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Cultural perspectives on marijuana consumption have undergone substantial reforms in recent years, and the decriminalization and legalization of cannabis are a matter of debate now. The conditions of determining factors are not the same among societies; therefore, each society should decide independently. Herein, the considerations that Iran should contemplate before legalizing cannabis were addressed. Global trends, social status, influence on the judiciary, costs, health effects, quality control, shifting substance use patterns, societal detachment, and changes in prevalence were the discussed determinant factors. Now that religious, cultural, and legal status has suppressed the increase in prevalence, legalization of recreational use that leads to a significant increase in consumption is not advisable. However, the legalization and production of medical cannabis should be on the agenda, as none of the items that hinder the legalization of recreational cannabis do not apply to medical cannabis. Research should continue to reduce uncertainties, especially by combining big data from sale systems of areas where recreational cannabis use has been legalized with big data sources like social media., Competing Interests: Declaration of Competing Interest The authors had no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Age-related macular degeneration (ARMD) leads to impaired vision and potential blindness. Globally, it accounts for approximately 9% of vision loss cases, and a projected 288 million individuals will be affected by 2040. Current treatments have limitations such as variable effectiveness, high costs, and potential side effects. Additionally, atrophic ARMD management remains challenging. As saffron has shown promising neuroprotective and antioxidant effects by potentially delaying disease progression, this study aims to review the mechanistic, pre-clinical, and clinical evidence of the effects, safety, and tolerability of saffron in ARMD treatment., Methods: The Scale for the Assessment of Narrative Review Articles was applied in this narrative review. To find relevant literature, the syntax "(saffron OR crocus) AND (retin* OR "geographic atrophy" OR "choroidal neovascular*" OR "macular degeneration")" was searched in PubMed/MEDLINE. Pre-clinical and clinical original investigations of the effects of saffron in ARMD along with the eligible studies cited in their reference lists were identified and included., Results: Saffron and its active compounds, crocin and crocetin, have shown promising results in improving visual function and delaying ARMD progression. Several clinical studies have found that daily supplementation with 20-50 mg of saffron or 5-15 mg of crocin for 3-12 months significantly improved best-corrected visual acuity, contrast sensitivity, and retinal function as measured by electroretinogram and microperimetry, with benefits observed in both dry and wet forms of ARMD. The effects were independent of genetic risk factors and maintained during the follow-up periods, suggesting the potential role of saffron as a long-term treatment option. Saffron reduces ARMD progression via anti-angiogenic, neuroprotective, and antioxidant mechanisms. Moreover, saffron is safe and well tolerated., Conclusions: Although further research is needed to confirm long-term safety and efficacy, current evidence supports the use of saffron or crocin supplements as a safe and tolerable adjunct therapy for ARMD management., Competing Interests: None., (© Author(s).)

Background: Bipolar disorder (BD) is associated with increased morbidity/mortality. Adverse outcome prediction might help with the management of patients with BD., Methods: We systematically reviewed the performance of machine learning (ML) studies in predicting adverse outcomes (relapse or recurrence, hospital admission, and suicide-related events) in patients with BD. Demographic, clinical, and neuroimaging-related poor outcome predictors were also reviewed. Three databases (PubMed, Scopus, and Web of Science) were explored from inception to July 2023., Results: Eighteen studies, accounting for >30,000 patients, were included. Support vector machine, decision trees, random forest, and logistic regression were the most frequently used ML algorithms. ML models' area under the receiver operating characteristic (ROC) curve (AUC), sensitivity, and specificity ranged from 0.71 to 0.98, 72.7-92.8 %, and 59.0-95.2 % for relapse/recurrence prediction (4 studies (3 on relapses and 1 on recurrences). The corresponding values were 0.78-0.88, 21.4-100 %, and 77.0-99.7 % for hospital admissions (3 studies, 21,266 patients), and 0.71-0.99, 44.4-97.9 %, and 38.9-95.0 % for suicide-related events (10 studies, 5558 patients). Also, one study addressed a combination of the interest outcomes. Adverse outcome predictors included early onset BD, BD type I, comorbid psychiatric or substance use disorder, circadian rhythm disruption, hospitalization characteristics, and neuroimaging parameters, including increased dynamic amplitude of low-frequency fluctuation, decreased frontolimbic functional connectivity and aberrant dynamic functional connectivity in corticostriatal circuitry., Conclusions: ML models can predict adverse outcomes of BD with relatively acceptable performance measures. Future studies with larger samples and nested cross-validation validation should be conducted to reach more reliable results., Competing Interests: Declaration of competing interest There are no financial/personal relationships with any people or organizations that could inappropriately influence this study. There are no potential competing interests including employment, consultancies, stock ownership, honoraria, paid expert testimony, patent applications/registrations, and grants or other funding., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Limited information exists linking food habits, diet quality, and lifestyle scores with anthropometric indices and happiness levels. Our aim was to examine the association between food habits, diet quality, and lifestyle scores with anthropometric indices and happiness levels in the Iranian population., Methods: This cross-sectional study included 200 students randomly selected from a university in Iran. Dietary intakes, physical activity (PA), and happiness levels of study participants were assessed using validated questionnaires. The anthropometric indices examined in this study included the body shape index (ABSI), body roundness index (BRI), and abdominal volume index (AVI). Multiple logistic regression models were used to examine the association between food habits, diet quality, and lifestyle scores with anthropometric indices and happiness levels., Results: The mean age and body mass index (BMI) of study participants were 23.5 years ± 4.52 and 23.8 kg/m2 ± 3.17, respectively. In the study population, no significant association was seen between ABSI, BRI, AVI and happiness with food habits, diet quality, and lifestyle scores respectively. After adjusting for potential confounders (age, energy intake, marital status, education, smoking, physical activity, gender, and BMI), the association remained not significant for ABSI and food habits, diet quality, and lifestyle scores respectively (OR: 0.56, 95% CI (0.25-1.34), P = 0.193; OR: 0.59, 95% CI (0.22-1.57), P = 0.413; OR:1.19, 95%CI (0.54-2.63), P = 0.652), BRI and food habits, diet quality, and lifestyle scores respectively (OR:1.98, 95% CI (0.41-9.49), P = 0.381; OR: 0.57, 95%CI (0.12-2.74), P = 0.512; OR: 1.19, 95% CI (0.3-4.71), P = 0.811), AVI and food habits, diet quality, and lifestyle scores (OR:1.15, 95% CI (0.53-2.48), P = 0.743, OR:1.01, 95% CI (0.47-2.18), P = 0.965; OR: 1.3, 95% CI (0.64-2.65), P = 0.465) and happiness and food habits, diet quality, and lifestyle scores respectively (OR:0.3, 95%CI (0.07-1.25), P = 0.972; OR: 0.77, 95%CI (0.18-3.19), P = 0.724, OR: 0.3, 95% CI (0.07-1.25), P = 0.083)., Conclusions: No significant association was detected between food habits, diet quality, and lifestyle scores with anthropometric indices and happiness levels. However, longitudinal studies are required to confirm these findings., (© 2024. The Author(s).)

Purpose of Review: Marital quality (MQ) is a psychosocial factor that has been neglected in cardiovascular prevention guidelines, although its association with cardiovascular diseases has been identified in several studies. Therefore, we aim to investigate how MQ either in positive or negative dimensions affect different cardiovascular risk factors and diseases., Recent Findings: We systematically searched different databases in September 2023 for longitudinal studies conducted to assess the contribution of MQ to well-established cardiovascular risk factors and diseases. Two independent researchers screened studies and carried out data extraction and quality assessment of included ones. From 12,175 potential studies screened, 40 were included. The presence of significant heterogeneity in methodology, follow-up, and subsequent effect estimates made it unfeasible to do a meta-analysis. Despite the variation, most studies found a significant association of negative MQ measures with physical inactivity (2/2), high levels of smoking (4/5) and alcohol (3/3) use, increased metabolic syndrome risk (3/3), elevated type 2 diabetes mellitus (T2DM) risk and poor T2DM management (3/6), elevated cardiovascular disease risk and progression (9/11), increased body weight and obesity risk (2/3), elevated blood pressure and hypertension risk (7/8). Positive MQ measures were mainly associated with improvement in blood pressure control (2/2), reduced T2DM risk and its good management (1/1), reduced body weight and obesity risk (2/2), and increased survival in cardiovascular diseases (4/4). Based on current evidence, MQ seems to play a crucial role in developing established cardiovascular risk factors and diseases and is worth considering in preventive strategies., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The present study was designed to evaluate the efficacy and safety of l-carnitine as an adjuvant agent to risperidone in the treatment of autism spectrum disorder (ASD)-associated behaviors. In this study, 68 children with confirmed ASD were randomly allocated to receive either l-carnitine (150 mg/day) or matched placebo in addition to risperidone. We utilized the Aberrant Behavior Checklist-Community Edition scale (ABC-C) and a checklist of potential adverse effects to assess changes in behavioral status and safety profile at weeks 0, 5 and 10 of the trial. The primary outcome was defined as a change in the irritability subscale score. Sixty patients with similar baseline characteristics completed the trial period. Although scores of ABC-C subscales significantly decreased in both groups over the trial period, the combination of l-carnitine and risperidone resulted in more reduction on the irritability and hyperactivity subscales compared to the combination of risperidone and placebo ( P  = 0.033 and P  < 0.001, respectively). However, changes in lethargy, stereotypic behavior and inappropriate speech subscales were similar between groups. In conclusion, l-carnitine adjuvant to risperidone could improve irritability and hyperactivity features in children with ASD. Results of this study should be considered preliminary and further clinical trials with larger sample sizes and longer follow-up periods are warranted., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Brain-derived neurotrophic factor (BDNF) dysfunction is one of the most important mechanisms underlying depression. It seems that selective serotonin reuptake inhibitors (SSRIs) improve depression via affecting BDNF level. In this systematic review, for the first time, we aimed to review the effect of three SSRIs including fluoxetine, escitalopram, and sertraline, on both depression and BDNF level in preclinical and clinical studies. PubMed electronic database was searched, and 193 articles were included in this study. After reviewing all manuscripts, only one important difference was found: subjects. We found that SSRIs induce different effects in animals vs. humans. Preclinical studies showed many controversial effects, while human studies showed only two effects: improvement of depression, with or without the improvement of BDNF. However, most studies used chronic SSRIs treatment, while acute SSRIs were not effectively used and evaluated. In conclusion, it seems that SSRIs are reliable antidepressants, and the improvement effect of SSRIs on depression is not dependent to BDNF level (at least in human studies)., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Previous researches conducted in both developed and developing countries have demonstrated a rising trend in the utilization of complementary and alternative medicine. The World Health Organization has underscored the importance of studying the prevalence and determinants of such alternative practices. This study delves into the knowledge, attitudes, and practices of Iranian adults towards Persian medicine, a distinct form of complementary and alternative medicine, through a national survey for the first time., Methods: A total of 2882 Iranian adults (aged ≥ 15 years) were randomly chosen from all regions. Data were gathered through structured door-to-door interviews using a survey questionnaire, wherein cases were selected randomly based on postal codes, and interviewers completed the forms at the participants' residences., Results: Approximately 46% of the subjects exhibited familiarity with Persian Medicine. The study revealed that the primary sources of knowledge about Persian Medicine were family, relatives, and friends, with only 2.9% indicating medical staff as their source of information. Furthermore, the study indicated that 21% of participants expressed a strong interest in using Persian Medicine, while 30.3% did not. When comparing Persian medicine to modern medicine, respondents indicated that Persian medicine is more cost-effective and has fewer side effects, yet modern medicine is more widely used globally; although, the majority responded "I don't know" to other questions. The results also demonstrated that approximately 37% of the participants had a history of Persian Medicine utilization in their lifetime., Conclusion: This study revealed that Iranian adults have low reliable knowledge (from medical staff, Persian medicine books and other publications) and limited familiarity with Persian medicine, with about one third of the participants expressing disinterest (attitude) and over half of them having not utilized this form of medicine (practice)., (© 2024. The Author(s).)

To investigate the response to antidepressants while controlling for sex, which has been controversial, 92 outpatient males and females with major depressive disorder were assigned to sertraline (100 mg/day) or citalopram (40 mg/day) in two strata and were assessed using Hamilton depression rating scale (HDRS) scores and brain-derived neurotrophic factor (BDNF), interleukin (IL)-6 and cortisol serum levels in this 8-week, randomized, parallel-group, double-blind clinical trial. Data of 40 sertraline and 40 citalopram recipients with equal representation of males and females assigned to each medication were analyzed, while their baseline characteristics were not statistically different (P > 0.05). There were no significant differences between sertraline and citalopram recipients in outcome changes (P > 0.05), all of which indicated improvement, but a significant time-treatment-sex interaction effect in BDNF levels was observed (P = 0.035). Regarding this, subgroup analyses illustrated a significantly greater increase in male BDNF levels following sertraline treatment (P = 0.020) with a moderate to large effect size (Cohen's d = 0.76 and ). Significant associations were observed between percentage changes in IL-6 levels and BDNF levels in sertraline recipients (P = 0.033) and HDRS scores in citalopram recipients (P < 0.001). Sex was an effect modifier in BDNF alterations following sertraline and citalopram administration. Further large-scale, high-quality, long-term studies are recommended., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Evidence has demonstrated the roles of inflammatory processes in pathogenesis of depression. We aim to assess the effects of adjunctive celecoxib with cognitive behavioral therapy (CBT), an anti-inflammatory agent, in treatment of postpartum depression and on levels of Brain-derived neurotrophic factor (BDNF) and inflammatory cytokines., Methods: This was a randomized, double-blind, placebo-controlled trial to investigate the effects of adjunctive celecoxib with CBT on postpartum depression. Fifty outpatient women with postpartum depression, participated in this study. Patients randomly received either a celecoxib capsule twice a day or a placebo capsule twice a day for 6 weeks. Patients were assessed using the Hamilton Depression Rating Scale (HDRS) and the adverse event checklist at baseline and weeks 2, 4, and 6., Results: Patients in the celecoxib group showed a greater decline in HDRS scores from baseline to all three study time points compared to the placebo group (p = 0.12 for week 2, p = 0.001 for week 4, p < 0.001 for week 6). Rate of response to treatment was significantly higher in the celecoxib group compared to the placebo group at week 4 (60 vs 24%, p = 0.010) and week 6 (96 vs 44%, p < 0.001). Rate of remission was significantly higher in the celecoxib group compared to the placebo group at week 4 (52 vs 20%, p = 0.018) and week 6 (96 vs 36%, p < 0.001). Levels of most inflammatory markers were significantly lower in the celecoxib group compared to the placebo group at week 6. Levels of BDNF were significantly higher in the celecoxib group compared to the placebo group at week 6 (p < 0.001)., Conclusions: Findings suggest adjunctive celecoxib is an effective treatment for the improvement of postpartum depressive symptoms., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: About one-fifth of cannabis users, the most commonly used illicit substance, have cannabis use disorder (CUD). Psychiatric disorders and suicide are more common in these patients, and the disability-adjusted life years were reported to be 0.69 million. Pharmacotherapy for CUD is an unmet public health need, as current evidence-based therapies have limited efficacy., Areas Covered: After explaining the pathophysiology of CUD, the effects of emerging pharmacological interventions in its treatment obtained from randomized controlled trials were reviewed in light of mechanisms of action. Superiority over control of cannabidiol, gabapentin, galantamine, nabilone plus zolpidem, nabiximols, naltrexone, PF-04457845, quetiapine, varenicline, and topiramate were observed through the cannabinoid, glutamatergic, γ-aminobutyric acidergic, serotonergic, noradrenergic, dopaminergic, opioidergic, and cholinergic systems. All medications were reported to be safe and tolerable., Expert Opinion: Adding pharmacotherapy to psychotherapy is the optimal treatment for CUD on a case-by-case basis. Drug development to add to psychotherapy is the main path, but time and cost suggest repurposing and repositioning existing drugs. Considering sample size, follow-up, and effect size, further studies using objective tools are necessary. The future of CUD treatment is promising.

Introduction: Autism spectrum disorder (ASD) is an early-onset disorder with a prevalence of 1% among children and reported disability-adjusted life years of 4.31 million. Irritability is a challenging behavior associated with ASD, for which medication development has lagged. More specifically, pharmacotherapy effectiveness may be limited against high adverse effects (considering side effect profiles and patient medication sensitivity); thus, the possible benefits of pharmacological interventions must be balanced against potential adverse events in each patient., Areas Covered: After reviewing the neuropathophysiology of ASD-associated irritability, the benefits and tolerability of emerging medications in its treatment based on randomized controlled trials were detailed in light of mechanisms and targets of action., Expert Opinion: Succeeding risperidone and aripiprazole, monotherapy with memantine may be beneficial. In addition, N-acetylcysteine, galantamine, sulforaphane, celecoxib, palmitoylethanolamide, pentoxifylline, simvastatin, minocycline, amantadine, pregnenolone, prednisolone, riluzole, propentofylline, pioglitazone, and topiramate, all adjunct to risperidone, and clonidine and methylphenidate outperformed placebo. These effects were through glutamatergic, γ-aminobutyric acidergic, inflammatory, oxidative, cholinergic, dopaminergic, and serotonergic systems. All medications were reported to be safe and tolerable. Considering sample size, follow-up, and effect size, further studies are necessary. Along with drug development, repositioning and combining existing drugs supported by the mechanism of action is recommended.

Background and Aim: Crocus sativus also known as saffron, is one of the most popular traditional plants. This study aims to evaluate the efficacy and safety of saffron extracts in ADHD., Method: This study includes clinical trial studies that assessed the efficacy and/or safety of saffron in ADHD patients. Non-English papers, review articles, commentaries, letters, observational studies, thesis, animal studies, in-vitro studies, and conference abstracts were not included. The risk of bias in randomized studies was evaluated based on the Cochrane RoB.2, and risk of bias in pre-post intervention studies was assessed using the ROBINS-I tool., Results: Four studies met our inclusion criteria with a total of 118 patients. The results manifested an efficient role of saffron as either an adjuvant therapy to MPH or a single therapy against ADHD, without significant safety issues., Discussion: Saffron demonstrates promise in improving ADHD symptoms, with an acceptable safety profile. Future well-designed multicentral studies are suggested., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Rationale: Inadequate responses to current schizophrenia treatments have accelerated research into novel therapeutic approaches., Objectives: This study investigated the efficacy and tolerability of adjunctive L-theanine, an ingredient with neuroimmunomodulatory and neuroprotective properties, for chronic schizophrenia., Methods: Eighty chronic schizophrenia inpatients were equally assigned to receive risperidone (6 mg/day) plus either L-theanine (400 mg/day) or matched placebo in this 8-week, randomized, parallel-group, double-blind, placebo-controlled trial. The participants were assessed using the Positive and Negative Syndrome Scale (PANSS) by recording the results of subscales at baseline and weeks 4 and 8 to measure treatment efficacy. Additionally, the participants were assessed for the Hamilton Depression Rating Scale (HDRS) and adverse events, including the Extrapyramidal Symptom Rating Scale (ESRS)., Results: Sixty patients, 30 in each group, were included in the analyses. All baseline demographic and clinical characteristics were comparable between the groups (p-values > 0.05). The reduction rates from baseline to endpoint in negative, general psychopathology, and total scores of PANSS were greater in the L-theanine group (p-values = 0.03, 0.01, and 0.04, respectively). Regarding general psychopathology scores, the reduction in the L-theanine group was also greater until week 4 (p-value < 0.01). The time × treatment interaction effect was significant on negative (p-value = 0.03), general psychopathology (p-value < 0.01), and total (p-value = 0.04) scores of PANSS, indicating additional improvements in the L-theanine group. The HDRS and side effects were comparable between the groups (p-values > 0.05)., Conclusions: L-Theanine adjunct to risperidone safely and tolerably outperformed adjunctive placebo for schizophrenia, and promising evidence indicated its effects on primary negative symptoms, which need to be scrutinized in further studies., Trial Registration: The study protocol was registered and published prospectively in the Iranian Registry of Clinical Trials ( http://www.irct.ir ; registration number: IRCT20090117001556N133) on 2020-12-12., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Borderline personality disorder (BPD) is a severe psychiatric disorder characterized by emotion dysregulation, impulsivity, and interpersonal disturbances. Several structural and functional neuroimaging abnormalities have been described in BPD. In particular, resting-state functional magnetic resonance imaging (rs-fMRI) studies have recently suggested various connectivity alterations within and between large-scale brain networks in BPD. This review aimed at providing an updated summary of the evidence reported by the available rs-fMRI studies in BPD individuals., Methods: A search on PubMed, Scopus, and Web of Science was performed to identify rs-fMRI alterations in BPD. A total of 15 studies met our inclusion criteria., Results: Overall, aberrant resting-state functional connectivity (rs-FC) within and between default mode network (DMN), salience network (SN), and central executive network (CEN) were observed in BPD compared to healthy controls, as well as selective functional impairments in bilateral amygdala, anterior and posterior cingulate cortex, hippocampus, and prefrontal cortex., Limitations: The observational design, small sample size, prevalence of females, high rates of concurrent comorbidities and medications, and heterogeneity across imaging methodologies limit the generalizability of the results., Conclusions: The identification of altered patterns of rs-FC within and between selective brain networks, including DMN, SN, and CEN, could further our knowledge of the clinical symptoms of BPD, and therefore, future studies with multimodal methodologies and longitudinal designs are warranted to further explore the neural correlates of this disorder., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier B.V.)

Objective: Celecoxib, a nonsteroidal anti-inflammatory agent, was found to be an effective add-on treatment for unipolar and bipolar depression. We investigated the potential beneficial effect of celecoxib monotherapy on depressive symptoms after Coronavirus disease (COVID-19)., Methods: This was a randomized, double-blind, placebo-controlled clinical trial investigating the therapeutic effects of celecoxib monotherapy in patients with moderate depressive symptoms following COVID-19 infection. Patients were randomized to receive either a celecoxib capsule (100 mg) twice daily or a placebo capsule twice daily for 6 weeks. Participants were assessed with the Hamilton Depression Rating Scale (HDRS) and the side effect checklist at baseline and weeks 3 and 6., Results: A total of 62 patients were included. GLM repeated-measures showed a significant effect of time × treatment (F = 12.95, df = 1.98, p < 0.001) for celecoxib, suggesting superior improvement of depressive symptoms in celecoxib compared to placebo from baseline to the study endpoint. HDRS scores in the celecoxib group showed a greater decline from baseline to both week 3 (t = 4.12, p < 0.001, Cohen's d = 1.10) and week 6 (t = 4.76, p < 0.001, Cohen's d = 1.27), compared to the placebo group. Rate of response to treatment (70% vs 9%, p < 0.001) and remission (67% vs 0%, p < 0.001) was significantly higher in celecoxib compared to the placebo group at week 6. Adverse event frequencies were not significantly different between the two groups., Conclusion: We demonstrated that treatment with celecoxib significantly improved depression scores of patients with depressive symptoms following COVID-19 infection. Further trials with larger sample sizes and longer study periods should assess our findings before any suggestion for clinical use. The trial was prospectively registered at the Iranian registry of clinical trials (www.irct.ir; registration number: IRCT20090117001556N142)., Competing Interests: Declaration of Competing Interest No conflict of interest exists for any of the authors associated with the manuscript. This study was supported by a grant from Tehran University of Medical Sciences (Grant Number: 40535)., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Suicide is a global public health issue causing around 700,000 deaths worldwide each year. Therefore, identifying suicidal thoughts and behaviors in patients can help lower the suicide-related mortality rate. This review aimed to investigate the feasibility of suicidality identification by applying supervised Machine Learning (ML) methods to Magnetic Resonance Imaging (MRI) data., Methods: We conducted a systematic search on PubMed, Scopus, and Web of Science to identify studies examining suicidality by applying ML methods to MRI features. Also, the Prediction Model Risk of Bias Assessment Tool (PROBAST) was employed for the quality assessment., Results: 23 studies met the inclusion criteria. Of these, 20 developed prediction models without external validation and 3 developed prediction models with external validation. The performance of ML models varied among the reviewed studies, with the highest reported values of accuracies and Area Under the Curve (AUC) ranging from 51.7 % to 100 % and 0.52 to 1, respectively. Over half of the studies that reported accuracy (12/21) or AUC (13/16) achieved values of ≥0.8. Our comparative analysis indicated that deep learning exhibited the highest predictive performance compared to other ML models. The most commonly identified discriminative imaging features were resting-state functional connectivity and grey matter volume within prefrontal-limbic structures., Limitations: Small sample sizes, lack of external validation, heterogeneous study designs, and ML model development., Conclusions: Most of the studies developed ML models capable of ML-based suicide identification, although ML models' predictive performance varied across the reviewed studies. Thus, further well-designed is necessary to uncover the true potential of different ML models in this field., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier B.V.)

Aim: The main aim of this study was to investigate the additional effects of L-theanine, an amino acid in tea and an analog of glutamate with neuroprotective and anti-depressant properties, on obsessive-compulsive disorder (OCD) symptoms in combination with fluvoxamine., Methods: Patients from either sex aged between 18 and 60 years diagnosed with OCD, based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), who had a Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score of more than 21 were enrolled in a double-blinded, parallel-group, placebo-controlled, clinical trial of 10 weeks to receive either L-theanine (100 mg twice daily) and fluvoxamine (100 mg daily initially followed by 200 mg daily after week 5) or placebo and fluvoxamine. The primary outcome of interest in this study was the Y-BOCS total score decrease from baseline., Results: From a total of 95 evaluated patients, 50 completed our study; 30 were randomly assigned to each group. Multivariate analysis (ANOVA) showed a significant effect of time × $$ \times $$ treatment for L-theanine in obsession subscale (F = 5.51, P = 0.008) of the Y-BOCS score but not in the total and compulsion scores. Our results showed significantly more improvement in obsession subscale scores in L-theanine compared to placebo group (P = 0.007, Cohen's d = 0.82). Also, total Y-BOCS scores were lower in L-theanine compared to placebo group at week 5 (P = 0.039, Cohen's d = 0.60) and 10 (P = 0.008, Cohen's d = 0.80). However, there was no significant between-group differences in compulsion subscale scores. Complete response was also more frequent in the L-theanine group (P = 0.0001)., Conclusion: Findings in this study suggest L-theanine as a relatively safe and effective adjuvant therapy for moderate to severe OCD., (© 2023 The Authors. Psychiatry and Clinical Neurosciences © 2023 Japanese Society of Psychiatry and Neurology.)

Objectives: This is an investigation of the efficacy and safety of famotidine, a selective histamine H2 receptor antagonist, on improvement of cognitive impairment, depression and anxiety symptoms developing post-COVID-19, in a 12-week, randomized controlled trial., Methods: A total of 50 patients with a confirmed diagnosis of COVID-19 and a score ≤ 23 on the Mini-Mental State Examination (MMSE) test or a score ≤ 22 on the Montreal Cognitive Assessment (MoCA) were randomly assigned to either the famotidine (40 mg twice daily) or the placebo group. Changes in MMSE scores at weeks 6 and 12 were the primary outcome, while changes in other scales were the secondary outcomes. Participants and evaluators were blinded., Results: At weeks 6 and 12, patients in the famotidine group had significantly higher MMSE scores (p = 0.014, p < 0.001, respectively). Regarding the MoCA scale, the famotidine group had a significantly higher score at weeks 6 and 12 (p = 0.001, p < 0.001, respectively). Considering the HAM-D scale (Hamilton Depression Rating Scale), at weeks 6 and 12, the famotidine group experienced a larger reduction (p = 0.009, p = 0.02, respectively). Additionally, comparison of the HAM-A scale scores (Hamilton Anxiety Rating Scale) at weeks 6 and 12 showed a statistically significant larger reduction in the famotidine group (p = 0.04, p = 0.02, respectively). The two groups did not differ in the frequency of adverse effects., Conclusion: Our study supports safety and efficacy of famotidine in treating cognitive impairment, depression and anxiety symptoms induced by COVID-19., Trial Registration: This trial was registered at the Iranian registry of clinical trials (IRCT: www.irct.ir; registration number: IRCT20090117001556N138)., Competing Interests: Declaration of Competing Interest No conflict of interest exists for any of the authors associated with the manuscript., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: Reboxetine is a potent and selective norepinephrine reuptake inhibitor that was effective in combination with citalopram for resistant obsessive-compulsive disorder (OCD). This study aims to assess its effectiveness and tolerability in combination with fluoxetine in treating OCD., Methods: In this 2-center, placebo-controlled, and double-blind, randomized clinical trial, 76 patients with OCD were assigned into 2 parallel groups to receive fluoxetine (up to 80 mg/d) plus placebo (F + P) or fluoxetine (up to 80 mg/d) plus reboxetine (F + R) (10 mg twice daily) for 10 weeks. Participants were assessed with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) at baseline and weeks 5 and 10., Results: A total of 76 patients completed the trial. There was no significant difference between the 2 groups in baseline Y-BOCS scores. General linear model repeated-measures showed significant effects on time × treatment interaction on total Y-BOCS ( F = 6.33, df = 1.42, P = 0.006) and obsession subscale scores ( F = 10.39, df = 1.48, P < 0.001), and insignificance on compulsion subscale scores ( F = 1.86, df = 1.24, P = 0.173). Reboxetine combination therapy demonstrated a higher partial and complete treatment response rate ( P < 0.01) according to the Y-BOCS total scores. There was no significant difference between the 2 groups in the frequency of adverse effects., Conclusions: Reboxetine combination therapy with fluoxetine can effectively improve symptoms in patients with OCD in a short period of treatment. However, further studies with larger sample sizes and longer follow-up periods are needed to confirm these findings.This trial was registered with the Iranian Registry of Clinical Trials ( www.irct.ir ; No IRCT20090117001556N129)., Competing Interests: Conflicts of Interest and Source of Funding: The authors have no conflicts of interest to declare. This study was funded by Tehran University of Medical Sciences and Health Services (grant number: 45986)., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Unsatisfactory responses to major depressive disorder (MDD) therapeutics available necessitated up-to-date treatment approaches. This study sought to investigate the efficacy and tolerability of adjunctive l-theanine, a green tea constituent with neuropsychotropic effects, for MDD., Methods: Sixty MDD (DSM-5) patients were equally assigned to receive sertraline (100 mg/d) plus either l-theanine (200 mg/d) or matched placebo in a six-week randomized, parallel-group, double-blind, placebo-controlled study. The participants were assessed using the Hamilton depression rating scale (HDRS) at baseline and weeks 2, 4, and 6. Changes in scores, early improvement, response and remission rates, and adverse events were compared between the groups., Results: Twenty-five participants in each group, a total of 50 patients, completed the study. All baseline characteristics were similar between the groups. The general linear model repeated-measures analysis demonstrated a significant time-treatment interaction effect for HDRS during the trial (p-value = 0.014), indicating more remarkable symptom improvement in the l-theanine group. A greater reduction in HDRS scores was observed in the l-theanine group from baseline to weeks 2, 4, and 6 (p-values = 0.02, 0.03, and 0.01, respectively). All patients responded to sertraline plus l-theanine until week 6. l-theanine was superior to placebo regarding response to treatment and remission rates at week 6 (p-values = 0.05 and 0.02, respectively). The frequency of side effects was comparable between the groups., Limitations: The small sample size and short study period were the limitations., Conclusions: l-theanine adjunct to sertraline outperforms placebo in treating MDD in a safe manner. Further long-term, large-scale studies are recommended to confirm this evidence., Competing Interests: Conflict of interest The authors had no competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Depression is the most prevalent and debilitating disease with great impact on societies. Evidence suggests Brain-Derived Neurotrophic Factor (BDNF) plays an important role in pathophysiology of depression. Depression is associated with altered synaptic plasticity and neurogenesis. BDNF is the main regulatory protein that affects neuronal plasticity in the hippocampus. A wealth of evidence shows decreased levels of BDNF in depressed patients. Important literature demonstrated that BDNF-TrkB signaling plays a key role in therapeutic action of antidepressants. Numerous studies have reported anti-depressant effects on serum/plasma levels of BDNF and neuroplasticity which may be related to improvement of depressive symptoms. Most of the evidence suggested increased levels of BDNF after antidepressant treatment. This review will summarize recent findings on the association between BDNF, neuroplasticity, and antidepressant response in depression. Also, we will review recent studies that evaluate the association between postpartum depression as a subtype of depression and BDNF levels in postpartum women., (Copyright© 2023 Avicenna Research Institute.)

Parkinson's disease (PD) is one of the most common neurodegenerative diseases. There is a wide range of sleep disturbances in patients with PD, such as insomnia and rapid eye movement (REM) sleep behavior disorder (or REM behavior disorder (RBD)). RBD is a sleep disorder in which a patient acts out his/her dreams and includes abnormal behaviors during the REM phase of sleep. On the other hand, melatonin is the principal hormone that is secreted by the pineal gland and significantly modulates the circadian clock and mood state. Furthermore, melatonin has a wide range of regulatory effects and is a safe treatment for sleep disturbances such as RBD in PD. However, the molecular mechanisms of melatonin involved in the treatment or control of RBD are unknown. In this study, we reviewed the pathophysiology of PD and sleep disturbances, including RBD. We also discussed the potential molecular mechanisms of melatonin involved in its therapeutic effect. It was concluded that disruption of crucial neurotransmitter systems that mediate sleep, including norepinephrine, serotonin, dopamine, and GABA, and important neurotransmitter systems that mediate the REM phase, including acetylcholine, serotonin, and norepinephrine, are significantly involved in the induction of sleep disturbances, including RBD in PD. It was also concluded that accumulation of α-synuclein in sleep-related brain regions can disrupt sleep processes and the circadian rhythm. We suggested that new treatment strategies for sleep disturbances in PD may focus on the modulation of α-synuclein aggregation or expression.

Transcranial magnetic stimulation (TMS) has become a promising strategy for bipolar disorder (BD). This study reviews neuroimaging findings, indicating functional, structural, and metabolic brain changes associated with TMS in BD. Web of Science, Embase, Medline, and Google Scholar were searched without any restrictions for studies investigating neuroimaging biomarkers, through structural magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), functional MRI (fMRI), magnetic resonance spectroscopy (MRS), positron emission tomography (PET), and single photon emission computed tomography (SPECT), in association with response to TMS in patients with BD. Eleven studies were included (fMRI = 4, MRI = 1, PET = 3, SPECT = 2, and MRS = 1). Important fMRI predictors of response to repetitive TMS (rTMS) included higher connectivity of emotion regulation and executive control regions. Prominent MRI predictors included lower ventromedial prefrontal cortex connectivity and lower superior frontal and caudal middle frontal volumes. SPECT studies found hypoconnectivity of the uncus/parahippocampal cortex and right thalamus in non-responders. The post-rTMS changes using fMRI mostly showed increased connectivity among the areas neighboring the coil. Increased blood perfusion was reported post-rTMS in PET and SPECT studies. Treatment response comparison between unipolar depression and BD revealed almost equal responses. Neuroimaging evidence suggests various correlates of response to rTMS in BD, which needs to be further replicated in future studies.

Postpartum depression (PPD) impairs mother-infant interaction and has negative effects on the child's emotional, behavioral, and cognitive skills. There is considerable evidence to suggest that inflammation plays a role in the pathogenesis of depression. Controlled trials indicate that celecoxib has antidepressant effects in patients with major depressive disorder. A 34-year-old woman with mild to moderate PPD received a celecoxib capsule twice a day. This treatment has not been reported in previous studies and is novel in clinical practice. The patient was assessed using the Hamilton Depression Rating Scale (HDRS). Moreover, levels of brain-derived neurotrophic factor (BDNF) and inflammatory cytokines were measured at baseline and at the end of celecoxib therapy. This case suggests that celecoxib can improve depressive symptoms in patients with mild to moderate PPD. No adverse effects occurred during follow-up., (© 2023 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Objectives: Studies have suggested that fingolimod, a sphingosine-1-phosphate receptor modulator, exerts neuroprotective and anti-inflammatory effects. Although fingolimod is approved for the treatment of relapsing-remitting multiple sclerosis, limited studies have investigated its effects in patients with schizophrenia. This study investigated the efficacy and safety of fingolimod adjuvant to risperidone in schizophrenia treatment., Methods: This eight-week, randomized, double-blinded, placebo-controlled trial included 80 (clinical trials registry code: IRCT20090117001556N137) patients with chronic schizophrenia. Participants were assigned to two equal arms and received risperidone plus either fingolimod (0.5 mg/day) or a matched placebo. The positive and negative symptom scale (PANSS) was used to measure and compare the effectiveness of treatment strategies at baseline and weeks 2, 4, 6, and 8. Treatment side effects were also compared., Results: Seventy participants completed the trial (35 in each arm). The baseline characteristics of the groups were comparable (P-value > 0.05). There were significant time-treatment interaction effects on negative symptoms (P-value = 0.003), general symptoms (P-value = 0.037), and the PANSS total score (P-value = 0.035), suggesting greater improvement in symptoms following the fingolimod adjuvant therapy. In contrast, the longitudinal changes in positive and depressive symptoms were similar between the groups (P-values > 0.05). Regarding the safety of treatments, there were no differences in extrapyramidal symptoms [assessed by the extrapyramidal symptom rating scale (ESRS)] or frequency of other complications between the fingolimod and the placebo groups (P-values > 0.05)., Conclusions: This study indicated that fingolimod is a safe and effective adjuvant agent for schizophrenia treatment. However, further clinical trials are required to suggest extensive clinical application., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest to disclose., (Copyright © 2023 Elsevier B.V. All rights reserved.)