A systematic review of written exposure therapy for the treatment of posttraumatic stress symptoms.

OBJECTIVE: Written exposure therapy (WET) is a brief treatment for posttraumatic stress disorder (PTSD), with an increasing number of studies published over the past several years. The current study conducted a systematic review to evaluate the current state of evidence for WET as a treatment for PTSD symptom severity. METHOD: Four databases were searched: PsycInfo, PTSDpubs, MEDLINE, and PubMed. Inclusion criteria included a peer-reviewed study of WET, a PTSD treatment outcome measure at pre- and posttreatment, and full-text available in English. RESULTS: Seventeen studies were identified for inclusion, seven of which were randomized controlled trials. Study sample sizes ranged from three to 277, with most studies (88%) examining adults. Five studies used a language translation version of WET, two studies examined a group format, and three studies examined PTSD symptom outcome when WET was delivered via telehealth. Within condition effect sizes for PTSD treatment outcome were moderate to large (d range = 0.48-6.45), and between condition effect sizes were large (d range = 1.05-5.25), except for three studies that included a trauma-focused treatment comparison condition (d range = 0.01-0.31). Dropout rates for WET were generally low, and less when compared with other trauma-focused treatments. CONCLUSIONS: The published studies indicate that WET is an efficacious and effective treatment for PTSD symptoms across a variety of samples, settings, and counties. Future work in this area should include investigation of the implementation and dissemination of WET. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Preclinical translational platform of neuroinflammatory disease biology relevant to neurodegenerative disease.

Neuroinflammation is a key driver of neurodegenerative disease, however the tools available to model this disease biology at the systems level are lacking. We describe a translational drug discovery platform based on organotypic culture of murine cortical brain slices that recapitulate disease-relevant neuroinflammatory biology. After an acute injury response, the brain slices assume a chronic neuroinflammatory state marked by transcriptomic profiles indicative of activation of microglia and astrocytes and loss of neuronal function. Microglia are necessary for manifestation of this neuroinflammation, as depletion of microglia prior to isolation of the brain slices prevents both activation of astrocytes and robust loss of synaptic function genes. The transcriptomic pattern of neuroinflammation in the mouse platform is present in published datasets derived from patients with amyotrophic lateral sclerosis, Huntington's disease, and frontotemporal dementia. Pharmacological utility of the platform was validated by demonstrating reversal of microglial activation and the overall transcriptomic signature with transforming growth factor-ß. Additional anti-inflammatory targets were screened and inhibitors of glucocorticoid receptors, COX-2, dihydrofolate reductase, and NLRP3 inflammasome all failed to reverse the neuroinflammatory signature. Bioinformatics analysis of the neuroinflammatory signature identified protein tyrosine phosphatase non-receptor type 11 (PTPN11/SHP2) as a potential target. Three structurally distinct inhibitors of PTPN11 (RMC-4550, TN0155, IACS-13909) reversed the neuroinflammatory disease signature. Collectively, these results highlight the utility of this novel neuroinflammatory platform for facilitating identification and validation of targets for neuroinflammatory neurodegenerative disease drug discovery.

Methodological considerations for collecting and analyzing data on multiply marginalized psychology trainees with disabilities.

OBJECTIVE/PURPOSE: Historically, psychology trainees from marginalized communities have been underrepresented both as researchers and as participants in research on trainee experiences and outcomes. The current research can be used to develop evidence-based strategies to understand and improve the recruitment, retention, advancement, and overall training experiences of trainees with marginalized identities. METHOD: We review the existing literature on the experiences of psychology trainees, particularly that focused on trainees from marginalized backgrounds. RESULTS: Quantitative, qualitative, and archival data collection and analysis methods each carry their own benefits and limitations, which must be considered and addressed intentionally to optimize the impact of research findings for multiply marginalized individuals. Mixed methods approaches are also discussed. Matching each limitation with a research design strategy is recommended, including the use of sample weights from population archival data to contextualize sample results, incorporating flexibility for reasonable accommodations for intensive qualitative studies, and other strategies. CONCLUSIONS/IMPLICATIONS: We provide guidance on selecting a methodology based on specific research and dissemination goals within this area and discuss implications and recommendations for both rehabilitation psychology specifically and the field more broadly. Training programs, governing bodies, faculty, researchers, and other invested parties have shared accountability to deliver diverse, equitable, and inclusive education and training experiences, and conducting high-quality research on the experiences of multiply marginalized trainees, including those with disabilities, is a key component of that process. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Emotion dysregulation, help-seeking attitudes, and posttraumatic stress disorder symptoms: A structural equation model.

Objective: Most college students have experienced an adverse event in their lifetime, yet help-seeking rates remain low. This study seeks to understand psychological factors that might contribute to delays in treatment initiation among trauma-affected students. Participants: Our sample consisted of 531 undergraduate students of which 27% scored above the clinical cutoff for PTSD using the PTSD Checklist for DSM-5 (PCL-5). Methods: This cross-sectional study explored relationships among help-seeking attitudes, emotion dysregulation, and PTSD symptoms using structural equation modeling. Results: Findings demonstrated that individuals with more severe emotion dysregulation had more severe PTSD symptoms and held more negative attitudes toward seeking help. Conclusions: Individuals who are the most in need of treatment hold attitudes that may impede help-seeking. We discuss clinical implications and ways college counseling centers can maximize outreach and programming efforts to increase treatment initiation and engagement.

Gadd45b Acts as Neuroprotective Effector in Global Ischemia-Induced Neuronal Death.

PURPOSE: Transient global ischemia arising in human due to cardiac arrest causes selective, delayed neuronal death in hippocampal CA1 and cognitive impairment. Growth arrest and DNA-damage-inducible protein 45 beta (Gadd45b) is a wellknown molecule in both DNA damage-related pathogenesis and therapies. Emerging evidence suggests that Gadd45b is an anti-apoptotic factor in nonneuronal cells and is an intrinsic neuroprotective molecule in neurons. However, the mechanism of Gadd45b pathway is not fully examined in neurodegeneration associated with global ischemia. METHODS: Rats were subjected to transient global ischemia by the 4-vessel occlusion or sham operation. The animals were sacrificed at 24 hours, 48 hours, and 7 days after ischemia. The hippocampal CA1 was microdissected and processed to examine mRNA and protein level. To assess neuronal death, tissue sections were cut and processed for Fluoro-Jade and Nissl staining. RESULTS: Here we show that ischemic insults increase abundance of Gadd45b and brain-derived neurotrophic factor, a known target of Gadd45 mediated demethylation, in selectively-vulnerable hippocampal CA1 neurons. We further show that knockdown of Gadd45b increases abundance of a pro-apoptotic Bcl-2 family member Bax while decreasing the antiapoptotic protein Bcl-2, which together promote neuronal death. CONCLUSION: These findings document a protective role of Gadd45b against neuronal insults associated with global ischemia and identify Gadd45b as a potential therapeutic target for the amelioration of hippocampal neurodegeneration.

Loss-of-Huntingtin in Medial and Lateral Ganglionic Lineages Differentially Disrupts Regional Interneuron and Projection Neuron Subtypes and Promotes Huntington's Disease-Associated Behavioral, Cellular, and Pathological Hallmarks.

Emerging studies are providing compelling evidence that the pathogenesis of Huntington's disease (HD), a neurodegenerative disorder with frequent midlife onset, encompasses developmental components. Moreover, our previous studies using a hypomorphic model targeting huntingtin during the neurodevelopmental period indicated that loss-of-function mechanisms account for this pathogenic developmental component (Arteaga-Bracho et al., 2016). In the present study, we specifically ascertained the roles of subpallial lineage species in eliciting the previously observed HD-like phenotypes. Accordingly, we used the Cre-loxP system to conditionally ablate the murine huntingtin gene (Httflx) in cells expressing the subpallial patterning markers Gsx2 (Gsx2-Cre) or Nkx2.1 (Nkx2.1-Cre) in Httflx mice of both sexes. These genetic manipulations elicited anxiety-like behaviors, hyperkinetic locomotion, age-dependent motor deficits, and weight loss in both Httflx;Gsx2-Cre and Httflx;Nkx2.1-Cre mice. In addition, these strains displayed unique but complementary spatial patterns of basal ganglia degeneration that are strikingly reminiscent of those seen in human cases of HD. Furthermore, we observed early deficits of somatostatin-positive and Reelin-positive interneurons in both Htt subpallial null strains, as well as early increases of cholinergic interneurons, Foxp2+ arkypallidal neurons, and incipient deficits with age-dependent loss of parvalbumin-positive neurons in Httflx;Nkx2.1-Cre mice. Overall, our findings indicate that selective loss-of-huntingtin function in subpallial lineages differentially disrupts the number, complement, and survival of forebrain interneurons and globus pallidus GABAergic neurons, thereby leading to the development of key neurological hallmarks of HD during adult life. Our findings have important implications for the establishment and deployment of neural circuitries and the integrity of network reserve in health and disease.SIGNIFICANCE STATEMENT Huntington's disease (HD) is a progressive degenerative disorder caused by aberrant trinucleotide expansion in the huntingtin gene. Mechanistically, this mutation involves both loss- and gain-of-function mechanisms affecting a broad array of cellular and molecular processes. Although huntingtin is widely expressed during adult life, the mutant protein only causes the demise of selective neuronal subtypes. The mechanisms accounting for this differential vulnerability remain elusive. In this study, we have demonstrated that loss-of-huntingtin function in subpallial lineages not only differentially disrupts distinct interneuron species early in life, but also leads to a pattern of neurological deficits that are reminiscent of HD. This work suggests that early disruption of selective neuronal subtypes may account for the profiles of enhanced regional cellular vulnerability to death in HD.