This study aimed to evaluate the diagnostic and surveillance performance of circulating tumour human papillomavirus DNA for post-treatment monitoring of human papilloma virus–positive oropharyngeal squamous cell carcinoma.

Systematic review and meta-analysis of prospective studies (2019–2024) identified from PubMed, Web of Science and Scopus. Random-effects models were used to pool circulating tumour human papillomavirus DNA detectability and summarise lead-times to recurrence.

Fifteen studies (n=1,447) were included; 10 cohorts (n=731) entered the quantitative meta-analysis. Pooled baseline detectability was 85.5 per cent (95 per cent confidence interval 78.2–90.6). Circulating tumour human papillomavirus DNA positivity preceded clinical recurrence by a mean of 76.8 days (median 87.5). Specificity and negative predictive value were consistently high, whereas sensitivity varied by assay platform and sampling frequency.

Serial circulating tumour human papilloma virus DNA testing is a reliable adjunct to post-treatment surveillance in HPV-positive oropharyngeal squamous cell carcinoma, offering a clinically meaningful lead-time to recurrence. Standardised assays and multicentre validation are warranted.

Evaluating pauses in natural speech is a promising strategy for improving reliability, validity, and efficiency in assessing cognitive functions in people with mild cognitive impairment (MCI) and Alzheimer’s dementia (AD).

We conducted a quantitative meta-analysis of studies employing automated pause analysis. We included measures of speaking rate for comparison.

We identified 13 studies evaluating pause measures and 8 studies of speaking rate in people with MCI (n’s = 276 & 109, respectively) and AD (n’s = 170 & 81, respectively) and healthy aged controls (n’s = 492 & 231, respectively). Studies evaluated speech across various tasks, including standard neuropsychological, reading, and free/conversational tasks. People with AD and MCI showed longer pauses than controls at approximately 1.20 and 0.62 standard deviations, respectively, though there was substantial heterogeneity across studies. A more modest effect, of 0.66 and 0.27 SDs, was observed between these groups in speech rate. The largest effects were observed for standardized memory tasks.

Of the many ways that speech can be objectified, pauses appear particularly important for understanding cognition in AD. Pause analysis has the benefit of being face valid, interpretable in ratio format as a reaction time, tied to known socio-cognitive functions, and relatively easy to measure, compute, and interpret. Automation of speech analysis can greatly expand the assessment of AD and potentially improve early identification of one of the most devastating and costly diseases affecting humans.

Alterations in the central and peripheral energy metabolism are increasingly recognized as key pathophysiological processes in psychiatric disorders. We investigated mitochondrial respiration and density linked to cellular energy metabolism and oxidative DNA damage in borderline personality disorder (BPD).

This cross-sectional case–control study compared three groups matched for age and body mass index: women with acute BPD, remitted BPD, and female healthy controls (n = 32, 15, 29). Peripheral blood mononuclear cells were investigated for differences in mitochondrial respiration, density, and markers of oxidative DNA damage.

Participants with acute BPD showed significantly reduced and less efficient mitochondrial ATP production compared to both remitted individuals and controls. Mitochondrial coupling and respiration were inversely associated with oxidative DNA damage, although DNA damage levels did not differ significantly across diagnostic groups. Sensitivity analyses indicated that comorbid major depressive episodes and antidepressant use did not account for the results.

These findings indicate mitochondrial alterations accompany acute symptom severity in BPD and may improve with remission. Unraveling causes and consequences of mitochondrial downregulation and its interplay with DNA maintenance in the context of stress and psychopathology could contribute to novel models and treatment strategies in BPD and related severe psychiatric disorders.

Respiratory diseases are increasing global health burden with persistently high morbidity and mortality. Extracellular vesicles (EVs), which are virtually released by all cell types and carry a variety of molecules like miRNAs, have emerged as crucial mediators of intercellular communication. They play a key role in maintaining lung homeostasis and are involved in the pathogenesis of various respiratory conditions. Furthermore, mesenchymal stromal cell-derived EVs (MSC-EVs) have shown significant therapeutic potential due to their anti-inflammatory, antimicrobial, and reparative properties.

This narrative review critically assesses the current body of literature on the roles of EVs in respiratory diseases. We examine evidence from pre-clinical and clinical studies that investigate EVs as biomarkers and therapeutics for conditions including asthma, bronchopulmonary dysplasia (BPD), chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), idiopathic pulmonary fibrosis (IPF), lung cancer, and pulmonary arterial hypertension (PAH).

EVs reflect the physiological or pathological state of their parental cells, making them promising multimodal biomarkers for the early diagnosis and monitoring of disease progression. Additionally, MSC-EVs function as effective, cell-free therapeutic agents. In a variety of disease models, they demonstrate efficacy by modulating immune responses, enhancing alveolar fluid clearance, and restoring epithelial and endothelial barrier integrity, leading to improved survival and outcomes.

EVs hold a dual and transformative potential in respiratory medicine. They may serve as valuable diagnostic and prognostic tools, and their application as cell-free therapeutics represents a novel and promising strategy for treating a wide spectrum of debilitating respiratory diseases.

While biomarkers are widely used in other medical fields, psychiatry has yet to introduce reliable biological diagnostic tools. Female reproductive transitions provide a unique window of opportunity for investigating psychiatric biomarkers. Hormonal changes across menstruation, pregnancy, parturition and perimenopause can have dramatic effects on mental health in vulnerable individuals, enabling the identification of unique biomarkers associated with these fluctuations.

This review integrates current evidence concerning potential biomarkers, with focus on recent human studies in perinatal depression, anxiety and obsessive–compulsive disorder, postpartum psychosis, premenstrual dysphoric disorder and perimenopausal depression.

We identified potential articles to be included in this narrative review by using PubMed to obtain articles in English since 2010 on the six conditions listed above, with the additional keywords of ‘biomarker’, ‘epigenetics’, ‘neuroactive steroid’, ‘immune’, ‘inflammatory’ and ‘neuroimaging’.

There is substantial published evidence regarding potential biomarkers of reproductive psychiatric disorders in the areas of epigenetics, neuroactive steroids, immune function and neuroimaging. This body of research holds significant potential to advance biomarker development, uncover disease mechanisms and improve diagnostic and therapeutic strategies, but there is as yet no clinically useful biomarker in commercial development for any reproductive psychiatric disorder.

There is an urgent need for longitudinal, large-scale and multi-modal studies to examine potential biomarkers and better understand their functions across various stages of reproduction.

The neurobiological basis of suicidal behaviour remains poorly understood. However, emerging evidence suggests that inflammation and vascular homeostasis factors may play a role in its pathophysiology. Childhood trauma, through immune system dysfunction and increased risk of suicidal behaviours, might influence these associations. This study examined the relationships between immune-inflammatory and vascular homeostasis-related markers and their interaction with childhood trauma in relation to a history of suicide attempts in individuals with depression.

A total of 328 patients with major depression were recruited: 166 with a history of suicide attempts and 162 without. Using multivariate binary logistic regression models adjusted for cofounders, we examined the associations between childhood trauma, levels of platelet-related immune markers (serotonin, MCP-1, TSP-1, TSP-2, PDGF-AB, PDGF-BB), and suicide attempt history. Independent associations between PDGF-BB, childhood trauma, and suicide attempts were further assessed using interaction models. Stratified sensitivity analyses based on childhood trauma history were also conducted.

Childhood trauma consistently emerged as associated with suicide attempts across all models. Among the measured biomarkers, higher TSP-2 levels were associated with a suicide attempt history, independent of childhood trauma. Meanwhile, while PDGF-BB alone was not directly linked to suicide attempt history, the interaction analysis revealed that individuals with lower PDGF-BB levels and more severe childhood trauma were more likely to have attempted suicide.

TSP-2 and PDGF-BB are potential biomarkers linked to suicide attempts, with distinct roles in the interplay between biological processes and early-life adversity. These insights can inform the biomarker-informed development of tailored prevention and treatment strategies.

C-reactive protein (CRP) level in blood is a standard marker for systemic inflammation. Inflammation is central in chronic subdural hematoma (CSDH) pathophysiology, and inflammatory biomarkers may hold clinical potential in assessing the level of inflammation induced by a CSDH. This study explores the role of CRP in patients with CSDH by (1) measuring systemic and subdural CRP levels, (2) investigating CRP as a potential predictor for recurrent CSDH and (3) comparing CRP levels between the first and second operations in patients with CSDH recurrence.

CRP levels were measured both in systemic blood and subdural fluid from adult CSDH patients. Recurrence rate and mortality within 90 days were recorded. In total, 111 patients were included, of whom 25 were operated on for CSDH recurrence.

Systemic CRP levels (2.54 mg/L (1.40–9.75)) were higher than subdural levels (2.09 mg/L [0.99–5.22]) (p < 0.0001) but within the clinically defined normal CRP range of < 3 mg/L. Neither systemic nor subdural CRP levels could predict recurrence. Both systemic and subdural CRP levels in recurrent CSDH patients were higher at the time of the second surgery compared to the first surgery (psystemic = 0.004 and psubdural < 0.0001).

This is the first study to establish a correlation between systemic and subdural CRP levels in CSDH patients. The increased levels of CRP at the time of the second surgery may demonstrate a constantly evolving inflammatory process toward the development of a recurrence.

Immune dysregulation appears involved in affective disorder pathophysiology. Inflammatory biomarkers have been linked with the cognitive impairment observed in people with bipolar disorders and as such are candidate markers that may improve with, and/or predict outcomes to, cognitive remediation therapies (CRT).

Nine candidate biomarkers were examined as putative mediators and/or moderators to improvements following CRT compared with treatment as usual (TAU) from a randomised controlled trial.

Euthymic adults with bipolar disorders who had been randomised to CRT (n = 23) or TAU (n = 21) underwent blood testing before and after a 12 week intervention period. Five cytokines and four growth factor proteins, selected a priori, were examined in association with global cognition and psychosocial functioning outcomes.

CRT attenuated a reduction in the brain-derived neurotrophic factor (BDNF), basic fibroblast growth factor and vascular endothelial growth factor-C compared to TAU. For the BDNF, lower baseline levels predicted better functional outcomes across the sample but was more pronounced in TAU versus CRT participants and indicated larger CRT effects in those with a higher BDNF. A moderation effect was also apparent for tumour necrosis factor-β and interleukin-16, with greater CRT versus TAU effects on functioning for participants with lower baseline levels.

Although preliminary, results suggest that CRT may exert some protective biological effects, and that people with lower levels of neurotrophins or cytokines may benefit more from CRT. We note an absence of associations with cognitive (versus functional) outcomes. These findings require further examination in large well-controlled studies.

Amygdala and dorsal anterior cingulate cortex responses to facial emotions have shown promise in predicting treatment response in medication-free major depressive disorder (MDD). Here, we examined their role in the pathophysiology of clinical outcomes in more chronic, difficult-to-treat forms of MDD.

Forty-five people with current MDD who had not responded to ⩾2 serotonergic antidepressants (n = 42, meeting pre-defined fMRI minimum quality thresholds) were enrolled and followed up over four months of standard primary care. Prior to medication review, subliminal facial emotion fMRI was used to extract blood-oxygen level-dependent effects for sad v. happy faces from two pre-registered a priori defined regions: bilateral amygdala and dorsal/pregenual anterior cingulate cortex. Clinical outcome was the percentage change on the self-reported Quick Inventory of Depressive Symptomatology (16-item).

We corroborated our pre-registered hypothesis (NCT04342299) that lower bilateral amygdala activation for sad v. happy faces predicted favorable clinical outcomes (rs[38] = 0.40, p = 0.01). In contrast, there was no effect for dorsal/pregenual anterior cingulate cortex activation (rs[38] = 0.18, p = 0.29), nor when using voxel-based whole-brain analyses (voxel-based Family-Wise Error-corrected p < 0.05). Predictive effects were mainly driven by the right amygdala whose response to happy faces was reduced in patients with higher anxiety levels.

We confirmed the prediction that a lower amygdala response to negative v. positive facial expressions might be an adaptive neural signature, which predicts subsequent symptom improvement also in difficult-to-treat MDD. Anxiety reduced adaptive amygdala responses.