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Neuroinflammation caused by COVID-19 negatively impacts brain metabolism and function, while preexisting brain pathology may make individuals more vulnerable to the adverse consequences of COVID-19. We used summary statistics from genome-wide association studies (GWAS) to perform Mendelian randomization (MR) analyses, thus assessing potential associations between multiple sclerosis (MS) and three COVID-19 outcomes (SARS-CoV-2 infection, COVID-19 hospitalization, and critical COVID-19). Genome-wide risk genes were compared between the GWAS datasets on hospitalized COVID-19 and MS. Literature-based analysis was conducted to construct molecular pathways connecting MS and COVID-19. The MR analyses indicated that genetic liability to MS confers a causal effect on hospitalized COVID-19 (OR: 1.09, 95% CI: 1.03-1.16) but not on SARS-CoV-2 infection (1.03, 1.00-1.05). Genetic liability to hospitalized COVID-19 confers a causal effect on MS (1.15, 1.02-1.30). Hospitalized COVID-19 and MS share five risk genes within two loci, including TNFAIP8, HSD17B4, CDC37, PDE4A, and KEAP1. Pathway analysis identified a panel of immunity-related genes that may mediate the links between MS and COVID-19. Our study suggests that MS was associated with a 9% increased risk for COVID-19 hospitalization, while hospitalized COVID-19 was associated with a 15% increased risk for MS. Immunity-related pathways may underlie the link between MS on COVID-19. This article is protected by copyright. All rights reserved.

Background and aims- Nicotine is a highly addictive substance in tobacco products that dysregulates several neurotransmitters in the brain and impairs executive function. Non-invasive brain stimulation (NIBS) methods such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are promising treatments for nicotine dependence. We investigated the efficacy and acceptability of NIBS in managing smoking cessation through a systematic review and network meta-analysis (NMA). Methods- We conducted a systematic review to identify randomized controlled trials (RCTs) that investigated the efficacy of NIBS for smoking cessation. All pairwise meta-analyses and NMA procedures were conducted using random-effects and frequentist models. The co-primary outcomes were (1) the change in number of cigarettes smoked per day (change in frequency of smoking) in patients with nicotine dependence after NIBS and (2) acceptability (the dropout rate). The effect sizes for co-primary outcomes of change in frequency of smoking and acceptability were assessed according to standardized mean difference (SMD) and odds ratio, respectively. Results- Twelve RCTs with 710 participants (mean age: 44.2 years, 31.2% female) were included. Compared with the sham control, 10-Hz rTMS over the left dorsolateral prefrontal cortex (DLPFC) was associated with the largest changes in smoking frequency [SMD = −1.22, 95% confidence interval (95% CI) = −1.77 to −0.66]. The 2-mA bifrontal tDCS (SMD = −0.97, 95% CI = −1.32 to −0.62) and 10-Hz deep rTMS over the bilateral DLPFC with cue provocation (SMD = −0.77, 95% CI = −1.20 to −0.34) were associated with a significantly larger decrease in smoking frequency versus the sham. None of the investigated NIBSs was associated with dropout rates significantly different from those of the sham control groups. Conclusion- Prefrontal non-invasive brain stimulation interventions appear to reduce the number of cigarettes smoked with good acceptability.

Background: Experiencing stressful life events and ways of coping with them can predispose to the onset of depressive mood disorders, while depression itself can be responsible for severe stress and can weaken resilience to stressors. Thus, variables relevant to the onset of depressive episodes and the course of depression have significant relationships with coping strategies to stressors. The aim of this research was to evaluate the most commonly used stress-coping strategies in patients treated for depression compared to patients with anxiety disorders and to healthy subjects. Methods: The multidimensional coping inventory (COPE Inventory) by C. S. Carver, M. F. Scheier, and J. K. Weintraub, covering 15 stress response strategies included in more general and overarching coping styles, was used in the study. Results: Patients with depression differed from the healthy subjects in a statistically significant way. Statistical analysis showed that people with depression are less likely than healthy subjects to use Active Coping, Planning, Seeking of Instrumental and Emotional Social Support, Suppression of Competing Activities, and Positive Reinterpretation. In contrast, they are more likely to use Denial, Mental Disengagement, and Behavioral Disengagement compared to those not treated for mental disorders. The patients with depressive disorders, compared to the group of patients with anxiety disorders, scored significantly differently on stress coping strategies in only two types of actions taken in stressful situations. Conclusion: The patients with depression differed from the healthy subjects in terms of the highest number of the stress coping strategies assessed. Compared to the healthy individuals, a tendency toward an avoidant behavior style was prevalent among the depressed patients. There was no statistically significant difference between the patients with the first episode of the disease and recurrent depressive disorders in terms of stress coping strategies.

OBJECTIVE: Circadian rhythm disruption is commonly observed in bipolar disorder (BD). Daylight is the most powerful signal to entrain the human circadian clock system. This exploratory study investigated if solar insolation at the onset location was associated with the polarity of the first episode of BD I. Solar insolation is the amount of electromagnetic energy from the Sun striking a surface area of the Earth.METHODS: Data from 7488 patients with BD I were collected at 75 sites in 42 countries. The first episode occurred at 591 onset locations in 67 countries at a wide range of latitudes in both hemispheres. Solar insolation values were obtained for every onset location, and the ratio of the minimum mean monthly insolation to the maximum mean monthly insolation was calculated. This ratio is largest near the equator (with little change in solar insolation over the year), and smallest near the poles (where winter insolation is very small compared to summer insolation). This ratio also applies to tropical locations which may have a cloudy wet and clear dry season, rather than winter and summer.RESULTS: The larger the change in solar insolation throughout the year (smaller the ratio between the minimum monthly and maximum monthly values), the greater the likelihood the first episode polarity was depression. Other associated variables were being female and increasing percentage of gross domestic product spent on country health expenditures. (All coefficients: P ≤ 0.001).CONCLUSION: Increased awareness and research into circadian dysfunction throughout the course of BD is warranted.

In recent decades, the prevalence of amphetamine and methamphetamine use disorders has at least doubled in some regions/countries, with accompanying high risks of drug overdose-associated mortality. Noninvasive brain stimulation (NIBS) methods may be effective treatments. However, the comparative efficacy of the NIBS protocol for amphetamine/methamphetamine use disorder (AUD/MUD) remains unknown to date. The aim of this network meta-analysis (NMA) was to compare the efficacy and acceptability of various NIBS methods/protocols for AUD/MUD management.A frequentist model-based NMA was conducted. We included randomized controlled trials (RCTs) that investigated the efficacy of NIBS and guideline-recommended pharmacologic treatments to reduce craving severity in patients with either AUD or MUD.Twenty-two RCTs including 1888 participants met the eligibility criteria. Compared with the sham/placebo group (study = 19, subjects = 891), a combination of intermittent theta burst stimulation over the left dorsolateral prefrontal cortex (DLPFC) and continuous TBS over the left ventromedial prefrontal cortex (study = 1, subjects = 19) was associated with the largest decreases in craving severity [standardized mean difference (SMD) = -1.50; 95% confidence intervals (95%CIs) = -2.70 to -0.31]. High-frequency repetitive transcranial magnetic stimulation over the left DLPFC was associated with the largest improvements in depression and quality of sleep (study = 3, subjects = 86) (SMD = -2.48; 95%CIs = -3.25 to -1.71 and SMD = -2.43; 95%CIs = -3.38 to -1.48, respectively). The drop-out rate of most investigated treatments did not significantly differ between groups.The combined TBS protocol over the prefrontal cortex was associated with the greatest improvement in craving severity. Since few studies were available for inclusion, additional large-scale randomized controlled trials are warranted.

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can exert antidepressant, anti-inflammatory and neuroprotective properties, but the exact molecular mechanism underlying their effects is still not fully understood. We conducted both in vitro and clinical investigations to test which EPA or DHA metabolites are involved in these anti-inflammatory, neuroprotective and antidepressant effects. In vitro, we used the human hippocampal progenitor cell line HPC0A07/03C, and pre-treated cells with either EPA or DHA, followed by interleukin 1beta (IL1β), IL6 and interferon-alpha (IFN-α). Both EPA and DHA prevented the reduction in neurogenesis and the increase in apoptosis induced by these cytokines; moreover, these effects were mediated by the lipoxygenase (LOX) and cytochrome P450 (CYP450) EPA/DHA metabolites, 5-hydroxyeicosapentaenoic acid (HEPE), 4-hydroxydocosahexaenoic acid (HDHA), 18-HEPE, 20-HDHA, 17(18)-epoxyeicosatetraenoic acid (EpETE) and 19(20)-epoxydocosapentaenoic acid (EpDPA), detected here for the first time in human hippocampal neurones using mass spectrometry lipidomics of the supernatant. In fact, like EPA/DHA, co-treatment with these metabolites prevented cytokines-induced reduction in neurogenesis and apoptosis. Moreover, co-treatment with 17(18)-EpETE and 19(20)-EpDPA and the soluble epoxide hydroxylase (sEH) inhibitor, TPPU (which prevents their conversion into dihydroxyeicosatetraenoic acid (DiHETE)/ dihydroxydocosapentaenoic acid (DiHDPA) metabolites) further enhanced their neurogenic and anti-apoptotic effects. Interestingly, these findings were replicated in a sample of n = 22 patients with a DSM-IV Major Depressive Disorder, randomly assigned to treatment with either EPA (3.0 g/day) or DHA (1.4 g/day) for 12 weeks, with exactly the same LOX and CYP450 lipid metabolites increased in the plasma of these patients following treatment with their precursor, EPA or DHA, and some evidence that higher levels of these metabolites were correlated with less severe depressive symptoms. Overall, our study provides the first evidence for the relevance of LOX- and CYP450-derived EPA/DHA bioactive lipid metabolites as neuroprotective molecular targets for human hippocampal neurogenesis and depression, and highlights the importance of sEH inhibitors as potential therapeutic strategy for patients suffering from depressive symptoms.

Repetitive transcranial magnetic stimulation (rTMS) and intermittent theta-burst stimulation (iTBS) are evidenced-based treatments for patients with major depressive disorder (MDD) who fail to respond to standard first-line therapies. However, although various TMS protocols have been proven to be clinically effective, the response rate varies across clinical applications due to the heterogeneity of real-world psychiatric comorbidities, such as generalized anxiety disorder, posttraumatic stress disorder, panic disorder, or substance use disorder, which are often observed in patients with MDD. Therefore, individualized treatment approaches are important to increase treatment response by assigning a given patient to the most optimal TMS treatment protocol based on his or her individual profile. This literature review summarizes different rTMS or TBS protocols that have been applied in researches investigating MDD patients with certain psychiatric comorbidities and discusses biomarkers that may be used to predict rTMS treatment response. Furthermore, we highlight the need for the validation of neuroimaging and electrophysiological biomarkers associated with rTMS treatment responses. Finally, we discuss on which directions future efforts should focus for developing the personalization of the treatment of depression with rTMS or iTBS.

Background: Oropharyngeal/esophageal candidiasis are the most common opportunistic infections observed in patients with human immunodeficiency virus (HIV). While the commonly recommended treatment ...

Background/objectives Obesity has recently been recognized as a neurocognitive disorder involving circuits associated with the reward system and the dorsolateral prefrontal cortex (DLPFC). Noninvasive brain stimulation (NIBS) has been proposed as a strategy for the management of obesity. However, the results have been inconclusive. The aim of the current network meta-analysis (NMA) was to evaluate the efficacy and acceptability of different NIBS modalities for weight reduction in participants with obesity. Methods Randomized controlled trials (RCTs) examining NIBS interventions in patients with obesity were analyzed using the frequentist model of NMA. The coprimary outcome was change in body mass index (BMI) and acceptability, which was calculated using the dropout rate. Results Overall, the current NMA, consisting of eight RCTs, revealed that the high-frequency repetitive transcranial magnetic stimulation (TMS) over the left DLPFC was ranked to be associated with the second-largest decrease in BMI and the largest decrease in total energy intake and craving severity, whereas the high-frequency deep TMS over bilateral DLPFC and the insula was ranked to be associated with the largest decrease in BMI. Conclusion This pilot study provided a "signal" for the design of more methodologically robust and larger RCTs based on the findings of the potentially beneficial effect on weight reduction in participants with obesity by different NIBS interventions.

Attention deficit hyperactivity disorder (ADHD) is one of the most prevalent psychiatric disorders in children. The orexigenic hormone ghrelin is important in neuroprotection and neurodevelopment, which may play an important role in psychopathogenesis of ADHD. This study aimed to systematically investigate the genomic and pharmacological manipulations of ghrelin functioning in ADHD-like symptoms in zebrafish models and validated the effects of ghrelin polymorphisms in human subjects with ADHD. We firstly generated ghrelinΔ/Δ zebrafish mutant, which displayed hyperactive, attention deficit-like and impulsive-like behaviors, as well as endophenotypes, mimicking human ADHD. GhrelinΔ/Δ zebrafish exhibited downregulated expression levels of wnt1, wnt3a, wnt5a that are critical for dopaminergic neuron development to possibly regulate their number and spatial organization. Pharmacological blockade of wnt signaling with XAV939 induced a reduced moving activity and less dopaminergic neurons; whereas, wnt agonist SB415286 rescued hyperactivity and dopaminergic neuron loss in ghrelinΔ/Δ zebrafish. In addition, we further identified and validated a SNP, rs696217, on orexigenic hormone preproghrelin/ghrelin (T408T, Met72Met) to be associated with a higher risk of ADHD in a case-controlled association study with 248 subjects with ADHD and 208 subjects of healthy controls. Together, our results reveal a novel endogenous role for orexigenic hormone ghrelin in ADHD, which provides insights into genetic regulation and drug screens for the identification of novel treatments of ADHD.

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.

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.

Importance The most supportive evidence of the inflammation theory of depression is that up to one-third of patients with Hepatitis C virus infection (HCV) develop clinical depressive episodes during interferon-α (IFN-α) therapy. As glutamate-mediated excitotoxicity has been found to be a consequence of excessive inflammation and a pathogenic mechanism of depression, it is plausible to investigate genes on ionotropic glutamate receptor pathways. Objective To identify the at-risk genetic variations on ionotropic glutamate receptor pathways for interferon-α-induced depression. Method We assessed 291 patients with chronic HCV undergoing IFN-α therapy and analyzed the single nucleotide polymorphisms (SNPs) in genes related to ionotropic glutamate receptors in this prospective case-control study. Patients who developed IFN-α-induced depression anytime during the treatment were defined as the case group, while those who did not were defined as the control group. Genomic DNA was extracted from peripheral blood and analyzed by Affymetrix TWB array. Allelic and haplotype association tests were conducted using χ2 tests to assess the difference in allele and haplotype frequencies between cases and controls. Additionally, we performed 5000 permutations to control gene-wide family-wise error rates and create empirical p-values. Stratified analyses were then done to control for confounders and adjust odds ratios for our significant SNPs. We also did an additional stratified analysis to re-assess genes with near-significant SNPs (empirical p-value=0.05-0.10), employing Bonferroni correction with the effective number of independent tests to control gene-wide family-wise error rates. Results The minor and major allele frequencies of rs7542 (empirical p-value=0.0310) in MAPK3, rs3026685 (empirical p-value=0.0378) in PICK1, rs56005409 (empirical p-value=0.0332) in PRKCA, rs12914792 (empirical p-value=0.0096), rs17245773 (empirical p-value=0.0340) in RASGRF1, and rs78387863 (empirical p-value=0.0086), rs74365480 (empirical p-value=0.0200) in RASGRF2 were found significantly different between cases and controls. Haplotype association tests also revealed one significant haplotype in PRKCA (empirical p-value=0.0200) and one in RASGRF1 (empirical p-value=0.0048). Stratified analyses showed no signs of confounders for most of our significant SNPs, except for rs78387863 in RASGRF2. After a re-assessment of our near-significant genes by stratified analyses, two SNPs in GRIN2B turned significant. Conclusions This study provided supportive evidence of the involvement of the RAS/RAF/mitogen-activated protein kinase (MAPK) signaling pathway and glutamate ionotropic receptor AMPA type subunit 2(GluR2) transportation in the pathogenesis of IFN-α-induced depression.

Background Currently, different psychological interventions have shown significant efficacy in the treatment of acrophobia. However, the superiority of these individual treatments remains unclear. This network meta-analysis (NMA) aimed to investigate the efficacy, acceptability, and superiority of different existing interventions for acrophobia. Methods We conducted a NMA of randomised controlled trials (RCTs) and compared the efficacy, acceptability, and superiority of different existing interventions for acrophobia. Results In total, 17 RCTs (946 participants) were included in this study. The NMA demonstrated that virtual reality (VR) coach-delivered psychotherapy (standardised mean difference [SMD]=-2.08, 95% confidence interval [CI]: -3.22 to -0.93), in vivo exposure augmented with oppositional action (SMD=-1.66, 95% CI: -2.81 to -0.51), VR exposure therapy with 20 mg cortisol administration (SMD=-1.61, 95% CI: -3.14 to -0.09), VR based cognitive behavioural therapy (VRbasedCBT; SMD=-1.14, 95% CI: -2.22 to -0.05), and in vivo exposure (SMD=-1.02, 95% CI: -1.81 to -0.23) were significantly superior than the placebo/control interventions in improving the symptoms of patients with acrophobia. The NMA further indicated that VR coach-delivered psychotherapy was associated with the best improvement among all the 19 treatments for acrophobia. Furthermore, only VRbasedCBT (odds ratio=2.55, 95% CI: 1.09 to 5.96) was associated with higher dropout rate than the control/placebo. Limitations Sample heterogeneity, non-standardised assessment tools, and limited RCTs in some of the treatment arms. Conclusions VR coach-delivered psychotherapy could be considered as a first-line intervention for treating acrophobia. However, because of the study limitations, the overall evidence was not sufficiently strong, which warrants future studies.

Background: Taking into account the role of oxidative stress in neurodegeneration, we sought to evaluate the expression of genes for select enzymes with antioxidant properties (paraoxonases PON1, PON2 and PON3 and myeloperoxidase MPO) at the mRNA and protein levels in patients with depressive disorders. We further sought to determine the impact of oxidative stress in the etiopathogenesis of this group of mood disorders. Methods: A total of 290 subjects (190 depressed patients, 100 healthy controls) took part in the study. Sociodemographic and clinical data were collected. The severity of depressive symptoms was assessed using the Hamilton Depression Rating Scale (HDRS). Venous blood was collected. RT-PCR was used to assess gene expression at the mRNA level, while enzyme-linked immunosorbent assay (ELISA) was used to assess gene expression at the protein level. Results: The expression of the PON2 and PON3 genes at the protein level was significantly higher in depressive patients than in healthy controls. mRNA expression of the PON1, PON2 and PON3 genes was slightly higher in patients with depressive disorders than in the control group, however, this relationship was not statistically significant. On the other hand, the expression of the MPO gene at both mRNA and protein levels was significantly lower in patients with depressive disorder than in the control group. Conclusions: Our results are not in agreement with many studies on enzymes involved in maintaining oxidative balance. Our findings may not support the utility of paraoxonases (PON) or myeloperoxidase (MPO) as promising biomarker candidates of depression pending larger and well controlled studies.

Depression is currently one of the most common psychiatric disorders and the number of patients receiving antidepressant treatment is increasing every year. Therefore, it is essential to understand the underlying mechanisms that are associated with higher prevalence of depression. The main component leading to the change in functioning, in the form of apathy, anhedonia, lack of motivation and sleep disturbances, is stress. This is the factor that in recent decades—due to the civilization speed, dynamic technological development as well as competitiveness and competition in relationships—significantly affects the psychophysical condition, which results in an increase in the prevalence of civilization diseases, including depression. To understand the mechanism of susceptibility to this disease, one should consider the significant role of the interaction between immune and nervous systems. Their joint development from the moment of conception is a matrix of later predispositions, both associated with the mobilization of the proinflammatory pathways (TNFα, IL-1β, IL-6) and associated with psychological coping with stress. Such an early development period is associated with epigenetic processes that are strongly marked in prenatal development up to 1 year of age and determinate the characteristic phenotype for various forms of pathology, including depression. Regarding the inflammatory hypothesis of depression, interleukin 17 (IL-17), among other proinflammatory cytokines, might play an important role in the development of depressive disorders. It is secreted by Th17 cells, crossed the placental barrier and acts on the brain structures of the fetus by increasing IL-17 receptor levels and affecting the intensity of its signaling in the brain.

Author(s): Kinoshita, Shotaro; Cortright, Kelley; Crawford, Allison; Mizuno, Yuya; Yoshida, Kazunari; Hilty, Donald; Guinart, Daniel; Torous, John; Correll, Christoph U; Castle, David J; Rocha, Deyvis; Yang, Yuan; Xiang, Yu-Tao; Kolbaek, Pernille; Dines, David; ElShami, Mohammad; Jain, Prakhar; Kallivayalil, Roy; Solmi, Marco; Favaro, Angela; Veronese, Nicola; Seedat, Soraya; Shin, Sangho; Salazar de Pablo, Gonzalo; Chang, Chun-Hung; Su, Kuan-Pin; Karas, Hakan; Kane, John M; Yellowlees, Peter; Kishimoto, Taishiro | Abstract: BackgroundDuring the COVID-19 pandemic, the use of telemedicine as a way to reduce COVID-19 infections was noted and consequently deregulated. However, the degree of telemedicine regulation varies from country to country, which may alter the widespread use of telemedicine. This study aimed to clarify the telepsychiatry regulations for each collaborating country/region before and during the COVID-19 pandemic.MethodsWe used snowball sampling within a global network of international telepsychiatry experts. Thirty collaborators from 17 different countries/regions responded to a questionnaire on barriers to the use and implementation of telepsychiatric care, including policy factors such as regulations and reimbursement at the end of 2019 and as of May 2020.ResultsThirteen of 17 regions reported a relaxation of regulations due to the pandemic; consequently, all regions surveyed stated that telepsychiatry was now possible within their public healthcare systems. In some regions, restrictions on prescription medications allowed via telepsychiatry were eased, but in 11 of the 17 regions, there were still restrictions on prescribing medications via telepsychiatry. Lower insurance reimbursement amounts for telepsychiatry consultations v. in-person consultations were reevaluated in four regions, and consequently, in 15 regions telepsychiatry services were reimbursed at the same rate (or higher) than in-person consultations during the COVID-19 pandemic.ConclusionsOur results confirm that, due to COVID-19, the majority of countries surveyed are altering telemedicine regulations that had previously restricted the spread of telemedicine. These findings provide information that could guide future policy and regulatory decisions, which facilitate greater scale and spread of telepsychiatry globally.

The field of nutritional psychiatry has generated observational and efficacy data supporting a role for healthy dietary patterns in depression onset and symptom management. To guide future clinical trials and targeted dietary therapies, this review provides an overview of what is currently known regarding underlying mechanisms of action by which diet may influence mental and brain health. The mechanisms of action associating diet with health outcomes are complex, multifaceted, interacting, and not restricted to any one biological pathway. Numerous pathways were identified through which diet could plausibly affect mental health. These include modulation of pathways involved in inflammation, oxidative stress, epigenetics, mitochondrial dysfunction, the gut microbiota, tryptophan-kynurenine metabolism, the HPA axis, neurogenesis and BDNF, epigenetics, and obesity. However, the nascent nature of the nutritional psychiatry field to date means that the existing literature identified in this review is largely comprised of preclinical animal studies. To fully identify and elucidate complex mechanisms of action, intervention studies that assess markers related to these pathways within clinically diagnosed human populations are needed.

Omega-3 polyunsaturated fatty acids (or omega-3 PUFAs, n-3 PUFAs) are essential nutrients throughout the life span. Recent studies have shown the importance of n-3 PUFAs supplementation during prenatal and perinatal period as a potential protective factor of neurodevelopmental disorders. N-3 PUFAs have been reported to be lower in youth with attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and major depressive disorder (MDD). N-3 PUFAs supplementation has shown potential effects in the improvement of clinical symptoms in youth with ADHD, ASD, and MDD, especially those with high inflammation or a low baseline n-3 index. Moreover, it has been suggested that n-3 PUFAs had positive effects on lethargy and hyperactivity symptoms in ASD. For clinical application, the following dosage and duration are recommended in youth according to available randomized controlled trials and systemic literature review: (1) ADHD: a combination of eicosapentaenoic acid (EPA) ＋ docosahexaenoic acid (DHA) ≥ 750 mg/d, and a higher dose of EPA (1,200 mg/d) for those with inflammation or allergic diseases for duration of 16-24 weeks; (2) MDD: a combination of a EPA ＋ DHA of 1,000-2,000 mg/d, with EPA:DHA ratio of 2 to 1, for 12-16 weeks; (3) ASD: a combination of EPA ＋ DHA of 1,300-1,500 mg/d for 16-24 weeks as add-on therapy to target lethargy and hyperactivity symptoms. The current review also suggested that n-3 index and inflammation may be potential treatment response markers for youth, especially in ADHD and MDD, receiving n-3 PUFA.

Background Cigarette smoking has shown to be associated with sleep disturbance, especially prolonged sleep onset latency (SOL). Cigarette smoking stimulates the release of dopamine (DA) and serotonin (5-HT), which might promote awakening and inhibit rapid eye movement sleep. Dopamine transporter (DAT) and serotonin transporter play a key role in the reuptake of DA and 5-HT from the synaptic cleft into presynaptic neurons. However, the relationship among cigarette smoking, sleep disturbance and neurotransmitters has never been investigated in human cerebrospinal fluid (CSF). Methods A total of 159 Chinese male subjects (81 active smokers and 78 non-smokers) who would undergo lumbar puncture before the surgery of anterior cruciate ligament reconstruction were recruited and 5mL-CSF samples were collected incidentally. CSF levels of DA, DAT, 5-HT, and serotonin transporter were measured using radioimmunoassay and ELISA. Sociodemographic data and the Pittsburgh Sleep Quality Index (PSQI) scale were collected before surgery. Results PSQI global scores, SOL, and CSF DA levels were significantly higher in active smokers compared to non-smokers (2.00 [1.00-4.75] scores vs 4.00 [3.00-6.00] scores, p = 0.001; 10.00 [5.00-15.00] minutes vs 15.00 [10.00-30.00] minutes, p = 0.002; 87.20 [82.31-96.06]ng/mL vs 107.45 [92.78-114.38] ng/mL, p < 0.001), while CSF DAT levels were significantly lower in active smokers (0.35 [0.31-0.39] ng/mL vs 0.29 [0.26-0.34] ng/mL, p < 0.001). Conclusion Cigarette smoking was indeed associated with sleep disturbance, shown by prolonged SOL, higher DA levels and lower DAT levels in CSF of active smokers.

Chronic pain and depression are conditions that are highly comorbid and present with overlapping clinical presentations and common pathological biological pathways in neuroinflammation, both of which can be reversed by the use of electroacupuncture (EA) and omega-3 polyunsaturated fatty acids (PUFAs). Transient receptor potential V1 (TRPV1), a Ca2+ permeable ion channel that can be activated by inflammation, is reported to be involved in the development of chronic pain and depression. Here, we investigated the role of TRPV1 and its related pathways in the murine models of cold stress-induced nociception and depression. Female C57BL/6 wild type and TRPV1 knockout mice were subjected to intermittent cold-stress (ICS) to initiate depressive-like and chronic pain behaviors, respectively. The Bio-Plex ELISA technique was utilized to analyze inflammatory mediators in mice plasma. The western blot and immunostaining techniques were used to analyze the presence of TRPV1 and related molecules in the medial prefrontal cortex (mPFC), hippocampus, periaqueductal gray (PAG), and amygdala. The ICS model significantly induced chronic pain (mechanical: 2.55 ± 0.31 g; thermal: 8.12 ± 0.87 s) and depressive-like behaviors (10.95 ± 0.95% in the center zone; 53.14 ± 4.01% in immobility). The treatment efficacy of EA, docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) were observed in both nociceptive and depression test results. Inflammatory mediators were increased after ICS induction and further reversed by the use of EA, EPA and DHA. A majority of TRPV1 proteins and related molecules were significantly decreased in the mPFC, hippocampus and PAG of mice. This decrease can be reversed by the use of EA, EPA and DHA. In contrast, these molecules were increased in the mice’s amygdala, and were attenuated by the use of EA, EPA and DHA. Our findings indicate that these inflammatory mediators can regulate the TRPV1 signaling pathway and initiate new potential therapeutic targets for chronic pain and depression treatment.

Inflammation theory has been consolidated by accumulating evidence, and many studies have suggested that the peripheral cytokine levels could be biomarkers for disease status and treatment outcome in major depressive disorder (MDD). Theta burst stimulation (TBS), a new form of repetitive transcranial magnetic stimulation (TMS) for MDD, has been demonstrated to improve depression via modulating dysfunctional neural network or hypothalamic–pituitary–adrenal axis hyperactivities in MDD. However, there is lack of exploratory studies investigating its effect on serum inflammatory cytokines. Here, we aimed to investigate the antidepressant efficacy of bilateral TBS monotherapy and its effects on the serum cytokine levels in MDD. We conducted a double-blind, randomized, sham-controlled trial, with 53 MDD patients who exhibited no responses to at least one adequate antidepressant treatment for the prevailing episode assigned randomly to one of two groups: bilateral TBS monotherapy (n = 27) or sham stimulation (n = 26). The TBS treatment period was 22 days. Blood samples from 31 study subjects were obtained for analyses. The bilateral TBS group exhibited significantly greater decreases in depression scores than the sham group at week 4 (56.5% vs. 33.1%; p0.001 [effect size (Cohen ’ s d) = 1.00]) and during the 20-week follow-up periods. Significantly more responders were also found at week 4 (70.3% vs. 23.1%, p = 0.001) and during the 20-week follow-up periods. However, we did not detect any significant effects of TBS on the cytokine panels or any correlations between improvement in depressive symptoms and changes in serum inflammatory markers. Our findings provided the first evidence that the antidepressant efficacy of bilateral TBS monotherapy might not work via immune-modulating mechanisms.

Background IFN-α-induced depression in patients undergoing hepatitis C virus (HCV) treatment provides powerful support for the inflammation hypothesis of depression. Most studies have focused on the occurrence of depressive symptoms, but there has been no study yet in depression-free HCV patients receiving IFN-α. We hypothesized that HCV patients who did not develop depression after IFN-α exposure might have a lower incidence of depressive disorders after the IFN-α treatment. Methods We conducted a twelve-year population-based cohort study of chronic HCV patients who received IFN-α therapy. The data were obtained from the Taiwan National Health Insurance Research Database. The study cohort was patients without any depressive disorder nor antidepressant use before and during IFN-α therapy. They were matched randomly by age, sex income and urbanization at a ratio of 1:4 with the control cohort of HCV patients without IFN-α therapy. The follow-up started after the last administration of IFN-α, and the primary outcome was the incidence of depressive disorders after IFN-α therapy. Results A total of 20,468 depression-free subjects were identified from records of HCV patients receiving IFN-α therapy. Patients without IFN-α-induced depression were associated with a significantly lower incidence (per 10,000 person-years) of new-onset depressive disorders (126.8, 95% Confidential Interval [CI] of 118.5–135.6) as compared to the control cohort (145.2, 95% CI of 140.0–150.6) (p Discussion Our study indicates that IFN-α treated depression-free patients have a lower risk for depressive disorders. This hypothesized mechanism might derive from an IFN-α-induced resilience factor as yet to be defined. Conclusions Our study might suggest a new possibility for a new pharmacological strategy against depression.

Hypothalamus-Pituitary-Adrenal (HPA) axis dysregulation, inflammation and imbalance of neurotrophins have been suggested in attention deficit hyperactivity disorder (ADHD), but the results have not been conclusive. The aim of this study is to investigate the levels of salivary cortisol across 4-time points during the day, and of morning plasma inflammatory biomarkers and neurotrophins, in youth with ADHD and in typically developing youth (TD), with stratification by age, ADHD subtypes and oppositional defiant disorder (ODD) comorbidity in Taiwan.We conducted a case-control study measuring saliva cortisol levels at 4 different time points during the day (at awakening, noon, 1800 h and bedtime) and morning plasma levels of inflammatory and neurotrophins biomarkers in youth with ADHD (n = 98, age 6-18 years old with mean age 9.32 ± 3.05 years) and TD (n = 21, age 6-18 years old with mean age 9.19 ± 2.96 years) in Taiwan.Our study showed that youth with ADHD had lower levels of bedtime salivary cortisol (effects size (ES) = -0.04, p = .023), with children with the combined form of the disorder (with inattention, hyperactivity and impulsivity all present) having the lowest awakening salivary cortisol levels. ADHD youth also had higher levels of plasma high-sensitivity C-reactive protein (hs-CRP) and interleukin (IL)-6 (ES = 0.85-1.20, p .0001), and lower plasma tumor necrosis factor-alpha (ES = -0.69, p = .009) and brain-derived neurotrophic factors (BDNF) (ES = -1.13, p .0001). Both ADHD groups regardless of ODD comorbidity had higher levels of IL-6 (p .0001) and lower levels BDNF (p .0001).The lower bedtime salivary cortisol levels and higher levels of inflammatory biomarkers in youth with ADHD further support the role of abnormal HPA axis and inflammation in ADHD. Moreover, the lower levels of BDNF in ADHD also indicate that BDNF may be a potential biomarker in this disorder that is part of a broader biological dysfunction.

Background The neuroprotective role of interleukin (IL)-33 is supported by numerous preclinical studies, but it remains uninvestigated in clinical studies of Alzheimer’s disease (AD). We aimed to examine the association between human blood levels of IL-33 and cognitive preservation in amnestic mild cognitive impairment (aMCI) and AD. Methods A total of 100 participants (26 controls, 35 aMCI patients, and 39 AD patients) completed two Mini-Mental State Examinations (MMSEs) over a 1-year interval. In all 100 participants at the second MMSE, we examined the plasma levels of IL-33, IL-β, IL-1 receptor agonist (IL-1RA), beta amyloid (Aβ), and tau and apolipoprotein E (ApoE) genotyping; we also performed Hopkins Verbal Learning Test, Trail Making Test, forward and backward digit span, and Clinical Dementia Rating. Results IL-33 expression showed a positive trend among controls (1/26 = 3.8%), aMCI (9/35 = 25.7%), and AD (17/39 = 43.6%) (trend analysis: P P = 0.006). The cognitive preservation was not associated with the lower levels of Aβ, tau, and ApoE ε4, while higher levels of ApoE ε4 and phosphorylated tau were indeed associated with cognitive decline. The aMCI patients with AD conversion during study period had higher proportion of IL-33(−) than non-AD converters (90.9% vs 53.3%, P = 0.04). Conclusions IL-33 or its associated signaling pathways may represent a new treatment paradigm for aMCI and AD.

Cardiovascular diseases (CVDs) and major depressive disorder (MDD) will be the two most disabling diseases by 2030. Patients with CVDs comorbid depression had lower levels of total omega-3 polyunsaturated fatty acids (n-3 PUFAs), docosahexaenoic acid (DHA), and a higher omega-6 to omega-3 ratio. However, there have been limited studies on the effects n-3 PUFAs on MDD in patients with CVDs.We have enrolled a total of 59 patients (64% males, mean age of 61.5 ± 9.0 years and mean education of 10.2 ± 4.2 years) with CVDs comorbid MDD. They were randomized into either receiving n-3 PUFAs (2 g per day of eicosapentaenoic acid (EPA) and 1 g of DHA) or placebo for 12 weeks. We assessed depression symptom severity with Hamilton Depression Rating Scale (HAMD) and Beck Depression Inventory (BDI), as well as blood fatty acid levels, electrocardiogram and blood biochemistry, at the baseline and at the endpoint.There were no differences between the n-3 PUFAs and placebo group in the changes of HAMD and BDI total scores, while PUFAs group had a greater reduction in HAMD Cognition subscale scores than the placebo group at week 8 (p 0.05). Moreover, subgroup analyses found that the n-3 group had a greater reduction of HAMD Core subscale scores than the placebo group at the end of week 12 (p 0.05) for the very severe DEP group (HAMD ≥ 23).Overall, n-3 PUFAs did not show a beneficial effect on depressive symptoms when compared with placebo. However, when stratified with depression severity, n-3 PUFAs supplementation improved core depression symptoms in the very severe MDD group. N-3 PUFAs supplementation may provide a treatment option for a subpopulation of patients with CVDs comorbid MDD.

Amyloid-β (Aβ) plaques is one of the typical pathological hallmark of Alzheimer disease (AD). Accumulating evidence suggests that the imbalance between Aβ production and clearance leads to extracellular Aβ accumulation in the brain. It is reported that the blood–brain barrier (BBB) transport plays a predominant role in Aβ clearance from brain to blood. In the present study, we investigated dynamic alterations of BBB transport function in the early disease stage of AD using APPswe/PS1dE9 C57BL/6J (APP/PS1) transgenic mice. Our results showed that the expression of lipoprotein receptor-related protein 1 (LRP-1), a main efflux transporter of BBB, started to decrease at the age of 4 months old. Interestingly, supplementing with fish oil which is rich in omega-3 polyunsaturated fatty acids (PUFAs) significantly enhanced the expression level of LRP-1 and promoted Aβ clearance from the bran to circulation, as revealed by reduced soluble/insoluble Aβ levels and senile plaques in the brain parenchyma and a corresponding increase of Aβ levels in plasma. Besides, fish oil supplement significantly inhibited the NF-κB activation, reduced the expression of interleukin-1β and tumor necrosis factor-α, and suppressed the glial activation in APP/PS1 mice. The results of the study provide evidence that BBB transport function could be impaired at a very early disease stage, which might contribute to Aβ pathological accumulation in AD, and omega-3 PUFAs intervention could be an effective strategy for the prevention of the progression of AD through promoting Aβ clearance from brain-to-blood.

Background Omega-3 polyunsaturated fatty acids (PUFAs) reduce depressive symptoms through an anti-inflammatory effect, and injection of both omega-3 PUFAs and estradiol (E2) induces antidepressant-like effects in rats by regulating the expression of inflammatory cytokines. The aims of this study were to examine the association of increased E2 during pregnancy with depressive symptoms and with inflammatory cytokines in women who were and were not supplemented with omega-3 PUFAs. Methods Pregnant women with Edinburgh Postnatal Depression Scale scores ≥9 were recruited at 12–24 weeks of gestation. The participants were randomly assigned to receive 1800 mg omega-3 fatty acids (containing 1206 mg eicosapentaenoic acid [EPA]) or placebo for 12 weeks. E2, omega-3 PUFAs, high-sensitivity C-reactive protein, interleukin-6, and adiponectin were measured at baseline and at the 12-week follow-up. Multivariable regression analyses were conducted to examine the association of the changes of E2 and omega-3 PUFAs with the changes in depressive symptoms and with the changes of inflammatory cytokines at follow-up by intervention group. Results Of the 108 participants in the trial, 100 (92.6%) completed the follow-up assessment including blood sampling. Multivariable regression analyses revealed that the increase of EPA and E2 was significantly associated with a decrease in depressive symptoms among the participants assigned to the omega-3 group, but not among those assigned to the placebo group. Neither E2 nor any PUFAs were associated with a change in inflammatory cytokines. Conclusion Supplementation with EPA and increased levels of E2 during pregnancy might function together to alleviate antenatal depression through a mechanism other than anti-inflammation.

Introduction Nowadays, depression is conceptualized as an immune-inflammatory and oxidative stress disorder associated with neuroprogressive changes as a consequence of peripherally activated immune-inflammatory pathways, including peripheral cytokines and immune cells which penetrate into the brain via the blood barrier, as well as nitro-oxidative stress and antioxidant imbalances. The aim of this study was to investigate whether personality traits predisposing to a depressive episode (hypochondria, dysthymic, hysteria) are associated with changes in peripheral gene expression for selected indicators of inflammation and oxidative balance. Material and methods One hundred four people meeting the diagnostic criteria specified for a depressive episode took part in the study. Selected scales of the Minnesota Multiphasic Personality Inventory (MMPI-2) were used to measure personality traits. Expression at the mRNA and protein level for manganese superoxide dismutase (MnSOD), myeloperoxidase (MPO), cyclooxygenase 2 (COX-2), inducible nitric oxide synthase (iNOS), and metalloproteinases 2 and 9 (MMP-2, MMP-9) was examined. Results Scales for the neurotic triad of the MMPI-2 test correlated significantly with the expression at the level of mRNA and protein for MnSOD, MPO and metalloproteinases 2 and 9. Conclusions The scales specified for the neurotic triad of the MMPI-2 test correspond substantially with the expression of MnSOD, MPO and metalloproteinases 2 and 9 at the mRNA and protein levels in the group of patients suffering from depression.

(1) Background: Only 60–70% of depressed patients respond to standard antidepressant treatments. Hence, it is essential to search for new, effective and safe therapies for unmet clinical needs of treatment-resistant depression (TRD). Agents targeting the components of the JAK-STAT signaling pathway have been shown to be relevant in immunology and are commonly used in the treatment of many hematological, rheumatological and dermatological diseases. The aim of this study was to investigate the role of elements of the JAK-STAT signaling pathway in the etiopathogenesis of depressive disorders. (2) Methods: A total of 290 subjects took part in the study (190 depressed patients, 100 healthy controls). Sociodemographic data were collected. The severity of depressive symptoms was assessed using the Hamilton Depression Rating Scale (HDRS). The gene expression at the mRNA protein levels of JAK (JAK1-JAK3) and STAT (STAT1-STAT5) was assessed by using RT-PCR and ELISA. (3) Results: Increased expression of JAK3 and decreased expression of STAT1 were observed in the group of depressed patients. (4) Conclusions: Further studies are necessary to determine whether moderation of the JAK-STAT signaling pathways is involved in the treatment of depression.

Music intervention (MI) has been applied as an effective adjunctive treatment for pain control in various clinical settings. However, no meta-analysis has yet been published on the analgesic effects of MI in infants and children. We performed a systematic review of PubMed, EMBASE, Web of Science, and Cochrane Library databases to identify randomized controlled trials (RCTs) with the keywords “pain” AND “music therapy” from inception to January 2022. Primary outcomes were pain intensity and vital signs. Standardized mean difference (SMD) values and the corresponding 95% confidence intervals (CIs) were computed using a random effect model. Subgroup analyses with age groups, types of pain, and music styles were conducted. A total of 38 RCTs involving 5601 participants met the selection criteria. MI significantly decreased the pain levels (SMD = −0.57, p < 0.001), both in the newborn group (p = 0.007) and in the infant/children group (p < 0.001). MI significantly reduced heart rate (SMD = −0.50, p < 0.001) and respiratory rate (SMD = −0.60, p = 0.002) and increased peripheral capillary oxygen saturation (SMD = 0.44, p < 0.001). In subgroup analyses of types of pain, MI had significant effects on prick pain (p = 0.003), chronic and procedural pain (p < 0.001), and postoperative pain (p = 0.018). As for music styles, significant analgesic effects were observed for classical music (p < 0.001), kids’ music (p < 0.001), and pop music (p = 0.001), but not for world music (p = 0.196), special composition (p = 0.092), and multiple music combinations (p = 0.420). In conclusion, our analysis provides supportive evidence about the efficacy of MI, especially classical, kids’, and pop music, in controlling prick, procedural, and postoperative pain in the pediatric population.

Objectives: The therapeutic use of nutrient-based ‘nutraceuticals’ and plant-based ‘phytoceuticals’ for the treatment of mental disorders is common; however, despite recent research progress, there have not been any updated global clinical guidelines since 2015. To address this, the World Federation of Societies of Biological Psychiatry (WFSBP) and the Canadian Network for Mood and Anxiety Disorders (CANMAT) convened an international taskforce involving 31 leading academics and clinicians from 15 countries, between 2019 and 2021. These guidelines are aimed at providing a definitive evidence-informed approach to assist clinicians in making decisions around the use of such agents for major psychiatric disorders. We also provide detail on safety and tolerability, and clinical advice regarding prescription (e.g. indications, dosage), in addition to consideration for use in specialised populations. Methods: The methodology was based on the WFSBP guidelines development process. Evidence was assessed based on the WFSBP grading of evidence (and was modified to focus on Grade A level evidence–meta-analysis or two or more RCTs–due to the breadth of data available across all nutraceuticals and phytoceuticals across major psychiatric disorders). The taskforce assessed both the ‘level of evidence’ (LoE) (i.e. meta-analyses or RCTs) and the assessment of the direction of the evidence, to determine whether the intervention was ‘Recommended’ (+++), ‘Provisionally Recommended’ (++), ‘Weakly Recommended’ (+), ‘Not Currently Recommended’ (+/−), or ‘Not Recommended’ (−) for a particular condition. Due to the number of clinical trials now available in the field, we firstly examined the data from our two meta-reviews of meta-analyses (nutraceuticals conducted in 2019, and phytoceuticals in 2020). We then performed a search of additional relevant RCTs and reported on both these data as the primary drivers supporting our clinical recommendations. Lower levels of evidence, including isolated RCTs, open label studies, case studies, preclinical research, and interventions with only traditional or anecdotal use, were not assessed. Results: Amongst nutraceuticals with Grade A evidence, positive directionality and varying levels of support (recommended, provisionally recommended, or weakly recommended) was found for adjunctive omega-3 fatty acids (+++), vitamin D (+), adjunctive probiotics (++), adjunctive zinc (++), methylfolate (+), and adjunctive s-adenosyl methionine (SAMe) (+) in the treatment of unipolar depression. Monotherapy omega-3 (+/−), folic acid (−), vitamin C (−), tryptophan (+/−), creatine (+/−), inositol (−), magnesium (−), and n-acetyl cysteine (NAC) (+/−) and SAMe (+/−) were not supported for this use. In bipolar disorder, omega-3 had weak support for bipolar depression (+), while NAC was not currently recommended (+/−). NAC was weakly recommended (+) in the treatment of OCD-related disorders; however, no other nutraceutical had sufficient evidence in any anxiety-related disorder. Vitamin D (+), NAC (++), methylfolate (++) were recommended to varying degrees in the treatment of the negative symptoms in schizophrenia, while omega-3 fatty acids were not, although evidence suggests a role for prevention of transition to psychosis in high-risk youth, with potential pre-existing fatty acid deficiency. Micronutrients (+) and vitamin D (+) were weakly supported in the treatment of ADHD, while omega-3 (+/−) and omega-9 fatty acids (−), acetyl L carnitine (−), and zinc (+/−) were not supported. Phytoceuticals with supporting Grade A evidence and positive directionality included St John’s wort (+++), saffron (++), curcumin (++), and lavender (+) in the treatment of unipolar depression, while rhodiola use was not supported for use in mood disorders. Ashwagandha (++), galphimia (+), and lavender (++) were modestly supported in the treatment of anxiety disorders, while kava (−) and chamomile (+/−) were not recommended for generalised anxiety disorder. Ginkgo was weakly supported in the adjunctive treatment of negative symptoms of schizophrenia (+), but not supported in the treatment of ADHD (+/−). With respect to safety and tolerability, all interventions were deemed to have varying acceptable levels of safety and tolerability for low-risk over-the-counter use in most circumstances. Quality and standardisation of phytoceuticals was also raised by the taskforce as a key limiting issue for firmer confidence in these agents. Finally, the taskforce noted that such use of nutraceuticals or phytoceuticals be primarily recommended (where supportive evidence exists) adjunctively within a standard medical/health professional care model, especially in cases of more severe mental illness. Some meta-analyses reviewed contained data from heterogenous studies involving poor methodology. Isolated RCTs and other data such as open label or case series were not included, and it is recognised that an absence of data does not imply lack of efficacy. Conclusions: Based on the current data and clinician input, a range of nutraceuticals and phytoceuticals were given either a supportive recommendation or a provisional recommendation across a range of various psychiatric disorders. However several had only a weak endorsement for potential use; for a few it was not possible to reach a clear recommendation direction, largely due to mixed study findings; while some other agents showed no obvious therapeutic benefit and were clearly not recommended for use. It is the intention of these guidelines to inform psychiatric/medical, and health professional practice globally.

This study examined whether the hemoglobin concentration is correlated with the hippocampal volume using voxel-based morphometry (VBM).This cross-sectional study included 1923 community dwellers, aged 40‒89 years, from the sixth wave of the National Institute for Longevity Sciences, Longitudinal Study of Aging. The hemoglobin levels were determined through blood examination. The regional cortical volumes were evaluated using three-dimensional T1-weighted magnetic resonance images. Following preprocessing with a statistical parametric mapping software, a VBM analysis of covariance design was implemented to identify the regional gray matter volumes related to hemoglobin concentration, while adjusting for age, sex, education, body mass index, depressive symptoms, alcohol consumption status, smoking status, medical history, and the estimated glomerular filtration rate.VBM analysis revealed a significantly positive correlation between the hemoglobin concentration and gray matter volume in the bilateral anterior hippocampus and the amygdala clusters as well as in the cingulate and middle temporal gyri, cerebellum, and superior sagittal and transverse sinuses.The hemoglobin concentration could be positively associated with the hippocampal volume among community-dwelling middle-aged and older adults, which highlights the importance of monitoring the hemoglobin concentration in older adults to decrease the possibility of neurodegeneration.

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).