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ENeuro Jun 2024Epilepsy is often comorbid with psychiatric illnesses, including anxiety and depression. Despite the high incidence of psychiatric comorbidities in people with epilepsy,...
Epilepsy is often comorbid with psychiatric illnesses, including anxiety and depression. Despite the high incidence of psychiatric comorbidities in people with epilepsy, few studies address the underlying mechanisms. Stress can trigger epilepsy and depression. Evidence from human and animal studies support that hypothalamic-pituitary-adrenal (HPA) axis dysfunction may contribute to both disorders as well as their comorbidity (Kanner, 2003). Here, we investigate if HPA axis dysfunction may influence epilepsy outcomes and psychiatric comorbidities. We generated a novel mouse model (/ KO mice) lacking the K/Cl co-transporter, KCC2, in corticotropin-releasing hormone (CRH) neurons, which exhibit stress- and seizure-induced HPA axis hyperactivation (Melon et al., 2018). We used the / KO mice to examine the impact on epilepsy outcomes, including seizure frequency/burden, comorbid behavioral deficits, and SUDEP risk. We found sex differences in HPA axis dysfunction's effect on chronically epileptic KCC2/Crh KO mice seizure burden, vulnerability to comorbid behavioral deficits, and SUDEP. Suppressing HPA axis hyperexcitability in this model using pharmacological or chemogenetic approaches decreased SUDEP incidence, suggesting that HPA axis dysfunction may contribute to SUDEP. Altered neuroendocrine markers were present in SUDEP cases compared to people with epilepsy or individuals without epilepsy. Together, these findings implicate HPA axis dysfunction in the pathophysiological mechanisms contributing to psychiatric comorbidities in epilepsy and SUDEP. Our work provides new insight into a potential novel pathophysiological mechanism contributing to psychiatric illnesses and SUDEP in epilepsy patients, implicating HPA axis dysfunction in negative outcomes associated with epilepsy. This study is the first to link HPA axis dysfunction to SUDEP risk. Chronically epileptic male mice with exaggerated HPA axis dysfunction had increased SUDEP incidence. The translational relevance of these findings is supported by neuroendocrine abnormalities observed in postmortem samples from individuals that died of SUDEP. These data suggest that neuroendocrine mechanisms should be further explored in psychiatric comorbidities in epilepsy and SUDEP risk. Further, neuroendocrine markers may be a biomarker for SUDEP risk.
PubMed: 38914464
DOI: 10.1523/ENEURO.0162-24.2024 -
PloS One 2024The cannabinoid receptor type 1 (CB1R) is a promising therapeutic target for various neurodegenerative diseases, including HIV-1-associated neurocognitive disorder...
Cannabinoid receptor 1 positive allosteric modulator ZCZ011 shows differential effects on behavior and the endocannabinoid system in HIV-1 Tat transgenic female and male mice.
The cannabinoid receptor type 1 (CB1R) is a promising therapeutic target for various neurodegenerative diseases, including HIV-1-associated neurocognitive disorder (HAND). However, the therapeutic potential of CB1R by direct activation is limited due to its psychoactive side effects. Therefore, research has focused on indirectly activating the CB1R by utilizing positive allosteric modulators (PAMs). Studies have shown that CB1R PAMs (ZCZ011 and GAT211) are effective in mouse models of Huntington's disease and neuropathic pain, and hence, we assess the therapeutic potential of ZCZ011 in a well-established mouse model of neuroHIV. The current study investigates the effect of chronic ZCZ011 treatment (14 days) on various behavioral paradigms and the endocannabinoid system in HIV-1 Tat transgenic female and male mice. Chronic ZCZ011 treatment (10 mg/kg) did not alter body mass, locomotor activity, or anxiety-like behavior regardless of sex or genotype. However, differential effects were noted in hot plate latency, motor coordination, and recognition memory in female mice only, with ZCZ011 treatment increasing hot plate latency and improving motor coordination and recognition memory. Only minor effects or no alterations were seen in the endocannabinoid system and related lipids except in the cerebellum, where the effect of ZCZ011 was more pronounced in female mice. Moreover, AEA and PEA levels in the cerebellum were positively correlated with improved motor coordination in female mice. In summary, these findings indicate that chronic ZCZ011 treatment has differential effects on antinociception, motor coordination, and memory, based on sex and HIV-1 Tat expression, making CB1R PAMs potential treatment options for HAND without the psychoactive side effects.
Topics: Animals; Female; Male; Mice, Transgenic; Endocannabinoids; Receptor, Cannabinoid, CB1; Mice; tat Gene Products, Human Immunodeficiency Virus; HIV-1; Allosteric Regulation; Behavior, Animal; Motor Activity; Disease Models, Animal
PubMed: 38913661
DOI: 10.1371/journal.pone.0305868 -
ELife Jun 2024Downregulating emotional overreactions toward threats is fundamental for developing treatments for anxiety and post-traumatic disorders. The prefrontal cortex (PFC) is...
Downregulating emotional overreactions toward threats is fundamental for developing treatments for anxiety and post-traumatic disorders. The prefrontal cortex (PFC) is critical for top-down modulatory processes, and despite previous studies adopting repetitive transcranial magnetic stimulation (rTMS) over this region provided encouraging results in enhancing extinction, no studies have hitherto explored the effects of stimulating the medial anterior PFC (aPFC, encompassing the Brodmann area 10) on threat memory and generalization. Here we showed that rTMS over the aPFC applied before threat memory retrieval immediately decreases implicit reactions to learned and novel stimuli in humans. These effects enduringly persisted 1 week later in the absence of rTMS. No effects were detected on explicit recognition. Critically, rTMS over the aPFC resulted in a more pronounced reduction of defensive responses compared to rTMS targeting the dorsolateral PFC. These findings reveal a previously unexplored prefrontal region, the modulation of which can efficiently and durably inhibit implicit reactions to learned threats. This represents a significant advancement toward the long-term deactivation of exaggerated responses to threats.
Topics: Humans; Fear; Prefrontal Cortex; Transcranial Magnetic Stimulation; Male; Young Adult; Female; Adult; Extinction, Psychological
PubMed: 38913410
DOI: 10.7554/eLife.85951 -
JMIR MHealth and UHealth Jun 2024Digital mental health services are increasingly being provided by employers as health benefit programs that can improve access to and remove barriers to mental health... (Observational Study)
Observational Study
BACKGROUND
Digital mental health services are increasingly being provided by employers as health benefit programs that can improve access to and remove barriers to mental health care. Stratified care models, in particular, offer personalized care recommendations that can offer clinically effective interventions while conserving resources. Nonetheless, clinical evaluation is needed to understand their benefits for mental health and their use in a real-world setting.
OBJECTIVE
This study aimed to examine the changes in clinical outcomes (ie, depressive and anxiety symptoms and well-being) and to evaluate the use of stratified blended care among members of an employer-sponsored digital mental health benefit.
METHODS
In a large prospective observational study, we examined the changes in depressive symptoms (9-item Patient Health Questionnaire), anxiety symptoms (7-item Generalized Anxiety Disorder scale), and well-being (5-item World Health Organization Well-Being Index) for 3 months in 509 participants (mean age 33.9, SD 8.7 years; women: n=312, 61.3%; men: n=175, 34.4%; nonbinary: n=22, 4.3%) who were newly enrolled and engaged in care with an employer-sponsored digital mental health platform (Modern Health Inc). We also investigated the extent to which participants followed the recommendations provided to them through a stratified blended care model.
RESULTS
Participants with elevated baseline symptoms of depression and anxiety exhibited significant symptom improvements, with a 37% score improvement in depression and a 29% score improvement in anxiety (P values <.001). Participants with baseline scores indicative of poorer well-being also improved over the study period (90% score improvement; P=.002). Furthermore, over half exhibited clinical improvement or recovery for depressive symptoms (n=122, 65.2%), anxiety symptoms (n=127, 59.1%), and low well-being (n=82, 64.6%). Among participants with mild or no baseline symptoms, we found high rates of maintenance for low depressive (n=297, 92.2%) and anxiety (n=255, 86.7%) symptoms and high well-being (n=344, 90.1%). In total, two-thirds of the participants (n=343, 67.4%) used their recommended care, 16.9% (n=86) intensified their care beyond their initial recommendation, and 15.7% (n=80) of participants underused care by not engaging with the highest level of care recommended to them.
CONCLUSIONS
Participants with elevated baseline depressive or anxiety symptoms improved their mental health significantly from baseline to follow-up, and most participants without symptoms or with mild symptoms at baseline maintained their mental health over time. In addition, engagement patterns indicate that the stratified blended care model was efficient in matching individuals with the most effective and least costly care while also allowing them to self-determine their care and use combinations of services that best fit their needs. Overall, the results of this study support the clinical effectiveness of the platform for improving and preserving mental health and support the utility and effectiveness of stratified blended care models to improve access to and use of digitally delivered mental health services.
Topics: Humans; Female; Male; Adult; Prospective Studies; Longitudinal Studies; Mental Health Services; Middle Aged; Surveys and Questionnaires; Depression; Telemedicine
PubMed: 38913405
DOI: 10.2196/48298 -
International Journal of Occupational... Jun 2024This article aims to present the overview of the situation during the coronavirus disease 2019 (COVID-19) pandemic about issues concerning the prevalence of mental... (Review)
Review
This article aims to present the overview of the situation during the coronavirus disease 2019 (COVID-19) pandemic about issues concerning the prevalence of mental disorders such as depression, anxiety, rate of suicide attempts, and long COVID (LC) infections in the general population during COVID-19 pandemic. Analysis of the literature (in English, Polish and Spanish language) on topics related to COVID-19, mental disorders (suicide attempts, depression, anxiety) and LC infection published during the 4 years (2020-2023) was done using Pubmed and PubMed Central search engine. Keywords such as "COVID-19," "mental disorders," "long COVID infection," "depression," "anxiety," "suicide attempts" were used during the search. The conduct of this review/comment followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) protocol, which corresponds to a checklist of 27 items designed to facilitate the development and reporting of a robust protocol for systematic reviews or meta-analyses. Overall 35 studies were selected and analyzed in the review on topics: including among others LC (14 studies), suicide attempts (7 studies), mental disorders (depression, anxiety) (14 studies). The main issues raised in the articles were: higher risk of LC symptoms in women, fatigue and brain fog listed as frequently encountered patient's complaints together with anxiety, depression, loneliness, especially in younger age groups and in women. Issues regarding LC, mental disorders and suicide attempts requires further research as the results vary in different countries. Int J Occup Med Environ Health. 2024;37(3).
PubMed: 38912617
DOI: 10.13075/ijomeh.1896.02373 -
Ochsner Journal 2024Attachment-based interventions have been extensively studied in neurotypical patient populations. In neurodivergent patient populations, however, emphasis on and...
Attachment-based interventions have been extensively studied in neurotypical patient populations. In neurodivergent patient populations, however, emphasis on and current research into attachment-based interventions are centered on early childhood. Minimal research has been conducted in school-aged children with autism spectrum disorder (ASD), and even less research has focused on attachment-based interventions for children with significant comorbidities such as catatonia. We present the case of a 12-year-old female that involved dyadic work in conjunction with biologic interventions for the treatment of ASD and catatonia. Psychosocial interventions were centered on an attachment-based framework and behavioral skills training that incorporated elements of parent management training. We observed and tracked the patient's uncooperativeness, underproductive speech, emotional withdrawal, and anxiety via the Brief Psychiatric Rating Scale for Children. Attachment- and behavioral-based interventions in conjunction with psychotropic medications and electroconvulsive therapy resulted in improvements. This case illustrates the potential advantages that attachment- and behavioral-based psychotherapeutic interventions can confer in complex cases involving neurodivergent patients. The case also highlights the lack of current research into and understanding of attachment theory in children and adolescents with ASD. Research is needed into the role of attachment-based interventions in patients with ASD and other psychiatric comorbidities, particularly in patient populations beyond preschool age. Initiating nonbiologic interventions in conjunction with biologic interventions may also enhance outcomes and warrants further investigation.
PubMed: 38912185
DOI: 10.31486/toj.23.0095 -
Frontiers in Psychology 2024There is controversy regarding the comorbidity of posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI). The present study translated the PTSD Checklist...
INTRODUCTION
There is controversy regarding the comorbidity of posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI). The present study translated the PTSD Checklist for DSM-5 (PCL-5) to Spanish and validated it in a sample of patients with TBI 6 months after the injury.
METHODS
The study included 233 patients (162 males and 71 females) recruited from four Spanish hospitals within 24 h of traumatic brain injury. A total of 12.2% of the sample met the provisional PTSD diagnostic criteria, and the prevalence was equal between male and female participants.
RESULTS
The analysis confirmed the internal consistency of the translated instrument ( = 0.95). The concurrent validity of the instrument was confirmed based on high correlation coefficients of 0.7 and 0.74 with the General Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire (PHQ-9), respectively. Exploratory factor analysis also confirmed that the items on the PCL-5 can be differentiated from the GAD-7 and PHQ-9 items. Confirmatory factor analysis (CFA) was used to examine the structural validity of the Spanish translation of the PCL-5 with three different models. CFA partially confirmed the four-factor PTSD model, whereas both the six-factor anhedonia model and the seven-factor hybrid model showed adequate fit. However, the difference between the anhedonia and hybrid models was not statistically significant; moreover, both models showed signs of overfitting. Therefore, the utility of these models should be reexamined in future studies.
CONCLUSION
Overall, the results suggest that the Spanish translation of the PCL-5 is a reliable and valid instrument for screening PTSD symptoms among Spanish TBI patients. The Spanish translation of the PCL-5 is also presented in the manuscript.
PubMed: 38911962
DOI: 10.3389/fpsyg.2024.1216435 -
Frontiers in Psychiatry 2024Frailty has been associated with mental illness (MI) observational studies, but the causal relationship between these factors remains uncertain. We aimed to assess the...
BACKGROUND
Frailty has been associated with mental illness (MI) observational studies, but the causal relationship between these factors remains uncertain. We aimed to assess the bidirectional causality between frailty and MI by two-sample Mendelian randomization (MR) analyses.
METHODS
To investigate the causal relationship among them, summary statistics of frailty index (FI) and six types of MI: anxiety, depression, affective disorder, mania, schizophrenia, and obsessive-compulsive disorder (OCD) were included in this MR study. This MR analysis was performed using inverse variance weighting (IVW), MR-Egger regression, and weighted median. The stability of the results was evaluated using Cochran's Q test, MR-Egger intercept test, Funnel Plots, and leave-one-out analysis.
RESULTS
Genetic predisposition to FI was significantly associated with increased anxiety (odds ratio [OR] = 1.62, 95% confidence interval [CI] 1.13-2.33, = 8.18E-03), depression (OR = 1.88, 95% CI 1.30-2.71, = 8.21E-04), affective disorder (OR = 1.70, 95% CI 1.28-2.27, = 2.57E-04). However, our study findings do not demonstrate a causal relationship between FI and mania (OR = 1.02, 95% CI 0.99-1.06, = 2.20E-01), schizophrenia (OR = 1.02, 95% CI 0.07-0.86, = 9.28E-01). In particular, although the IVW results suggest a potential causal relationship between FI and OCD (OR = 0.64, 95% CI 0.07-0.86, = 2.85E-02), the directions obtained from the three methods we employed ultimately show inconsistency. Therefore, the result must be interpreted with caution. The results of the reverse MR analysis indicated a statistically significant and causal relationship between anxiety (OR = 1.06, 95% CI 1.01-1.11, = 2.00E-02), depression (OR = 1.14, 95% CI 1.04-1.26, = 7.99E-03), affective disorder (OR = 1.15, 95% CI 1.09-1.21, = 3.39E-07), and schizophrenia (OR = 1.02, 95% CI 1.01-1.04, = 1.70E-03) with FI. However, our findings do not provide support for a link between mania (OR = 1.46, 95% CI 0.79-2.72, = 2.27E-01), OCD (OR = 1.01, 95% CI 1.00-1.02, = 2.11E-01) and an increased risk of FI.
CONCLUSION
The MR results suggest a potential bidirectional causal relationship between FI and anxiety, depression, and affective disorder. Schizophrenia was found to be associated with a higher risk of FI. The evidence was insufficient to support a causal relationship between Fl and other Ml. These findings offer new insights into the development of effective management strategies for frailty and MI.
PubMed: 38911707
DOI: 10.3389/fpsyt.2024.1397813 -
Frontiers in Psychiatry 2024Internalizing symptoms associated with anxiety and depression have been correlated with harmful alcohol use among Latino/as, but little attention has been paid to...
Internalizing symptoms associated with anxiety and depression have been correlated with harmful alcohol use among Latino/as, but little attention has been paid to assessing the association between perceived discrimination and harmful alcohol use. The present study was designed to investigate the association between perceived discrimination, internalizing symptoms associated with anxiety and depression, and harmful alcohol use among Latino/a immigrants living in the United States (US). Our sample included 426 Latino/a immigrants. Their mean age was 40.05 years ( = 6.50), 65.50% were women, 80.00% had a partner, 54.20% lived on less than $2,000 a month, and 41.50% reported having attained a college degree. Perceived discrimination was assessed using the Perceived Discrimination Scale, anxious symptoms were assessed using the GAD-7, depressive symptoms were assessed using the CES-D short form, and harmful alcohol use was assessed using AUDIT. We estimated a linear regression model using cross-sectional, self-reported data. The model was statistically significant, = 0.38, (8, 425) = 32.09, < 0.01. Discrimination was significantly associated with AUDIT scores, (β = 0.21, < 0.01) after accounting for covariates and for symptoms of anxiety and depression. Our results indicate that experiences of discrimination in the US are associated with increased harmful alcohol use even after controlling for other variables. These findings may be useful in designing coping interventions specifically for Latino/a immigrants to reduce the risk of alcohol use disorder. This study also has political and public health implications for acknowledging the detrimental health consequences of experiencing discrimination, providing support to the position that reducing racism and discrimination represent important public health priorities.
PubMed: 38911705
DOI: 10.3389/fpsyt.2024.1358648 -
Nature and Science of Sleep 2024Bedtime procrastination (BP) has become an important factor affecting individual well-being. This study aimed to assess the stability and changes in BP and examine risk...
Latent Profiles and Transitions of Bedtime Procrastination Among Chinese College Students: The Predictive Roles of Anxiety, Depression, Problematic Smartphone Use and Self-Control.
BACKGROUND
Bedtime procrastination (BP) has become an important factor affecting individual well-being. This study aimed to assess the stability and changes in BP and examine risk and protective factors.
METHODS
The study recruited 1423 respondents. Latent profile analysis was used to identify subgroups of BP and latent transition analysis to determine transition probabilities for each subgroup. Logistic regression examined associations between identified classes and related factors.
RESULTS
Three subgroups of BP were identified. In terms of stability and changes, the moderate bedtime procrastination group showed the highest stability (66%), followed by the severe bedtime procrastination group (62.4%), and the mild bedtime procrastination group had a 52% probability of switching to moderate bedtime procrastination. In terms of influencing factors, more problematic phone use (PSU) (OR: 1.08; 95% CI = 1.05-1.12), more depression (OR: 1.17; 95% CI = 1.06-1.29) and anxiety (OR: 1.16; 95% CI = 1.05-1.28) are all factors that aggravate the transition from mild to moderate sleep procrastination. Similarly, PSU (OR: 1.15; 95% CI = 1.12-1.19), anxiety (OR: 1.10; 95% CI = 1.06-1.14), and depression (OR: 1.10; 95% CI = 1.06-1.14) increased the risk of severe bedtime procrastination. Self-control emerged as a protective factor against BP.
CONCLUSION
This study identified three subgroups of BP at two time points and the rule of transition for each subgroup. Our findings indicate that BP were relatively stable, with some changes over time. The results also highlight the important function that PSU, depression, anxiety, and self-control can play in preventing and intervening in BP.
PubMed: 38911318
DOI: 10.2147/NSS.S462055