Addressing methodological concerns in omega-3 trial for bipolar disorder relapse prevention.

Our response addresses concerns raised about our pilot trial on omega-3 for bipolar disorder. We clarify randomization procedures, highlight the benefits of eicosapentaenoic-predominant formulations for a specific bipolar patients subgroup, and justify the use of Kaplan-Meier analysis despite limitations. We acknowledge analytical challenges due to strict inclusion criteria and encourage future research on specific bipolar subtypes and larger-scale trials for robust validation.

Mothering and mother-child interactions in the unaffected siblings of autistic children.

AIM: To investigate parenting and mother-child interactions in unaffected siblings of autistic children. METHOD: This cross-sectional study enrolled 274 probands with a DSM-5 diagnosis of autism spectrum disorder (ASD) (87.4% male; mean [SD] age = 11 years 4 months [3 years 2 months]), their unaffected siblings (n = 274, 46.72% male; mean [SD] age = 11 years 3 months [3 years 4 months]), and 296 age-balanced and sex-balanced typically developing children (82.77% male; mean [SD] age = 11 years 3 months [2 years 8 months]). Maternal parenting styles and mother-child interactions were assessed using maternal reporting. RESULTS: Regardless of the child's age, maternal educational level, or presence of attention-deficit/hyperactivity disorder, autistic children received more overprotective and controlling parental behaviour than unaffected children. Correlates for parenting, mother-child interactions, and behavioural problems in the home setting in children with ASD and typically developing children were autistic traits, maternal anxiety and depressive symptoms, and maternal autistic characteristics; those in unaffected siblings were age, autistic traits, maternal educational level, and maternal autistic characteristics. INTERPRETATION: The diagnosis of ASD in a child can significantly influence maternal parenting behaviours, mother-child interactions, and the child's behavioural problems in the home setting. Furthermore, maternal anxiety or depressive symptoms, along with autistic characteristics in both mother and child, might shape parenting practices and exacerbate behavioural difficulties in autistic children.

Training in neuropsychiatry: views of early career psychiatrists from across the world.

BACKGROUND: Training and practice in neuropsychiatry varies across the world. However, little is known about the experiences and opinions of early career psychiatrists (ECPs) across different countries regarding neuropsychiatry. AIMS AND METHOD: To investigate neuropsychiatry training experiences, practices and opinions among ECPs across different countries. An online survey was distributed to ECPs in 35 countries across the world. RESULTS: A total of 522 participants took part in this study. Responses show that neuropsychiatry is integrated to a variable extent in psychiatric training curricula across the world. Most respondents were not aware of the existence of neuropsychiatric training or of neuropsychiatric units. Most agreed that training in neuropsychiatry should be done during or after the psychiatry training period. Lack of interest among specialty societies, lack of time during training, and political and economic reasons are regarded as the main barriers. CLINICAL IMPLICATIONS: These findings call for an improvement in the extent and in the quality of neuropsychiatry training across the world.

Omega-3 polyunsaturated fatty acids in the prevention of relapse in patients with stable bipolar disorder: A 6-month pilot randomized controlled trial.

This study investigated the efficacy and safety of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in relapse prevention of bipolar disorder (BD), addressing the shortcomings of current medications. Thirty-one stable BD patients were randomized to receive n-3 PUFAs or placebo for 6 months and intergroup differences in the incidence of the recurrence of bipolar depression were assessed. Differences in depression severity, manic symptoms, and routine biochemical parameters were also assessed. Interestingly, n-3 PUFAs demonstrated a favorable preventive effect on bipolar depression recurrence (p=0.005; Log-Rank) and reduced depression severity compared to placebo, and were well-tolerated, suggesting their potential as a safe prophylactic therapy for BD.

Roles of Omega-3 Polyunsaturated Fatty Acids in Managing Cognitive Impairment in Chronic Obstructive Pulmonary Disease: A Review.

Chronic obstructive pulmonary disease (COPD) contributes significantly to the death of people worldwide, especially the elderly. An essential feature of COPD is pulmonary inflammation, which results from long-term exposure to noxious substances from cigarette smoking and other environmental pollutants. Pulmonary inflammatory mediators spill over to the blood, leading to systemic inflammation, which is believed to play a significant role in the onset of a host of comorbidities associated with COPD. A substantial comorbidity of concern in COPD patients that is often overlooked in COPD management is cognitive impairment. The exact pathophysiology of cognitive impairment in COPD patients remains a mystery; however, hypoxia, oxidative stress, systemic inflammation, and cerebral manifestations of these conditions are believed to play crucial roles. Furthermore, the use of medications to treat cognitive impairment symptomatology in COPD patients has been reported to be associated with life-threatening adverse effects, hence the need for alternative medications with reduced side effects. In this Review, we aim to discuss the impact of cognitive impairment in COPD management and the potential mechanisms associated with increased risk of cognitive impairment in COPD patients. The promising roles of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) in improving cognitive deficits in COPD patients are also discussed. Interestingly, ω-3 PUFAs can potentially enhance the cognitive impairment symptomatology associated with COPD because they can modulate inflammatory processes, activate the antioxidant defence system, and promote amyloid-beta clearance from the brain. Thus, clinical studies are crucial to assess the efficacy of ω-3 PUFAs in managing cognitive impairment in COPD patients.

Omega-3 Polyunsaturated Fatty Acids for Core Symptoms of Attention-Deficit/Hyperactivity Disorder: A Meta-Analysis of Randomized Controlled Trials.

Objective: Previous studies have shown conflicting results for the effectiveness of omega-3 polyunsaturated fatty acids (PUFAs) in improving attention-deficit/hyperactivity disorder (ADHD) symptoms. This inconsistency may be due to differences in dosage, composition, and treatment duration. The current meta-analysis aims to address this inconsistency by improving subtype analyses and focusing on heterogeneity in treatment duration, omega-3 PUFA composition, and eicosapentaenoic acid (EPA) dose.Data Sources and Study Selection: We searched PubMed, EMBASE, PsycINFO, and Cochrane Library for randomized controlled trials of omega-3 PUFAs for ADHD, without publication year or language limitations, up to November 27, 2022. The primary outcome was the improvement of ADHD core symptoms. Subgroup analyses were conducted based on the formula, dosages, and composition ratios of omega-3 PUFAs. To ensure methodological quality, the Cochrane Risk-of-Bias Tool 1.0 was utilized to assess the risk of bias for each study included in the analysis. The pooled data were then analyzed using the random-effect meta-analysis, and the inverse variance method was employed.Data Extraction: The outcomes of interest were extracted using a data extraction form developed for this study.Results: Twenty-two studies with 1,789 participants were included in the analysis. Overall, omega-3 PUFAs did not significantly improve ADHD core symptoms compared to placebo (standardized mean difference [SMD]: -0.16; 95% CI, -0.34 to 0.01; P = .07). However, in the subgroup of studies with a treatment duration of at least 4 months, omega-3 PUFAs were significantly more effective than placebo (SMD: -0.35; 95% CI,-0.61 to -0.09; P = .007). Neither high eicosapentaenoic acid (EPA) dosage nor high EPA/docosahexaenoic acid (DHA) ratio was found to improve ADHD symptoms.Conclusions: Our findings indicate that omega-3 PUFAs did not improve ADHD core symptoms, but long-term supplementation may have potential benefits. The main limitation of the study was the moderate heterogeneity and small sample sizes in subgroup analyses and the lack of dietary pattern information.

CASP3 gene expression and the role of caspase 3 in the pathogenesis of depressive disorders.

BACKGROUND: The aim of our study was to evaluate the expression of the CASP3 gene at both mRNA and protein levels in patients with depressive disorders and to determine the impact of caspase 3 in the pathogenesis of depression; METHODS: A total of 290 subjects, including 190 depressed patients and 100 healthy controls, participated in the study. Socio-demographic and clinical data were collected, and the severity of depressive symptoms was assessed using the Hamilton Depression Rating Scale. Venous blood was collected and gene expression was evaluated using RT-PCR and ELISA at the mRNA and protein levels, respectively; RESULTS: The expression of the CASP3 gene was significantly lower in depressed patients compared to healthy controls at both the mRNA and protein levels. Additionally, a positive correlation was observed between CASP3 gene expression and disease duration as well as the number of depressive episodes; CONCLUSIONS: Further studies are needed to investigate the role of caspase 3 in depressive disorders.

Safety of Supplementation of Omega-3 Polyunsaturated Fatty Acids: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

There is no comprehensive review of the evidence to support omega-3 polyunsaturated fatty acids (PUFAs) as a relatively safe and tolerable intervention. This study aimed to provide a meta-analytic and comprehensive review on the adverse effects of all kinds of ω-3 PUFA supplementation reported in randomized controlled trials (RCTs) in human subjects. A systematic review of RCTs published between 1987 and 2023 was carried out based on searches of 8 electronic databases. All RCTs that compared the adverse effects of ω-3 PUFAs containing eicosapentaenoic acid, docosahexaenoic acid, or both compared with controls (a placebo or a standard treatment) were included. The primary outcome was the adverse effects related to ω-3 PUFA prescription. A total of 90 RCTs showed that the ω-3 PUFA group, when compared with the placebo, had significantly higher odds of occurrence of diarrhea (odds ratio [OR] = 1.257, P = 0.010), dysgeusia (OR = 3.478, P < 0.001), and bleeding tendency (OR = 1.260, P = 0.025) but lower rates of back pain (OR = 0.727, P < 0.001). The subgroup analysis showed that the prescription ω-3 PUFA products (RxOME3FAs) had higher ω-3 PUFA dosages than generic ω-3 PUFAs (OME3FAs) (3056.38 ± 1113.28 mg/d compared with 2315.92 ± 1725.61 mg/d), and studies on RxOME3FAs performed more standard assessments than OME3FAs on adverse effects (63% compared with 36%). There was no report of definite ω-3 PUFA-related serious adverse events. The subjects taking ω-3 PUFAs were at higher odds of experiencing adverse effects; hence, comprehensive assessments of the adverse effects may help to detect minor/subtle adverse effects associated with ω-3 PUFAs. This study was registered at PROSPERO as CRD42023401169.

The now and future of ChatGPT and GPT in psychiatry.

ChatGPT has sparked extensive discussions within the healthcare community since its November 2022 release. However, potential applications in the field of psychiatry have received limited attention. Deep learning has proven beneficial to psychiatry, and GPT is a powerful deep learning-based language model with immense potential for this field. Despite the convenience of ChatGPT, this advanced chatbot currently has limited practical applications in psychiatry. It may be used to support psychiatrists in routine tasks such as completing medical records, facilitating communications between clinicians and with patients, polishing academic writings and presentations, and programming and performing analyses for research. The current training and application of ChatGPT require using appropriate prompts to maximize appropriate outputs and minimize deleterious inaccuracies and phantom errors. Moreover, future GPT advances that incorporate empathy, emotion recognition, personality assessment, and detection of mental health warning signs are essential for its effective integration into psychiatric care. In the near future, developing a fully-automated psychotherapy system trained for expert communication (such as psychotherapy verbatim) is conceivable by building on foundational GPT technology. This dream system should integrate practical 'real world' inputs and friendly AI user and patient interfaces via clinically validated algorithms, voice comprehension/generation modules, and emotion discrimination algorithms based on facial expressions and physiological inputs from wearable devices. In addition to the technology challenges, we believe it is critical to establish generally accepted ethical standards for applying ChatGPT-related tools in all mental healthcare environments, including telemedicine and academic/training settings.

Omega-3 polyunsaturated fatty acids (n-3 PUFAs), somatic and fatigue symptoms in cardiovascular diseases comorbid major depressive disorder (MDD): A randomized controlled trial.

INTRODUCTION: Cardiovascular diseases (CVDs) and major depressive disorder (MDD) are the two most disabling diseases. Patients with CVDs comorbid depression had somatic and fatigue symptoms and were associated with chronic inflammation and omega-3 polyunsaturated fatty acid (n-3 PUFA) deficits. However, there have been limited studies on the effects of n-3 PUFAs on somatic and fatigue symptoms in patients with CVDs comorbid MDD. METHOD: Forty patients with CVDs comorbid MDD (58% males, mean age of 60 ± 9 years) were enrolled and randomised to receive either n-3 PUFAs (2 g of eicosapentaenoic acid [EPA] and 1 g of docosahexaenoic acid[DHA] per day) or placebo in a 12-week double-blind clinical trial. We assessed the somatic symptoms with Neurotoxicity Rating Scale (NRS) and fatigue symptoms with Fatigue Scale at baseline, weeks 1, 2, 4, 8 and 12, as well as blood levels of Brain-Derived Neurotrophic Factor (BDNF), inflammatory biomarkers and PUFAs, at the baseline and week 12. RESULTS: The n-3 PUFAs group had a greater reduction in Fatigue scores than the placebo group at Week 4 (p =.042), while there were no differences in the changes of NRS scores. N-3 PUFAs group also had a greater increase in EPA (p =.001) and a greater decrease in total n-6 PUFAs (p =.030). Moreover, in the subgroup analyses in the younger age group (age < 55), the n-3 PUFAs group had a greater reduction on NRS total scores at Week 12 (p =.012) and NRS Somatic scores at Week 2 (p =.010), Week 8 (p =.027), Week 12 (p =.012) than the placebo group. In addition, the pre- and post-treatment changes of EPA and total n-3 PUFAs levels were negatively associated with the changes of NRS scores at Weeks 2, 4, and 8 (all p <.05), and the changes of BDNF levels were negatively associated with NRS scores at Weeks 8 and 12 (both p <.05) in the younger age group. In the older age group (age ≥ 55), there were a lesser reduction on NRS scores at Weeks 1, 2 and 4 (all p <.05), but a greater reduction on Fatigue score at Week 4 (p =.026), compared to the placebo group. There was no significant correlation between the changes of blood BDNF, inflammation, PUFAs and NRS and Fatigue scores in general and in the older age group. CONCLUSION: Overall, n-3 PUFAs improved the fatigue symptoms in patients with CVDs comorbid MDD and the general somatic symptoms in specific subpopulation of younger age patients, and perhaps via the interplay between BDNF and EPA. Our findings provide promising rationales for future studies to investigate the treatment effects of omega-3 fatty acids on fatigue and somatic symptoms of chronic mental and medical diseases.

Personalized Medicine of Omega-3 Fatty Acids in Depression Treatment in Obese and Metabolically Dysregulated Patients.

The co-occurrence of depression and obesity has become a significant public health concern worldwide. Recent studies have shown that metabolic dysfunction, which is commonly observed in obese individuals and is characterized by inflammation, insulin resistance, leptin resistance, and hypertension, is a critical risk factor for depression. This dysfunction may induce structural and functional changes in the brain, ultimately contributing to depression's development. Given that obesity and depression mutually increase each other's risk of development by 50-60%, there is a need for effective interventions that address both conditions. The comorbidity of depression with obesity and metabolic dysregulation is thought to be related to chronic low-grade inflammation, characterized by increased circulating levels of pro-inflammatory cytokines and C-reactive protein (CRP). As pharmacotherapy fails in at least 30-40% of cases to adequately treat major depressive disorder, a nutritional approach is emerging as a promising alternative. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are a promising dietary intervention that can reduce inflammatory biomarkers, particularly in patients with high levels of inflammation, including pregnant women with gestational diabetes, patients with type 2 diabetes mellitus, and overweight individuals with major depressive disorder. Further efforts directed at implementing these strategies in clinical practice could contribute to improved outcomes in patients with depression, comorbid obesity, and/or metabolic dysregulation.

Omega-3 Polyunsaturated Fatty Acids in Managing Comorbid Mood Disorders in Chronic Obstructive Pulmonary Disease (COPD): A Review.

Chronic obstructive pulmonary disease (COPD) is the third-leading cause of mortality globally, significantly affecting people over 40 years old. COPD is often comorbid with mood disorders; however, they are frequently neglected or undiagnosed in COPD management, thus resulting in unintended treatment outcomes and higher mortality associated with the disease. Although the exact link between COPD and mood disorders remains to be ascertained, there is a broader opinion that inflammatory reactions in the lungs, blood, and inflammation-induced changes in the brain could orchestrate the onset of mood disorders in COPD. Although the current management of mood disorders such as depression in COPD involves using antidepressants, their use has been limited due to tolerability issues. On the other hand, as omega-3 polyunsaturated fatty acids (n-3 PUFAs) play a vital role in regulating inflammatory responses, they could be promising alternatives in managing mood disorders in COPD. This review discusses comorbid mood disorders in COPD as well as their influence on the progression and management of COPD. The underlying mechanisms of comorbid mood disorders in COPD will also be discussed, along with the potential role of n-3 PUFAs in managing these conditions.

Psychological Outcomes and Quality of Life of Fibromyalgia Patients with Vitamin D Supplementation-A Meta-Analysis.

The efficacy of current pharmaceutical treatments for fibromyalgia are limited. Vitamin D has shown promise in relieving pain. However, there is a lack of comprehensive analysis of psychological outcomes with vitamin D supplementation in fibromyalgia. This study aimed to investigate the impact of vitamin D supplementation on psychological outcomes and quality of life in fibromyalgia patients, given the unmet clinical need for effective treatment options. A meta-analysis of randomized controlled trials comparing vitamin D to placebo and prospective studies examining changes before and after vitamin D supplementation for patients with fibromyalgia was conducted to evaluate the effects of vitamin D on psychological outcomes, quality of life, and pain scores in patients with fibromyalgia. Databases were searched for relevant articles published from earliest available date to October 31, 2022. (PROSPERO number, CRD42022369889). We included 8 trials with a total of 694 participants and found that vitamin D supplementation had significant positive effects on physical function (standard mean differences (SMD) = 0.44, 95% CI = [0.10, 0.77 ]), role limitations due to emotional health (SMD = 0.57, 95% CI = [0.32, 0.82]), social function (SMD = 0.50, 95% CI = [0.08, 0.93]), and general health (SMD = 0.36, 95% CI = [0.11, 0.61]). Improvement of the Fibromyalgia Impact Questionnaire (FIQ) scores was noted (SMD = -0.414, 95% CI = [-0.808, -0.021]), but not on the Visual Analog Scale (VAS) (SMD = -0.15, 95% CI = [-0.771, 0.471]) and the Beck's Depression Inventory (BDI) scores (SMD = -0.456, 95% CI = [-1.27, 0.30]). In conclusion, vitamin D supplementation might be an alternative option for improvement of psychological outcomes and quality of life in patients with fibromyalgia.

Change of employment status in patients with depression - A longitudinal study using national claims data.

Depression increases an individual's risk of work disability, sick leave, unemployment, and early retirement. This population-based study identified 3673 depressive patients utilizing national claim data from Taiwan and aimed to investigate changes in employment status among depressive patients, compared to matched controls, with the longest observation of up to 12 years. This study found depressive patients had an adjusted hazard ratio of 1.24 for changing to non-income earners compared to controls. Moreover, younger age, lower payroll bracket, urbanity, and geographical area were associated with increased risk among patients with depression. Despite these increased risks, most depressive patients remained employed.

The Clinical Observation of Inflammation Theory for Depression: The Initiative of the Formosa Long COVID Multicenter Study (FOCuS).

There is growing evidence that the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with increased risks of psychiatric sequelae. Depression, anxiety, cognitive impairments, sleep disturbance, and fatigue during and after the acute phase of COVID-19 are prevalent, long-lasting, and exerting negative consequences on well-being and imposing a huge burden on healthcare systems and society. This current review presented timely updates of clinical research findings, particularly focusing on the pathogenetic mechanisms underlying the neuropsychiatric sequelae, and identified potential key targets for developing effective treatment strategies for long COVID. In addition, we introduced the Formosa Long COVID Multicenter Study (FOCuS), which aims to apply the inflammation theory to the pathogenesis and the psychosocial and nutrition treatments of post-COVID depression and anxiety.

Global child and adolescent mental health perspectives: bringing change locally, while thinking globally.

Child and adolescent mental health (CAMH) are a global priority. Different countries across the globe face unique challenges in CAMH services that are specific to them. However, there are multiple issues that are also similar across countries. These issues have been presented in this commentary from the lens of early career CAMH professionals who are alumni of the Donald J Cohen Fellowship program of the IACAPAP. We also present recommendations that can be implemented locally, namely, how promoting mental health and development of children and adolescents can result in better awareness and interventions, the need to improve quality of care and access to care, use of technology to advance research and practices in CAMH, and how investing in research can secure and support CAMH professionals and benefit children and adolescents across the globe. As we continue to navigate significant uncertainty due to dynamic circumstances globally, bolstering collaborations by "bringing change locally, while thinking globally" are invaluable to advancing global CAMH research, clinical service provision, and advancement of the field.

Comparative efficacy of omega-3 polyunsaturated fatty acids on major cardiovascular events: A network meta-analysis of randomized controlled trials.

The role of omega-3 polyunsaturated fatty acids (PUFAs) in primary and secondary prevention on major cardiovascular events (MCE) is inconclusive due to the potential heterogeneity in study designs of formulas, dosages, and ratios of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from the findings of previous randomized controlled trials (RCTs). Here we conducted a comprehensive narrative review of pre-clinical studies and updated a network meta-analysis (NMA) to determine the comparative efficacy against MCE with different EPA/DHA dosages and formulas. We found that pure EPA was ranked the best option in the secondary prevention (hazard ratio: 0.72, 95% confidence interval: 0.65 to 0.81) from the NMA of 39 RCTs with 88,359 participants. There was no evidence of omega-3 PUFAs' efficacy in primary prevention. The mechanisms of omega-3 PUFAs' cardiovascular protection might link to the effects of anti-inflammation and stabilization of endothelial function from PUFA's derivatives including eicosanoids and the special pre-resolving mediators (SPMs).

Identification of Genetic Variations in the NAD-Related Pathways for Patients with Major Depressive Disorder: A Case-Control Study in Taiwan.

Background and Objectives: Nicotinamide adenine dinucleotide (NAD) is an important coenzyme in various physiological processes, including sirtuins (SIRTs) and kynurenine pathway (KP). Previous studies have shown that lower NAD levels can be indicative of increased risks of cancer and psychiatric disorders. However, there has been no prior study exploring the link between NAD homeostasis and psychiatric disorders from a genetic perspective. Therefore, we aimed to investigate the association of genetic polymorphism in the pathways of NAD biosynthesis with major depressive disorder (MDD). Methods: A total of 317 patients were included in the case group and were compared with sex-matched control group of 1268 participants (1:4 ratio) from Taiwan Biobank (TWB). All subjects in the control group were over 65 years old, which is well past the average age of onset of MDD. Genomic DNA extracted from patients' blood buffy coat was analyzed using the Affymetrix TWB array. Full-model tests were conducted for the analysis of single nucleotide polymorphism (SNPs) in all candidate genes. We focused on genes within the NAD-related candidate pathways, including 15 in KP, 12 in nicotinate metabolism, 7 in SIRTs, and 19 in aldehyde dehydrogenases (ALDHs). A total of 508 SNPs were analyzed in this study. After significant SNPs were determined, 5000 genome-wide max(T) permutations were performed in Plink. Finally, we built a predictive model with logistic regression and assessed the interactions of SNPs with the haplotype association tests. Results: We found three SNPs that were significantly associated with MDD in our NAD-related candidate pathways, one within the KP (rs12622574 in ACMSD) and two within the nicotinate metabolism (rs28532698 in BST1 and rs3733593 in CD38). The observed association with MDD was significant in the dominant model of inheritance with marital status, education level, and body mass index (BMI) adjusted as covariates. Lastly, in haplotype analysis, the three associated SNPs consisted of one haploblock in ACMSD, four haploblocks in BST1, and two haploblocks in CD38. Conclusions: This study provides the first evidence that genetic variations involved in NAD homeostasis in the KP and nicotinate metabolism may be associated with the occurrence of MDD.