Neurobiology and Treatment of Posttraumatic Stress Disorder.

The recent worldwide surge of warfare and hostilities exposes increasingly large numbers of individuals to traumatic events, placing them at risk of developing posttraumatic stress disorder (PTSD) and challenging both clinicians and service delivery systems. This overview summarizes and updates the core knowledge of the genetic, molecular, and neural circuit features of the neurobiology of PTSD and advances in evidence-based psychotherapy, pharmacotherapy, neuromodulation, and digital treatments. While the complexity of the neurobiology and the biological and clinical heterogeneity of PTSD have challenged clinicians and researchers, there is an emerging consensus concerning the underlying mechanisms and approaches to diagnosis, treatment, and prevention of PTSD. This update addresses PTSD diagnosis, prevalence, course, risk factors, neurobiological mechanisms, current standard of care, and innovations in next-generation treatment and prevention strategies. It provides a comprehensive summary and concludes with areas of research for integrating advances in the neurobiology of the disorder with novel treatment and prevention targets.

REM sleep in narcolepsy.

Narcolepsy is mainly associated with excessive daytime sleepiness, but the characteristic feature is abnormal rapid eye movement (REM) sleep phenomena. REM sleep disturbances can manifest as cataplexy (in narcolepsy type 1), sleep paralysis, sleep-related hallucinations, REM sleep behavior disorder, abnormal dreams, polysomnographic evidence of REM sleep disruption with sleep-onset REM periods, and fragmented REM sleep. Characterization of REM sleep and related symptoms facilitates the differentiation of narcolepsy from other central hypersomnolence disorders and aids in distinguishing between narcolepsy types 1 and 2. A circuit comprising regions within the brainstem, forebrain, and hypothalamus is involved in generating and regulating REM sleep, which is influenced by changes in monoamines, acetylcholine, and neuropeptides. REM sleep is associated with brainstem functions, including autonomic control, and REM sleep disturbances may be associated with increased cardiovascular risk. Medications used to treat narcolepsy (and REM-related symptoms of narcolepsy) include stimulants/wake-promoting agents, pitolisant, oxybates, and antidepressants; hypocretin agonists are a potential new class of therapeutics. The role of REM sleep disturbances in narcolepsy remains an area of active research in pathophysiology, symptom management, and treatment. This review summarizes the current understanding of the role of REM sleep and its dysfunction in narcolepsy.

Neuron-Astrocyte Interactions: A Human Perspective.

This chapter explores the intricate interactions between neurons and astrocytes within the nervous system with a particular emphasis on studies conducted in human tissue or with human cells. We specifically explore how neuron-astrocyte interactions relate to processes of cellular development, morphology, migration, synapse formation, and metabolism. These findings enrich our understanding of basic neurobiology and how disruptions in these processes are relevant to human diseases.The study of human neuron-astrocyte interactions is made possible because of transformative in vitro advancements that have facilitated the generation and sustained culture of human neural cells. In addition, the rise of techniques like sequencing at single-cell resolution has enabled the exploration of numerous human cell atlases and their comparisons to other animal model systems. Thus, the innovations outlined in this chapter illuminate the convergence and divergence of neuron-astrocyte interactions across species. As technologies progress, continually more sophisticated in vitro systems will increasingly reflect in vivo environments and deepen our command of neuron-glial interactions in human biology.

A Case Report of Schizophrenia With a Partially Empty Sella: Related or Incidental?

A 55-year-old male patient who had a history of schizophrenia for 20 years was admitted to the Department of Psychiatry, in a tertiary care center. The patient presented with an exacerbation of symptoms for three months, with no apparent cause, leading to the suspicion of an underlying organic cause. The patient was overweight, was newly diagnosed as a case of type 2 diabetes mellitus, and also had swelling over his left ear. The magnetic resonance imaging (MRI) brain and laboratory testing that were done while he was in the hospital revealed the existence of a partially empty sella. With the MRI findings, it can be said that the partially empty sella and the occurrence of schizophrenia can be related to each other. In the existing literature, a few studies indicate the correlation between the two, and future studies can help with identifying the association.

Microstructural alterations in white matter and related neurobiology based on the new clinical subtypes of Parkinson's disease.

Background and objectives: The advent of new clinical subtyping systems for Parkinson's disease (PD) has led to the classification of patients into distinct groups: mild motor predominant (PD-MMP), intermediate (PD-IM), and diffuse malignant (PD-DM). Our goal was to evaluate the efficacy of diffusion tensor imaging (DTI) in the early diagnosis, assessment of clinical progression, and prediction of prognosis of these PD subtypes. Additionally, we attempted to understand the pathological mechanisms behind white matter damage using single-photon emission computed tomography (SPECT) and cerebrospinal fluid (CSF) analyses. Methods: We classified 135 de novo PD patients based on new clinical criteria and followed them up after 1 year, along with 45 healthy controls (HCs). We utilized tract-based spatial statistics to assess the microstructural changes of white matter at baseline and employed multiple linear regression to examine the associations between DTI metrics and clinical data at baseline and after follow-up. Results: Compared to HCs, patients with the PD-DM subtype demonstrated reduced fractional anisotropy (FA), increased axial diffusivity (AD), and elevated radial diffusivity (RD) at baseline. The FA and RD values correlated with the severity of motor symptoms, with RD also linked to cognitive performance. Changes in FA over time were found to be in sync with changes in motor scores and global composite outcome measures. Furthermore, baseline AD values and their rate of change were related to alterations in semantic verbal fluency. We also discovered the relationship between FA values and the levels of α-synuclein and ß-amyloid. Reduced dopamine transporter uptake in the left putamen correlated with RD values in superficial white matter, motor symptoms, and autonomic dysfunction at baseline as well as cognitive impairments after 1 year. Conclusions: The PD-DM subtype is characterized by severe clinical symptoms and a faster progression when compared to the other subtypes. DTI, a well-established technique, facilitates the early identification of white matter damage, elucidates the pathophysiological mechanisms of disease progression, and predicts cognitively related outcomes. The results of SPECT and CSF analyses can be used to explain the specific pattern of white matter damage in patients with the PD-DM subtype.

Beyond Belief and Practice: An Exploratory Literature Review and Discussion of the Differential Impact of Spirituality and Religiosity on Mental Health Disorders.

The relationship between spirituality and religiosity and their impact on mental health is intricate and underexplored. This exploratory review aims to elucidate the distinct effects of these constructs, highlighting their contributions to psychological well-being and clinical practices. By dissecting the impacts of spirituality and religiosity on mental health, the study focuses on their individual and combined roles in shaping therapeutic approaches and theoretical understandings in the field. A literature review was conducted using PubMed, focusing on articles discussing spirituality, religiosity, and their intersection with mental health and psychopathology. Out of 312 identified articles, 69 peer-reviewed articles were included after screening for relevance. The results indicate that spirituality and religiosity significantly influence mental health yet are often conflated, leading to research inconsistencies and clinical challenges. Spirituality, as a broad and individualistic pathway, enhances personal well-being and resilience, often transcending organized religious practices. In contrast, religiosity, with its structured community support, sometimes imposes constraints that exacerbate stress under specific doctrinal pressures. Neurobiological evidence suggests that both constructs interact with cognitive processes and brain function, influencing emotional regulation and stress response. The study concludes that distinguishing between spirituality and religiosity is essential for precise academic discourse and effective clinical practice. This differentiation allows for more personalized therapeutic approaches, accommodating an individual's spiritual and religious contexts. The authors propose a refined framework for future research and therapeutic applications to be sensitive to the nuanced experiences of individuals and to better tailor interventions in clinical settings.

Gekko gecko as a model organism for understanding aspects of laryngeal vocal evolution.

The ability to communicate through vocalization plays a key role in the survival of animals across all vertebrate groups. Although avian reptiles have received much attention relating to their stunning sound repertoire, non-avian reptiles have been wrongfully assumed to have less elaborate vocalization types, and little is known about the biomechanics of sound production and their underlying neural pathways in this group. We investigated alarm calls of Gekko gecko using audio and cineradiographic recordings. Acoustic analysis revealed three distinct call types: a sinusoidal call type (type 1); a train-like call type, characterized by distinct pulse trains (type 3); and an intermediate type, which showed both sinusoidal and pulse train components (type 2). Kinematic analysis of cineradiographic recordings showed that laryngeal movements differ significantly between respiratory and vocal behavior. During respiration, animals repeatedly moved their jaws to partially open their mouths, which was accompanied by small glottal movements. During vocalization, the glottis was pulled back, contrasting with what has previously been reported. In vitro retrograde tracing of the nerve innervating the laryngeal constrictor and dilator muscles revealed round to fusiform motoneurons in the hindbrain-spinal cord transition ipsilateral to the labeled nerve. Taken together, our observations provide insight into the alarm calls generated by G. gecko, the biomechanics of this sound generation and the underlying organization of motoneurons involved in the generation of vocalizations. Our observations suggest that G. gecko may be an excellent non-avian reptile model organism for enhancing our understanding of the evolution of vertebrate vocalization.

Psychopathological and Organic Features of Atypical Anorexia Nervosa in Developmental Age: A Systematic Review.

PURPOSE: This study aimed to comprehensively report the epidemiological and clinical features of atypical anorexia nervosa (AAN) in children and adolescents. METHODS: In May 2024, a systematic review was performed using Medline, Cochrane Library, ClinicalTrials.gov, and relevant websites. Following PRISMA guidelines, 234 articles were screened for studies on DSM-5-defined AAN. A standardized checklist-the JBI critical appraisal tool-was adopted in assessing methodology, and 13 retained studies passed the screening and critical appraisal process for the final review. The Newcastle-Ottawa Scale was utilized to assess the risk of bias in cohort and case-control studies, ensuring a comprehensive evaluation of methodological quality. RESULTS: AAN prevalence in young age groups is 2.8%, with a cumulative 2.8% incidence over 8 years. Incidence is 366 per 100,000 person-years, and the average episode duration is 11.6 months, with a 71% remission rate. Diagnostic persistence for AAN is less stable than other restrictive feeding and eating disorders (FEDs). AAN individuals exhibit higher EDE-Q scores, more severe distress, and distinct BMI differences compared to those with anorexia nervosa and controls. The diagnostic transition from the DSM-IV to the DSM-5 shows that AAN patients are predominantly female, slightly older, and with higher weight. CONCLUSIONS: This study yields concrete insights into the features of AAN in the developmental age, highlighting demographic variations, clinical presentations, and treatment outcomes. Recognizing the unique challenges faced by AAN individuals is vital for tailoring effective interventions and improving overall care within the FED spectrum.

Cannabidiol effects on fear processing and implications for PTSD: Evidence from rodent and human studies.

Cannabidiol (CBD) modulates aversive memory and its extinction, with potential implications for treating anxiety- and stress-related disorders. Here, we summarize and discuss scientific evidence showing that CBD administered after the acquisition (consolidation) and retrieval (reconsolidation) of fear memory attenuates it persistently in rats and mice. CBD also reduces fear expression and enhances fear extinction. These effects involve the activation of cannabinoid type-1 (CB1) receptors in the dorsal hippocampus, bed nucleus of stria terminalis, and medial prefrontal cortex, comprising the anterior cingulate, prelimbic, and infralimbic subregions. Serotonin type-1A (5-HT1A) receptors also mediate some CBD effects on fear memory. CBD effects on fear memory acquisition vary, depending on the aversiveness of the conditioning procedure. While rodent findings are relatively consistent and encouraging, human studies investigating CBD's efficacy in modulating aversive/traumatic memories are still limited. More studies are needed to investigate CBD's effects on maladaptive, traumatic memories, particularly in post-traumatic stress disorder patients.

SPEctacle Correction for the TReatment of Amblyopia (SPECTRA): study protocol for a prospective non-randomised interventional trial in adults with anisometropic/mixed mechanism amblyopia.

INTRODUCTION: Amblyopia is a neurodevelopmental vision disorder typically affecting one eye, resulting in compromised binocular function. While evidence-based treatments exist for children, there are no widely accepted treatments for adults. This trial aims to assess the efficacy of appropriate optical treatment in improving vision and visual functions in adults with amblyopia. This is hypothesised to significantly improve visual acuity of the amblyopic eye and other visual functions. METHODS AND ANALYSIS: SPEctacle Correction for the TReatment of Amblyopia is a prospective non-randomised interventional trial. The following criteria for amblyopia will be used: best corrected visual acuity (BCVA) in the amblyopic eye of 0.3 to 1.0 (inclusive) logMAR VA and in the fellow eye, 0.1 logMAR or better, with an interocular VA difference of ≥2 logMAR lines. Eligible participants aged 18-39 will receive full/near-full optical treatment requiring wear for at least half their waking hours for the trial duration. A difference of ≥1.00D spherical equivalent between a participant's current refractive correction and the study prescription is required for eligibility. Primary outcome is the change in amblyopic eye BCVA from baseline to 24-week postenrolment. Secondary outcomes include distance and near VA of both eyes, stereoacuity, contrast sensitivity, interocular suppression, angle of strabismus and fixation stability measured at monthly intervals. Visual evoked potentials will also be measured at baseline, week 12 and week 24. Treatment compliance and quality of life for all participants will be monitored.Analyses comparing baseline and week 24 will utilise pairwise comparisons. Linear mixed models will be fitted to the data for measures taken monthly. This allows estimates and inferences to be drawn from the coefficients of the model, while handling missing data. ETHICS AND DISSEMINATION: Human ethics approval was obtained from the respective ethics board of the Hong Kong Polytechnic University (HSEARS20210915002) and the University of Waterloo (#44235). The study protocol will conform to the principles of the Declaration of Helsinki. Results will be disseminated through peer-reviewed journals and conferences. TRIAL REGISTRATION NUMBER: NCT05394987; clinicaltrials.org.

Comparative Efficacy of Omega-3 Fatty Acid with Other Interventions for Depression in Children and Adolescents: A Systematic Review and Network Meta-Analysis.

Background: The administration of omega-3 polyunsaturated fatty acid supplements is recommended as an adjuvant therapy for adults diagnosed with major depressive disorder. The evaluation of replicated data in combination treatment with omega-3 has been extensively conducted in adults over the past decade. However, the generalizability of these findings to pediatric groups is still uncertain. The objectives of this evaluation were twofold: (1) to evaluate the effectiveness of omega-3 and associated combination therapies in reducing the severity of depressive symptoms, and (2) to include remission rates (i.e., reduction of more than 50% in depression symptoms) as a measure of therapeutic efficacy. Methods: We conducted a literature search on PubMed/EMBASE from inception to October 2023. Data analyses were conducted using Stata (version 17.0). Results: We identified a total of 3168 articles. After eligibility screening of identified studies, nine studies (n = 561 participants) were included in our analysis herein. Pairwise comparisons revealed no significant improvement in depression symptoms for any intervention versus placebo. However, a clustered ranking plot identified omega-3 plus inositol as the most effective treatment for pediatric depression (77.3% efficacy). Omega-3 paired with psychoeducational psychotherapy significantly lowered the remission rate compared to placebo (standardized mean difference = 0.44, 95% confidence interval: 0.00-0.87, p = 0.048), resulting in a 91.5% remission rate, making it the most effective treatment in the study. Conclusions: Taken together, this network meta-analysis presents compelling evidence supporting the antidepressant effects of omega-3 in pediatric groups with depression. Future research should aim to investigate omega-3 as monotherapy for young individuals with depression, as well as investigate the efficacy of omega-3 in comparison to psychosocial interventions for affected individuals.

Neurobiology of Obsessive-Compulsive Disorder from Genes to Circuits: Insights from Animal Models.

Obsessive-compulsive disorder (OCD) is a chronic, severe psychiatric disorder that has been ranked by the World Health Organization as one of the leading causes of illness-related disability, and first-line interventions are limited in efficacy and have side-effect issues. However, the exact pathophysiology underlying this complex, heterogeneous disorder remains unknown. This scenario is now rapidly changing due to the advancement of powerful technologies that can be used to verify the function of the specific gene and dissect the neural circuits underlying the neurobiology of OCD in rodents. Genetic and circuit-specific manipulation in rodents has provided important insights into the neurobiology of OCD by identifying the molecular, cellular, and circuit events that induce OCD-like behaviors. This review will highlight recent progress specifically toward classic genetic animal models and advanced neural circuit findings, which provide theoretical evidence for targeted intervention on specific molecular, cellular, and neural circuit events.

'It takes a village': deciphering the role of the gut microbiome in the health and performance of military personnel.

The human gut microbiome can be impacted by a range of environmental and lifestyle factors including diet, antibiotics, physical fitness and acute and chronic stressors. There is also evidence to suggest that specific compositional and/or functional features of the gut microbiome are mediators of aspects of health and performance including disease susceptibility, cognitive and physical states and the immune response. Therefore, understanding microbe-to-microbe and nutrient-to-microbe interactions in the gut and how they interact with host biology (eg, via the gut-brain axis) could enable better design of interventions aimed at modulating the gut microbiome to improve the health and performance of the military. Accordingly, this review summarises a thematic session hosted at the 6th International Conference on Soldier Physical Performance which provided an overview of military-relevant research related to the gut microbiome. It articulates a timely opportunity to leverage this rapidly advancing area to improve personnel health and military performance.

Noradrenergic alterations associated with early life stress.

Significant stress in childhood or adolescence is linked to both structural and functional changes in the brain in human and analogous animal models. In addition, neuromodulators, such as noradrenaline (NA), show life-long alterations in response to these early life stressors, which may impact upon the sensitivity and time course of key adrenergic activities, such as rapid autonomic stress responses (the 'fight or flight response'). The locus-coeruleus noradrenergic (LC-NA) network, a key stress-responsive network in the brain, displays numerous changes in response to significant early- life stress. Here, we review the relationship between NA and the neurobiological changes associated with early life stress and set out future lines of research that can illuminate how brain circuits and circulating neurotransmitters adapt in response to childhood stressors.

The communication mechanism of the gut-brain axis and its effect on central nervous system diseases: A systematic review.

Gut microbiota is involved in intricate and active metabolic processes the host's brain function, especially its role in immune responses, secondary metabolism, and symbiotic connections with the host. Gut microbiota can promote the production of essential metabolites, neurotransmitters, and other neuroactive chemicals that affect the development and treatment of central nervous system diseases. This article introduces the relevant pathways and manners of the communication between the brain and gut, summarizes a comprehensive overview of the current research status of key gut microbiota metabolites that affect the functions of the nervous system, revealing those adverse factors that affect typical communication between the brain-gut axis, and outlining the efforts made by researchers to alleviate these neurological diseases through targeted microbial interventions. The relevant pathways and manners of communication between the brain and gut contribute to the experimental design of new treatment plans and drug development. The factors that may cause changes in gut microbiota and affect metabolites, as well as current intervention methods are summarized, which helps improve gut microbiota brain dialogue, prevent adverse triggering factors from interfering with the gut microbiota system, and minimize neuropathological changes.

Sex Differences in White Matter Diffusivity in Children with Developmental Dyslexia.

Despite the high prevalence of developmental dyslexia in the U.S. population, research remains limited and possibly biased due to the overrepresentation of males in most dyslexic samples. Studying biological sex differences in the context of developmental dyslexia can help provide a more complete understanding of the neurological markers that underly this disorder. The current study aimed to explore sex differences in white matter diffusivity in typical and dyslexic samples in third and fourth graders. Participants were asked to complete behavioral/cognitive assessments at baseline followed by MRI scanning and diffusion-weighted imaging sequences. A series of ANOVAs were conducted for comparing group membership (developmental dyslexia or typically developing), gender status (F/M), and white matter diffusivity in the tracts of interest. The Results indicated significant differences in fractional anisotropy in the left hemisphere components of the inferior and superior (parietal and temporal) longitudinal fasciculi. While males with dyslexia had lower fractional anisotropy in these tracts compared to control males, no such differences were found in females. The results of the current study may suggest that females may use a more bilateral/alternative reading network.

Research on clinical aspects of bipolar disorder: A review of Indian studies.

Background: Bipolar disorder is one of the severe mental disorders that are associated with significant morbidity of the patients. Despite advancements in our understanding about the disorder, it remains a challenging proposition to treat bipolar disorder, largely since the prophylactic treatment of the disorder requires assessment of complex clinical algorithms. The revisions of the classificatory systems have also changed the conceptualization of the disorder. In this background, we conducted a review of the Indian studies conducted on the clinical aspects of bipolar disorder. Methods: A narrative review was conducted with focus on the literature published from India. The databases searched included PubMed, Scopus, and Google Scholar, and articles published over the last 15 years by Indian authors were included for this review. Results: In our review, we could access a substantial volume of research published from India. We could identify studies that catered to most of the relevant themes in bipolar disorder including epidemiology, etiology, comorbidities, stigma, disability, clinical course, cognitive profile, pathways to care, and recovery. Conclusion: The research trajectory was in line with the research conducted elsewhere in the world. However, certain dissimilarities in terms of focus could also be observed. The possible reason behind this deviation could be the difference in clinical need and unique challenges faced in the management and rehabilitation of patients in bipolar disorder in Indian scenario.