[Posted 25/Jul/2022]

AUDIENCE: Psychiatry, Pediatric, Family Medicine

KEY FINDINGS: The connectivity strength of the VS within the reward network showed distinct patterns of association with depressive disorders and anhedonia from mid to late adolescence, suggesting that the role of this circuitry in depression changes with age. This study replicates, in an independent sample, the association between the VS and depression previously reported in younger adolescents. The findings suggest a role of VS connectivity_rw in anhedonia but not in low mood.

BACKGROUND: Research in adolescent depression has found aberrant intrinsic functional connectivity (iFC) among the ventral striatum (VS) and several brain regions implicated in reward processing. The present study probes this question by taking advantage of the availability of data from a large youth cohort, the IMAGEN Consortium.

DETAILS: iFC data from 303 adolescents (48% of them female) were used to examine associations of VS connectivity at baseline (at age 14) with depressive disorders at baseline and at 2-year (N=250) and 4-year (N=219) follow-ups. Eleven regions of interest, key nodes of the reward system, were used to probe the reward network and calculate the connectivity strength of the VS within this network (VS connectivity_rw). The main analyses assessed associations of VS connectivity_rw with depressive disorders, anhedonia, and low mood using logistic regression. Autoregressive models accounting for carryover effects over time were conducted to further evaluate these brain-behavior associations. Higher right VS connectivity_rw was associated with higher probability of depressive disorders at baseline (odds ratio=2.65, 95% CI=1.40, 5.05). This finding was confirmed in the autoregressive model, adjusting for carryover effects of the depressive disorders across the three time points. VS connectivity_rw was not predictive of depressive disorders at follow-up assessments. Longitudinal associations between VS connectivity_rw and anhedonia emerged in the structural equation model: left VS connectivity_rw was associated with anhedonia at 2 years (odds ratio=2.20, 95% CI=1.54, 3.14), and right VS connectivity_rw was linked to anhedonia at 4 years (odds ratio=1.87, 95% CI=1.09, 3.21). VS connectivity_rw did not predict low mood at any time point in the structural equation model.

Copyright © American Psychiatric Association. All rights reserved.

Source: Pan, P. M., Sato, J. R., Martinot, M. P.,, et al. (2022). Longitudinal Trajectory of the Link Between Ventral Striatum and Depression in Adolescence. Am J Psychiatry. 2022; 179(7): 470-481. Published: July, 2022. DOI: 10.1176/appi.ajp.20081180.

[Posted 27/Oct/2025]

AUDIENCE: Infectious Disease, Microbiologists

KEY FINDINGS: Enhanced antibiotic performance observed in preclinical mouse models. Potential to improve treatment outcomes for multiple intracellular bacterial infections. Ongoing efforts include mechanism elucidation and patent development.

BACKGROUND: Antibiotic resistance has severely limited the effectiveness of conventional treatments against persistent bacterial infections. Some pathogens, such as Staphylococcus aureus, Mycobacterium tuberculosis, and Salmonella enterica, can survive inside immune cells, remaining dormant and shielded from antibiotic action. The increasing prevalence of such infections underscores an urgent need for alternative approaches that do not rely solely on developing stronger antibiotics.

DETAILS: Researchers at the University of North Carolina (UNC) School of Medicine, led by Dr. Brian Conlon and Dr. Kuan-Yi Lu, identified a novel small molecule that modifies immune cell behavior to enhance antibiotic performance. Instead of directly targeting bacteria, the molecule reprograms the host's immune cells to activate dormant pathogens, rendering them more susceptible to antibiotic killing.

The team screened approximately 5,000 small molecules through the UNC Small Molecule Screening Core. They used luminescent reporter strains of S. aureus to identify compounds that triggered bacterial activation. The most promising compound was subsequently tested in mouse models, where it significantly improved antibiotic efficacy when administered alongside standard treatments.

In animal models, the selected molecule substantially improved pathogen clearance for S. aureus, M. tuberculosis, and S. enterica when used in combination with existing antibiotics. This finding supports a new therapeutic concept: targeting the host cell environment can potentiate antibiotic activity and overcome intracellular bacterial persistence. The discovery presents an innovative direction for combating infections that evade standard therapy.

Copyright © UNC School of Medicine. All rights reserved.

Source: Conlon, B. and Kuan-Yi, L. UNC Researchers Discover Method to Combat Antibiotic Treatment Failure. UNC Health Newsroom. 2025; Published: October 14, 2025.

A Cohort Study Investigating Adherence of Dose and Duration to UK Clinical Guidelines

[Posted 14/Oct/2025]

AUDIENCE: Psychiatry, Family Medicine

KEY FINDINGS: This study highlights how antipsychotic prescribing in dementia is discordant with current NICE guidelines on both duration and dose. More than half of those who discontinued their treatment then restarted treatment. These findings emphasise a persistent gap between clinical guidelines and real-world prescribing, underscoring the need for interventions that prioritise safety and person-centred dementia care.

BACKGROUND: In the UK, it is recommended by the National Institute for Health and Care Excellence (NICE) that if antipsychotics are initiated in people living with dementia, treatment should be at the lowest dose for the shortest time possible (1-3 months). In this study, authors aimed to investigate how dose and duration of antipsychotic medication adhere to UK clinical guidelines and explore treatment restart details in those who stop treatment.

DETAILS: Authors did a retrospective cohort study using longitudinal UK primary care data from the IQVIA Medical Research Database. Authors included people living with dementia aged 60-85 years who received their first antipsychotic prescription between Jan 1, 2000, and Dec 31, 2023. Individuals with any previous antipsychotic prescriptions in their records more than 1 year before a dementia diagnosis and those who had missing social deprivation information were excluded from the study. Duration of first and subsequent antipsychotic treatment episodes, medication dosage, and treatment discontinuation and reinitiation rates were investigated. Duration and discontinuation were defined by grouping consecutive prescriptions into treatment episodes using the waiting time distribution method (80% inter-arrival density, 59 days). Daily doses were derived from strength and frequency information and categorised as low or moderate or high based on established minimum effective dose equivalences. People with lived experience of dementia care contributed throughout this project, shaping the research question and advising on interpretation and dissemination strategies. In the dataset search, authors identified 108,910 people with a record indicating dementia at any time. In total, 99,091 cases were excluded (ie, individuals with no antipsychotic prescription between the ages of 60 and 85 years between 2000 and 2023, a previous history of antipsychotics, missing deprivation information, or only one eligible prescription). Authors included 9819 people living with dementia aged 60-85 years who received their first antipsychotic prescription between 2000 and 2023 in the study. 5310 (54.1%) were female and 4509 (45.9%) were male, with a mean age of 77.1 years (SD 5.6 years), and ethnicity data were not available. The first treatment episode lasted a median of 7 months (IQR 6.6-8.7), exceeding NICE guidelines of 1-3 months and 18.1% [95% CI 17.4-18.9]) were initiated on a prescription above the minimum effective dose (ie, low dose). Of the 1781 participants who started on a moderate or high dose, 519 (29.1%) had a moderate or high dose in all quarters of the first year of treatment. 1 year after treatment initiation, 5136 (78.3%) of 6559 eligible individuals remained on medication (48.9% [95% CI 47.7-50.1] on low dose, 14.8% [13.9-15.6] on moderate or high dose of haloperidol, olanzapine, quetiapine or risperidone; and 14.6% [13.8-15.5] on other antipsychotics). Of the 5547 individuals eligible to restart treatment after initial discontinuation, 3106 (56%) restarted with a median treatment duration of 2.6 months (IQR 0.0-9.9).

Copyright © Elsevier Ltd. All rights reserved.

Source: Smsith, H. C., Petersen, I., Hayes, J. F., et al. (2024). Antipsychotic Prescriptions in People With Dementia in Primary Care: A Cohort Study Investigating Adherence of Dose and Duration to UK Clinical Guidelines. The Lancet Psychiatry. 2025; 12(10): 758-767. Published: October, 2025. DOI: 10.1016/S2215-0366(25)00261-5.

[Posted 10/Oct/2025]

AUDIENCE: Neurology, Internal Medicine

KEY FINDINGS: Having a family history of PD predicts slower progression of cognitive decline and caudate dopaminergic degeneration, and less FOG compared with those without a family history independent of PRS. Taken together, information on family history could be used as a proxy for the clinical heterogeneity of PD.

BACKGROUND: Evidence suggests that either family history or polygenic risk score (PRS) is associated with developing Parkinson disease (PD). However, little is known about the longitudinal prognosis of PD according to family history and higher PRS.

DETAILS: From the Parkinson's Progression Markers Initiative database, 395 patients with PD who followed up for more than 2 years were grouped into those with family history within first-degree, second-degree, and third-degree relatives (N = 127 [32.2%]) vs those without (N = 268 [67.8%]). The PRS of 386 patients was computed using whole-genome sequencing data. Longitudinal assessment of motor, cognition, and imaging based on dopaminergic degeneration was conducted during the regular follow-up period. Effects of family history, PRS, or both on longitudinal changes of cognition, motor severity, and nigrostriatal degeneration were tested using a linear mixed model. The risk of freezing of gait (FOG) according to family history was assessed using the Kaplan-Meier analysis and Cox regression models. During a median follow-up of 9.1 years, PD with positive family history showed a slower decline of caudate dopamine transporter uptake (ß estimate of family history x time = 0.02, 95% CI = 0.002-0.036, p = 0.027). Family history of PD and higher PRS were independently associated with a slower decline of Montreal Cognitive Assessment (ß estimate of family history x time = 0.12, 95% CI = 0.02-0.22, p = 0.017; ß estimate of PRS x time = 0.09, 95% CI = 0.03-0.16, p = 0.006). In those 364 patients without FOG at baseline, PD with positive family history had a lower risk of FOG (hazard ratio of family history = 0.57, 95% CI = 0.38-0.84, p = 0.005).

Copyright © American Academy of Neurology. All Rights Reserved.

Source: Park, M. and Lee, Y. (2025). Association of Family History and Polygenic Risk Score With Longitudinal Prognosis in Parkinson Disease. Neurology Genetics. 2025; Published: October, 2025. DOI: 10.1212/NXG.0000000000200115.

[Posted 9/Oct/2025]

AUDIENCE: Gastroenterology, Internal Medicine

KEY FINDINGS: Elevated DUOX2 signalling contributes to epithelial barrier dysfunction, microbiome alterations and subclinical inflammation. Butyrate and HDAC inhibitors reversed these effects, indicating that DUOX2 may be a therapeutic target in IBD.

BACKGROUND: Inflammatory bowel diseases (IBDs) are characterised by dysbiosis and a leaky gut. The NADPH oxidase dual oxidase 2 (DUOX2) is upregulated in patients with IBD, yet its role in driving the disease remains unclear. Authors interrogated the functional consequences of epithelial DUOX2 activity for the host and microbiome.

DETAILS: DUOX2 function was studied in mice with epithelial-specific DUOX2 overactivation (vTLR4), inactivation (vTLR4 DUOXA IEC-KO) and wild-type controls. Authors assessed the effect of dysbiosis on DUOX2 signalling and intestinal permeability (FITC-dextran, serum zonulin, bacterial translocation) with germ-free (GF) mice engrafted with IBD or healthy microbiota. RNA sequencing of colonic mucosa and microbiota and faecal metabolomics were used to characterise the host-microbe interface. Mechanistic studies were conducted in mouse colonoids, IBD biopsies and patient serum samples. DUOX2 activity increased permeability and bacterial translocation and induced subclinical inflammation in vTLR4 mice. GF vTLR4 mice had increased DUOX2 activity and permeability but no subclinical inflammation. In patients with IBD, DUOX2 expression was positively associated with plasma zonulin levels and negatively associated with ZO-1 expression. Engraftment of GF mice with IBD stool increased DUOX2 activity and triggered low-grade inflammation and permeability defects in mice. DUOX2 activity functionally altered the microbiome, reduced butyrate metabolism and promoted proinflammatory and pro-oncogenic bacterial metabolites. Butyrate and histone deacetylase (HDAC) inhibitors blocked DUOX2 activation and reversed its effects.

Copyright © BMJ Publishing Group Ltd & British Society of Gastroenterology. All rights reserved.

Source: Hazime, H., Ducasa, G. M., Santander, A. M., et al. (2025). DUOX2 Activation Drives Bacterial Translocation and Subclinical Inflammation in IBD-Associated Dysbiosis. dysbiosisGut. 2025; 74: 1589-1601. Published: October, 2025. DOI: 10.1136/gutjnl-2024-334346.

A Retrospective Repeated Cross-Sectional Study

[Posted 3/Oct/2025]

AUDIENCE: Family Medicine, Infectious Disease

KEY FINDINGS: Medicare beneficiaries aged 65 years and older with HIV in the USA were more likely to receive opioid prescriptions and have OUD indicators than matched beneficiaries without HIV. Findings could help guide clinical opioid prescription guidelines and public health surveillance among this vulnerable ageing population.

BACKGROUND: There is longstanding concern that people with HIV receive prescription opioids at higher rates and have a disproportionate burden of opioid use disorder (OUD) compared with their counterparts without HIV. We aimed to evaluate trends of opioid prescriptions and indicators of OUD in an understudied but growing population of older adults with HIV.

DETAILS: For this retrospective repeated cross-sectional study, authors constructed annual cohorts through a nationally representative sample of fee-for-service Medicare beneficiaries aged 65 years and older in the USA with Part D coverage (ie, prescription drug) enrolled between Jan 1, 2008, and Dec 31, 2021. Beneficiaries were eligible for inclusion in each cross-sectional cohort if they had reached the age of 65 years by Jan 1 of the calendar year and had 1 year of continuous Medicare enrolment in Part A (inpatient hospital care), B (outpatient care), and D. Beneficiaries with HIV were matched in a 1:3 ratio to beneficiaries without HIV on age, sex, race or ethnicity, US state, and dual eligibility status (Medicare and Medicaid). The main outcomes were receipt of at least one opioid prescription and any indicator of OUD (ie, formal diagnosis, medication for OUD, or opioid-related or emergency department visits) during each calendar year. Generalised estimating equations were used to estimate odds ratios (ORs) of each outcome, comparing matched beneficiaries with or without HIV. Due to data availability, our analysis of indicators of OUD was restricted to 2008-16. Across all years, 163,429 beneficiaries with HIV and 490,287 beneficiaries without HIV were included (475,516 [72.7%] were male, 178,200 [27.3%] were female; 305,776 [46.8%] were non-Hispanic White, 238,172 [36.4%] were Black [or African American], 84,128 [12.9%] were Hispanic, 8964 [1.4%] were Asian or Pacific Islander, and 16,676 [2.6%] were other races or ethnicities). During 2008-21, 57,373 (35.1%) of 163,429 people with HIV and 138,547 (28.3%) of 490,287 people without HIV received at least one opioid prescription. During 2008-16, 2408 (3.1%) of 76,637 people with HIV and 2831 (1.2%) of 229,911 people without HIV had any indicator of OUD. Across all analysed years, beneficiaries with HIV had significantly increased odds of receiving at least one opioid prescription (OR 1.38, 95% CI 1.36-1.39) and having indicators of OUD (2.61, 2.47-2.76) compared with their matched counterparts without HIV.

Copyright © The Author(s). Elsevier Ltd. All rights reserved.

Source: Shiau, S., Drago, F., Kinkade, C. W., et al. (2024). Prescription Opioid Use and Opioid Use Disorder Among Older Adults With HIV in the USA From 2008 to 2021: A Retrospective Repeated Cross-Sectional Study. The Lancet Primary Care. 2025; 1(3): 100017. Published: September, 2025. DOI: 10.1016/j.lanprc.2025.100017.