity (FC) patterns following suppression of dlPFC excitability by 1-Hz repetitive transcranial magnetic stimulation (rTMS). In a sham-controlled within-subject design, 1-Hz active or sham rTMS was applied to the right dlPFC of 19 healthy volunteers during two separate counterbalanced sessions. Following active and sham rTMS, functional magnetic resonance imaging (fMRI) was conducted in the resting state (rs-fMRI) and during approach–avoidance task responses to pictures with positive and negative emotional content (task-based fMRI). Activation and generalized psychophysiological interaction analyses were performed on task-based fMRI, and seed-based FC analysis was applied to rs-fMRI data. Task-based fMRI revealed greater and more lateralized activation in the right hemisphere during negative picture responses compared to positive picture responses. After active rTMS, greater activation was observed in the left middle prefrontal cortex compared to sham rTMS. Further, rTMS reduced response times and error rates in approach to positive pictures compared to negative pictures. Significant FC changes due to rTMS were observed predominantly in the frontoparietal network (FPN) and visual network (VN) during the task, and in the default mode network (DMN) and VN at rest. Suppression of right dlPFC activity by 1-Hz rTMS alters large-scale neural networks and modulates emotion, supporting potential applications for the treatment of mood disorders.

Lysophosphatidic Acid (LPA) and Its Receptors in Mood Regulation: A Systematic Review of the Molecular Mechanisms and Therapeutic Potential.

Mood disorders affect over 300 million individuals worldwide, often characterized by their chronic and refractory nature, posing significant threats to patient life. There has been a notable increase in mood disorders among American adolescents and young adults, with a rising number of suicide attempts and fatalities, highlighting a growing association between mood disorders and suicidal outcomes. Dysregulation within the neuroimmune-endocrine system is now recognized as one of the fundamental biological mechanisms underlying mood and mood disorders. Lysophosphatidic acid (LPA), a novel mediator of mood behavior, induces anxiety-like and depression-like phenotypes through its receptors LPA1 and LPA5, regulating synaptic neurotransmission and plasticity. Consequently, LPA has garnered substantial interest in the study of mood regulation. This study aimed to elucidate the molecular mechanisms of lysophosphatidic acid and its receptors, along with LPA receptor ligands, in mood regulation and to explore their potential therapeutic efficacy in treating mood disorders. A comprehensive literature search was conducted using the PubMed and Web of Science databases, identifying 208 articles through keyword searches up to June 2024. After excluding duplicates, irrelevant publications, and those restricted by open access limitations, 21 scientific papers were included in this review. The findings indicate that LPA/LPA receptor modulation could be beneficial in treating mood disorders, suggesting that pharmacological agents or gintonin, an extract from ginseng, may serve as effective therapeutic strategies. This study opens new avenues for future research into how lysophosphatidic acid and its receptors, as well as lysophosphatidic acid receptor ligands, influence emotional behavior in animals and humans.

Adherence to clinical practice guidelines for using electroconvulsive therapy in elderly depressive patients

ObjectivesElectroconvulsive therapy (ECT) is one of the most effective treatments in mood disorders, mainly in major depressive episode (MDE) in the context of either unipolar (MDD) or bipolar disorder (BD). However, ECT remains a neglected and underused treatment. Older people are at high risk patients for the development of adverse drug reactions. In this context, we sought to determine the duration of MDEs and the number of lines of treatment before the initiation of ECT in patients aged 65 years or over according to the presence or absence of first-line indications for using ECT from international guidelines.MethodsIn this multicenter, retrospective study including patients aged 65 years or over with MDEs in MDD or BD who have been treated with ECT for MDEs, data on the duration of MDEs and the number of lines of treatment received before ECT were collected. The reasons for using ECT, specifically first-line indications (suicidality, urgency, presence of catatonic and psychotic features, previous ECT response, patient preference) were recorded. Statistical comparisons between groups used standard statistical tests.ResultsWe identified 335 patients. The mean duration of MDEs before ECT was about 9 months. It was significantly shorter in BD than in MDD- about 7 and 10 months, respectively. The co-occurrence of chronic medical disease increased the duration before ECT in the MDD group. The presence of first-line indications for using ECT from guidelines did not reduce the duration of MDEs before ECT, except where there was a previous response to ECT. The first-line indications reduced the number of lines of treatment before starting ECT.ConclusionEven if ECT seems to be a key treatment in the elderly population due to its efficacity and safety for MDEs, the delay before this treatment is still too long.

Correlating Substance Abuse Disorders and Mood Disorder: Clinical Implications of a Dimensional Approach

Background: Substance use disorder (SUD) often co-occurs with mood disorders like anxiety and depression. This study investigates the relationship between SUD and mood disorders using a dimensional approach. Methods: A total of 290 participants, including 145 with SUD and 145 healthy controls, were assessed. The General Health Questionnaire (GHQ-12) evaluated mental health, followed by interviews using the Hamilton Anxiety Rating Scale (HAM-A) and Hamilton Depression Rating Scale (HAM-D). Demographic information, substance use behaviours, and mental health symptoms were collected and analysed. Results: Of the participants, 90% were men and 10% women; 68.2% were married. Most SUD patients were smokers (71.0%) and alcohol users (35.8%), with others using drugs or tobacco (33.7% and 19.3%). The majority (84.8%) used drugs for a high. HAM-D results showed moderate to severe depression in 7.5% of SUD patients and 5.5% of controls. HAM-A results indicated 80.6% of the SUD group had anxiety, compared to 88.9% of controls with no anxiety. Conclusion: SUD patients frequently experience concurrent anxiety and depression, highlighting the need for dual diagnosis and integrated treatment for SUD and mood disorders.

Arginine vasopressin in mood disorders: A potential biomarker of disease pathology and a target for pharmacologic intervention.

Vasopressin or arginine-vasopressin (AVP) is a neuropeptide molecule known for its antidiuretic effects and serves to regulate plasma osmolality and blood pressure. The existing literature suggests that AVP plays a multifaceted-though less well-known-role in the central nervous system (CNS), particularly in relation to the pathophysiology and treatment of mood disorders. Animal models have demonstrated that AVP is implicated in regulating social cognition, affiliative and prosocial behaviors, and aggression, often in conjunction with oxytocin. In humans, AVP is implicated in mood disorders through its effects on the hypothalamic-pituitary-adrenal (HPA) axis as well as on the serotoninergic and glutamatergic systems. Measuring plasma AVP has yielded interesting but mixed results in mood and stress-related disorders. Recent advances have led to the development of copeptin as a stable and reliable surrogate biomarker for AVP. Another interesting but relatively unexplored issue is the interaction between the osmoregulatory system and mood disorder pathophysiology, given that psychotropic medications often cause dysregulation of AVP receptor expression or signaling that can subsequently lead to clinical syndromes like syndrome of inappropriate diuresis and diabetes insipidus. Finally, pharmaceutical trials of agents that act on V1a and V1b receptor antagonists are still underway. This narrative review summarizes: (1) the neurobiology of the vasopressinergic system in the CNS; (2) the interaction between AVP and the monoaminergic and glutamatergic pathways in the pathophysiology and treatment of mood disorders; (3) the iatrogenic AVP dysregulation caused by psychotropic medications; and (4) the pharmaceutical development of AVP receptor antagonists for the treatment of mood disorders.

Effects of psilocybin on uncertain punishment learning

Psilocybin may provide a useful treatment for mood disorders including anxiety and depression but its mechanisms of action for these effects are not well understood. While recent preclinical work has begun to assess psilocybin’s role in affective behaviors through innate anxiety or fear conditioning, there is scant evidence for its role in conflict between reward and punishment. The current study was designed to determine the impact of psilocybin on the learning of reward-punishment conflict associations, as well as its effects after learning, in male and female rats. We utilized a chained schedule of reinforcement that involved execution of safe and risky reward-guided actions under uncertain punishment. Different patterns of behavioral suppression by psilocybin emerged during learning versus after learning of risky action-reward associations. Psilocybin increased behavioral suppression in female rats as punishment associations were learned. After learning, psilocybin decreased behavioral suppression in both sexes. Thus, psilocybin produces divergent effects on action suppression during approach-avoidance conflict depending on when the conflict is experienced. This observation may have implications for its therapeutic mechanism of action.

(108) ENHANCING PELVIC EXAM COMFORT AND DIAGNOSTIC ACCURACY: REVIEWING THE UTILITY OF NITROUS OXIDE FOR HYPERTONIC PELVIC FLOOR ASSESSMENT

Abstract Introduction Nitrous oxide is an anesthetic, anxiolytic, and analgesic commonly used for general and dental anesthesia, sedation, and severe pain. Studies show that nitrous oxide is also used in several in-office gynecological and urological procedures as a sedative and anxiolytic agent with a safer drug profile than other anesthetic agents. It is also being trialed as a treatment for mood disorders. Nitrous oxide does not render individuals unconscious, making it a more favorable option for stressful and painful medical procedures than general anesthesia because it allows the patient to feel more in control of their body and aware of the proceedings. Objective To analyze the use of in-office nitrous oxide during medical procedures and evaluate its effectiveness in reducing pain and anxiety levels to predict the utility of it during pelvic exams in patients with vestibulodynia. Methods A literature review was performed through the PubMed database between 2007-2022. The authors independently and thoroughly screened abstracts and full-text articles and assessed the relevant medical literature that acknowledged the use of nitrous oxide in in-office medical procedures. Key terms used to refine the search include [“nitrous oxide in medical procedures”], [“nitrous oxide in gynecology”], [“nitrous oxide in urology”]. Results One study explored the use of nitrous oxide during childbirth in women diagnosed with PTSD, and the results were significant for nitrous oxide reducing PTSD symptom severity. Multiple studies suggest the use of nitrous oxide during dental procedures reduces patient anxiety; one specifically measured sixty anxious patients pre- and post-endodontic procedures and noted a significant reduction in anxiety during the procedure with the use of nitrous oxide. Various studies of gynecological and urological procedures report the successful use of nitrous oxide in reducing peri-procedural pain compared to other analgesic alternatives. A common example is its use during intrauterine device insertion, which is correlated with higher patient satisfaction as it decreases pain. Additionally, a study among patients undergoing extracorporeal shockwave lithotripsy found no significant difference between the use of meperidine, an opioid, and nitrous oxide in post-procedural Visual Analog Scale pain scores with no adverse events reported in the nitrous oxide group. Another study revealed that using local anesthesia in transrectal prostate biopsies resulted in some patients experiencing notable anxiety and pain. At the same time, no such relationship was observed among patients who received nitrous oxide before this procedure. Conclusions Vestibulodynia is a subset of genitopelvic pain isolated to the vulvar vestibule. Vestibulodynia has three proposed etiologies: tissue neural proliferation, musculoskeletal, and hormonally mediated. Discriminating these three etiologies can be difficult, especially when a proper pelvic exam cannot be achieved due to patients’ discomfort. The three etiologies are biologically intertwined, often resulting in vestibulodynia patients experiencing pelvic floor hypertonicity without regard to specific etiology. A painful pelvic exam is stressful and often an anxiety-producing experience for patients with pelvic hypertonicity and vulvodynia. Hence, with the data provided, we suspect that nitrous oxide will be a useful treatment option to mitigate these consequences for the patient, with the added benefit of easing the exam for the provider, leading to a more accurate diagnosis. Disclosure No.

A Briefing on the Canadian Mood and Anxiety Disorder Treatment (Canmat) 2023 Depression Guidelines and Advice for Their Application in Primary Care

The Canadian Mood And Anxiety Disorder Treatment (CANMAT) guidelines for depression, last published in 2016, have now been updated with literature through to 2023, and have been recently published in 2024 (Lam et al , Canadian J Psych, In press 2024). This 92-page document thoroughly addresses aspects of depression management, using evidence based on the literature, and supplemented by an expert consensus of the 57 co-authors. While thorough, this document remains cumbersome for a busy primary care clinician to sort through and apply to everyday practice. Here, we present a summary of evidence for the treatment of depression, along with practical advice for clinical decision making in primary care.

Shared and unique transcriptomic signatures of antidepressant and probiotics action in the mammalian brain.

Understanding the shared and divergent mechanisms across antidepressant (AD) classes and probiotics is critical for improving treatment for mood disorders. Here we examine the transcriptomic effects of bupropion (NDRI), desipramine (SNRI), fluoxetine (SSRI) and a probiotic formulation (Lacidofil®) on 10 regions across the mammalian brain. These treatments massively alter gene expression (on average, 2211 differentially expressed genes (DEGs) per region-treatment combination), highlighting the biological complexity of AD and probiotic action. Intersection of DEG sets against neuropsychiatric GWAS loci, sex-specific transcriptomic portraits of major depressive disorder (MDD), and mouse models of stress and depression reveals significant similarities and differences across treatments. Interestingly, molecular responses in the infralimbic cortex, basolateral amygdala and locus coeruleus are region-specific and highly similar across treatments, whilst responses in the Raphe, medial preoptic area, cingulate cortex, prelimbic cortex and ventral dentate gyrus are predominantly treatment-specific. Mechanistically, ADs concordantly downregulate immune pathways in the amygdala and ventral dentate gyrus. In contrast, protein synthesis, metabolism and synaptic signaling pathways are axes of variability among treatments. We use spatial transcriptomics to further delineate layer-specific molecular pathways and DEGs within the prefrontal cortex. Our study reveals complex AD and probiotics action on the mammalian brain and identifies treatment-specific cellular processes and gene targets associated with mood disorders.

A scoping review of the effects of mushroom and fungus extracts in rodent models of depression and tests of antidepressant activity.

One of the most important developments in psychopharmacology in the past decade has been the emergence of novel treatments for mood disorders, such as psilocybin for treatment-resistant depression. Psilocybin is most commonly found in different species of mushroom; however, the literature on mushroom and fungus extracts with potential antidepressant activity extends well beyond just psilocybin-containing mushrooms, and includes both psychedelic and non-psychedelic species. In the current review, we systematically review the preclinical literature on mushroom and fungus extracts, and their effects of animal models of depression and tests of antidepressant activity. The PICO structure, PRISMA checklist and the Cochrane Handbook for systematic reviews of intervention were used to guide the search strategy. A scoping search was conducted in electronic databases PubMed, CINAHL, Embase and Web of Science. The literature search identified 50 relevant and suitable published studies. These included 19 different species of mushrooms, as well as seven different species of other fungi. Nearly all studies reported antidepressant-like effects of treatment with extracts. Treatments were most commonly delivered orally, in both acute and chronically administered studies to predominantly male rodents. Multiple animal models of depression were used, the most common being unpredictable chronic mild stress, while the tail suspension test and forced swim test were most frequently used as standalone antidepressant screens. Details on each experiment with mushroom and fungus species are discussed in detail, while an evaluation is provided of the strengths and weaknesses of these studies.

Diurnal cognitive functioning in patients with myasthenia gravis with the role of chronotype and depression: a pilot study.

Myasthenia gravis (MG) is an autoimmune disease manifested by fatigue and weakness of the skeletal muscles. Recent research has indicated that MG patients perform significantly worse than healthy controls in cognitive domains such as attention, verbal fluency, visual learning, and memory. This study aimed to investigate the diurnal fluctuations in cognitive performance in patients with myasthenia gravis in relation to selected clinical and socioeconomic parameters of the disease course, along with the role of chronotype and depression. The participants were recruited from a neurology outpatient clinic. Patients' cognitive functions were assessed twice: in the morning and the evening of the same day. Neuropsychological diagnosis included attention, memory, executive, verbal, and visuospatial abilities. Mood was measured with the Beck Depression Inventory-II and Positive and Negative Affect Schedule. The Morningness-Eveningness Questionnaire was used to examine chronotype. The analyses performed showed no significant differences between subjects and within subjects, apart from semantic fluency. Patients receiving antidepressant treatment obtained better results on attention and working memory tasks. The data obtained show that diurnal neuropsychological performance in MG patients is associated with depression. Routine assessment and treatment of mood disorders could significantly improve cognitive functioning in myasthenia gravis patients.

Environmental enrichment enhances the antidepressant effect of ketamine and ameliorates spatial memory deficits in adult rats

Ketamine is a rapid-acting antidepressant associated with various cognitive side effects. To mitigate these side effects while enhancing efficacy, it can be co-administered with other antidepressants. In our study, we adopted a similar strategy by combining ketamine with environmental enrichment, a potent sensory-motor paradigm, in adult male Wistar rats. We divided the animals into four groups based on a combination of housing conditions and ketamine versus vehicle injections. The groups included those housed in standard cages or an enriched environment for 50 days, which encompassed a 13-day-long behavioral testing period. Each group received either two doses of ketamine (20 mg/kg, IP) or saline as a vehicle. We tested the animals in the novel object recognition test (NORT), forced swim test (FST), open field test (OFT), elevated plus maze (EPM), and Morris water maze (MWM), which was followed by ex vivo c-Fos immunohistochemistry. We observed that combining environmental enrichment with ketamine led to a synergistic antidepressant effect. Environmental enrichment also ameliorated the spatial memory deficits caused by ketamine in the MWM. There was enhanced neuronal activity in the habenula of the enrichment only group following the probe trial of the MWM. In contrast, no differential activity was observed in enriched animals that received ketamine injections. The present study showed how environmental enrichment can enhance the antidepressant properties of ketamine while reducing some of its side effects, highlighting the potential of combining pharmacological and sensory-motor manipulations in the treatment of mood disorders.

Sex Differences in Diagnosis and Treatment Timing of Comorbid Depression/Anxiety and Disease Subtypes in Patients With ADHD: A Database Study

Objective: Our study examined the impact of sex, ADHD subtype, and comorbid illnesses (depression/anxiety) on the timing of diagnosis and treatment for ADHD. Method: To analyze ADHD patients, four health databases were used to assess subtype, comorbid mood, and antidepressant or anxiolytic drug exposure. Analyses were stratified by sex and age. Standardized mean differences measured intergroup differences. Results: Females with ADHD were identified at older ages and had higher rates of depression and anxiety diagnoses and treatments before and after their initial ADHD diagnosis. Predominantly inattentive ADHD patients were diagnosed later and more likely to receive mood disorder diagnosis and treatment than hyperactive impulsive ADHD patients. Conclusions: Results suggest a more complex ADHD presentation in females, potentially causing late diagnosis and delayed treatment.

Ketamine for mood disorders, anxiety, and suicidality in children and adolescents: a systematic review.

Mood disorders, anxiety, and suicidality in youth are increasing and rapid-acting treatments are urgently needed. One potential is ketamine or its enantiomer esketamine, which was FDA approved in 2019 to treat major depressive disorder with suicidality in adults. This systematic review evaluated the evidence for the clinical use of ketamine to treat mood disorders, anxiety, and suicidality in youth. The PRISMA guidelines were used, and a protocol registered prospectively ( https://osf.io/9ucsg/ ). The literature search included Pubmed/MEDLINE, Ovid/MEDLINE, Scopus, CINAHL, PsychInfo, and Google Scholar. Trial registries and preprint servers were searched, and authors contacted for clarification. Studies reported on the clinical use of ketamine to treat anxiety, depression, bipolar disorder, or suicidality in youth ≤19years old and assessed symptoms before and after ketamine use. Study screening and data extraction were conducted independently by 2-4 authors. Safety, tolerability, and efficacy data were collected. The Cochrane Risk of Bias guidelines assessed the quality of the evidence. Twenty-two published reports based on 16 studies were identified: 7 case studies, 6 observational studies, 3 randomized trials, and 6 secondary data analyses. Studies reported immediate improvements in depression, anxiety, and suicidality. Improvements were maintained for weeks-months following treatment. Ketamine was well-tolerated with the most common side effects being dizziness, nausea, and mild dissociation. Transient hemodynamic changes were reported, all of which resolved quickly and did not require medical intervention. Initial evidence suggests ketamine is safe and may be effective for mood disorders, anxiety, and suicidality in youth. Further randomized trials are warranted.

How to Solve Clinical Challenges in Mood Disorders; Machine Learning Approaches Using Electrophysiological Markers.

Differentiating between the diagnoses of mood disorders and other psychiatric disorders, and predicting treatment response in depression has long been a concern for clinicians. Machine learning (ML) is one part of artificial intelligence that focuses on instructing computers to mimic the cognitive abilities of the human brain through training. This study will review the research on the use of ML techniques to differentiate diagnoses and predict treatment responses in mood disorders based on electroencephalography (EEG) data. There have been several attempts to differentiate between the diagnoses of bipolar disorder and major depressive disorder , mood disorders, and other psychiatric disorders using ML techniques found on EEG markers. Previous studies have shown that accuracy varies depending on which EEG markers are used, the sample size, and the ML technique. Also, precise and improved ML approaches can be developed by adapting the various feature selection and validation methods that reflect each disease's characteristics. Although ML faces some limitations and challenges in solving for consistent and improved accuracy in the diagnosis and treatment of mood disorders, it has a great potential to understand mood disorders better and provide valuable tools to personalize both identification and treatment.

Lifetime prevalence, risk, and treatment of mood and anxiety disorders in Qatar's national mental health study.

To estimate lifetime prevalence, risk, and treatment for mental disorders and their correlates in Qatar's general population for the first time. We conducted a national phone survey of 5,195 Qatari and Arab residents in Qatar (2019-2022) using the Composite International Diagnostic Interview Version 3.3 and estimated lifetime mood and anxiety defined diagnoses. Survival-based discrete time models, lifetime morbid risk, and treatment projections were estimated. Lifetime prevalence of any disorder was 28.0% and was associated with younger cohorts, females, and migrants, but lower formal education. Treatment contact in the year of disorder onset were 13.5%. The median delay in receiving treatment was 5years (IQR=2-13). Lifetime treatment among those with a lifetime disorder were 59.9% for non-healthcare and 63.5% for healthcare; it was 68.1% for any anxiety and 80.1% for any mood disorder after 50years of onset.Younger cohorts and later age of onset were significantly predictors of treatment. Lifetime prevalence of mental disorders in Qatar is comparable to other countries. Treatment is significantly delayed and delivered largely in non-healthcare sectors thus the need for increased literacy of mental illness to reduce stigma and improve earlier help-seeking in healthcare settings.

Twelve-month prevalence, persistence, severity, and treatment of mood and anxiety disorders in Qatar's national mental health study.

To estimate 12-month prevalence, persistence, severity, and treatment of mental disorders and socio-demographic correlates in Qatar. We conducted the first national population-based telephone survey of Arab adults between 2019 and 2022 using the Composite International Diagnostic Interview and estimated 12-month DSM-5 mood and anxiety disorders and their persistence (the proportion of lifetime cases who continue to meet 12-month criteria). The 12-month prevalence of any disorder was 21.1% (10.4% mild, 38.7% moderate, and 50.9% severe) and was associated with: younger age, female, previously married, and with persistence of any disorder. Persistence was 74.7% (64.0% mood and 75.6% anxiety) and was significantly associated with secondary education or lower. Minimally adequate treatment received among those with any 12-month mental disorder was 10.6% (74.6% in healthcare and 64.6% non-healthcare sectors). Severity and the number of disorders significantly associated with each other and with treatment received (χ2=7.24, p=0.027) including adequate treatment within the mental health specialty sector (χ2=21.42, p<0.001). Multimorbidity and sociodemographics were associated with 12-month mental disorder. Treatment adequacy in Qatar are comparable to high-income countries. Low treatment contact indicate need for population-wide mental health literacy programes in addition to more accessible and effective mental health services.

Psilocybin promotes neuroplasticity and induces rapid and sustained antidepressant-like effects in mice.

Psilocybin offers new hope for treating mood disorders due to its rapid and sustained antidepressant effects, as standard medications require weeks or months to exert their effects. However, the mechanisms underlying this action of psilocybin have not been identified. To investigate whether psilocybin has rapid and sustained antidepressant-like effects in mice and investigate whether its potential mechanisms of action are related to promoted neuroplasticity. We first examined the antidepressant-like effects of psilocybin in normal mice by the forced swimming test and in chronic corticosterone (CORT)-exposed mice by the sucrose preference test and novelty-suppressed feeding test. Furthermore, to explore the role of neuroplasticity in mediating the antidepressant-like effects of psilocybin, we measured structural neuroplasticity and neuroplasticity-associated protein levels in the prefrontal cortex (PFC) and hippocampus. We observed that a single dose of psilocybin had rapid and sustained antidepressant-like effects in both healthy mice and chronic CORT-exposed mice. Moreover, psilocybin ameliorated chronic CORT exposure-induced inhibition of neuroplasticity in the PFC and hippocampus, including by increasing neuroplasticity (total number of dendritic branches and dendritic spine density), synaptic protein (p-GluA1, PSD95 and synapsin-1) levels, BDNF-mTOR signalling pathway activation (BDNF, TrkB and mTOR levels), and promoting neurogenesis (number of DCX-positive cells). Our results demonstrate that psilocybin elicits robust, rapid and sustained antidepressant-like effects which is accompanied by the promotion of neuroplasticity in the PFC and hippocampus.

P2X7 receptor: a potential target for treating comorbid anxiety and depression.

In clinical practice, depression and anxiety frequently coexist, and they are both comorbid with somatic diseases. The P2X7R is an adenosine 5'-triphosphate (ATP)-gated non-selective cation channel that is widely expressed in immune-related cells. Under conditions of stress, chronic pain, and comorbid chronic physical illness, P2X7R activation in glial cells leads to neuroinflammation. This could contribute to the development of anxiety and depression-related emotional disturbances. Previous studies have shown that the P2X7 receptor (P2X7R) plays an important role in the pathogenesis of both anxiety and depression. Thus, the P2X7R may play a role in the comorbidity of anxiety and depression. Positron emission tomography can be used to assess the degree and location of neuroinflammation by monitoring functional and expression-related changes in P2X7R, which can facilitate clinical diagnoses and guide the treatment of patients with anxiety and depression. Moreover, single nucleotide polymorphisms (SNPs) in the P2X7R gene are associated with susceptibility to different types of psychiatric disorders. Thus, evaluating the SNPs of the P2X7R gene could enable personalized mood disorder diagnoses and treatments. If the P2X7R were set as a therapeutic target, selective P2X7R antagonists may modulate P2X7R function, thereby altering the balance of intra- and extra-cellular ATP. This could have therapeutic implications for treating anxiety and depression, as well as for pain management. According to in vitro and in vivo studies, the P2X7R plays an important role in anxiety and depression. In this review, we consider the potential of the P2X7R as a therapeutic target for comorbid anxiety and depression, and discuss the potential diagnostic and therapeutic value of this receptor.