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Cover page of Mixed Methods Findings from a Stepped Wedge Hybrid Implementation Trial of ATTAIN NAV: A Mental Health Family Navigation Intervention for Autistic Youth

Mixed Methods Findings from a Stepped Wedge Hybrid Implementation Trial of ATTAIN NAV: A Mental Health Family Navigation Intervention for Autistic Youth

(2025)

ATTAIN NAV (Access to Tailored Autism Integrated Care through Family Navigation) was delivered by family navigators to promote access to and engagement with mental health services for school-age autistic youth. This study used a mixed method, stepped wedge design to test the effects of family navigation on service and clinical outcomes while gathering information on implementation. Primary care providers from six clinics in California and 56 caregiver-child dyads enrolled in and completed the study. Clinics were randomized to either a technology-enhanced or standard family navigation condition. Caregivers completed assessments at baseline and post about child, family and services outcomes, and a subset participated in a post qualitative interview. Quantitative findings demonstrated improvements in child challenging behavior and parent activation across conditions although these improvements were more pronounced for families in the standard FN condition. At post-intervention, families in the standard FN condition reported higher levels of navigation satisfaction, a shorter time to attend their first mental health appointment, and higher engagement with their navigator. Qualitative findings complemented and expanded the quantitative survey findings. The ATTAIN NAV model of family navigation for autistic children with co-occurring mental health needs demonstrates promising implementation, service, and clinical benefits. Clinical Trials Registration. NCT05344378.

Cover page of Multi-sector determinants of implementation and sustainment for non-specialist treatment of depression and post-traumatic stress disorder in Kenya: a concept mapping study

Multi-sector determinants of implementation and sustainment for non-specialist treatment of depression and post-traumatic stress disorder in Kenya: a concept mapping study

(2025)

Background

The global shortage of trained mental health workers disproportionately impacts mental health care access in low- and middle-income countries. In Kenya, effective strategies are needed to scale-up the workforce to meet the demand for depression and post-traumatic stress disorder treatment. Task-shifting - delegating specific tasks to non-specialist workers - is one workforce expansion approach. However, non-specialist workers remain underutilized in Kenya due to a paucity of research on how to scale-up and sustain such service models.

Methods

Purposive sampling was used to recruit experts from policy, healthcare practice, research, and mental health advocacy roles in Kenya (N = 30). Participants completed concept mapping activities to explore factors likely to facilitate or hinder a collaborative Ministry of Health-researcher training of the mental health non-specialist workforce. Participants brainstormed 71 statements describing determinants and implementation strategies, sorted and rated the importance and changeability of each. Multidimensional scaling and hierarchical cluster analysis quantified relationships between statements. The Exploration, Preparation, Implementation, and Sustainment (EPIS) framework guided cluster interpretation activities.

Results

Twelve determinant clusters were identified: 1) Current workforce characteristics, 2) Exploration considerations, 3) Preparation considerations, 4) Sustainment considerations, 5) Inner context implementation processes and tools, 6) Local capacity and partnerships, 7) Financing for community health teams, 8) Outer context resource allocation/policy into action, 9) Workforce characteristics to enhance during implementation, 10) Workforce implementation strategies, 11) Cross-level workforce strategies, and 12) Training and education recommendations. Cluster 8 was rated the most important and changeable.

Conclusion

Concept mapping offers a rapid, community-engaged approach for identifying determinants and implementation strategies to address workforce shortages. Organizing results by EPIS phases can help prioritize strategy deployment to achieve implementation goals. Scale-up and sustainment of the non-specialist workforce in Kenya requires formal partnerships between the Ministry of Health and community health worker teams to distribute financial resources and collaboratively standardize training curriculum.

Cover page of Parenting Training Plus Behavioral Treatment for Children With Obesity

Parenting Training Plus Behavioral Treatment for Children With Obesity

(2025)

Importance

Family-based behavioral treatment (FBT) is recommended for childhood obesity treatment; however, it is not effective for all families. Since parenting training (PT) has been associated with healthy weight and eating behaviors, intensive PT may augment delivery of behavior change strategies and improve child weight loss outcomes.

Objective

To compare the efficacy of child overweight or obesity treatment that adds intensive PT to standard FBT with the efficacy of FBT alone.

Design, setting, and participants

This 2-arm randomized clinical trial (Reinforced, Enhanced, Families, Responsibility, Education, Support, and Health [ReFRESH]) conducted from April 2017 to November 2022 at an academic center in San Diego, California, included children aged 7 to 12 years with overweight or obesity (body mass index [BMI]≥85th to <99.9th percentile) and one of their parents.

Interventions

Parent-child dyads were randomized 1:1 to the intervention group, which received FBT plus PT, or the control group, which received FBT alone. Both groups received twenty 60-minute sessions over 6 months with separate parent and child groups led by staff and nine 20-minute behavior change coaching sessions. The FBT plus PT group sessions incorporated additional intensive parenting skills training in an interactive format.

Main outcomes and measures

The primary outcome was change from baseline in child BMI z score and BMI as a percentage of the 95th BMI percentile (BMIp95) after treatment (month 6) and at 6- and 12-month follow-up. Secondary outcomes included the proportion of children who attained clinically meaningful weight loss (ie, reduction of ≥0.20 BMI z score units) and intervention dropout rates. Intention-to-treat analysis was conducted using linear mixed models and logistic regression.

Results

A total of 140 parent-child dyads were included, with 70 in each treatment arm. Mean (SD) child age was 9.91 (1.54) years, and baseline BMI z score was 2.28 (0.80); 71 children (50.7%) were female. There were no significant between-group differences in BMI z score or BMIp95 after treatment or at the follow-up time points. Both groups had significant decreases in weight status after treatment (combined BMI z score: β, -0.14 [95% CI, -0.21 to -0.07]; P < .001; combined BMIp95: β, -3.46 [95% CI, -5.41 to -1.51]; P < .001). More children in the FBT plus PT arm compared with the FBT arm had a reduction of at least 0.20 BMI z score units (34 [48.6%] vs 22 [31.4%]; P = .01) after treatment (adjusted odds ratio, 2.10 [95% CI, 1.01-4.47]). Both treatments were well accepted, with no between-group differences in risk of dropout (hazard ratio, 1.01 [95% CI, 0.72-1.43]).

Conclusions and relevance

In this randomized clinical trial examining the effect of parenting training on child weight status, there were no significant differences in weight status between groups; children in both groups had a significant reduction in weight status. However, more children had clinically meaningful weight loss in the FBT plus PT group. Further work is needed to determine factors associated with treatment response and changes in parenting skills.

Trial registration

ClinicalTrials.gov Identifier: NCT02976636.

Increased Prevalence of Childhood Complex Trauma in Comorbid Posttraumatic Stress Disorder and Substance Use Disorders Compared to Either Disorder Alone: A Systematic Review

(2025)

Objective

Childhood complex trauma (CCT) prevalence among individuals with comorbid posttraumatic stress disorder (PTSD) and substance use disorder (SUD) is unknown. We conducted a meta-analysis to compare CCT prevalence in samples of PTSD alone, SUD alone and comorbid PTSD+SUD.

Method

A systematic review of PTSD, CCT and SUD literature was conducted using online databases. Binary outcome meta-analytic models were fitted comparing CCT prevalence in comorbid PTSD + SUD to PTSD and SUD only.

Results

Seven studies were included, and estimates for CCT prevalence were higher, on average, among individuals with comorbid PTSD+SUD (35%-78%) compared to PTSD alone (4%-70%) and SUD alone (2%-65%). A meta-analysis of four studies indicated individuals with comorbid PTSD+SUD were 18% more likely to have experienced CCT compared to individuals with PTSD only (RR = 1.18, 95% CI [1.13, 1.25]) and 24% more likely compared to individuals with SUD only (RR = 1.24, 95% CI [1.20, 1.29]).

Conclusions

Further research is needed to establish a more accurate prevalence rate for individuals with comorbid PTSD and SUD. Evidence of greater CCT prevalence will inform research study design and clinical targets during treatment for individuals with comorbid PTSD and SUD.

Cover page of Neurophysiological Markers of Reward Processing Can Inform Preclinical Neurorehabilitation Approaches for Cognitive Impairments Following Brain Injury

Neurophysiological Markers of Reward Processing Can Inform Preclinical Neurorehabilitation Approaches for Cognitive Impairments Following Brain Injury

(2025)

Brain stimulation therapies may be used to correct motor, social, emotional, and cognitive consequences of traumatic brain injury (TBI). Neuromodulation applied with anatomical specificity can ameliorate desired symptoms while leaving functional circuits intact. Before applying precision medicine approaches, preclinical animal studies are needed to explore potential neurophysiological signatures that could be modulated with neurostimulation. This review discusses potential neural signatures of cognition, particularly reward processing, which is chronically impaired after brain injury. Electrophysiology, compared to other types of biomarkers, can detect deficits missed by structural measures, holds translational potential between humans and animals, and directly informs neuromodulatory treatments. Disturbances in oscillatory activity underscore structural, molecular, and behavioral impairments seen following TBI. For instance, cortico-striatal beta frequency activity (15–30 Hz) during reward processing represents subjective value and is chronically disturbed after frontal TBI in rodents. We use the example of evoked beta oscillations in the cortico-striatal network as a putative marker of reward processing that could be targeted with electrical stimulation to improve decision making after TBI. This review highlights the necessity of collecting electrophysiological data in preclinical models to understand the underlying mechanisms of cognitive behavioral deficits after TBI and to develop targeted stimulation treatments in humans.

Glycation metabolites predict incident age-related comorbidities and mortality in older people with HIV

(2025)

Glycation is a class of modifications arising from non-enzymatic reactions of reducing sugars with proteins, lipids, and/or DNA, generating advanced glycation end-products (AGEs). AGEs are linked to many age-related comorbidities. In response to HIV-1 infection, activated T-cells and macrophages shift their predominate metabolism from oxidative phosphorylation to glycolysis. Increased glycolytic flux enhances AGE formation, which may increase age-related comorbidities. In this prospective, multicenter cohort study of antiretroviral therapy treated people with HIV, we explored predictive associations by baseline plasma AGE concentrations and their corresponding detoxification metabolites, with incident comorbidities and mortality. AGEs included dicarbonyl sugars: 3-deoxyglucosone, glyoxal, and methylglyoxal. Methylglyoxal-derived metabolites included carboxyethyl-arginine, carboxyethyl-lysine, and methylglyoxal hydroimidazolone-1. Detoxification metabolites included reduced and oxidized glutathione, and the glyoxalase cycle products lactoyl-glutathione and lactoyl-Lysine modified proteins. Plasma was collected at study entry, in the fasting state, and assayed by liquid chromatography-mass spectroscopy. Incident clinical outcomes included diabetes, chronic kidney disease, hypertension, neurocognitive impairment, peripheral neuropathy, frailty, fractures, recurrent falls, and all-cause mortality. Among 376 participants, higher baseline plasma concentrations of methylglyoxal derived AGEs predicted increased risks of diabetes, chronic kidney disease, and recurrent falls, while higher 3-deoxyglucosone predicted an increased risk of peripheral neuropathy. By contrast, higher baseline concentrations of reduced or oxidized glutathione, lactoyl-glutathione, and/or lactoyl-Lysine modified proteins predicted lower risks of diabetes, neurocognitive impairment, frailty, fractures, recurrent falls, and all-cause mortality. These findings support growing experimental evidence of the potential to mitigate age-related declines by interventions that reduce glycation or increase glutathione.

Cover page of Pharmacologic Augmentation of Computerized Auditory Training in Chronic Psychosis: Preliminary Findings From a Single-Site, Double-Blind Study

Pharmacologic Augmentation of Computerized Auditory Training in Chronic Psychosis: Preliminary Findings From a Single-Site, Double-Blind Study

(2025)

Background

Computerized auditory training (AT) modestly improves symptoms, cognition, and functioning in schizophrenia. We assessed whether d-amphetamine (AMPH) or memantine (MEM) can enhance gains from 30-h of AT.

Methods

Antipsychotic-medicated individuals with chronic psychosis (n = 68; mean age 47.03y; M:F = 39:29) completed up to 30 AT sessions (2-3/week; n = 50 completed 30 sessions) in 3 groups: "AMPH group" (AMPH (5 mg po) 1-h before each AT session); "MEM group" (titrated to 10 mg MEM bid and maintained that dose throughout training); "PBO group" (PBO dosed identically to either AMPH or MEM). Primary (PANSS total, MCCB Composite, WHODAS) and secondary (PANSS positive, PANSS negative, YMRS, PHQ-9, PSYRATS) outcome measures were acquired at baseline, after 10, 20, and 30 AT sessions, and 12 weeks post-training. Pill identity (active/PBO) was blind to subjects and staff.

Results

Marginally significant between-group gains for AMPH vs PBO were detected for one of three primary outcomes (WHODAS, P =.050; but not PANSS total or MCCB Composite), and for 3 of 5 secondary clinical outcomes (PANSS positive, YMRS, PSYRATS, P's≤.027-.049). Within-subject gains over time were detected for primary and secondary clinical measures for AMPH (P's≤.014-.004) and MEM (P's≤.02-.001) groups; some of these would not survive conservative correction for multiple comparisons. No measures detected symptom worsening; treatment satisfaction exceeded subjects' expectations.

Conclusions

Results are mixed; drug-associated gains in several measures vs PBO suggest that these regimens may augment AT-induced functional and clinical improvement in psychosis patients, independent of changes in neurocognition. Assessment in larger samples seems warranted.

Cover page of Impaired mnemonic pattern separation associated with PTSD symptoms paradoxically improves with regular cannabis use

Impaired mnemonic pattern separation associated with PTSD symptoms paradoxically improves with regular cannabis use

(2025)

Posttraumatic stress disorder (PTSD) is associated with poor hippocampal function and disrupted pattern recognition. Cannabis use is highly prevalent in individuals with PTSD, yet the impact on these cognitive functions is poorly understood. Participants (n = 111) with a range of PTSD symptoms with and without regular cannabis use completed the mnemonic similarity task. We hypothesized that regular use would be associated with alterations in pattern separation ability in individuals with PTSD symptoms. High PTSD symptoms were associated with reduced pattern separation performance in minimal users. Regular users with high PTSD symptoms showed greater pattern separation, but reduced pattern separation with low PTSD symptoms. These results suggest that regular cannabis use may disrupt pattern separation and similar hippocampal-dependent processes, while it may improve pattern separation in individuals with high PTSD symptoms. These cross-sectional results require longitudinal follow-up studies to evaluate the causal effects of regular cannabis use on cognitive function in PTSD.