Other Recent Work

Sex/gender differences in the clinical trajectory of Alzheimer’s disease: Insights into diagnosis and cognitive reserve

(2025)

The two-times higher prevalence of Alzheimer's disease (AD) in females versus males is well-known; however, there are also sex/gender differences in clinical presentation and diagnostic accuracy that are less examined but equally important to understand in terms of improving early detection, intervention and disease tracking in each sex/gender. This review explores how these disparities in clinical presentation manifest across the AD continuum, with a focus on the earlier stages of preclinical AD and mild cognitive impairment (MCI). We summarize evidence indicating that female's verbal memory advantage may mask early cognitive decline, leading to delayed MCI diagnosis and limiting opportunities for early intervention. Conversely, females demonstrate steeper cognitive decline at later disease stages compared to males. These patterns align with the cognitive reserve theory, suggesting female's verbal memory strength may act as a domain-specific resilience factor. Lastly, this review emphasizes the need for sex-sensitive diagnostic tools to improve early detection accuracy and equity in clinical practice.

Cover page of Effects of Cigarette Smoking and 3‐Day Smoking Abstinence on Translocator Protein 18 kDa Availability: A [18F]FEPPA Positron Emission Tomography Study

Effects of Cigarette Smoking and 3‐Day Smoking Abstinence on Translocator Protein 18 kDa Availability: A [18F]FEPPA Positron Emission Tomography Study

(2025)

With the many negative health consequences of cigarette smoking, quitting is known to improve health in multiple domains. Using positron emission tomography/computed tomography (PET/CT) scanning, our group previously demonstrated that smokers have lower levels than nonsmokers of translocator protein binding both acutely and following overnight abstinence. Here, we sought to determine the effects of longer smoking abstinence on this marker of gliosis for microglia and astroglia, as well as explore associations between the marker and smoking-related symptoms. This observational study was performed in an academic VA medical centre. Fifty-nine generally healthy Veterans who were either nonsmokers (n = 15) or smokers (n = 44) participated in the study. Participants completed an intake visit to evaluate for inclusion/exclusion criteria, [¹⁸F]FEPPA PET/CT scanning and a structural magnetic resonance imaging scan. Smokers were alternately assigned either to smoke to satiety (n = 24) before scanning or undergo three nights of continuous abstinence prior to scanning using contingency management (n = 20 completed this protocol and scanning). The smoker satiety group had a significantly lower mean whole brain (WB) standardized uptake value (SUV) for [¹⁸F]FEPPA binding than both the nonsmoking (-15.3%) and abstinent smoker (-12.3%) groups. The nonsmoking control and abstinent smoker groups had mean WB SUVs that were not significantly different from one another (3.0% group difference). In an exploratory analysis, a significant inverse relationship was found between WB SUVs and mood ratings for smokers, indicating that higher levels of TSPO binding were associated with worse mood. The central findings here support previous studies demonstrating lower levels of the marker for gliosis in satiated smokers and imply normalization with elimination of cigarette smoke constituents from the body, although other explanations for study results (e.g., alterations in radioligand delivery or clearance of radioligand by cigarette smoke constituents) are possible. These findings may represent a previously unknown health benefit of quitting smoking.

Longitudinal analysis of the ABCD® study

(2025)

The Adolescent Brain Cognitive Development® (ABCD) Study provides a unique opportunity to investigate developmental processes in a large, diverse cohort of youths, aged approximately 9-10 at baseline and assessed annually for 10 years. Given the size and complexity of the ABCD Study, researchers analyzing its data will encounter a myriad of methodological and analytical considerations. This review provides an examination of key concepts and techniques related to longitudinal analyses of the ABCD Study data, including: (1) characterization of the factors associated with variation in developmental trajectories; (2) assessment of how level and timing of exposures may impact subsequent development; (3) quantification of how variation in developmental domains may be associated with outcomes, including mediation models and reciprocal relationships. We emphasize the importance of selecting appropriate statistical models to address these research questions. By presenting the advantages and potential challenges of longitudinal analyses in the ABCD Study, this review seeks to equip researchers with foundational knowledge and tools to make informed decisions as they navigate and effectively analyze and interpret the multi-dimensional longitudinal data currently available.

Relationship of Perceived Burdensomeness and Thwarted Belongingness to Suicide Ideation Persistence and Suicide Behavior Over 12 Months in People With Serious Mental Illness

(2025)

Background and hypothesis

People with serious mental illness (SMI) have an increased risk of suicide ideation (SI) and suicide behavior (SB). Longitudinal studies on factors contributing to SI/SB in SMI are lacking. Interpersonal biases (ie, perceived burdensomeness and thwarted belongingness) are cross-sectionally related to SI/SB, but do they relate to longitudinal suicide risk or other illness factors? Ecological momentary assessment (EMA) offers a powerful approach to a deeper understanding of these complex relationships.

Study design

Participants with SMI (N = 180) completed 3 in-lab visits (baseline, 6-month, and 12-month) and 10 days of EMA (3×/day) following the baseline visit. At all timepoints, participants were assessed for SI/SB and were classified as persistent, intermittent, or no SI or any reports of SB over the 12-month follow-up. Multinomial logistic regression models examined whether EMA burdensomeness, belongingness, social motivations, and psychotic symptoms predicted SI persistence or SB over 12 months. Time-series network analysis compared participants' EMA data by baseline SI.

Study results

Burdensomeness and belongingness related to persistent SI 12 months, as did voices, suspiciousness, and social motivations. Only burdensomeness and belongingness related to increased risk of SB over 12 months. Network analyses revealed unique lagged relationships in the baseline SI group: of suspiciousness to belongingness and social avoidance motivation to burdensomeness when compared to the baseline group without SI.

Conclusions

These findings indicate the importance of interpersonal risk factors and suspiciousness to trajectories of SI and SB over 12 months in SMI. Pending replication, these constructs may be potential suicide prevention treatment targets in SMI.

Cigarette smoking is associated with reduced neuroinflammation and better cognitive control in people living with HIV

(2025)

People living with HIV (HIV+) are roughly twice as likely to smoke cigarettes (Smok+) as the general population. With the advent of effective antiretroviral therapies, it is increasingly important to understand the effects of chronic HIV infection and cigarette smoking on brain function and cognition since HIV+ individuals have heightened neuroinflammation and cognitive deficits even with such therapies. Based on prior studies demonstrating that smoking reduces a marker for neuroinflammation in HIV- individuals, we hypothesized that HIV+/Smok+ individuals would have less neuroinflammation and better cognitive control than HIV+/Smok- individuals. Fifty-nine participants (HIV-/Smok- [n = 16], HIV-/Smok+ [n=14], HIV+/Smok- [n = 18], and HIV+/Smok+ [n = 11]) underwent baseline eligibility tests, positron emission tomography (PET) scanning to determine levels of a marker for neuroinflammation, and assessment of cognitive control with the reverse-translated 5-choice continuous performance test (5C-CPT), with smokers having smoked to satiety prior to testing. For the PET data, a significant effect of smoking status on whole brain (WB) standardized uptake value (SUV) was found between HIV+/Smok+ and HIV+/Smok- participants (due to 18.8% lower WB SUV in the HIV+/Smok+ group). HIV+/Smok- participants exhibited a mean 13.5% higher WB SUV than HIV-/Smok- participants. For the 5C-CPT, HIV+/Smok+ participants performed significantly better than HIV+/Smok- participants (d prime), and HIV+/Smok- participants performed worse than HIV-/Smok- participants. Thus, HIV+/Smok+ individuals demonstrated lower levels of the neuroinflammation marker and better cognitive control than HIV+/Smok- individuals. Given that HIV+ individuals whose HIV is well-controlled can still have chronic neurocognitive complications, study results suggest possible paths for future research into nicotine-related treatments to prevent such complications.

Attitudes Towards Dementia Among a Diverse Group of Refugees Resettled in the United States

(2025)

Background

Forced migration results in exposure to trauma, interrupted access to healthcare, and loss of social support and may increase dementia risk. Literature on refugees' knowledge of dementia and its risk factors is scant. This study investigates refugee perspectives on dementia and their access to cognitive healthcare in the United States (US).

Methods

We conducted 6 focus groups and 30 individual in-depth interviews (total of 69 participants) with Arab, African, and Afghan refugees resettled in San Diego, California. Data was coded using inductive thematic analysis.

Results

Organized by the socioecological model of health, the following themes emerged: (1) mental trauma due to migration was linked to dementia (individual); (2) fear of dementia and burdening caregivers due to limited support systems (interpersonal); (3) reliance on virtual communities for dementia information and the stress of local community loss increasing dementia risk (community); (4) healthcare providers, both in the US and in refugee camps, didn't address cognitive health concerns (institutions); and (5) discriminatory immigration and healthcare policies as barriers to healthy aging (policy).

Discussion

Despite being a heterogeneous group, refugees share specific experiences, knowledge gaps, and barriers to healthy aging. Tailored interventions and policies are needed to address this population's cognitive health needs. This includes addressing their mental health and social support concerns as well as training clinicians to screen for/discuss dementia with aging refugee patients.

Genomics-informed neuropsychiatric care for neurodevelopmental disorders: Results from a multidisciplinary clinic

(2025)

Purpose

Patients with neurodevelopmental disorders (NDDs) have high rates of neuropsychiatric comorbidities. Genomic medicine may help guide care because pathogenic variants are identified in up to 50% of patients with NDDs. We evaluate the impact of a genomics-informed, multidisciplinary, neuropsychiatric specialty clinic on the diagnosis and management of patients with NDDs.

Methods

We performed a retrospective study of 316 patients from the University of California, Los Angeles Care and Research in Neurogenetics Clinic, a genomics-informed multidisciplinary clinic.

Results

Among the 246 patients who underwent genetic testing, 41.8% had a pathogenic or likely pathogenic variant. Patients had 62 different genetic diagnoses, with 12 diagnoses shared by 2 or more patients, whereas 50 diagnoses were found in only single patients. Genetic diagnosis resulted in direct changes to clinical management in all patients with a pathogenic or likely pathogenic variant, including cascade testing (30.6%), family counseling (22.2%), medication changes (13.9%), clinical trial referral (2.8%), medical surveillance (30.6%), and specialty referrals (69.4%).

Conclusions

A genomics-informed model can provide significant clinical benefits to patients with NDDs, directly affecting management across multiple domains for most diagnosed patients. As precision treatments advance, establishing a genetic diagnosis will be critical for proper management. With the growing number of rare neurogenetic disorders, clinician training should emphasize core principles of genomic medicine over individual syndromes.

Guided Self-Help vs Group Treatment for Children With Obesity: A Randomized Clinical Trial.

(2025)

Background and objectives

Family-based behavioral treatment (FBT) for children with obesity is provided in weekly parent and child groups over 6 months. A guided self-help FBT program (gshFBT) is provided to the dyad in short meetings. Both interventions provide the same content; however, gshFBT provides this content in less time (FBT = 23 hours, gshFBT = 5.3 hours). This study aimed to evaluate whether gshFBT is noninferior to FBT on child weight loss and cost-effectiveness.

Methods

150 children aged between 7.0 and 12.9 years with a BMI between the 85th and 99.9th percentile and their parent were recruited and randomized to a 6-month program of gshFBT (n = 75) or FBT (n = 75) and were followed 12 months post-treatment.

Results

A total of 150 children (mean age = 10.1 years, 49% female, mean BMIz = 2.09) and their parent (mean age = 41.5 years, 87% female, 45% Hispanic, 37% White non-Hispanic, 9.7% Asian, 4.8% Black, 7.3% other) were recruited from the San Diego Metropolitan area. Joint LME models showed that gshFBT was noninferior to FBT on child weight loss (ΔBMIz = -0.02 [90% credible interval [CI] -0.08-0.05, P = .65]; ΔBMIp95% = -1.57 [90% CI -4.46-1.31, P = .28]) and cost less (cost/dyad gshFBT = $1498; FBT = $2775).

Conclusion

The gshFBT program provided similar weight losses for children with less contact hours and with lower cost than FBT. The reduced time and ease of scheduling for the family in gshFBT will allow for an increased reach of treatment to a greater proportion of families in need.

M19 Adult Consequences of Repeated Nicotine and Δ9-Tetrahydrocannabinol (THC) Vapor Inhalation in Adolescent Rats

(2025)

Sex Differences in Inflammatory Markers in Bipolar Disorder

(2025)

Department of Psychiatry, UCSD