A key step toward understanding psychiatric disorders that disproportionately impact female mental health is delineating the emergence of sex-specific patterns of brain organisation at the critical transition from childhood to adolescence. Prior work suggests that individual differences in the spatial organisation of functional brain networks across the cortex are associated with psychopathology and differ systematically by sex.

We aimed to evaluate the impact of sex on the spatial organisation of person-specific functional brain networks.

We leveraged person-specific atlases of functional brain networks, defined using non-negative matrix factorisation, in a sample of n = 6437 youths from the Adolescent Brain Cognitive Development Study. Across independent discovery and replication samples, we used generalised additive models to uncover associations between sex and the spatial layout (topography) of personalised functional networks (PFNs). We also trained support vector machines to classify participants’ sex from multivariate patterns of PFN topography.

Sex differences in PFN topography were greatest in association networks including the frontoparietal, ventral attention and default mode networks. Machine learning models trained on participants’ PFNs were able to classify participant sex with high accuracy.

Sex differences in PFN topography are robust, and replicate across large-scale samples of youth. These results suggest a potential contributor to the female-biased risk in depressive and anxiety disorders that emerge at the transition from childhood to adolescence.

Community-engaged partnerships (community/academia/government) can play a role in developing effective protocols that address public health crises. Systemic racism, prioritization of money over humanity, and the repression of the local democratic processes through the State of Michigan Emergency Manager Law (Order of Act 439) all played a role in the Flint Water Crisis. Despite decades of collaboration between Flint-based community organizations and academic institutions, ways to navigate such crises and conduct relevant research were ineffective.

The Michigan Institute for Clinical and Health Research Community Engagement program at the University of Michigan and Flint’s Community Based Organization Partners co-developed the Research Readiness and Partnership Protocol (R2P2) to provide community-engaged recommendations that inform a rapid research response to public health emergencies. The R2P2 Workgroup conducted an extensive literature review and key interviews to inform protocol development.

This manuscript provides an overview of the Workgroup’s methods, key interview findings, and the main principles identified. Detailed recommendations and key elements to address prior to and during a crisis will be presented including methods for: establishing and maintaining trust, ensuring transparency, supporting clear communication, establishing a “front door” to academic institutions including a means to “sound the alarm,” addressing academic incentives, achieving equitable resource sharing, and addressing systemic racism.

This manuscript of community perspectives provides essential elements to develop meaningful community-academic research partnerships to address public health crises impacting communities, particularly communities of color. Furthermore, this work highlights an opportunity for greater acknowledgment and utilization of community-based participatory research (CBPR) by academic institutions.

Trace amine-associated receptor 1 (TAAR1) agonists offer a new approach, but there is uncertainty regarding their effects, exact mechanism of action and potential role in treating psychosis.

To evaluate the available evidence on TAAR1 agonists in psychosis, using triangulation of the output of living systematic reviews (LSRs) of animal and human studies, and provide recommendations for future research prioritisation.

This study is part of GALENOS (Global Alliance for Living Evidence on aNxiety, depressiOn and pSychosis). In the triangulation process, a multidisciplinary group of experts, including those with lived experience, met and appraised the first co-produced living systematic reviews from GALENOS, on TAAR1 agonists.

The animal data suggested a potential antipsychotic effect, as TAAR1 agonists reduced locomotor activity induced by pro-psychotic drug treatment. Human studies showed few differences for ulotaront and ralmitaront compared with placebo in improving overall symptoms in adults with acute schizophrenia (four studies, n = 1291 participants, standardised mean difference (SMD) 0.15, 95% CI −0.05 to 0.34). Large placebo responses were seen in ulotaront phase three trials. Ralmitaront was less efficacious than risperidone (one study, n = 156 participants, SMD = −0.53, 95% CI −0.86 to −0.20). The side-effect profile of TAAR1 agonists was favourable compared with existing antipsychotics. Priorities for future studies included (a) using different animal models of psychosis with greater translational validity; (b) animal and human studies with wider outcomes including cognitive and affective symptoms and (c) mechanistic studies and investigations of other potential applications, such as adjunctive treatments and long-term outcomes. Recommendations for future iterations of the LSRs included (a) meta-analysis of individual human participant data, (b) including studies that used different methodologies and (c) assessing other disorders and symptoms.

This co-produced, international triangulation examined the available evidence and developed recommendations for future research and clinical applications for TAAR1 agonists in psychosis. Broader challenges included difficulties in assessing the risk of bias, reproducibility, translation and interpretability of animal models to clinical outcomes, and a lack of individual and clinical characteristics in the human data. The research will inform a separate, independent prioritisation process, led by lived experience experts, to prioritise directions for future research.

This study investigated the relationship between various intrapersonal factors and the discrepancy between subjective and objective cognitive difficulties in adults with attention-deficit hyperactivity disorder (ADHD). The first aim was to examine these associations in patients with valid cognitive symptom reporting. The next aim was to investigate the same associations in patients with invalid scores on tests of cognitive symptom overreporting.

The sample comprised 154 adults who underwent a neuropsychological evaluation for ADHD. Patients were divided into groups based on whether they had valid cognitive symptom reporting and valid test performance (n = 117) or invalid cognitive symptom overreporting but valid test performance (n = 37). Scores from multiple symptom and performance validity tests were used to group patients. Using patients’ scores from a cognitive concerns self-report measure and composite index of objective performance tests, we created a subjective-objective discrepancy index to quantify the extent of cognitive concerns that exceeded difficulties on objective testing. Various measures were used to assess intrapersonal factors thought to influence the subjective-objective cognitive discrepancy, including demographics, estimated premorbid intellectual ability, internalizing symptoms, somatic symptoms, and perceived social support.

Patients reported greater cognitive difficulties on subjective measures than observed on objective testing. The discrepancy between subjective and objective scores was most strongly associated with internalizing and somatic symptoms. These associations were observed in both validity groups.

Subjective cognitive concerns may be more indicative of the extent of internalizing and somatic symptoms than actual cognitive impairment in adults with ADHD, regardless if they have valid scores on cognitive symptom overreporting tests.

To determine whether poorer performance on the Boston Naming Test (BNT) in individuals with transactive response DNA-binding protein 43 pathology (TDP-43+) is due to greater loss of word knowledge compared to retrieval-based deficits.

Retrospective clinical-pathologic study of 282 participants with Alzheimer’s disease neuropathologic changes (ADNC) and known TDP-43 status. We evaluated item-level performance on the 60-item BNT for first and last available assessment. We fit cross-sectional negative binomial count models that assessed total number of incorrect items, number correct of responses with phonemic cue (reflecting retrieval difficulties), and number of “I don’t know” (IDK) responses (suggestive of loss of word knowledge) at both assessments. Models included TDP-43 status and adjusted for sex, age, education, years from test to death, and ADNC severity. Models that evaluated the last assessment adjusted for number of prior BNT exposures.

43% were TDP-43+. The TDP-43+ group had worse performance on BNT total score at first (p = .01) and last assessments (p = .01). At first assessment, TDP-43+ individuals had an estimated 29% (CI: 7%–56%) higher mean number of incorrect items after adjusting for covariates, and a 51% (CI: 15%–98%) higher number of IDK responses compared to TDP-43−. At last assessment, compared to TDP-43−, the TDP-43+ group on average missed 31% (CI: 6%–62%; p = .01) more items and had 33% more IDK responses (CI: 1% fewer to 78% more; p = .06).

An important component of poorer performance on the BNT in participants who are TDP-43+ is having loss of word knowledge versus retrieval difficulties.

Shared genetic risk between schizophrenia (SCZ) and bipolar disorder (BD) is well-established, yet the extent to which they share environmental risk factors remains unclear. We compare the associations between environmental exposures during childhood/prior to disorder onset with the risk of developing SCZ and BD.

We conducted a Swedish register-based nested case–control study using 4184 SCZ cases and 18 681 BD cases diagnosed 1988–2013. Cases were matched to five controls by birth year, birth region, and sex. Conditional logistic regression was used to estimate incidence rate ratios (IRR) for SCZ and BD for each exposure (severe childhood infections, adverse childhood experiences (ACEs), substance use disorders (SUDs), urban birth/longest residence).

All SUD types were associated with very high risk (IRR 4.9–25.5), and all forms of ACEs with higher risk (IRR 1.5–4.3) for both disorders. In the mutually adjusted models, ACEs demonstrated slightly higher risk for BD (SCZ IRR 1.30, 1.19-1.42; BD IRR 1.49, 1.44–1.55), while for SUD, risk was higher for SCZ (SCZ IRR 9.43, 8.15–10.92; BD IRR 5.50, 5.15–5.88). Infections were associated with increased risk of BD (IRR 1.21, 1.17–1.26) but not SCZ. Urban birth and urban longest residence were associated with higher risk of SCZ (IRR 1.19, 1.03–1.37), while only the combination of urban birth and rural longest residence showed higher risk for BD (IRR 1.24, 1.13–1.35).

There were both shared and unique environmental risk factors: SUDs and ACEs were risk factors for both disorders, while infections were more strongly associated with BD and urbanicity with SCZ.

We compared dissociative seizure specific cognitive behavior therapy (DS-CBT) plus standardized medical care (SMC) to SMC alone in a randomized controlled trial. DS-CBT resulted in better outcomes on several secondary trial outcome measures at the 12-month follow-up point. The purpose of this paper is to evaluate putative treatment mechanisms.

We carried out a secondary mediation analysis of the CODES trial. 368 participants were recruited from the National Health Service in secondary / tertiary care in England, Scotland, and Wales. Sixteen mediation hypotheses corresponding to combinations of important trial outcomes and putative mediators were assessed. Twelve-month trial outcomes considered were final-month seizure frequency, Work and Social Adjustment Scale (WSAS), and the SF-12v2, a quality-of-life measure providing physical (PCS) and mental component summary (MCS) scores. Mediators chosen for analysis at six months (broadly corresponding to completion of DS-CBT) included: (a) beliefs about emotions, (b) a measure of avoidance behavior, (c) anxiety and (d) depression.

All putative mediator variables except beliefs about emotions were found to be improved by DS-CBT. We found evidence for DS-CBT effect mediation for the outcome variables dissociative seizures (DS), WSAS and SF-12v2 MCS scores by improvements in target variables avoidance behavior, anxiety, and depression. The only variable to mediate the DS-CBT effect on the SF-12v2 PCS score was avoidance behavior.

Our findings largely confirmed the logic model underlying the development of CBT for patients with DS. Interventions could be additionally developed to specifically address beliefs about emotions to assess whether it improves outcomes.

Treatment of childhood central nervous system (CNS) tumors can lead to sensorineural hearing loss (SNHL), with prior research indicating associations between SNHL and cognitive difficulties. Infants (0-3 years) treated for CNS tumors are at particular risk for neurocognitive deficits due to increased vulnerability of the developing brain and missed developmental opportunities secondary to prolonged treatment. This study expands upon existing research by examining the association between treatment-related SNHL and later neurocognitive outcomes among infants.

Serial audiology and neurocognitive assessments were conducted as part of a prospective, multisite, longitudinal trial (SJYC07). Children with newly diagnosed CNS tumors were treated with chemotherapy, with or without focal proton or photon radiation therapy (RT). SNHL was dichotomized based on hearing in the better ear as present versus not present (Chang grade ≥1a vs. <1a). Neurocognitive assessments included intellectual functioning (IQ), and parent ratings of executive functioning and behavioral functioning. Demographic and clinical variables investigated included: sex, age at diagnosis (years), treatment type (chemotherapy only vs. chemotherapy + RT), risk group (low vs. intermediate vs. high), and socioeconomic status (SES, continuous). Logistic regression models were used to identify factors associated with SNHL. Change point longitudinal models were used to examine the effect of each covariate individually and the potential impact of SNHL on trajectories of neurocognitive outcomes.

Of 135 patients (median age at diagnosis= 1.5 years), 67% had mild-to-severe SNHL as defined by Chang grade ≥1a at last follow-up. SNHL occurred early after treatment with a 1-year cumulative incidence 63.0% ±4.3%. SNHL was associated with age at diagnosis (p <.001) but not sex, treatment exposure or study risk arm (p >.10). At pretreatment baseline, IQ was associated with age at diagnosis (older age= higher IQ) and SES (higher SES= higher IQ) with a change in the trajectory of IQ after SNHL (stable prior to SNHL and declined 1.46 points/year after SNHL), which was impacted by tumor location (patients with supratentorial tumors stable prior to SNHL and declined 2.84 points/year after SNHL; whereas, patients with infratentorial tumors increased 1.93 points/year prior to SNHL and were stable after SNHL). At pre-treatment baseline, adaptive functioning was associated with age at diagnosis (older age= higher skills) with a change in adaptive functioning after SNHL that varied by age. There was a change in trajectory of attention problems (stable before SNHL and worsening 1.39 points/year after SNHL). SNHL was not associated with parent report of emerging executive functioning.

Children with brain tumors experience SNHL and cognitive difficulties early in treatment that can worsen over time. Younger age at diagnosis is associated with greater risk for SNHL and cognitive difficulties. Analyses of the time course between the emergence of SNHL and cognitive late effects suggests even mild SNHL is associated with a clinically signficant decline in IQ and attention problems. These findings have notable implications with respect to refining monitoring guidelines, informing modifications to treatment, advocating for interventions, and helping educate parents, teachers, and providers about the significant impact of mild SNHL.

The Immigrant Health Paradox (IHP) suggests that immigrants have better health upon arrival in comparison to their U.S.-born Latinx counterparts, indicating that immigrants’ unique experiences may buffer against negative health outcomes, including cognition. Some studies indicate that IHP-related cognitive health benefits diminish with increased time spent in the U.S., while others suggest that this relationship may be age-dependent such that compared to migration during earlier or later life, migration during young/middle adulthood may be related to better cognition-potentially due to higher simultaneous cognitive demands associated with this age epoch (e.g., language acquisition, acculturation). However, this literature is equivocal and has methodological limitations (e.g., cognition typically assessed with cognitive screeners, lack of clinical populations) Thus, this study aimed to examine the role of age related to IHP and cognition within a well-characterized sample of HIV+ Latinx adults. It was hypothesized that compared to U.S.-born Latinx adults and those who immigrated earlier or later in life, the Latinx immigrant subgroup who migrated during young/middle adulthood would demonstrate better cognitive functioning.

This cross-sectional study included a HIV+ sample (A/=105) of 34 Latinx immigrants (Mage=45.56, SD=6.99) and 71 U.S.-born Latinx individuals (Mage=46.03, SD=7.63), who completed a comprehensive sociocultural questionnaire and cognitive battery. Demographically-adjusted average T-scores were computed for each cognitive test and domain (e.g., learning, memory). A series of Welch’s-corrected ANOVAS with post hoc Games-Howell tests for multiple comparisons were conducted to compare cognitive function across three groups: Latinx immigrants who migrated during earlier (<19 yrs) or later adulthood (>50 yrs), young/middle adulthood (20-49 yrs), and U.S.-born Latinx adults.

Compared to the other Latinx subgroups, Latinx immigrants who migrated during middle adulthood performed worse in Verbal Fluency (F(2,98)=8.04, p<.001), Attention/Working Memory (f(2,96)=6.10, p<.01), Executive Function (f(2,99)=5.11, p<.01), and Processing Speed (F(2,101)=3.36, p<.05). Posthoc Games-Howell tests showed that the mean Verbal Fluency (p<.01, 95% C.I.=[-21.37, -2.66]), Attention/Working Memory (p<.05, 95% C.I.=[-16.82, -1.59]), Executive Function (p<.01, 95% C.I.=[-14.66, -2.49]) and Processing Speed (p<.05, 95% C.I.=[-13.60, -1.31]) T-scores were significantly lower in Latinx immigrants who migrated in young/middle adulthood compared to the U.S.-born Latinx sample. Further, there were no differences between the U.S.-born Latinx group compared to the Latinx immigrant group who migrated earlier or later in life (ps>.05).

This preliminary study is the first to examine whether the potential protective cognitive effects of the IHP vary across the lifespan among Latinx immigrants with HIV, using a comprehensive neuropsychological battery. Age-related IHP benefits were not observed in this study. Moreover, Latinx immigrants who migrated during young/middle adulthood had worse cognitive functioning compared to their U.S.-born Latinx counterparts and those that migrated earlier or later in life. A possible explanation for this study’s unexpected findings is that the IHP is outdated due to the current sociopolitical climate immigrants experience compared to the 1980s when the theory was developed. Future studies, with larger samples, longitudinal designs, and greater sociocultural characterization (e.g., immigration reason/s, country of origin, discrimination), are needed to better understand the role of IHP in cognition.