Transdiagnostic depression severity and its relationship to global and prefrontal-amygdala structural properties in people with major depression and post-traumatic stress disorder.

While some studies have used a transdiagnostic approach to relate depression to metabolic or functional brain alterations, the structural substrate of depression across clinical diagnostic categories is underexplored. In a cross-sectional study of 52 patients with major depressive disorder and 51 with post-traumatic stress disorder, drug-naïve, and spanning mild to severe depression severity, we examined transdiagnostic depressive correlates with regional gray matter volume and the topological properties of gray matter-based networks. Locally, transdiagnostic depression severity correlated positively with gray matter volume in the right middle frontal gyrus and negatively with nodal topological properties of gray matter-based networks in the right amygdala. Globally, transdiagnostic depression severity correlated positively with normalized characteristic path length, a measure implying brain integration ability. Compared with 62 healthy control participants, both major depressive disorder and post-traumatic stress disorder patients showed altered nodal properties in regions of the fronto-limbic-striatal circuit, and global topological organization in major depressive disorder in particular was characterized by decreased integration and segregation. These findings provide evidence for a gray matter-based structural substrate underpinning depression, with the prefrontal-amygdala circuit a potential predictive marker for depressive symptoms across clinical diagnostic categories.

Elucidating trauma-related and disease-related regional cortical activity in post-traumatic stress disorder.

Trauma exposure may precipitate a cascade of plastic modifications within the intrinsic activity of brain regions, but it remains unclear which regions could be responsible for the development of post-traumatic stress disorder based on intrinsic activity. To elucidate trauma-related and post-traumatic stress disorder-related alterations in cortical intrinsic activity at the whole-brain level, we recruited 47 survivors diagnosed with post-traumatic stress disorder, 64 trauma-exposed controls from a major earthquake, and 46 age- and sex-matched healthy controls. All subjects were scanned with an echo-planar imaging sequence, and 5 parameters including the amplitude of low-frequency fluctuations, fractional amplitude of low-frequency fluctuations, regional homogeneity, degree centrality, and voxel-mirrored homotopic connectivity were calculated. We found both post-traumatic stress disorder patients and trauma-exposed controls exhibited decreased amplitude of low-frequency fluctuations in the bilateral posterior cerebellum and inferior temporal gyrus, decreased fractional amplitude of low-frequency fluctuation and regional homogeneity in the bilateral anterior cerebellum, and decreased fractional amplitude of low-frequency fluctuation in the middle occipital gyrus and cuneus compared to healthy controls, and these impairments were more severe in post-traumatic stress disorder patients than in trauma-exposed controls. Additionally, fractional amplitude of low-frequency fluctuation in left cerebellum was positively correlated with Clinician-Administered PTSD Scale scores in post-traumatic stress disorder patients. We identified brain regions that might be responsible for the emergence of post-traumatic stress disorder, providing important information for the treatment of this disorder.

Can you remember silence? Epigenetic memory and reversibility as a site of intervention.

Just over 20 years ago, molecular biologists Leonie Ringrose and Renato Paro published an article with a provocative title, "Remembering Silence", in BioEssays. The article focused on how epigenetic elements could return to their silent state, operationally defined as their epigenetic status before their modulation by experimental or environmental factors. Though Ringrose and Paro's article was on fruit flies and factors affecting embryological growth, the article asked a question of considerable importance to rapidly expanding research in neuroepigenetics on the correlation between trauma and neuropsychiatric risk: If you experience a traumatic event and, as a result, acquire an epigenetic trait that is considered pathological, can you free yourself of that trait? Ultimately, we are interested in how a return to silence is envisioned in neuroepigenetics research, how interventions purported to bring about that silence might function, and what this might mean for people who live in the aftermath of trauma.

Resilience and Mental-Health Symptoms in ICU Healthcare Professionals Facing Repeated COVID-19 Waves.

Rationale: Psychological resilience (the ability to thrive in adversity) may protect against mental-health symptoms in healthcare professionals during coronavirus disease (COVID-19) waves. Objectives: To identify determinants of resilience in ICU staff members. Methods: In this cross-sectional survey in 21 French ICUs, staff members completed the 10-item Connor-Davidson Resilience Scale, Hospital Anxiety and Depression Scale, and Impact of Event Scale-Revised (for post-traumatic stress disorder [PTSD]). Factors independently associated with resilience were identified. Measurements and Main Results: The response rate was 73.1% (950 of 1,300). The median 10-item Connor-Davidson Resilience Scale score was 29 (interquartile range, 25-32). Symptoms of anxiety, depression, and PTSD were present in 61%, 39%, and 36% of staff members, respectively. Distress associated with the COVID-19 infodemic was correlated with symptoms of depression and PTSD. More resilient respondents less often had symptoms of anxiety, depression, and PTSD. Greater resilience was independently associated with male sex, having provided intensive care during the early waves, having managed more than 50 patients with COVID-19, and, compared with earlier waves, working longer hours, having greater motivation, and more often involving families in end-of-life decisions. Independent risk factors for lower resilience were having managed more than 10 patients who died of COVID-19, having felt frightened or isolated, and greater distress from the COVID-19 infodemic. Conclusions: This study identifies modifiable determinants of resilience among ICU staff members. Longitudinal studies are needed to determine whether prior resilience decreases the risk of mental ill health during subsequent challenges. Hospital and ICU managers, for whom preserving mental well-being among staff members is a key duty, should pay careful attention to resilience.

Cortico-limbic interactions and carotid atherosclerotic burden during chronic stress exposure.

BACKGROUND AND AIMS: Chronic stress associates with cardiovascular disease, but mechanisms remain incompletely defined. Advanced imaging was used to identify stress-related neural imaging phenotypes associated with atherosclerosis. METHODS: Twenty-seven individuals with post-traumatic stress disorder (PTSD), 45 trauma-exposed controls without PTSD, and 22 healthy controls underwent 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI). Atherosclerotic inflammation and burden were assessed using 18F-FDG PET (as maximal target-to-background ratio, TBR max) and MRI, respectively. Inflammation was assessed using high-sensitivity C-reactive protein (hsCRP) and leucopoietic imaging (18F-FDG PET uptake in spleen and bone marrow). Stress-associated neural network activity (SNA) was assessed on 18F-FDG PET as amygdala relative to ventromedial prefrontal cortex (vmPFC) activity. MRI diffusion tensor imaging assessed the axonal integrity (AI) of the uncinate fasciculus (major white matter tract connecting vmPFC and amygdala). RESULTS: Median age was 37 years old and 54% of participants were female. There were no significant differences in atherosclerotic inflammation between participants with PTSD and controls; adjusted mean difference in TBR max (95% confidence interval) of the aorta 0.020 (-0.098, 0.138), and of the carotids 0.014 (-0.091, 0.119). Participants with PTSD had higher hsCRP, spleen activity, and aorta atherosclerotic burden (normalized wall index). Participants with PTSD also had higher SNA and lower AI. Across the cohort, carotid atherosclerotic burden (standard deviation of wall thickness) associated positively with SNA and negatively with AI independent of Framingham risk score. CONCLUSIONS: In this study of limited size, participants with PTSD did not have higher atherosclerotic inflammation than controls. Notably, impaired cortico-limbic interactions (higher amygdala relative to vmPFC activity or disruption of their intercommunication) associated with carotid atherosclerotic burden. Larger studies are needed to refine these findings.

New recognition of the heart-brain axis and its implication in the pathogenesis and treatment of PTSD.

Post-traumatic stress disorder (PTSD) is a complex psychological disorder provoked by distressing experiences, and it remains without highly effective intervention strategies. The exploration of PTSD's underlying mechanisms is crucial for advancing diagnostic and therapeutic approaches. Current studies primarily explore PTSD through the lens of the central nervous system, investigating concrete molecular alterations in the cerebral area and neural circuit irregularities. However, the body's response to external stressors, particularly the changes in cardiovascular function, is often pronounced, evidenced by notable cardiac dysfunction. Consequently, examining PTSD with a focus on cardiac function is vital for the early prevention and targeted management of the disorder. This review undertakes a comprehensive literature analysis to detail the alterations in brain and heart structures and functions associated with PTSD. It also synthesizes potential mechanisms of heart-brain axis interactions relevant to the development of PTSD. Ultimately, by considering cardiac function, this review proposes novel perspectives for PTSD's prophylaxis and therapy.

Cortical morphological changes and associated transcriptional signatures in post-traumatic stress disorder and psychological resilience.

BACKGROUND: Individuals who have experienced severe traumatic events are estimated to have a post-traumatic stress disorder (PTSD) prevalence rate ranging from 10 to 50%, while those not affected by trauma exposure are often considered to possess psychological resilience. However, the neural mechanisms underlying the development of PTSD, especially resilience after trauma, remain unclear. This study aims to investigate changes of cortical morphometric similarity network (MSN) in PTSD and trauma-exposed healthy individuals (TEHI), as well as the associated molecular alterations in gene expression, providing potential targets for the prevention and intervention of PTSD. METHODS: We recruited PTSD patients and TEHI who had experienced severe earthquakes, and healthy controls who had not experienced earthquakes. We identified alterations in the whole-brain MSN changes in PTSD and TEHI, and established associations between these changes and brain-wide gene expression patterns from the Allen Human Brain Atlas microarray dataset using partial least squares regression. RESULTS: At the neuroimaging level, we found not only trauma-susceptible changes in TEHI same as those in PTSD, but also unique neurobiological alterations to counteract the deleterious impact of severe trauma. We identified 1444 and 2214 genes transcriptionally related to MSN changes in PTSD and TEHI, respectively. Functional enrichment analysis of weighted gene expression for PTSD and TEHI revealed distinct enrichments in Gene Ontology biological processes and Kyoto Encyclopedia of Genes and Genomes pathways. Furthermore, gene expression profiles of astrocytes, excitatory neurons, and microglial cells are highly related to MSN abnormalities in PTSD. CONCLUSIONS: The formation of resilience may be by an active compensatory process of the brain. The combination of macroscopic neuroimaging changes and microscopic human brain transcriptomics could offer a more direct and in-depth understanding of the pathogenesis of PTSD and psychological resilience, shedding light on new targets for the prevention and treatment of PTSD.

A guided single session intervention to reduce intrusive memories of work-related trauma: a randomised controlled trial with healthcare workers in the COVID-19 pandemic.

BACKGROUND: Intrusive memories of psychologically traumatic events bring distress both sub-clinically and clinically. This parallel-group, two-arm randomised controlled trial evaluated the effect of a brief behavioural intervention on reducing intrusive memories in frontline healthcare workers exposed to traumatic events during the COVID-19 pandemic. METHODS: Participants with at least two intrusive memories of work-related trauma in the week before recruitment were randomised 1:1 to an imagery-competing task intervention (n = 73) or attention-based control task (n = 71). The number of intrusive memories was assessed at baseline and 5 weeks after the guided session (primary endpoint). RESULTS: The intervention significantly reduced intrusive memory frequency compared with control [intervention Mdn = 1.0 (IQR = 0-3), control Mdn = 5.0 (IQR = 1-17); p < 0.0001, IRR = 0.30; 95% CI = 0.17-0.53] and led to fewer post-traumatic stress-related symptoms at 1, 3 and 6 month follow-ups (secondary endpoints). Participants and statisticians were blinded to allocation. Adverse events data were acquired throughout the trial, demonstrating safety. There was high adherence and low attrition. CONCLUSIONS: This brief, single-symptom, repeatable digital intervention for subclinical-to-clinical samples after trauma allows scalability, taking a preventing-to-treating approach after trauma. TRIAL REGISTRATION: 2020-07-06, ClinicalTrials.gov identifier: NCT04460014.

Disruptions in Sleep Health and Independent Associations with Psychological Distress in Close Family Members of Cardiac Arrest Survivors: A Prospective Study.

BACKGROUND: While recent guidelines have noted the deleterious effects of poor sleep on cardiovascular health, the upstream impact of cardiac arrest-induced psychological distress on sleep health metrics among families of cardiac arrest survivors remains unknown. METHODS: Sleep health of close family members of consecutive cardiac arrest patients admitted to an academic center (8/16/2021 - 6/28/2023) was self-reported using the Pittsburgh Sleep Quality Index (PSQI). The baseline PSQI, focused on sleep in the month before cardiac arrest, was administered during hospitalization and repeated one month after cardiac arrest, alongside the Patient Health Questionnaire-8 (PHQ-8) to assess depression severity. Multivariable linear regressions analyzed associations between total PHQ-8 scores and changes in global PSQI scores between baseline and one month with higher scores indicating deterioration. A prioritization exercise explored potential interventions categorized into the family's information and well-being needs to reduce psychological distress. RESULTS: In our sample of 102 close family members (mean age 52±15 years, 70% female, 21% Black, 33% Hispanic), mean global PSQI scores showed a significant decline between baseline and one month after cardiac arrest (6.2±3.8 vs. 7.4±4.1; p<0.01). This deterioration was notable for sleep quality, duration, and daytime dysfunction. Higher PHQ-8 scores were significantly associated with higher change in PSQI scores, after adjusting for family members' age, sex, race/ethnicity, prior psychiatric history, and patient's discharge disposition [B=0.4 (95% C.I 0.24, 0.48); p<0.01, ß=0.5]. Most families expressed a higher priority for information-based interventions over well-being needs to help alleviate psychological distress during the first month following cardiac arrest (76% vs. 34%, p<0.01). CONCLUSIONS: A significant sleep health decline was observed among close family members of cardiac arrest survivors during the acute period, with psychological distress associated with this disruption. Understanding these temporal associations will help guide the development of targeted interventions to support families during this uncertain time.

Prevalence of anxiety, depression, and post-traumatic stress disorder among Omani children and adolescents diagnosed with cancer: a prospective cross-sectional study.

BACKGROUND: Children and adolescents diagnosed with cancer often experience psychological distress, encompassing anxiety, depression, and post-traumatic stress disorder (PTSD). This study aimed to evaluate the prevalence of these conditions among Omani children and adolescents diagnosed with cancer, alongside identifying contributing factors. METHODS: A prospective cross-sectional study was conducted from October 2021 to June 2023 among a cohort of Omani children and adolescents (6-18 years old) diagnosed with cancer at three primary cancer referral centres in Oman. Validated Arabic-language versions of the Screen for Child Anxiety Related Disorders, the Center for Epidemiologic Studies Depression Scale for Children, and the Impact of Event Scale-Revised instruments were used to assess symptoms of anxiety, depression, and PTSD, respectively. An initial assessment (T1) was undertaken within the first 3 months of diagnosis, followed by a second assessment (T2) 3-6 months later. RESULTS: Of 113 eligible participants, 101 agreed to participate in the study (response rate: 95.6%), with 92 (91.0%) completing both assessments and included in the final analysis. Prevalence rates of anxiety, depression, and PTSD decreased from 43.5%, 56.5%, and 32.6%, respectively, at T1, to 38.0%, 35.9%, and 23.9% at T2. All average scores were below diagnostic cut-off points, except for the depression score at T1. Anxiety and depression scores decreased significantly (p = 0.043 and 0.001, respectively) between T1 and T2, as did the overall prevalence of depression (p = 0.004). At T1, linear regression analysis showed significant correlations between anxiety scores and the child's age and PTSD score (p < 0.05); these variables were also correlated with depression scores (p ≤ 0.001). At T2, significant correlations were observed between anxiety scores and the child's age and PTSD scores (p < 0.001). At both T1 and T2, anxiety, depression, and PTSD scores remained significantly correlated (p < 0.001). CONCLUSIONS: Omani children and adolescents recently diagnosed with cancer exhibit a high prevalence of anxiety, depression, and PTSD over time. Age-appropriate communication, ongoing support, and mental health services are recommended to help this patient group cope with their diagnosis and manage their emotional wellbeing. There is a need for future research to determine the effectiveness of specific psychological interventions in reducing the frequency of these disorders.

Post-traumatic stress disorder symptom remission and cognition in a large cohort of civilian women.

BACKGROUND: Post-traumatic stress disorder (PTSD) is associated with cognitive impairments. It is unclear whether problems persist after PTSD symptoms remit. METHODS: Data came from 12 270 trauma-exposed women in the Nurses' Health Study II. Trauma and PTSD symptoms were assessed using validated scales to determine PTSD status as of 2008 (trauma/no PTSD, remitted PTSD, unresolved PTSD) and symptom severity (lifetime and past-month). Starting in 2014, cognitive function was assessed using the Cogstate Brief Battery every 6 or 12 months for up to 24 months. PTSD associations with baseline cognition and longitudinal cognitive changes were estimated by covariate-adjusted linear regression and linear mixed-effects models, respectively. RESULTS: Compared to women with trauma/no PTSD, women with remitted PTSD symptoms had a similar cognitive function at baseline, while women with unresolved PTSD symptoms had worse psychomotor speed/attention and learning/working memory. In women with unresolved PTSD symptoms, past-month PTSD symptom severity was inversely associated with baseline cognition. Over follow-up, both women with remitted and unresolved PTSD symptoms in 2008, especially those with high levels of symptoms, had a faster decline in learning/working memory than women with trauma/no PTSD. In women with remitted PTSD symptoms, higher lifetime PTSD symptom severity was associated with a faster decline in learning/working memory. Results were robust to the adjustment for sociodemographic, biobehavioral, and health factors and were partially attenuated when adjusted for depression. CONCLUSION: Unresolved but not remitted PTSD was associated with worse cognitive function assessed six years later. Accelerated cognitive decline was observed among women with either unresolved or remitted PTSD symptoms.

Alterations in fear learning as a mechanism linking childhood exposure to violence with PTSD symptoms: a longitudinal study.

BACKGROUND: Fear learning is a core component of conceptual models of how adverse experiences may influence psychopathology. Specifically, existing theories posit that childhood experiences involving childhood trauma are associated with altered fear learning processes, while experiences involving deprivation are not. Several studies have found altered fear acquisition in youth exposed to trauma, but not deprivation, although the specific patterns have varied across studies. The present study utilizes a longitudinal sample of children with variability in adversity experiences to examine associations among childhood trauma, fear learning, and psychopathology in youth. METHODS: The sample includes 170 youths aged 10-13 years (M = 11.56, s.d. = 0.47, 48.24% female). Children completed a fear conditioning task while skin conductance responses (SCR) were obtained, which included both acquisition and extinction. Childhood trauma and deprivation severity were measured using both parent and youth report. Symptoms of anxiety, externalizing problems, and post-traumatic stress disorder (PTSD) were assessed at baseline and again two-years later. RESULTS: Greater trauma-related experiences were associated with greater SCR to the threat cue (CS+) relative to the safety cue (CS-) in early fear acquisition, controlling for deprivation, age, and sex. Deprivation was unrelated to fear learning. Greater SCR to the threat cue during early acquisition was associated with increased PTSD symptoms over time controlling for baseline symptoms and mediated the relationship between trauma and prospective changes in PTSD symptoms. CONCLUSIONS: Childhood trauma is associated with altered fear learning in youth, which may be one mechanism linking exposure to violence with the emergence of PTSD symptoms in adolescence.

Amygdala-related electrical fingerprint is modulated with neurofeedback training and correlates with deep-brain activation: proof-of-concept in borderline personality disorder.

BACKGROUND: The modulation of brain circuits of emotion is a promising pathway to treat borderline personality disorder (BPD). Precise and scalable approaches have yet to be established. Two studies investigating the amygdala-related electrical fingerprint (Amyg-EFP) in BPD are presented: one study addressing the deep-brain correlates of Amyg-EFP, and a second study investigating neurofeedback (NF) as a means to improve brain self-regulation. METHODS: Study 1 combined electroencephalography (EEG) and simultaneous functional magnetic resonance imaging to investigate the replicability of Amyg-EFP-related brain activation found in the reference dataset (N = 24 healthy subjects, 8 female; re-analysis of published data) in the replication dataset (N = 16 female individuals with BPD). In the replication dataset, we additionally explored how the Amyg-EFP would map to neural circuits defined by the research domain criteria. Study 2 investigated a 10-session Amyg-EFP NF training in parallel to a 12-weeks residential dialectical behavior therapy (DBT) program. Fifteen patients with BPD completed the training, N = 15 matched patients served as DBT-only controls. RESULTS: Study 1 replicated previous findings and showed significant amygdala blood oxygenation level dependent activation in a whole-brain regression analysis with the Amyg-EFP. Neurocircuitry activation (negative affect, salience, and cognitive control) was correlated with the Amyg-EFP signal. Study 2 showed Amyg-EFP modulation with NF training, but patients received reversed feedback for technical reasons, which limited interpretation of results. CONCLUSIONS: Recorded via scalp EEG, the Amyg-EFP picks up brain activation of high relevance for emotion. Administering Amyg-EFP NF in addition to standardized BPD treatment was shown to be feasible. Clinical utility remains to be investigated.

Neighborhood social composition and refugee mental health - quasi-experimental evidence of associations from a Danish population register study.

BACKGROUND: Refugees are at an elevated risk of some mental disorders with studies highlighting the contributing role of post-migration factors. Studies of migrant groups show neighborhood social composition, such as ethnic density, to be important. This is the first longitudinal study to examine this question for refugees and uses a novel quasi-experimental design. METHODS: We followed a cohort of 44 033 refugees from being first assigned housing under the Danish dispersal policy, operating from 1986 to 1998, until 2019. This comprised, in effect, a natural experiment whereby the influence of assigned neighborhood could be determined independently of endogenous factors. We examined three aspects of neighborhood social composition: proportion of co-nationals, refugees, and first-generation migrants; and subsequent incidence of different mental disorders. RESULTS: Refugees assigned to neighborhoods with fewer co-nationals (lowest v. highest quartile) were more likely to receive a subsequent diagnosis of non-affective psychosis, incident rate ratio (IRR) 1.25 (95% confidence interval (CI) 1.06-1.48), and post-traumatic stress disorder (PTSD), IRR 1.21 (95% CI I.05-1.39). A comparable but smaller effect was observed for mood disorders but none observed for stress disorders overall. Neighborhood proportion of refugees was less clearly associated with subsequent mental disorders other than non-affective psychosis, IRR 1.24 (95% CI 1.03-1.50). We found no statistically significant associations with proportion of migrants. CONCLUSIONS: For refugees, living in a neighborhood with a lower proportion of co-nationals is related to subsequent increased risk of diagnosed mental disorders particularly non-affective psychosis and PTSD.

Salivary inflammatory biomarkers as a predictor of post-traumatic stress disorder and depressive symptom severity in trauma patients: A prospective study.

BACKGROUND: Although post-traumatic stress disorder (PTSD) and depression screening are recommended for traumatic injury patients, routine screening is still uncommon. Salivary inflammatory biomarkers have biological plausibility and potential feasibility and acceptability for screening. This study tested prospective associations between several salivary inflammatory biomarkers (proinflammatory cytokines interleukin-1ß, interleukin-6, tumor necrosis factor-α; and C-reactive protein), collected during hospitalization and PTSD and depressive symptoms at 5-month follow-up. METHODS: Adult traumatic injury patients (N = 696) at a major urban Level 1 trauma center provided salivary samples and completed PTSD and depressive symptom measures during days 0-13 of inpatient hospitalization. At 5-month follow-up, 368 patients (77 % male, 23 % female) completed the Clinician-Administered PTSD Scale for DSM-IV and the Self-rated Inventory of Depressive Symptomatology. Analyses focused on a latent inflammatory cytokine factor and C-reactive protein at baseline predicting 5-month PTSD and depression symptom outcomes and included baseline symptom levels as covariates. RESULTS: A latent factor representing proinflammatory cytokines was not related to 5-month PTSD or depressive symptom severity. Higher salivary CRP was related to greater PTSD symptom severity (ß = .10, p = .03) at 5-month follow-up and more severity in the following depressive symptoms: changes in weight and appetite, bodily complaints, and constipation/diarrhea (ß's from .14 to .16, p's from .004 -.03). CONCLUSION: In a primarily Latine and Black trauma patient sample, salivary CRP measured after traumatic injury was related to greater PTSD symptom severity and severity in several depressive symptom clusters. Our preliminary findings suggest that salivary or systemic CRP may be useful to include in models predicting post-trauma psychopathology.

Cannabidiol ameliorates PTSD-like symptoms by inhibiting neuroinflammation through its action on CB2 receptors in the brain of male mice.

Post-traumatic stress disorder (PTSD) is a debilitating mental health disease related to traumatic experience, and its treatment outcomes are unsatisfactory. Accumulating research has indicated that cannabidiol (CBD) exhibits anti-PTSD effects, however, the underlying mechanism of CBD remains inadequately investigated. Although many studies pertaining to PTSD have primarily focused on aberrations in neuronal functioning, the present study aimed to elucidate the involvement and functionality of microglia/macrophages in PTSD while also investigated the modulatory effects of CBD on neuroinflammation associated with this condition. We constructed a modified single-prolonged stress (SPS) mice PTSD model and verified the PTSD-related behaviors by various behavioral tests (contextual freezing test, elevated plus maze test, tail suspension test and novel object recognition test). We observed a significant upregulation of Iba-1 and alteration of microglial/macrophage morphology within the prefrontal cortex and hippocampus, but not the amygdala, two weeks after the PTSD-related stress, suggesting a persistent neuroinflammatory phenotype in the PTSD-modeled group. CBD (10 mg/kg, i.p.) inhibited all PTSD-related behaviors and reversed the alterations in both microglial/macrophage quantity and morphology when administered prior to behavioral assessments. We further found increased pro-inflammatory factors, decreased PSD95 expression, and impaired synaptic density in the hippocampus of the modeled group, all of which were also restored by CBD treatment. CBD dramatically increased the level of anandamide, one of the endocannabinoids, and cannabinoid type 2 receptors (CB2Rs) transcripts in the hippocampus compared with PTSD-modeled group. Importantly, we discovered the expression of CB2Rs mRNA in Arg-1-positive cells in vivo and found that the behavioral effects of CBD were diminished by CB2Rs antagonist AM630 (1 mg/kg, i.p.) and both the behavioral and molecular effects of CBD were abolished in CB2Rs knockout mice. These findings suggest that CBD would alleviate PTSD-like behaviors in mice by suppressing PTSD-related neuroinflammation and upregulation and activation of CB2Rs may serve as one of the underlying mechanisms for this therapeutic effect. The present study offers innovative experimental evidence supporting the utilization of CBD in PTSD treatment from the perspective of its regulation of neuroinflammation, and paves the way for leveraging the endocannabinoid system to regulate neuroinflammation as a potential therapeutic approach for psychiatric disorders.

New Insights into Contradictory Changes in Brain-Derived Neurotrophic Factor (BDNF) in Rodent Models of Posttraumatic Stress Disorder (PTSD).

Post-traumatic stress disorder (PTSD) is a neuropsychiatric disorder that may develop after experiencing traumatic events. Preclinical studies use various methods to induce PTSD-like models such as fear-conditioning, single-prolonged stress (SPS), restraint stress, and social defeat. Brain-derived neurotrophic factor (BDNF) is a crucial neurotrophin in mood regulation. Evidence shows BDNF changes in different neuropsychiatric disorders particularly PTSD. This review examined BDNF alterations in preclinical rodent models of PTSD where we demonstrated a wide range of paradoxical changes in BDNF. We found that the fear-conditioning model produced the most inconsistent alterations in BDNF, and suggest that conclusions drawn from these changes be approached with caution. We suggest that BDNF maladaptive changes in social defeat and restraint stress models may be related to the duration of stress, while the SPS model appears to have more consistent results. Ultimately, we propose that evaluating BDNF alterations in the process of treating PTSD symptoms may not be a reliable factor.

The effect of cognitive behavioural therapy and eye movement desensitization and reprocessing techniques on infertile women: a randomized controlled trial.

RESEARCH QUESTION: What effects do training programmes based on cognitive behavioural therapy (CBT) and eye movement desensitization and reprocessing (EMDR) techniques applied to infertile women affected psychologically and emotionally by infertility have on post-traumatic stress disorder (PTSD) and psychological development? DESIGN: This randomized controlled study was conducted between May 2021 and August 2022. The study population included 90 infertile women referred to the IVF unit of a hospital in a province in eastern Turkey: 30 in the CBT group, 30 in the EMDR group and 30 in the control group. Data were collected using a personal information form, the Subjective Units of Disturbance Scale (SUDS), the Validity of Cognition (VoC) scale, the Infertility Distress Scale (IDS), the Impact of Event Scale-Revised (IES-R) and the Post-traumatic Growth Inventory (PTGI). Women in the experimental groups (CBT and EMDR groups) received the intervention in six sessions over 3 weeks. Pre-tests were administered to both experimental groups and the control group, and post-tests were conducted 3 weeks after the intervention. RESULTS: The mean scores on the SUDS, IDS and IES-R for women in the experimental groups were significantly lower compared with those for women in the control group following the interventions (P < 0.001). The mean scores on the VoC scale and PTGI for women in the experimental groups were significantly higher compared with those for women in the control group following the interventions (P < 0.001). CONCLUSION: The use of CBT and EMDR techniques reduced the negative psychological and emotional effects of infertility among infertile women.

Perpetuating and protective factors in insomnia across racial/ethnic groups of veterans.

Few studies have examined racial/ethnic differences in rates and correlates of insomnia among veterans. This study compared rates of insomnia and interest in sleep treatment among veterans of diverse racial/ethnic backgrounds. Consistent with the 3P model, we tested racial discrimination as a predictor of insomnia, with post-traumatic stress disorder symptoms and romantic partners as perpetuating and protective moderators of this association, respectively. A total of 325 veterans (N = 236 veterans of colour; 12% Asian, 36% Black, 14% Hispanic/Latine) completed questionnaires online from remote locations. Descriptive statistics were used to compare patterns across racial/ethnic groups. Linear regression was used to test moderators of the association between racial discrimination and insomnia severity. Overall, 68% of participants screened positive for insomnia: 90% of Asian; 79% of Hispanic/Latine; 65% of Black; and 58% of White participants. Of those, 74% reported interest in sleep treatment, and 76% of those with partners reported interest in including their partner in treatment. Racial discrimination and post-traumatic stress disorder were correlated with more severe insomnia, while romantic partners were correlated with less severe insomnia. Only post-traumatic stress disorder moderated the association between racial discrimination and insomnia severity. Rates of insomnia were highest among Asian and Hispanic/Latine participants, yet these groups were among the least likely to express interest in sleep treatment. Racial discrimination may exacerbate insomnia symptoms among veterans, but only among those who do not already have disturbed sleep in the context of post-traumatic stress disorder. Romantic partners may serve as a protective factor in insomnia, but do not seem to mitigate the impact of racial discrimination.