Neuropeptide Y (NPY) has been implicated in stress resilience and depression, yet findings on circulating levels in major depressive disorder (MDD) remain inconsistent, possibly due to confounders such as age, sex, and body mass index (BMI). This study aimed to assess NPY concentrations in individuals with MDD and in matched controls from the Danish PRISME cohort of public-sector employees.

We investigated plasma NPY (p-NPY) concentrations in 77 adults with a current ICD-10 diagnosis of MDD and 77 age- and sex-matched controls. The plasma samples were analysed using a commercial ELISA kit. A general linear model examined the effects of group, age, sex, and BMI, including a sex-by-group interaction. Plasma NPY values were log10-transformed prior to analysis.

p-NPY concentrations did not differ significantly between MDD and controls (p = .785). No main effect of sex or sex-by-group interaction was observed (all p > .17), and BMI was unrelated to p-NPY (p = .917). By contrast, age was a strong predictor (β = .38, p < .001), explaining 13% of the variance in p-NPY levels.

In this community-based sample of high-functioning individuals with MDD, we found no evidence of altered p-NPY concentrations compared with matched controls. Instead, age emerged as a robust determinant of circulating NPY levels, independent of depression status and BMI, after adjustment for sex. These findings suggest that peripheral NPY variation may be more strongly related to demographic factors than to depression per se in this type of cohort and may not generalise to more severe or chronic forms of the disorder.

Dementia is a group of symptoms, characterized by a loss of cognition that interferes with everyday tasks, difficulty focusing, planning, problem solving, and behavioral changes, such as apathy, anxiety, or depression. The leading cause of dementia is Alzheimer’s disease, but vascular dementia or mild cognitive impairment are also frequently occurring. There are six drugs legislated in Europe for use in the treatment of dementia. There are unmet clinical needs to find more effective, better tolerated or complementary therapeutic options. The aim of this study is to comprehensively analyze the results of clinical trials and other human studies regarding the efficacy and safety of herbal interventions used in patients with dementia.

We enrolled a total of 48 studies for this systematic review, of which 27 were included into the statistical analysis of effect size (Cohen’s d).

We found significant improvements mainly after administration of Ginkgo biloba, Crocus sativus, Salvia officinalis, and Melissa officinalis.It should be emphasized that some herbs and herbal formulations demonstrated efficacy comparable to that of donepezil, a widely used and approved medication, suggesting potential for phytopharmaceutical therapies as complementary approaches. In some studies, the observed effects were similar to those reported for conventional treatments, indicating promising directions for further research in Alzheimer’s disease and dementia.

In light of the evidence, phytopharmaceuticals have a promising role as a co-therapeutic option or alternative for patients with dementia who do not tolerate or have contraindications to standard medications. However, further research is necessary to translate these initial promising results into clinical practice.

Phytopharmaceuticals have a promising role as a complementary or alternative option for dementia patients who cannot tolerate or respond to standard medications. Certain phytopharmaceuticals demonstrated comparable short-term symptomatic effects to standard treatments in small trials; however, evidence is insufficient to support equivalence or superiority.

Many of the studies reviewed are limited by very small sample sizes, which is associated with a high risk of bias when interpreting large effect sizes (Cohen’s d). The short duration of interventions (often only 3 to 6 months) is insufficient to assess whether phytotherapeutics can constitute disease-modifying treatments (DMTs).

In Africa, bewitchment is described as a moral framework that helps individuals and societies make sense out of disease and misfortune. Numerous African belief systems attribute difficult-to-treat health problems to bewitchment, rather than a conventional medical diagnosis, especially if biomedical doctors are unable to resolve the condition. This study examines one such illness, known as xifula, in rural Limpopo Province, South Africa.

Using convenience sampling, 95 participants (≥18 years old) were interviewed to gauge their knowledge of the condition known as xifula. Data was analysed using NVivo software.

Xifula is a cultural concept of distress related to bewitchment. The most common symptom of xifula is swelling of the legs or hands, followed by chronic headaches. Participants noted that xifula can start as a minor ailment, but then grows into a larger problem. After a long period without healing, however, xifula can begin to represent a significant threat to the individual’s health. Nearly all participants noted that xifula cannot be treated by Western biomedical professionals and instead requires a traditional healer to treat the condition.

This research highlights the importance of context-specific education about the diagnosis and treatment of common ailments, as beliefs about afflictions, their causes, and appropriate treatments suggest a need for tailored information. As biomedical and traditional healthcare currently exist as parallel, siloed structures of diagnosis and treatment in Africa, there should also be efforts to bridge the divide between the two.

This study was funded by a grant from the John Templeton Foundation.

Patients with Parkinson’s disease (PD) suffer from interrelated motor and non-motor symptoms. While most research focuses on motor improvement, this study investigated whether targeting mood via sequential bilateral dorsolateral prefrontal cortex (DLPFC) tDCS could favorably affect motor function in patients maintaining a stable medication ‘ON’ state. Additionally, we employed wearable smart devices to objectively evaluate real-world changes in daily activity and sleep patterns, complementing traditional clinician-rated scales.

PD patients with mild-to-moderate depressive symptoms were enrolled. All participants completed a 7-day baseline monitoring period using a smart band. Participants received ten sessions of bilateral tDCS targeting the DLPFC (anode F3, cathode F4) at 2 mA for 30 minutes, three times a week. Clinical assessments and smart band monitoring were repeated during the final week of treatment. Pre–post changes and correlations were analyzed while controlling for potential confounders.

Following tDCS, it was significant improvements in K-MADRS, STAI, AS, UPDRS part III, and PDQ-39. Smart device data showed a significant increase in daily step counts after treatment, while changes in physical activity time and sleep duration were not significant. Changes in step count were strongly correlated with improvements in apathy, and this relationship remained significant after confounding variables (rho = –0.76, p < 0.001).

Bilateral DLPFC tDCS significantly improved mood and motor function in patients with PD. Smart band data further showed an increase in daily step counts after the intervention, with reductions in apathy. These findings suggest that tDCS may enhance goal-directed behavior by modulating mood-related pathways, highlighting apathy as an important therapeutic target in PD.

Estimating the prevalence of use of substances such as heroin remains a challenge. The aim of this study is to identify the scientific publications in Spain that have used surveys to investigate heroin use, to describe their methodology and to contrast the formulation of the questions with users’ input on key aspects associated with use.

A scoping review was conducted until November 2024 in MEDLINE (Ovid), EMBASE and Web of Science. The review included questionnaire-based research studies assessing heroin use in Spain. Information on study, population, data collection and consumption characteristics was compiled from each included study. In addition, in-depth interviews were conducted with Spanish heroin current users and ex-users.

Twenty-nine questionnaire-based research studies assessing heroin use in Spain were identified, none of them were specifically oriented to estimate and characterize heroin use at the population level. Most of the studies focused on specific population groups, mainly drug users, students, or inmates. The majority addressed lifetime, past-year, and past-month use, although users found the past 3 or 6 months more relevant. Few studies explored other use characteristics; however, interviews with heroin ex-users highlighted the importance of factors like route of administration and age of first use.

Studies on heroin use differ in terms of population, geographic scope, time frame, and data collection methods. Incorporating users’ perspectives in the design of surveys is essential to enhance standardization and optimize data comparability.

We tested the hypothesis that resuming dietary control in early-treated phenylketonuria (PKU) is associated with improvements in white matter integrity, using data from the ReDAPT study, which previously demonstrated cognitive and psychiatric improvements with reduced phenylalanine (Phe) levels.

We re-initiated dietary control for early-treated patients with PKU and assessed the T1w/T2w ratio from standard T1- and T2-weighted magnetic resonance images, a marker of myelination and microstructural integrity. General linear mixed model (GLMM) analyses were performed to assess change in the T1w/T2w ratio from baseline over twelve months after resumption of dietary control.

Seven participants (mean age 31 years; five female) with neuroimaging were included, with a mean of 16 years off diet and baseline Phe levels of 1157 µmol/L. GLMM analyses showed significant increases in T1w/T2w ratio over time for the whole brain (β = 0.47 [95%CI = 0.28, 0.66]), left hemisphere (β = 0.36 [95%CI = 0.19, 0.54]), and right hemisphere regions of interest (β = 0.52 [95%CI = 0.30, 0.72]). Longer time off diet was also positively associated with greater T1w/T2w changes. There was no evidence for the effects of gender or age at baseline.

This study demonstrated significant increases in the T1w/T2w ratio in PKU patients as they resumed dietary control over a 12-month period. Raw Phe levels were not strongly associated with neuroimaging measures. These findings support the importance of lifelong treatment for PKU, and also demonstrate the potential reversibility of white matter changes in the disease.

Psychedelics such as psilocybin are known for their hallucinogenic properties and have also been reported to produce long-lasting therapeutic effects in depression and possibly also other psychiatric disorders. Several lines of evidence suggest that psilocybin exerts its effects through activation of 5-HT2A receptors located postsynaptically to serotonergic neurons, e.g., in the frontal cortex, parts of the limbic system, including the amygdala and hippocampus, and striatum. The present study was conducted to shed further light on psilocybin-induced changes in gene expression.

Samples from the medial prefrontal cortex, cingulate cortex, hippocampus, amygdala, and striatum were collected from 24 male Wistar rats 90 minutes after they had been injected with either saline or psilocybin (2 mg/kg) and subjected to multi-region transcriptional profiling using 3prime-RNASeq technology.

Nfkbia and Sgk1 were upregulated in all the studied regions, Ddit4 was upregulated in four regions, and Gpd1, Apold1, Sox9, Tsc22d3, and Slc2a1 were differentially expressed in two regions. Other cases of differentially expressed genes were region-specific.

Whereas psilocybin was not found to alter the expression of genes encoding enzymes, transporters, or receptors implicated in the serotonergic signaling, or those specifically involved in the regulation of the synaptic activity of other neurotransmitters, a common denominator for many of the genes impacted by psilocybin is that they have previously been found to be activated by glucocorticoids.

There are differences in IgA responses to tryptophan catabolites (TRYCATs) in major neurocognitive psychosis (MNP) versus simple neurocognitive psychosis (SNP) and normal controls. MNP and SNP are distinct schizophrenia classes which are differentiated by neurocognitive deficits, phenome features, and biomarker pathways. Nevertheless, there is no data on serum concentrations of those TRYCATs in MNP and SNP. The aim of the present study is to examine serum concentrations of tryptophan and TRYCATs in MNP versus SNP and controls.

This case-control study examines serum levels of tryptophan and TRYCATs in 52 MNP patients, 68 SNP patients and 60 controls in association with overall severity of schizophrenia (OSOS).

MNP patients show lower tryptophan, kynurenic acid (KA), 3-OH-anthranilic acid (3HAA), and higher anthranilic acid (AA) and quinolinic acid (QA) than SNP patients and controls. There were no differences between SNP and controls in these TRYCATs. Kynurenine (KYN) was lower in MNP+SNP than in controls. We found that 36.5% of the variance in OSOS was explained by the combined effects of lowered tryptophan, KA, and 3-HK, and increased QA and AA. The most important biomarkers of MNP and OSOS were the QA/KA ratio followed by the QA/3HAA ratio.

The alterations in serum TRYCAT levels further emphasize that MNP and SNP represent two biologically distinct subtypes of schizophrenia. The reductions in TRYCATs diminish the antioxidant and immunoregulatory functions of the TRYCAT pathway. Elevated QA levels may exacerbate the disruption of the blood-brain barrier and the immune-related and oxidative neurotoxicity in MNP.