Suicidal ideation and behaviours are common among adolescents, posing significant challenges. Parents have a protective role in mitigating this risk, yet they often feel ill-equipped to support their adolescents, and their specific support needs are not well understood.

To explore the lived experiences of parents with suicidal adolescents and identify their support needs in the context of a therapist-assisted online parenting programme.

Semi-structured interviews were conducted with three stakeholder groups based in Australia: nine parents with lived experience caring for a suicidal adolescent, five young people who experienced suicidality during adolescence and five clinical/research experts in youth mental health/suicide prevention. Inductive thematic analysis was used to analyse and interpret findings.

Three key themes highlight the experience of parenting a suicidal adolescent: the traumatising emotional experience, uncertainty and parent empowerment. Six themes described parents’ support needs: validation and support, practical and tailored strategies, rebuilding the parent–adolescent relationship, parental self-care, flexible and accessible modes of delivery, and understanding non-suicidal self-injury.

Findings highlight key themes of parenting a suicidal adolescent and parental support needs. An online parenting programme could offer parents flexible access to evidence-based parenting strategies. Yet, a purely digital approach may not address the complexities of the parent-adolescent dynamic and provide adequate tailoring. As such, a hybrid approach incorporating therapist support can provide parents with both the compassionate support and practical guidance they seek.

Whole genome sequencing (WGS) can help identify transmission of pathogens causing healthcare-associated infections (HAIs). However, the current gold standard of short-read, Illumina-based WGS is labor and time intensive. Given recent improvements in long-read Oxford Nanopore Technologies (ONT) sequencing, we sought to establish a low resource approach providing accurate WGS-pathogen comparison within a time frame allowing for infection prevention and control (IPC) interventions.

WGS was prospectively performed on pathogens at increased risk of potential healthcare transmission using the ONT MinION sequencer with R10.4.1 flow cells and Dorado basecaller. Potential transmission was assessed via Ridom SeqSphere+ for core genome multilocus sequence typing and MINTyper for reference-based core genome single nucleotide polymorphisms using previously published cutoff values. The accuracy of our ONT pipeline was determined relative to Illumina.

Over a six-month period, 242 bacterial isolates from 216 patients were sequenced by a single operator. Compared to the Illumina gold standard, our ONT pipeline achieved a mean identity score of Q60 for assembled genomes, even with a coverage rate as low as 40×. The mean time from initiating DNA extraction to complete analysis was 2 days (IQR 2–3.25 days). We identified five potential transmission clusters comprising 21 isolates (8.7% of sequenced strains). Integrating ONT with epidemiological data, >70% (15/21) of putative transmission cluster isolates originated from patients with potential healthcare transmission links.

Via a stand-alone ONT pipeline, we detected potentially transmitted HAI pathogens rapidly and accurately, aligning closely with epidemiological data. Our low-resource method has the potential to assist in IPC efforts.

The association between cannabis and psychosis is established, but the role of underlying genetics is unclear. We used data from the EU-GEI case-control study and UK Biobank to examine the independent and combined effect of heavy cannabis use and schizophrenia polygenic risk score (PRS) on risk for psychosis.

Genome-wide association study summary statistics from the Psychiatric Genomics Consortium and the Genomic Psychiatry Cohort were used to calculate schizophrenia and cannabis use disorder (CUD) PRS for 1098 participants from the EU-GEI study and 143600 from the UK Biobank. Both datasets had information on cannabis use.

In both samples, schizophrenia PRS and cannabis use independently increased risk of psychosis. Schizophrenia PRS was not associated with patterns of cannabis use in the EU-GEI cases or controls or UK Biobank cases. It was associated with lifetime and daily cannabis use among UK Biobank participants without psychosis, but the effect was substantially reduced when CUD PRS was included in the model. In the EU-GEI sample, regular users of high-potency cannabis had the highest odds of being a case independently of schizophrenia PRS (OR daily use high-potency cannabis adjusted for PRS = 5.09, 95% CI 3.08–8.43, p = 3.21 × 10−10). We found no evidence of interaction between schizophrenia PRS and patterns of cannabis use.

Regular use of high-potency cannabis remains a strong predictor of psychotic disorder independently of schizophrenia PRS, which does not seem to be associated with heavy cannabis use. These are important findings at a time of increasing use and potency of cannabis worldwide.

Depression is an independent risk factor for cardiovascular disease (CVD), but it is unknown if successful depression treatment reduces CVD risk.

Using eIMPACT trial data, we examined the effect of modernized collaborative care for depression on indicators of CVD risk. A total of 216 primary care patients with depression and elevated CVD risk were randomized to 12 months of the eIMPACT intervention (internet cognitive-behavioral therapy [CBT], telephonic CBT, and select antidepressant medications) or usual primary care. CVD-relevant health behaviors (self-reported CVD prevention medication adherence, sedentary behavior, and sleep quality) and traditional CVD risk factors (blood pressure and lipid fractions) were assessed over 12 months. Incident CVD events were tracked over four years using a statewide health information exchange.

The intervention group exhibited greater improvement in depressive symptoms (p < 0.01) and sleep quality (p < 0.01) than the usual care group, but there was no intervention effect on systolic blood pressure (p = 0.36), low-density lipoprotein cholesterol (p = 0.38), high-density lipoprotein cholesterol (p = 0.79), triglycerides (p = 0.76), CVD prevention medication adherence (p = 0.64), or sedentary behavior (p = 0.57). There was an intervention effect on diastolic blood pressure that favored the usual care group (p = 0.02). The likelihood of an incident CVD event did not differ between the intervention (13/107, 12.1%) and usual care (9/109, 8.3%) groups (p = 0.39).

Successful depression treatment alone is not sufficient to lower the heightened CVD risk of people with depression. Alternative approaches are needed.

ClinicalTrials.gov Identifier: NCT02458690

Cognitive training has shown promise for improving cognition in older adults. Aging involves a variety of neuroanatomical changes that may affect response to cognitive training. White matter hyperintensities (WMH) are one common age-related brain change, as evidenced by T2-weighted and Fluid Attenuated Inversion Recovery (FLAIR) MRI. WMH are associated with older age, suggestive of cerebral small vessel disease, and reflect decreased white matter integrity. Higher WMH load associates with reduced threshold for clinical expression of cognitive impairment and dementia. The effects of WMH on response to cognitive training interventions are relatively unknown. The current study assessed (a) proximal cognitive training performance following a 3-month randomized control trial and (b) the contribution of baseline whole-brain WMH load, defined as total lesion volume (TLV), on pre-post proximal training change.

Sixty-two healthy older adults ages 65-84 completed either adaptive cognitive training (CT; n=31) or educational training control (ET; n=31) interventions. Participants assigned to CT completed 20 hours of attention/processing speed training and 20 hours of working memory training delivered through commercially-available Posit Science BrainHQ. ET participants completed 40 hours of educational videos. All participants also underwent sham or active transcranial direct current stimulation (tDCS) as an adjunctive intervention, although not a variable of interest in the current study. Multimodal MRI scans were acquired during the baseline visit. T1- and T2-weighted FLAIR images were processed using the Lesion Segmentation Tool (LST) for SPM12. The Lesion Prediction Algorithm of LST automatically segmented brain tissue and calculated lesion maps. A lesion threshold of 0.30 was applied to calculate TLV. A log transformation was applied to TLV to normalize the distribution of WMH. Repeated-measures analysis of covariance (RM-ANCOVA) assessed pre/post change in proximal composite (Total Training Composite) and sub-composite (Processing Speed Training Composite, Working Memory Training Composite) measures in the CT group compared to their ET counterparts, controlling for age, sex, years of education and tDCS group. Linear regression assessed the effect of TLV on post-intervention proximal composite and sub-composite, controlling for baseline performance, intervention assignment, age, sex, years of education, multisite scanner differences, estimated total intracranial volume, and binarized cardiovascular disease risk.

RM-ANCOVA revealed two-way group*time interactions such that those assigned cognitive training demonstrated greater improvement on proximal composite (Total Training Composite) and sub-composite (Processing Speed Training Composite, Working Memory Training Composite) measures compared to their ET counterparts. Multiple linear regression showed higher baseline TLV associated with lower pre-post change on Processing Speed Training sub-composite (ß = -0.19, p = 0.04) but not other composite measures.

These findings demonstrate the utility of cognitive training for improving postintervention proximal performance in older adults. Additionally, pre-post proximal processing speed training change appear to be particularly sensitive to white matter hyperintensity load versus working memory training change. These data suggest that TLV may serve as an important factor for consideration when planning processing speed-based cognitive training interventions for remediation of cognitive decline in older adults.

Late life depression (LLD) refers to a diagnosis of major depressive disorder in people older than 60, and has been linked to significant cognitive impairment and increased risk of Alzheimer's disease. Although anxiety and depression are highly comorbid, the impact of anxiety on cognition in LLD is far less researched. This is important given that over 20% of middle aged and older adults endorse clinically significant chronic worry. Generalized anxiety disorder in older adults with major depression is associated with poorer cognition and worse treatment outcomes compared with those without anxiety. Therefore, the purpose of the study is to examine the role of anxiety on memory in LLD. We hypothesized that presence of anxiety among older depressed adults would be associated with worse cognitive performance over time.

Participants included 124 individuals (69.4% female, 90.3% Caucasian) aged 60 or above (M = 71.5, SD = 7.4) who met criteria for major depression, single episode or recurrent. They completed the State Trait Anxiety Inventory, Montgomery Asberg Depression Rating Scale, and a measure of verbal episodic memory (WMS-IV Logical Memory) as part of a larger neuropsychological battery. Data were collected from baseline to three years as part of a larger NIMH-supported longitudinal study. Two-level linear mixed-effect models were fitted to predict memory. State and trait anxiety were used as time-varying predictors. The between-person (level 2) and within-person (level 1) effects of anxiety on memory were assessed controlling for the time trend, age, education, gender, race, and change in depression over time.

Plot trajectories across variables revealed a negative correlation such that as anxiety decreased, memory improved over time. Hierarchical linear mixed-effect models revealed that average state anxiety was a marginally significant between-person (level2) predictor for memory [B=-0.041, t(128)=-1.8, p=0.083]. Individuals with greater average state anxiety were more likely to experience memory decline compared to those with lower average state anxiety. In addition, the within-person effect (level 1) of state anxiety was significant [B=-0.096, t(253)=-2.7, p=0.007]. As an individual's anxiety increased over time, their memory declined. Trait anxiety showed a significant within-person effect on memory [B=-0.087, t(254)=-2.0, p=0.048], but a non-significant between-person effect [B=-0.005, t(124)=-0.06, p=0.95].

Anxiety appears to increase the risk of memory decline in older adults with major depression, a cohort who are already at risk of cognitive decline. Changes in anxiety increased risk of memory decline even when accounting for changes in depression over time. Although the causal link between anxiety and cognitive impairment remains unclear, it is possible that anxiety and worry may compete for cognitive resources necessary for demanding tasks and situations, detracting from abilities, such as attention and working memory. Older adults with depression may also have difficulty coping adaptively with anxiety, which may negatively affect cognition. Finally, presence of anxiety may represent a form of mild behavioral impairment, a prodrome of cognitive decline leading to dementia. Overall, the present study highlights the negative impact of anxiety on memory performance, indicating that treatment interventions targeting anxiety in older adults are essential to help prevent cognitive decline.

The concept of cognitive reserve (CR) explains why individuals with higher education, intelligence, or occupational attainment exhibit less severe cognitive changes in the presence of age-related or neurodegenerative pathology. CR may be a useful construct in understanding the cognitive performance of patients with late life depression (LLD), a cohort who are twice as likely to later receive a clinical diagnosis of dementia. It follows that depressed older adults with low CR may be at greater risk of cognitive decline compared to non-depressed older adults matched for CR. However, the literature on CR and LLD is limited to cross-sectional studies with mixed findings as to whether proxies of CR moderate cognitive outcomes in LLD. For example, both higher and lower education levels in LLD are associated with greater cognitive impairment in LLD compared to similarly educated non-depressed older adults. Longitudinal studies may help disentangle the association between CR and cognitive outcomes in LLD. The current study investigated the interaction between proxies of CR (e.g., education) and depression status on cognitive functioning over three years. We hypothesized that depressed older adults with low CR would demonstrate greater cognitive impairment and decline compared to depressed elders with high CR and non-depressed older adults with comparable CR.

Older adults with LLD and non-depressed older adults age 59+ participated. All participants were free of dementia at baseline. We divided both patients and non-depressed participants into low (<16) and high (>=16) education groups based upon the median years of education (16) of the entire sample. All participants underwent detailed neuropsychological testing. Composite measures of episodic memory (CERAD Wordlist and recall, LM I and LM II, BVRT), processing speed-executive functioning (SDMT and Trail Making Part B), working memory (forward, reverse, ascending Digit Span), and verbal fluency (Animal Naming and COWA) were calculated based on the non-depressed older adults.

The baseline sample included 210 non-depressed older adults and 465 older adults with major depression (LLD). 150 non-depressed older adults and 235 LLD patients provided three-year follow-up data. Separate ANOVAs revealed a statistically significant interaction between education and depression status at baseline on the composite score of executive functioning F (1, 668) = 8.74, p <.003. Consistent with our hypothesis, LLD with low education performed significantly worse compared to non-depressed with low education (z-score difference -1.35) and this effect was significantly greater than the difference between LLD patients and non-depressed with high education (z-score difference -0.36). No other interactions were found at baseline. Longitudinal analyses also revealed significant interactions between education and depression on memory over time, although sensitivity analyses did not suggest findings consistent with our hypothesis.

Cognitive reserve contribute to group differences between LLD and non-depressed older adults in cognitive performance but may not alter cognitive trajectories over time. Future studies should further explore structural and functional brain changes associated with CR in LLD.

Nonpathological aging has been linked to decline in both verbal and visuospatial memory abilities in older adults. Disruptions in resting-state functional connectivity within well-characterized, higherorder cognitive brain networks have also been coupled with poorer memory functioning in healthy older adults and in older adults with dementia. However, there is a paucity of research on the association between higherorder functional connectivity and verbal and visuospatial memory performance in the older adult population. The current study examines the association between resting-state functional connectivity within the cingulo-opercular network (CON), frontoparietal control network (FPCN), and default mode network (DMN) and verbal and visuospatial learning and memory in a large sample of healthy older adults. We hypothesized that greater within-network CON and FPCN functional connectivity would be associated with better immediate verbal and visuospatial memory recall. Additionally, we predicted that within-network DMN functional connectivity would be associated with improvements in delayed verbal and visuospatial memory recall. This study helps to glean insight into whether within-network CON, FPCN, or DMN functional connectivity is associated with verbal and visuospatial memory abilities in later life.

330 healthy older adults between 65 and 89 years old (mean age = 71.6 ± 5.2) were recruited at the University of Florida (n = 222) and the University of Arizona (n = 108). Participants underwent resting-state fMRI and completed verbal memory (Hopkins Verbal Learning Test - Revised [HVLT-R]) and visuospatial memory (Brief Visuospatial Memory Test - Revised [BVMT-R]) measures. Immediate (total) and delayed recall scores on the HVLT-R and BVMT-R were calculated using each test manual’s scoring criteria. Learning ratios on the HVLT-R and BVMT-R were quantified by dividing the number of stimuli (verbal or visuospatial) learned between the first and third trials by the number of stimuli not recalled after the first learning trial. CONN Toolbox was used to extract average within-network connectivity values for CON, FPCN, and DMN. Hierarchical regressions were conducted, controlling for sex, race, ethnicity, years of education, number of invalid scans, and scanner site.

Greater CON connectivity was significantly associated with better HVLT-R immediate (total) recall (ß = 0.16, p = 0.01), HVLT-R learning ratio (ß = 0.16, p = 0.01), BVMT-R immediate (total) recall (ß = 0.14, p = 0.02), and BVMT-R delayed recall performance (ß = 0.15, p = 0.01). Greater FPCN connectivity was associated with better BVMT-R learning ratio (ß = 0.13, p = 0.04). HVLT-R delayed recall performance was not associated with connectivity in any network, and DMN connectivity was not significantly related to any measure.

Connectivity within CON demonstrated a robust relationship with different components of memory function as well across verbal and visuospatial domains. In contrast, FPCN only evidenced a relationship with visuospatial learning, and DMN was not significantly associated with memory measures. These data suggest that CON may be a valuable target in longitudinal studies of age-related memory changes, but also a possible target in future non-invasive interventions to attenuate memory decline in older adults.

Parkinson’s disease (PD) is associated with metabolic disorders such as insulin resistance. Pharmacological intervention used to treat insulin resistance, like GLP-1 agonists, may have auspicious results in the treatment for PD. The objective of this clinical trial was to assess the therapeutic effect of liraglutide on non-motor symptoms, such as, but not limited to, cognitive function and emotional well-being, and quality of life for individuals with PD.

In a single-center, randomized, double-blind, placebo-controlled trial, PD patients self-administered liraglutide injections once-daily (1.2 or 1.8 mg, as tolerated) or placebo in a 2:1 study design for 52 weeks after titration. Primary outcomes included adjusted difference in the OFF-state Movement Disorders Society Unified PD Rating Scale (MDS-UPDRS) part III, non-motor symptom scale (NMSS) and Mattis Dementia Rating Scale (MDRS-2). Secondary outcomes included quality of life scores (Parkinson Disease Questionnaire, PDQ-39) and other neuropsychological tests, including Delis-Kaplan Executive Function System (DKEFS), Geriatric Depression Scale (GDS), and Parkinson’s Anxiety Scale (PAS) scores.

Sixty-three subjects were enrolled and randomized to liraglutide (n=42) or placebo (n=21). Mean age in years was 63.5 (9.8) and 64.2 (6.4) for liraglutide and placebo cohorts, respectively (p=0.78), and mean age at symptom onset was 58.9 (10.5) and 59.3 (7.5) for liraglutide and placebo cohorts, respectively (p=0.86). At 54 weeks, NMSS scores had improved by 6.6 points in the liraglutide group and worsened by 6.5 points in the placebo group, a 13.1 point adjusted mean difference (p<0.05). Further analysis showed all nine NMSS sub-domain changes favoring the liraglutide group, with one (attention/memory) reaching statistical significance (p<0.05). Secondary outcome analyses revealed a significant improvement of PDQ-39 (p<0.001) and Parkinson’s Anxiety Scale - Avoidance Behavior scores (p<0.05) in the treatment group. MDRS-2 sub-scores did not further differentiate study groups, while DKEFS letter fluency scores favored placebo group (p<0.05).

Treatment with liraglutide improved self-reported non-motor symptoms of PD, activities of daily living, and quality of life. These results validate similar outcomes reported with other GLP-1 agonists implicating consideration for novel treatment opportunities for individuals with PD. Notably, the absence of significant performance-based cognitive changes over the duration of the trial for the participants in this study has several plausible explanations given participant-related baseline demographic and clinical factors. Implications for neuropsychologists will be discussed.