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Research on nutraceutical and dietary interventions in psychiatry has grown substantially, but progress is hindered by methodological inconsistencies and limited reporting standards. To address this, the International Society for Nutritional Psychiatry Research presents the first guidelines on clinical trial design, conduct, and reporting for future clinical trials in this area. Recommendations were developed using a Delphi process including eighteen researchers with considerable clinical trial expertise and experience in either methodology, nutraceutical, or dietary interventions in psychiatry. These guidelines provide forty-nine recommendations for clinical trial design and outcomes, five for trial reporting, and seven for future research priorities. The recommendations included in these guidelines are designed to inform both nutraceutical and dietary clinical trial interventions in Nutritional Psychiatry. Common themes include an emphasis on the importance of a multidisciplinary research team and integration of co-design processes into the conduct and design of clinical research, methods to improve transparency and replicability of trial outcomes, and measures to address common biases in nutrition trials. Furthermore, we provide recommendations for future research including examining a greater variety of nutraceutical and dietary interventions, scalable delivery models, effectiveness and implementation studies, and the need to investigate these interventions in the prevention and management of less studied psychiatric conditions (e.g. schizophrenia and bipolar disorder). Recommendations included within these guidelines are intended to improve the rigor and clinical relevance of ongoing and future clinical trials in Nutritional Psychiatry.
An aberrant right subclavian artery represents the most common aortic arch vascular anomaly. Conventional wisdom states that these anomalies do not result in dysphagia, but rather serve as “red herrings”. Clearly, in the vast majority of cases, this holds true. Nonetheless, one should never say never.
Methods:
Herein, we present a cohort of four children with debilitating dysphagia resulting from an aberrant right subclavian artery. Subclavian reimplantation via a right posterolateral thoracotomy was performed successfully in all cases.
Results:
Dysphagia resolved postoperatively, and all patients were able to advance to a normal diet. They were able to gain appropriate weight postoperatively and continue to do well at most recent clinical follow-up.
Conclusions:
This case series suggests that aberrant right subclavian artery anatomy should be considered a potential aetiology of dysphagia, albeit rarely. Surgical intervention for select patients can provide dramatic resolution of symptoms.
The prevalence of medical illnesses is high among patients with psychiatric disorders. The current study aimed to investigate multi-comorbidity in patients with psychiatric disorders in comparison to the general population. Secondary aims were to investigate factors associated with metabolic syndrome and treatment appropriateness of mental disorders.
Methods
The sample included 54,826 subjects (64.73% females; 34.15% males; 1.11% nonbinary gender) from 40 countries (COMET-G study). The analysis was based on the registration of previous history that could serve as a fair approximation for the lifetime prevalence of various medical conditions.
Results
About 24.5% reported a history of somatic and 26.14% of mental disorders. Mental disorders were by far the most prevalent group of medical conditions. Comorbidity of any somatic with any mental disorder was reported by 8.21%. One-third to almost two-thirds of somatic patients were also suffering from a mental disorder depending on the severity and multicomorbidity. Bipolar and psychotic patients and to a lesser extent depressives, manifested an earlier (15–20 years) manifestation of somatic multicomorbidity, severe disability, and probably earlier death. The overwhelming majority of patients with mental disorders were not receiving treatment or were being treated in a way that was not recommended. Antipsychotics and antidepressants were not related to the development of metabolic syndrome.
Conclusions
The finding that one-third to almost two-thirds of somatic patients also suffered from a mental disorder strongly suggests that psychiatry is the field with the most trans-specialty and interdisciplinary value and application points to the importance of teaching psychiatry and mental health in medical schools and also to the need for more technocratically oriented training of psychiatric residents.
Non-native speech is difficult for native listeners to understand. While listeners can learn to understand non-native speech after exposure, it is unclear how to optimize this learning. Experimental subjects transcribed non-native speech and were paid either a flat rate or based on their performance. Participants who were paid based on performance demonstrated improved performance overall and faster learning than participants who were paid a flat rate. These results suggest that exposure alone is not sufficient to optimize learning of non-native speech and that current models of this process must be revised to account for the effects of motivation and incentive.
Paleoproterozoic massive Cu-Zn±Pb±Au±Ag sulphide deposits metamorphosed to the middle-upper amphibolite facies in central-south Colorado formed in a volcanic arc setting on the edge of the Yavapai crustal province. Previously published U-Pb ages on spatially related granitoids range from ∼1.9 to ∼1.1 Ga, while Pb isotope studies on galena from massive sulphides suggest mineralization formed at around 1.8–1.7 Ga. Some deposits in the Dawson-Green Mountain trend (DGMT) and the Gunnison belt are composed of Cu-Zn-Au-(Pb-Ag) mineralization that were overprinted by later Au-(Ag-Cu-Bi-Se-Te) mineralization. Sulphide mineralization is spatially related to amphibolite and bimodal, mafic-felsic volcanic rocks (gabbro, amphibolite, rhyolite and dacite) and granitoids, but it occurs mostly in biotite-garnet-quartz±sillimanite±cordierite schists and gneisses, spatially related to nodular sillimanite rocks, and in some locations, exhalative rocks (iron formations, gahnite-rich rocks and quartz-garnetite). The major metallic minerals of the massive sulphides include chalcopyrite, sphalerite, pyrite, pyrrhotite, and magnetite, with minor galena and gahnite. Altered rocks intimately associated with mineralization primarily consist of various amphiboles (gedrite, tremolite and hornblende), gahnite, biotite, garnet, cordierite, carbonate and rare högbomite. The Zn/Cd ratios of sphalerite (44 to 307) in deposits in the DGMT fall within the range of global volcanogenic massive sulphide (VMS) deposits but overlap with sphalerite from sedimentary exhalative (Sedex) deposits. Sulphur isotope values of sulphides (δ34S = −3.3 to +6.5) suggest sulphur was largely derived from magmatic sources, and that variations in isotopic values resulting from thermochemical sulphate reduction are due to small differences in physicochemical conditions. The preferred genetic model is for the deposits to be bimodal-mafic (Gunnison) to mafic-siliciclastic VMS deposits (Cotopaxi, Cinderella-Bon Ton, DGMT).
Prior trials suggest that intravenous racemic ketamine is a highly effective for treatment-resistant depression (TRD), but phase 3 trials of racemic ketamine are needed.
Aims
To assess the acute efficacy and safety of a 4-week course of subcutaneous racemic ketamine in participants with TRD. Trial registration: ACTRN12616001096448 at www.anzctr.org.au.
Method
This phase 3, double-blind, randomised, active-controlled multicentre trial was conducted at seven mood disorders centres in Australia and New Zealand. Participants received twice-weekly subcutaneous racemic ketamine or midazolam for 4 weeks. Initially, the trial tested fixed-dose ketamine 0.5 mg/kg versus midazolam 0.025 mg/kg (cohort 1). Dosing was revised, after a Data Safety Monitoring Board recommendation, to flexible-dose ketamine 0.5–0.9 mg/kg or midazolam 0.025–0.045 mg/kg, with response-guided dosing increments (cohort 2). The primary outcome was remission (Montgomery-Åsberg Rating Scale for Depression score ≤10) at the end of week 4.
Results
The final analysis (those who received at least one treatment) comprised 68 in cohort 1 (fixed-dose), 106 in cohort 2 (flexible-dose). Ketamine was more efficacious than midazolam in cohort 2 (remission rate 19.6% v. 2.0%; OR = 12.1, 95% CI 2.1–69.2, P = 0.005), but not different in cohort 1 (remission rate 6.3% v. 8.8%; OR = 1.3, 95% CI 0.2–8.2, P = 0.76). Ketamine was well tolerated. Acute adverse effects (psychotomimetic, blood pressure increases) resolved within 2 h.
Conclusions
Adequately dosed subcutaneous racemic ketamine was efficacious and safe in treating TRD over a 4-week treatment period. The subcutaneous route is practical and feasible.
There is mounting interest in the potential efficacy of low carbohydrate and very low carbohydrate ketogenic diets in various neurological and psychiatric disorders.
Aims
To conduct a systematic review and narrative synthesis of low carbohydrate and ketogenic diets (LC/KD) in adults with mood and anxiety disorders.
Method
MEDLINE, Embase, PsycINFO and Cochrane databases were systematically searched for articles from inception to 6 September 2022. Studies that included adults with any mood or anxiety disorder treated with a low carbohydrate or ketogenic intervention, reporting effects on mood or anxiety symptoms were eligible for inclusion. PROSPERO registration CRD42019116367.
Results
The search yielded 1377 articles, of which 48 were assessed for full-text eligibility. Twelve heterogeneous studies (stated as ketogenic interventions, albeit with incomplete carbohydrate reporting and measurements of ketosis; diet duration: 2 weeks to 3 years; n = 389; age range 19 to 75 years) were included in the final analysis. This included nine case reports, two cohort studies and one observational study. Data quality was variable, with no high-quality evidence identified. Efficacy, adverse effects and discontinuation rates were not systematically reported. There was some evidence for efficacy of ketogenic diets in those with bipolar disorder, schizoaffective disorder and possibly unipolar depression/anxiety. Relapse after discontinuation of the diet was reported in some individuals.
Conclusions
Although there is no high-quality evidence of LC/KD efficacy in mood or anxiety disorders, several uncontrolled studies suggest possible beneficial effects. Robust studies are now needed to demonstrate efficacy, to identify clinical groups who may benefit and whether a ketogenic diet (beyond low carbohydrate) is required and to characterise adverse effects and the risk of relapse after diet discontinuation.
There is a consensus in psycholinguistic research that listening to unfamiliar speech constitutes a challenging listening situation. In this commentary, we explore the problems with the construct of non-native and ask whether using this construct in research is useful, specifically to shift the communicative burden from the language learner to the perceiver, who often occupies a position of power. We examine what factors affect perception of non-native talkers. We frame this question by addressing the observation that not all “difficult” listening conditions provide equal challenges. Given this, we ask how cognitive and social factors impact perception of unfamiliar accents and ask what our psycholinguistic measurements are capturing. We close by making recommendations for future work. We propose that the issue is less with the terminology of native versus non-native, but rather how our unexamined biases affect the methodological assumptions that we make. We propose that we can use the existing dichotomy to create research programs that focus on teaching perceivers to better understand talkers more generally. Finally, we call on perceivers and researchers alike to question the idea of speech being “native,” “non-native,” “unfamiliar,” and “accented” to better align with reality as opposed to our inherently biased views.
This article is a clinical guide which discusses the “state-of-the-art” usage of the classic monoamine oxidase inhibitor (MAOI) antidepressants (phenelzine, tranylcypromine, and isocarboxazid) in modern psychiatric practice. The guide is for all clinicians, including those who may not be experienced MAOI prescribers. It discusses indications, drug-drug interactions, side-effect management, and the safety of various augmentation strategies. There is a clear and broad consensus (more than 70 international expert endorsers), based on 6 decades of experience, for the recommendations herein exposited. They are based on empirical evidence and expert opinion—this guide is presented as a new specialist-consensus standard. The guide provides practical clinical advice, and is the basis for the rational use of these drugs, particularly because it improves and updates knowledge, and corrects the various misconceptions that have hitherto been prominent in the literature, partly due to insufficient knowledge of pharmacology. The guide suggests that MAOIs should always be considered in cases of treatment-resistant depression (including those melancholic in nature), and prior to electroconvulsive therapy—while taking into account of patient preference. In selected cases, they may be considered earlier in the treatment algorithm than has previously been customary, and should not be regarded as drugs of last resort; they may prove decisively effective when many other treatments have failed. The guide clarifies key points on the concomitant use of incorrectly proscribed drugs such as methylphenidate and some tricyclic antidepressants. It also illustrates the straightforward “bridging” methods that may be used to transition simply and safely from other antidepressants to MAOIs.
Psilocybin is a tryptamine alkaloid found in some mushrooms, especially those of the genus Psilocybe. Psilocybin has four metabolites including the pharmacologically active primary metabolite psilocin, which readily enters the systemic circulation. The psychoactive effects of psilocin are believed to arise due to the partial agonist effects at the 5HT2A receptor. Psilocin also binds to various other receptor subtypes although the actions of psilocin at other receptors are not fully explored. Psilocybin administered at doses sufficient to cause hallucinogenic experiences has been trialed for addictive disorders, anxiety and depression. This review investigates studies of psilocybin and psilocin and assesses the potential for use of psilocybin and a treatment agent in neuropsychiatry. The potential for harm is also assessed, which may limit the use of psilocybin as a pharmacotherapy. Careful evaluation of the number needed to harm vs the number needed to treat will ultimately justify the potential clinical use of psilocybin. This field needs a responsible pathway forward.
Shade coffee is a well-studied cultivation strategy that creates habitat for tropical birds while also maintaining agricultural yield. Although there is a general consensus that shade coffee is more “bird-friendly” than a sun coffee monoculture, little work has investigated the effects of specific shade tree species on insectivorous bird diversity. This study involved avian foraging observations, mist-netting data, temperature loggers, and arthropod sampling to investigate bottom-up effects of two shade tree taxa - native Cordia sp. and introduced Grevillea robusta - on insectivorous bird communities in central Kenya. Results indicate that foliage-dwelling arthropod abundance, and the richness and overall abundance of foraging birds were all higher on Cordia than on Grevillea. Furthermore, multivariate analyses of the bird community indicate a significant difference in community composition between the canopies of the two tree species, though the communities of birds using the coffee understorey under these shade trees were similar. In addition, both shade trees buffered temperatures in coffee, and temperatures under Cordia were marginally cooler than under Grevillea. These results suggest that native Cordia trees on East African shade coffee farms may be better at mitigating habitat loss and attracting insectivorous birds that could promote ecosystem services. Identifying differences in prey abundance and preferences in bird foraging behaviour not only fills basic gaps in our understanding of the ecology of East African coffee farms, it also aids in developing region-specific information to optimize functional diversity, ecosystem services, and the conservation of birds in agricultural landscapes.
This study aimed to explore effects of adjunctive minocycline treatment on inflammatory and neurogenesis markers in major depressive disorder (MDD). Serum samples were collected from a randomised, placebo-controlled 12-week clinical trial of minocycline (200 mg/day, added to treatment as usual) for adults (n = 71) experiencing MDD to determine changes in interleukin-6 (IL-6), lipopolysaccharide binding protein (LBP) and brain derived neurotrophic factor (BDNF). General Estimate Equation modelling explored moderation effects of baseline markers and exploratory analyses investigated associations between markers and clinical outcomes. There was no difference between adjunctive minocycline or placebo groups at baseline or week 12 in the levels of IL-6 (week 12; placebo 2.06 ± 1.35 pg/ml; minocycline 1.77 ± 0.79 pg/ml; p = 0.317), LBP (week 12; placebo 3.74 ± 0.95 µg/ml; minocycline 3.93 ± 1.33 µg/ml; p = 0.525) or BDNF (week 12; placebo 24.28 ± 6.69 ng/ml; minocycline 26.56 ± 5.45 ng/ml; p = 0.161). Higher IL-6 levels at baseline were a predictor of greater clinical improvement. Exploratory analyses suggested that the change in IL-6 levels were significantly associated with anxiety symptoms (HAMA; p = 0.021) and quality of life (Q-LES-Q-SF; p = 0.023) scale scores. No other clinical outcomes were shown to have this mediation effect, nor did the other markers (LBP or BDNF) moderate clinical outcomes. There were no overall changes in IL-6, LBP or BDNF following adjunctive minocycline treatment. Exploratory analyses suggest a potential role of IL-6 on mediating anxiety symptoms with MDD. Future trials may consider enrichment of recruitment by identifying several markers or a panel of factors to better represent an inflammatory phenotype in MDD with larger sample size.
Many mental disorders, including depression, bipolar disorder and schizophrenia, are associated with poor dietary quality and nutrient intake. There is, however, a deficit of research looking at the relationship between obsessive–compulsive disorder (OCD) severity, nutrient intake and dietary quality.
Aims
This study aims to explore the relationship between OCD severity, nutrient intake and dietary quality.
Method
A post hoc regression analysis was conducted with data combined from two separate clinical trials that included 85 adults with diagnosed OCD, using the Structured Clinical Interview for DSM-5. Nutrient intakes were calculated from the Dietary Questionnaire for Epidemiological Studies version 3.2, and dietary quality was scored with the Healthy Eating Index for Australian Adults – 2013.
Results
Nutrient intake in the sample largely aligned with Australian dietary guidelines. Linear regression models adjusted for gender, age and total energy intake showed no significant associations between OCD severity, nutrient intake and dietary quality (all P > 0.05). However, OCD severity was inversely associated with caffeine (β = −15.50, 95% CI −28.88 to −2.11, P = 0.024) and magnesium (β = −6.63, 95% CI −12.72 to −0.53, P = 0.034) intake after adjusting for OCD treatment resistance.
Conclusions
This study showed OCD severity had little effect on nutrient intake and dietary quality. Dietary quality scores were higher than prior studies with healthy samples, but limitations must be noted regarding comparability. Future studies employing larger sample sizes, control groups and more accurate dietary intake measures will further elucidate the relationship between nutrient intake and dietary quality in patients with OCD.
One of the basic goals of second language (L2) speech research is to understand the perception-production link, or the relationship between L2 speech perception and L2 speech production. Although many studies have examined the link, they have done so with strikingly different conceptual foci and methods. Even studies that appear to use similar perception and production tasks often present nontrivial differences in task characteristics and implementation. This conceptual and methodological variation makes meaningful synthesis of perception-production findings difficult, and it also complicates the process of developing new perception-production models that specifically address how the link changes throughout L2 learning. In this study, we scrutinize theoretical and methodological issues in perception-production research and offer recommendations for advancing theory and practice in this domain. We focus on L2 sound learning because most work in the area has focused on segmental contrasts.
Obsessive–compulsive disorder (OCD) is often challenging to treat and resistant to psychological interventions and prescribed medications. The adjunctive use of nutraceuticals with potential neuromodulatory effects on underpinning pathways such as the glutamatergic and serotonergic systems is one novel approach.
Objective
To assess the effectiveness and safety of a purpose-formulated combination of nutraceuticals in treating OCD: N-acetyl cysteine, L-theanine, zinc, magnesium, pyridoxal-5′ phosphate, and selenium.
Methods
A 20-week open label proof-of-concept study was undertaken involving 28 participants with treatment-resistant DSM-5-diagnosed OCD, during 2017 to 2020. The primary outcome measure was the Yale-Brown Obsessive–Compulsive Scale (YBOCS), administered every 4 weeks.
Results
An intention-to-treat analysis revealed an estimated mean reduction across time (baseline to week-20) on the YBOCS total score of −7.13 (95% confidence interval = −9.24, −5.01), with a mean reduction of −1.21 points per post-baseline visit (P ≤ .001). At 20-weeks, 23% of the participants were considered “responders” (YBOCS ≥35% reduction and “very much” or “much improved” on the Clinical Global Impression-Improvement scale). Statistically significant improvements were also revealed on all secondary outcomes (eg, mood, anxiety, and quality of life). Notably, treatment response on OCD outcome scales (eg, YBOCS) was greatest in those with lower baseline symptom levels, while response was limited in those with relatively more severe OCD.
Conclusions
While this pilot study lacks placebo-control, the significant time effect in this treatment-resistant OCD population is encouraging and suggests potential utility especially for those with lower symptom levels. Our findings need to be confirmed or refuted via a follow-up placebo-controlled study.
The bulk of the work on non-native speech has focused on average differences between L1 and L2 speakers. However, there is growing evidence that variability also plays an important role in distinguishing L1 from L2 speech. While some studies have demonstrated greater variability for non-native than native speech (e.g., Baese-Berk & Morrill, 2015; Wade et al., 2007), others have demonstrated that under some circumstances non-native speech maybe less variable and that variability in non-native speech may shift as a function of many factors, including task (Baese-Berk & Morrill, to appear; Baese-Berk, Morrill, & Bradlow, 2016) and L1-L2 pairing (Vaughn, Baese-Berk, & Idemaru, to appear). In the present study, we ask how variability manifests in L1 and L2 speech by speakers from a variety of language backgrounds. Specifically, we ask whether a speaker whose L1 speaking rate is highly variable is also highly variable in their L2. We also ask whether variability in speaking rate in L1 or L2 differs as a function of task (e.g., read vs. spontaneous speech) and complexity of the task (e.g., more or less complicated reading passages). The results of this study will inform our understanding of the myriad complex factors that influence non-native speech.
The aims of this study were to evaluate changes in inflammatory and oxidative stress levels following treatment with N-acetylcysteine (NAC) or mitochondrial-enhancing agents (CT), and to assess the how these changes may predict and/or moderate clinical outcomes primarily the Montgomery-Åsberg Depression Rating Scale (MADRS).
Methods:
This study involved secondary analysis of a placebo-controlled randomised trial (n = 163). Serum samples were collected at baseline and week 16 of the clinical trial to determine changes in Interleukin-6 (IL-6) and total antioxidant capacity (TAC) following adjunctive CT and/or NAC treatment, and to explore the predictability of the outcome or moderator effects of these markers.
Results:
In the NAC-treated group, no difference was observed in serum IL-6 and TAC levels after 16 weeks of treatment with NAC or CT. However, results from a moderator analysis showed that in the CT group, lower IL-6 levels at baseline was a significant moderator of MADRS χ2 (df) = 4.90, p = 0.027) and Clinical Global Impression-Improvement (CGI-I, χ2 (df) = 6.28 p = 0.012). In addition, IL-6 was a non-specific but significant predictor of functioning (based on the Social and Occupational Functioning Assessment Scale (SOFAS)), indicating that individuals with higher IL-6 levels at baseline had a greater improvement on SOFAS regardless of their treatment (p = 0.023).
Conclusion:
Participants with lower IL-6 levels at baseline had a better response to the adjunctive treatment with the mitochondrial-enhancing agents in terms of improvements in MADRS and CGI-I outcomes.
Little is known about the early phases of bipolar disorders (BPAD) and most of current knowledge derives from putative “high-risk” studies conducted in populations of bipolar off-spring; such information may therefore be relevant only to a subgroup of at-risk subjects.
Methods
Retrospective assessment of the phase preceding the emergence of mania and of premorbid characteristics of patients treated for a first episode of psychotic mania. The collected data was used mainly to generate hypotheses.
Results
Before onset of a first episode of psychotic mania, patients go through a phase of change from previous mental state where they present mood symptoms, sleep disruption and general functional decline. These clinical manifestations are likely to have low specificity. However, their occurrence in patients presenting certain risk factors or markers of vulnerability that were identified at a relatively high prevalence in our sample, may be an indicator of impending first episode mania.
Limitations
This is a retrospective study, in a small sample of patients presenting with psychotic mania. Criteria identified need therefore to be validated in larger prospective studies.
Conclusions
Early identification of patients at risk to develop a first episode of psychotic mania is unlikely to be possible on the basis of symptoms alone. However, the occurrence of certain clinical characteristics in patients who have risk factors or markers of vulnerability to BPAD may be a sign of impending first episode mania.
We have developed ultra-high risk criteria for bipolar affective disorder (bipolar at-risk - BAR) which include general criteria such as being in the peak age range of the onset of the disorder and a combination of specific criteria including sub-threshold mania, depressive symptoms, cyclothymic features and genetic risk. In the current study, the predictive and discriminant validity of these criteria were tested in help seeking adolescents and young adults.
Method:
This medical file-audit study was conducted at ORYGEN Youth Health (OYH), a public mental health program for young people aged between 15 and 24 years and living in metropolitan Melbourne, Australia. BAR criteria were applied to the intake assessments of all non-psychotic patients who were being treated in OYH on 31 January.08. All entries were then checked for conversion criteria. Hypomania/mania related additions or alterations to existing treatments or initiation of new treatment by the treating psychiatrist served as conversion criteria to mania.
Results:
The BAR criteria were applied to 173 intake assessments. Of these, 22 patients (12.7%) met BAR criteria. The follow-up period of the sample was 265.5 days on average (SD 214.7). There were significantly more cases in the BAR group (22.7%, n = 5) than in the non-BAR group (0.7%, n = 1) who met conversion criteria (p < .001).
Conclusions:
These findings support the notion that people who develop a first episode of mania can be identified during the prodromal phase. The proposed criteria need further evaluation in prospective clinical trials.