Medical Bulletin 08/November/2025

Autism is a rising neurodevelopmental condition characterized by social and behavioral challenges, often accompanied by gastrointestinal issues and pronounced food selectivity. With past research hinting at links between microbiome composition and AUTISM SPECTRUM DISORDER symptoms, this study set out to disentangle the complex relationship between microbial communities, diet, and behavior in affected children versus their siblings and parents.

Researchers recruited 17 AUTISM SPECTRUM DISORDER children, 9 non-AUTISM SPECTRUM DISORDER siblings, and 27 parents from Italian families, extending dietary analysis to 79 individuals in total. Fecal samples were collected and analyzed using advanced DNA sequencing to assess both bacterial and fungal components of the microbiota. Seven-day food diaries and food-frequency questionnaires provided a detailed snapshot of dietary intake, categorized into eight food groups. Microbial diversity and community structure were evaluated using robust statistical approaches, with dietary and microbiome data integrated using linear mixed-effects models that controlled for shared genetics and environment within families.

Gut microbiome analysis showed no significant differences in bacterial or fungal diversity between children with AUTISM SPECTRUM DISORDER and their family members, contradicting some previous reports of microbiome “dysbiosis” in autism. However, dietary profiles differed markedly: AUTISM SPECTRUM DISORDER children ate more sugary foods and fewer vegetables than both siblings and parents, and these group-level dietary distinctions were statistically significant. Smaller differences in fruit and processed food intake mainly distinguished children from adults, rather than AUTISM SPECTRUM DISORDER from non-AUTISM SPECTRUM DISORDER.

The study’s strengths include its within-family design, which controls for genetics and environment, and its integration of both microbiome and dietary data. However, the small sample size and cross-sectional nature limit the ability to draw causal conclusions. Notably, some associations faded on more complex modeling, highlighting the need for larger studies.

Lead author Dr. Valentina Pontrelli notes that these results support a model in which dietary habits, influenced by AUTISM SPECTRUM DISORDER behaviors, may be the primary drivers of microbiome differences within families. Larger, multi-omic studies will be necessary to clarify whether subtle microbiome effects emerge when genetic and dietary variables are rigorously controlled, and to optimize dietary interventions for children with AUTISM SPECTRUM DISORDER.

REFERENCE: Di Benedetto, G., Sorge, G., Sarchiapone, M., & Di Martino, L. (2025). Dietary Patterns, Not Gut Microbiome Composition, Are Associated with Behavioral Challenges in Children with Autism: An Observational Study. Nutrients 17(21): 3476. DOI: 10.3390/nu17213476, https://www.mdpi.com/2072-6643/17/21/3476

Can creatine help with depression? New Review Finds Inconclusive Evidence

Scientists have explored creatine’s potential to alleviate depressive symptoms, presenting a comprehensive systematic review and meta-analysis published recently in the British Journal of Nutrition. Depression affects nearly 280 million people globally, with many facing inadequate treatment options that are often slow to take effect and burdened by adverse effects. Creatine, widely known for its role in enhancing physical performance, has drawn interest for its central involvement in brain energy metabolism—areas disrupted in depression.

Creatine supports brain energy homeostasis and neurotransmitter regulation, with lower brain creatine levels linked to depression and treatment resistance. Dietary creatine intake correlates inversely with depression prevalence, hinting at its therapeutic promise. Despite encouraging preclinical and clinical data, creatine is not yet included in major depression treatment guidelines.

The meta-analysis assessed randomized controlled trials (RCTs) comparing oral creatine supplementation to placebo, including studies with co-interventions like antidepressants or psychotherapy. Researchers pooled data using robust statistical models, evaluating risk of bias and the quality of evidence via GRADE criteria, and performed subgroup analyses by diagnosis and study bias risk.

From 11 eligible RCTs (mostly small, with fewer than 100 participants), creatine at a median dose of 5 grams daily was associated with a statistically significant but small reduction in depression symptom scores. However, study heterogeneity was substantial, and the overall certainty of evidence was very low. Higher-quality studies reported no effect, and correcting for publication bias further diminished the significance, suggesting possible overestimation of benefit.

Subgroup analyses indicated a larger effect in affective disorder populations versus healthy participants. Side effects were generally mild, mostly gastrointestinal, and a few trials reported slight increases in serum creatinine. One trial showed no quality-of-life improvement over five years.

While creatine supplementation may modestly reduce depressive symptoms, current evidence is inconclusive and likely biased. The observed effects fall below clinical significance thresholds, indicating they might not be detectable in practice. The authors call for larger, well-designed trials with rigorous blinding and minimal co-interventions to definitively assess creatine’s antidepressant efficacy, aiming to clarify its potential as a safe, adjunctive treatment for depression.

REFERENCE: Eckert I, Lima J, Dariva AA (2025). Creatine supplementation for treating symptoms of depression: a systematic review and meta-analysis. British Journal of Nutrition, 1-37. DOI: 10.1017/S0007114525105588, https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/creatine-supplementation-for-treating-symptoms-of-depression-a-systematic-review-and-metaanalysis/32402D649A44771955050ED518B6E564

Common Acne Drug May Offer Protection Against Schizophrenia: Study

Scientists have discovered a potential new use for a widely prescribed antibiotic: reducing the risk of schizophrenia in adolescents receiving mental health care. A recent study published in the American Journal of Psychiatry analyzed health records from more than 56,000 young psychiatric patients in Finland and found that those treated with doxycycline were 30-35% less likely to develop schizophrenia later in life compared to peers given other antibiotics.

Schizophrenia is a severe mental health disorder most commonly emerging in early adulthood and marked by hallucinations, delusions, and disorganized thinking. Preventing its onset has been a key goal for mental health research, especially in adolescents attending psychiatric services who are at elevated risk.

The collaborative study, led by researchers from the University of Edinburgh along with colleagues from the University of Oulu and University College Dublin, used advanced statistical models on comprehensive Finnish healthcare data. They tracked antibiotic prescriptions and subsequent schizophrenia diagnoses over many years, comparing risk among adolescents prescribed doxycycline—a broad-spectrum antibiotic widely used for infections and acne—with those receiving other antibiotics. Confounding factors were rigorously addressed to isolate doxycycline’s impact.

The research showed a significantly reduced risk of schizophrenia among doxycycline users, consistent across different dosage levels. Further analyses suggested this effect was unlikely due to acne treatment alone or hidden differences between groups. The authors hypothesize doxycycline’s neuroprotective role stems from its anti-inflammatory properties and influence on synaptic pruning—a brain developmental process implicated in schizophrenia when dysregulated.

Lead investigator Professor Ian Kelleher emphasized that while these observational findings cannot confirm causality, they provide a promising new direction for preventive therapies targeting inflammation in high-risk youth. The study highlights the potential to repurpose existing medications in adolescent psychiatry to mitigate severe mental illnesses, calling for future randomized controlled trials to validate doxycycline’s protective effect.

This discovery opens exciting possibilities for early intervention to reduce lifelong schizophrenia burden through safe, accessible treatments.

REFERENCE: Ulla Lång, Johanna Metsälä, Hugh Ramsay, Fiona Boland, Katriina Heikkilä, Anna Pulakka, Anne Lawlor, Karen O’Connor, Juha Veijola, Eero Kajantie, Colm Healy, Ian Kelleher. Doxycycline Use in Adolescent Psychiatric Patients and Risk of Schizophrenia: An Emulated Target Trial. American Journal of Psychiatry, 2025; DOI: 10.1176/appi.ajp.20240958