Neuropsychiatric Changes Research Articles

Clinical considerations regarding suspected “BvFTD-by-proxy”: a case series

ABSTRACT A diagnosis of behavioral variant frontotemporal dementia (bvFTD) often relies on informant reports of significant behavioral changes. “BvFTD-by-proxy” describes situations of neuropsychiatric changes reported solely by an informant under circumstances that may raise questions regarding their objectivity. We present three cases of bvFTD-like symptoms reported by spouses, where progression was unclear, testing showed mild but stable executive dysfunction, and neuroimaging was unremarkable. The subjective nature of bvFTD criteria leaves patients vulnerable to misleading informant reports, especially amid relational discord, and may threaten patient autonomy. Recognizing and managing this situation is critical but time-consuming, often requiring coordinated care across multiple providers.

The application and interpretation of laboratory biomarkers for the evaluation of vitamin B12 status.

Vitamin B12 (cobalamin; B12) is an essential micronutrient, but deficiency is common. The prompt diagnosis and treatment of B12 deficiency protects against megaloblastic anaemia, neuropathy and neuropsychiatric changes. Biomarkers of B12 status include the measurement of serum B12 (also known as total B12 or serum cobalamin), holotranscobalamin (holoTC or 'active B12'), methylmalonic acid (MMA) and total plasma homocysteine (Hcy). There is no 'gold standard' test for deficiency and the sensitivity and specificity of each biomarker for the evaluation of B12 status is affected by analytical and biological factors that may confer a high degree of diagnostic uncertainty. Limited access to technical and clinical expertise can lead to an over-reliance on the serum B12 test, which is readily available and highly automated. In some cases, the sequential use of different B12 status biomarkers or the calculation of a composite B12 status score, derived from a panel of B12 biomarkers and adjusted for folate status and age, can be used to detect deficient states that may otherwise be overlooked when using a single biomarker approach. This review summarizes the utility of B12-related biomarkers and describes approaches to their application and interpretation.

Novel risk loci in LGI1-antibody encephalitis: genome-wide association study discovery and validation cohorts.

Encephalitis with antibodies to leucine-rich glioma-inactivated 1 (LGI1-Ab-E) is a common form of autoimmune encephalitis, presenting with seizures and neuropsychiatric changes, predominantly in older males. More than 90% of patients carry the human leucocyte antigen (HLA) class II allele, HLA-DRB1*07:01. However, this is also present in 25% of healthy controls. Therefore, we hypothesised the presence of additional genetic predispositions. In this genome-wide association study and meta-analysis, we studied a discovery cohort of 131 French LGI1-Ab-E and a validation cohort of 126 American, British and Irish LGI1-Ab-E patients, ancestry-matched to 2613 and 2538 European controls, respectively. Outside the known major HLA signal, we found two single nucleotide polymorphisms (SNPs) at genome-wide significance (p < 5 x 10-8), implicating PTPRD, a protein tyrosine phosphatase, and LINC00670, a non-protein coding RNA gene. Meta-analysis defined four additional non-HLA loci, including the protein coding COBL gene. Polygenic risk scores with and without HLA variants proposed a contribution of non-HLA loci. In silico network analyses suggested LGI1 and PTPRD mediated interactions via the established receptors of LGI1, ADAM22 and ADAM23. Our results identify new genetic loci in LGI1-Ab-E. These findings present opportunities for mechanistic studies and offer potential markers of susceptibility, prognostics and therapeutic responses.

Chronic Low-Dose-Rate Radiation-Induced Persistent DNA Damage and miRNA/mRNA Expression Changes in Mouse Hippocampus and Blood.

Our previous study demonstrated that the acute high-dose-rate (3.3 Gy/min) γ-ray irradiation (γ-irradiation) of postnatal day-3 (P3) mice with 5 Gy induced depression and drastic neuropathological changes in the dentate gyrus of the hippocampus of adult mice. The present study investigated the effects of chronic low-dose-rate (1.2 mGy/h) γ-irradiation from P3 to P180 with a cumulative dose of 5 Gy on animal behaviour, hippocampal cellular change, and miRNA and mRNA expression in the hippocampus and blood in female mice. The radiation exposure did not significantly affect the animal's body weight, and neuropsychiatric changes such as anxiety and depression were examined by neurobehavioural tests, including open field, light-dark box, elevated plus maze, tail suspension, and forced swim tests. Immunohistochemical staining did not detect any obvious loss of mature and immature neurons (NeuN and DCX) or any inflammatory glial response (IBA1, GFAP, and PDGFRα). Nevertheless, γH2AX foci in the stratum granulosum of the dentate gyrus were significantly increased, suggesting the chronic low-dose-rate irradiation induced persistent DNA damage foci in mice. miRNA sequencing and qRT-PCR indicated an increased expression of miR-448-3p and miR-361-5p but decreased expression of miR-193a-3p in the mouse hippocampus. Meanwhile, mRNA sequencing and qRT-PCR showed the changed expression of some genes, including Fli1, Hs3st5, and Eif4ebp2. Database searching by miRDB and TargetScan predicted that Fli1 and Hs3st5 are the targets of miR-448-3p, and Eif4ebp2 is the target of miR-361-5p. miRNA/mRNA sequencing and qRT-PCR results in blood showed the increased expression of miR-6967-3p and the decreased expression of its target S1pr5. The interactions of these miRNAs and mRNAs may be related to the chronic low-dose-rate radiation-induced persistent DNA damage.

Effects of immunosuppression after limb fracture in mice on nociceptive, cognitive, and anxiety-related outcomes.

Chronic pain is a common and problematic consequence of injuries with few proven methods for prevention or treatment. In addition to pain, functional limitations and neuropsychiatric changes such as cognitive impairment and anxiety worsen outcomes. To determine whether inhibiting activation of the adaptive immune response after limb fracture would reduce pain, functional loss, memory changes, and anxiety. These experiments used a murine tibial fracture/cast immobilization model that develops these adverse outcomes. Adaptive immunity was blocked using the immunosuppressant FK506 beginning at the time of fracture. The administration of FK506 reduced mechanical allodynia and hind limb unweighting for weeks after cast removal as well as nonevoked pain measures. Fracture was associated with working memory loss in the Y-maze assay in vehicle- but not FK506-treated mice. Object recognition memory was not improved with FK506 after fracture. Also, vehicle- but not FK506-treated mice developed an anxiety phenotype. Impaired running wheel performance after cast removal over the following 2 weeks was not improved with FK506 administration. In addition, FK506 treatment blocked Immunoglobulin M (IgM) accumulation in the skin of the fractured limbs, and hippocampal enhancement of matrix metalloproteinase-8 expression, a metalloproteinase associated with neuroplastic changes after injuries, was completely blocked. Taken together, our results show that blocking the adaptive immune response after limb trauma reduces the severity of nociceptive and biological changes. The same treatment may reduce the adverse consequences of anxiety and memory deficits using some measures, but other measures of memory are not affected, and activity is not enhanced.

Deep Brain Stimulation and Neuropsychiatric Anthropology – The “Prosthetisability” of the Lifeworld

Deep Brain Stimulation (DBS) represents a key area of neuromodulation that has gained wide adoption for the treatment of neurological and experimental testing for psychiatric disorders. It is associated with specific therapeutic effects based on the precision of an evolving mechanistic neuroscientific understanding. At the same time, there are obstacles to achieving symptom relief because of the incompleteness of such an understanding. These obstacles are at least in part based on the complexity of neuropsychiatric disorders and the incompleteness of DBS devices to represent prosthetics that modulate the breadth of pathological processes implicated in these disorders. Neuroprostheses, such as an implanted DBS system, can have vast effects on subjects in addition to the specific neuropsychiatric changes they are intended to produce. These effects largely represent blind spots in the current debate on neuromodulation. Anthropological accounts can illustrate the broad existential dimensions of patients’ illness and responses to neural implants. In combination with current neuroscientific understanding, neuropsychiatric anthropology may illuminate the possibilities and limits of neurodevices as technical “world enablers”.

Disrupted social perception in frontotemporal dementia and Alzheimer's disease – Associated cognitive processes and clinical implications

BackgroundSocial perception refers to the ability to adapt and update one's behaviour in accordance with the current context and provides the foundation for many complex social and emotional interactions. Alterations in social cognition are a hallmark of the behavioural variant of frontotemporal dementia (bvFTD), yet the capacity for social perception in this syndrome remains unclear. MethodsWe examined social perception in 18 bvFTD and 13 Alzheimer's disease (AD) patients, in comparison with 17 healthy older controls, using a social perception task derived from the Dewey Story Test. Participants also completed a comprehensive neuropsychological battery and carers provided ratings of behavioural and neuropsychiatric changes. Results: Overall, bvFTD and AD performance diverged significantly from control ratings on the social perception task, however, no significant difference was found between patient groups. Standardised values relative to the mean control rating revealed considerable variability within the patient groups in terms of the direction of deviation, i.e., over- or under-rating the vignettes relative to healthy controls (range z-scores = −1.79 to +1.63). Greater deviation from control ratings was associated with more pronounced memory (p = .007) and behavioural (p = .009) disturbances in bvFTD; whilst social perception performance correlated exclusively with verbal fluency in AD (p = .003). ConclusionsSocial perception is comparably disrupted in bvFTD and AD, yet likely reflects the differential breakdown of distinct cognitive processes in each dementia syndrome. Our findings have important clinical implications for the development of targeted interventions to manage disease-specific changes in social perception in dementia.

Ab. No. 94 Efficacy of Transcranial Direct Current Stimulation (TDCS) on the Quality of Sleep for Management of Sleep APNEA: A Review Study

Introduction: The purpose of the study was to evaluate the therapeutic efficacy of tDCS on quality of sleep for the conservative management of sleep apnea. Sleep Apnea is characterized by excessive diurnal sleepiness and neuropsychiatric changes (mood swings), affecting quality of life. Hence, this study explores the efficacy of tDCS on sleep quality to widen the spectrum of management for sleep apnea. Methods: Randomized clinical trials and cross over trials published within 2016 to 2023. The research was performed on various databases including PubMed, SCOPUS, and search engines including Research Gate and Google scholar. The data was limited to last 8 years (2016 to 2023). 20 Articles were identified out of which 7 articles full filled the inclusion criteria were selected. PRISMA methodology guidelines were used for data extraction. Qualitative analysis of study was done using PEDro scale. According to PEDro analysis, majority of articles included were good quality (score 4 to 6). Result: Total of 7 studies on efficacy of tDCS on sleep were reviewed, the data showed significant results on improving sleep quality. It was identified that tDCS uses cortico-thalamo-cortical feedback loop initiating slow wave activity which increases stage 3 and 4 (deep sleep) in Non Rapid eye Movement (NREM) sleep. Hence, improving the sleep quality and thereby quality of life. Conclusion: The use of tDCS in the treatment of sleep disorders such as sleep apnea is effective as an auxiliary source in the treatment, ensuring the resumption of patients’ quality of life by improving the quality and time of sleep. Thus, tDCS can be implemented as a choice of modality for management of individuals with sleep apnea. Implications: tDCS has found to be portable, feasible and relatively safe, thus can be used in management of sleep apnea patients.

Infectious Diseases and Their Role in Neuroimmune Disease

Recent findings suggest a relationship between a post-infectious immune response and neurologic changes. These changes, manifesting as various neurological symptoms, including memory issues and cognitive alterations, may be linked to a form of post-infectious autoimmunity. We have coined the term “Alzheimer’s of the Immune System,” or AIS, to describe this syndrome and various immune partners that may play a role in this immune dysfunction have been identified. Here, we will discuss several clinical presentations that feed into the hypothesis of infectious-immune axis and its mechanism of action. We propose that these disorders fall under the umbrella of AIS and discuss the role of immuno therapy in their management. First, we consider pediatric acute-onset neuropsychiatric syndrome (PANS), a broad diagnostic criterion created to describe children with severe, sudden onset of neuropsychiatric changes. Research exploring the link between immune dysregulation in PANS and its amelioration with intravenous immunoglobulin treatment strongly suggests the association of PANS with a pro-inflammatory state. Next, we delve into autism spectrum disorder (ASD), characterizing it as a neuroimmune disorder. ASD marked by communication and social skill deficits, as well as repetitive and stereotypical behaviors, is characterized by related but distinct profiles of immune dysregulation, inflammation, and endogenous autoantibodies that persist within the affected individual. Further definition of the role of immune dysregulation in ASD thus necessitates a deeper understanding of the interaction between both the mother’s and child’s immune systems, and their potential role in diagnosis and treatment. Lastly, we discuss post-viral fatigue syndrome in patients who have recovered from SARS-CoV-2 infection as another example of neuroimmune condition recently added to the growing list. Further research is needed to validate our hypothesis of AIS, including large scale randomized control trials of different immuno therapies. By unravelling the infectious-immune axis and its mechanism of action, we equip physicians with valuable tools for identifying optimal forms of treatment and management for these conditions.

Global Impact of the COVID-19 Pandemic on Caregivers of Older Adults with Alzheimer's Disease: An Integrative Literature Review

Alzheimer's disease is a progressive neurodegenerative disease marked by deterioration of cognition and short-term memory, in addition to neuropsychiatric and behavioral changes, determining the need for caregivers. In view of this, the objective of this study was to globally analyze the impact of social isolation during the COVID-19 pandemic for caregivers of older adults with Alzheimer's disease through integrative literature review. Using the keywords “caregivers”, “Alzheimer's disease” and “COVID-19” and their combinations the search was performed in the Karger, PubMed and SciELO, BIREME, Dynamed, Scopus, Medline Complete and ACS Publication databases. Articles in Portuguese and English that addressed caregivers of older adults with Alzheimer's disease in the context of the COVID-19 pandemic were included, excluding those that did not include the three descriptors and that were not published between 2020 and 2023. From the 12 selected articles, caregivers' emotional disturbances and increased burden were identified during this pandemic period, determining a decline in the caregiver's mental health during the pandemic. Literature findings validate the relationship between the pandemic and the worsening quality of life of caregivers, who, due to physical and emotional overload, presented behavioral disorders such as increased stress, depression and anxiety.

Risk of Neuropsychiatric Symptoms Among People Who Develop Cognitive Impairment With and Without a History of Post-traumatic Stress Disorder.

We aimed to prospectively assess the change in neuropsychiatric symptoms among people who develop cognitive impairment and have a history of post-traumatic stress disorder (PTSD). We analyzed longitudinal data from the National Alzheimer's Coordinating Center Unified Data Set (March 2015 to December 2021). Analyses included individuals who were cognitively normal and who had nonmissing assessment of PTSD at the initial visit and had at least 1 follow-up visit with cognitive impairment. We compared the difference in the mean neuropsychiatric symptom score at the first Unified Data Set visit versus the first visit with a Clinical Dementia Rating of 0.5 between those with and without a history of PTSD. The mean neuropsychiatric symptom score change did not differ between those with and without a history of PTSD (1.06 vs. 0.77, respectively; P =0.79). The null results found in this study warrant future research. Several methodological limitations might explain these results.

STUDY OF THE PSYCHOTROPIC EFFECT OF GLYCYRRHIZA GLABRA ROOT EXTRACT UNDER CONDITIONS OF DAPSONE-INDUCED EXPOSURE

Relevance. Dapsone (4,4'-diaminodiphenylsulfone) is used as a powerful antibacterial agent in the treatment of infectious diseases. Despite the com-plex pharmacological effect and high efficacy, dapsone has a number of negative properties, one of which is the occurrence of severe neuropsychiatric pathology with long-term use in the presence of predisposing factors. In this connection, correction of dapsone-induced changes on the part of various systems, including the nervous system, is an urgent task. As a means of correcting dapsone-induced neuropsychiatric changes, an extract of licorice naked horses can act. The aim of the study was to evaluate the effect of licorice root extract on dapsone–induced changes in behavioral reactions and the severity of the psychomodulatory effect of licorice extract. Material and methods. All experiments were carried out on white mongrel rats (6-8 months), which were divided into groups (n= 10): group 1 con-sisted of control rats receiving an equiobject of water for injection; group 2 - individuals receiving intragastric dapsone (Novartis; Switzerland) at a dose of 25 mg/kg for 28 days; group 3 – animals receiving intragastric dapsone at a dose of 25 mg / kg and licorice extract naked through a probe at a dose of 50 mg / kg for 28 days. The effect of licorice root extract on the behavioral reactions of rats under the conditions of course use of dapsone was evaluated using the "Porsolt" and "Open Field" tests. Results. Against the background of intragastric administration of licorice root extract, there was a restoration of the ratio of immobilization time, active and passive swimming in the Porsolt test, an increase in horizontal and specific mink activity of animals, a decrease in the number of boluses, groom-ing and freezing in the "Open Field" test compared with the group of animals receiving intragastric dapsone. Conclusions. Evaluation of the effect of licorice root extract on dapsone-induced changes in behavioral reactions showed the presence of an antide-pressant and psychomodulatory effect in the extract, which can be used in the development of a psychocorrective agent based on this medicinal plant

Factors Influencing the Total Functional Capacity Score as a Critical Endpoint in Huntington's Disease Research.

Background: The Total Functional Capacity (TFC) score is commonly used in Huntington's disease (HD) research. The classification separates each disease stage (1-5), e.g., as an inclusion criterion or endpoint in clinical trials accepted by the Food and Drug Administration (FDA). In addition to the quantification of age- and CAG-repeat-dependent effects as well as interacting effects of both on the TFC, we aimed to investigate factors influencing the TFC, such as neuropsychiatric, educational, and cognitive disease burden using data from the largest HD observational study to date. In addition, we analyzed data from pre-manifest stages to investigate the influence of the above-mentioned factors on the TFC in that stage. Methods: A moderated regression analysis was conducted to analyze the interaction effects of age and CAG-repeat length on the TFC in HD patients. A simple slope analysis was calculated to illustrate the effects. Depending on TFC results, motor-manifest patients were grouped into five stages. Data from pre-manifest participants were analyzed with regard to years to onset and CAP scores. Results: We identified N = 10,314 participants as manifest HD. A significant part of variance on the TFC was explained by age (R2 = 0.029, F (1;10,281) = 308.02, p < 0.001), CAG-repeat length (∆R2 = 0.132, ∆F (1;10,280) = 1611.22, p < 0.001), and their interaction (∆R2 = 0.049, ∆F (1;10,279) = 634.12, p < 0.001). The model explained altogether 20.9% of the TFC score's variance (F = 907.60, p < 0.001). Variance of psychiatric and cognitive symptoms significantly differed between stages. Exploratory analysis of median data in pre-manifest participants revealed the highest scores for neuropsychiatric changes between 5 to <20 years from the disease onset. Conclusions: TFC is mainly explained by the neurobiological factors, CAG-repeat length, and age, with subjects having more CAG-repeats showing a faster decline in function. Our study confirms TFC as a robust measure of progression in manifest HD.

The AppNLGF mouse model of amyloid pathology: age‐related behavioural characterisation

AbstractBackground2nd generation knock‐in models of amyloid pathology have been generated to overcome the non‐specific effects of the overexpression of human APP mutation in mice (Saito et al., 2014). AppNLGF mice are a relatively new model that expresses human mutant APP at endogenous levels without cellular artefacts noted in transgenic mice (Sasaguri et al., 2022). The key question of how this more restricted expression of human APP mutations influences behaviour in mice has yet to be fully understood. The aim of this study was to establish the profile of memory and anxiety processes in AppNLGF mice with age.MethodsTo monitor the effect of progressive Aβ deposition, AppNLGF mice underwent testing at 4‐6, 8‐10, 12‐14, and 22‐23 months old. Behavioural tests were selected to interrogate key neuronal networks affected in AD. Spatial recognition memory was assessed using the Object Location Test (OLT). Spatial working memory was tested using Spontaneous Alternation (SA) testing. Anxiety‐like behaviours were observed with Open Field (OF) and Elevated Plus Maze (EPM) tests.ResultsDuring OLT, AppNLGF mice showed no significant difference in object discrimination compared to control animals at all ages tested. However, at 8‐10 and 22‐23m/o, AppNLGFs were unable to discriminate the object in the novel location. Furthermore, AppNLGFs showed intact alternation in SA testing until 22‐23m/o. Interestingly, AppNLGFs exhibited decreased inner zone exploration in OF testing at 22‐23m/o, but consistently showed substantial preference for open arms in the EPM test from as early as 4m/o.ConclusionThe AppNLGF model shows subtle cognitive deficits that are most apparent at an advanced age. The severity of the deficits is relatively mild compared to transgenic models assessed on similar tasks. This is probably related to the absence of overexpression‐related artefacts and may speak to the more subtle effects of amyloid on synaptic plasticity. These mice also lack key cellular AD hallmarks such as tau hyperphosphorylation and cell loss. Nevertheless, AppNLGFs robustly display substantial early anxiolytic‐like behaviour in the EPM test, and anxiogenic‐like behaviour in the OF test at an advanced age, suggesting that amyloid pathology may contribute to behavioural and neuropsychiatric changes.

МЕЖДИСЦИПЛИНАРНЫЙ ПОДХОД К ДИАГНОСТИКЕ И ЛЕЧЕНИЮ ПАЦИЕНТОВ С ДИСФУНКЦИОНАЛЬНЫМ СОСТОЯНИЕМ ВИСОЧНО-НИЖНЕЧЕЛЮСТНОГО СУСТАВА

The article is devoted to improving the effectiveness of diagnosis and treatment of a dysfunctional state of the TMJ from the standpoint of an interdisciplinary approach. The nature and prevalence of dental disorders, postural imbalance, and neuropsychiatric changes were determined. The algorithm of diagnosis and treatment of this group of patients is described.&#x0D; Purpose: to improve algorithms for the diagnosis and treatment of patients with a dysfunctional TMJ condition.&#x0D; Materials and methods. 136 patients with a dysfunctional state of the TMJ were examined, including 25 men (18.38%), 111 women (81.62%), aged 18 to 81 years. The median age was 43.17 years. Dental examination, registration of neuropsychiatric status and postural status of patients were carried out on the basis of diagnostic algorithms developed by us.&#x0D; Results. The examination revealed a high need for dental treatment of dentists of different profiles in patients with a dysfunctional state of the TMJ. The analysis of the postural status revealed deformities of the trunk in the neck, shoulder blades and pelvis, which led to moderate (59.18%) and severe violations (24.19%) of the postura. In this group of patients, the quality of life decreases, the mental (60%) and physical components of health are at an average level (80%), there is high personal anxiety (80%), with an average (60%) and high (40%) level of situational anxiety.&#x0D; Conclusions. The multifactorial and multi-morbidity of dysfunctional TMJ conditions requires an interdisciplinary approach to the diagnosis and treatment of patients suffering from this pathology. Dental treatment of patients should be carried out with the correction of neuropsychiatric status and postural status, which significantly increases the effectiveness of therapy and allows achieving more stable results.

Neuronal damage and inflammatory biomarkers are associated with the affective and chronic fatigue-like symptoms due to end-stage renal disease

BackgroundMany biochemical, immunological, and neuropsychiatric changes are associated with end-stage renal disease (ESRD). Neuronal damage biomarkers such as glial fibrillary acidic protein (GFAP), neurofilament light chain (NFL), S100 calcium-binding protein B (S100B), ionized calcium-binding adaptor molecule-1 (IBA1), and myelin basic protein (MBP) are among the less-studied biomarkers of ESRD. AimWe examined the associations between these neuro-axis biomarkers, inflammatory biomarkers, e.g., C-reactive protein (CRP), interleukin (IL-6), IL-10, and zinc, copper, and neuropsychiatric symptoms due to ERSD. MethodsELISA techniques were used to measure serum levels of neuronal damage biomarkers in 70 ESRD patients, and 46 healthy controls. ResultsESRD patients have higher scores of depression, anxiety, fatigue, and physiosomatic symptoms than healthy controls. Aberrations in kidney function tests and the number of dialysis interventions are associated with the severity of depression, anxiety, fibro-fatigue and physiosomatic symptoms, peripheral inflammation, nestin, and NFL. Serum levels of neuronal damage biomarkers (NFL, MBP, and nestin), CRP, and interleukin (IL)-10 are elevated, and serum zinc is decreased in ESRD patients as compared with controls. The neuronal damage biomarkers NFL, nestin, S100B and MBP are associated with the severity of one or more neuropsychiatric symptom domains. Around 50 % of the variance in the neuropsychiatric symptoms is explained by NFL, nestin, S00B, copper, and an inflammatory index. ConclusionsThe severity of renal dysfunction and/or the number of dialysis interventions may induce peripheral inflammation and, consequently, neurotoxicity to intermediate filament proteins, astrocytes, and the blood-brain barrier, leading to the neuropsychiatric symptoms of ESRD.

3 Neuropsychiatric Change and Childhood Adversity Levels in an Opioid Treatment Population

Objective:Early life adversity is strongly correlated with a number of negative health outcomes, with some of the highest risks are related to later illicit drug use and substance use disorders (SUDs). Specifically, it has been found that an ACEs score of &gt;4 confers a 7-10-fold risk of substance abuse. Subsequent research has identified a number of neurobiological effects of childhood trauma, including structural and functional disruptions of the LHPA axis, the brain's primary stress-response system. It has been hypothesized that various trauma-induced neurobiological changes may lead to later physical health, mental health, and psychosocial problems in persons with early life adversity. One area that such changes might affect is a person's ability to stop abusing substances, with factors such as trauma-related mood, self-efficacy, or cognitive functioning as considerations in early treatment success. This study followed a group of participants in a residential substance abuse treatment program across their first month of abstinence, to assess natural change in cognitive performance as well as potential effect of early life adversity on changes in neuropsychiatric outcomes.Participants and Methods:Participants were 37 adults (mean age=33.9 years, SD=6.7) who had completed detoxification and were first assessed during their first week of residential treatment. Follow-up assessment was completed 4 weeks later. Participants were primarily male (62%) and white (62%). They were all in treatment for opioid abuse, with a majority of participants reporting a history of polysubstance abuse. To measure adverse and protective factors, participants completed the Adverse Childhood Experiences scale and Protective And Compensatory Experiences Scale at baseline. Participants also completed the NIH Toolbox cognition battery and a set of self-report measures of cognitive functioning, mood, anxiety, and self-efficacy at baseline and follow up.Results:Results of paired samples t-test comparison between baseline and follow-up testing found a significant improvement in self-reported depression symptoms, anxiety symptoms, and self-efficacy (all p&lt;.001). Interestingly, participants overall reported an increase in cognitive problems between baseline and retest, even though on objective cognitive testing (NIH Toolbox cognition battery) there was significant improvement in cognitive performance. Participants generally had a high level of childhood adversity (mean ACE score of 4.5), with an average level of childhood compensatory experiences. Considering the specific effect for childhood adversity, ACE score was found to be predictive in amount of anxiety and self-reported cognitive change but not for objective cognitive performance or change in other factors.Conclusions:Consistent with previous research, these patients had a high level of past trauma, which interacted with a number of other neuropsychiatric measures and support the importance of assessing for trauma history and integrating trauma-focused treatment into substance abuse treatment programs.

Long COVID syndrome: psychological and sexual dysfunction among survivors of COVID-19 infection.

To explore the neuropsychiatric symptoms, sleep disturbances, and sexual dysfunction in patients with long COVID syndrome, which can help in building better follow-up strategies for coronavirus disease 2019 (COVID-19) survivors. A cross-sectional research was undertaken at the premises of a psychiatry unit at a tertiary care unit in Karachi, Pakistan, between August 2022 and April 2023. All individuals aged 18 years or older, who had a history of contracting COVID-19 infection in the last 12 months presented to the department of Psychiatry with neuropsychiatric symptoms were recruited. Using a predefined questionnaire, data was collected from the participants. A linear logistic regression was used to find the impact of age, sex, hospitalization, and duration of home isolation on the likelihood of persistent neuropsychiatric symptoms or sexual dysfunction. A total of 457 patients were included. It was found that individuals were less likely to experience neuropsychiatric symptoms as age increased (OR=0.968, 95% CI: 0.949-0.986, P=0.001). Females were 4.8 times more likely to experience neuropsychiatric symptoms than males, and the association was extremely significant (OR=4.851, 95% CI: 3.085-7.626, P<0.0001). An increase in age raised the odds of having sleep disturbances among the survivors by 2.7 times (OR=2.672, 95% CI: 2.654-2.684, P<0.0001). The odds of having sleep disturbances were three times more likely in female participants as compared to male participants (OR=3.00, 95% CI: 1.771-5.094, P<0.0001). The majority of the COVID-19 survivors are presenting with persistent neuropsychiatric and sexual symptoms in our setting. Therefore, it is necessary to maintain proper follow-up with the survivors of COVID-19 and counsel the patients to inform the family physician if these symptoms persist for longer than a month. Increasing such practices of regular follow-ups with COVID-19 survivors can help in detecting early neuropsychiatric and sexual changes.

P08 Appearance matters: a case of adult-onset Parry-Romberg syndrome with linear scleroderma en coup de sabre and neurological involvement

Abstract Introduction We describe the case of an adult patient who initially presented with neurological symptoms. Investigations were suggestive of a neuroinflammatory disorder but the diagnosis was unclear. It was only as time passed that the cutaneous signs and symptoms of Parry-Romberg syndrome (PRS) and linear scleroderma en coup de sabre (LSCS) became apparent to clinicians as the underlying cause for her presentation. Case description This female patient, with no past medical history, presented in 2015 when she was 43 years old. She reported a one-day history of malaise and lethargy, left-sided headache, numbness affecting the right face and right arm and dysphasia. Her symptoms gradually improved over the following few days. An MRI brain showed extensive T2 hyperintensity in the right frontal and frontoparietal regions. Cerebrospinal fluid (CSF) showed a lymphocytosis and oligoclonal bands, which were present in the CSF only. A repeat MRI brain a few weeks later showed slightly less extensive changes. This was treated by neurologists as a neuroinflammatory disorder with intravenous methylprednisolone pulses. At follow-up, she mentioned that she had noticed a change in her appearance, with the right side of her face becoming increasingly asymmetrical over the last few years. Neurologists were puzzled regarding the diagnosis, but given that she was almost asymptomatic at review, they decided to monitor her with serial MRI scans. There were no further neurological episodes and no interval changes on repeat scans. In 2020, she was referred to ophthalmology, as she had noticed that her right eye had become increasingly sunken. MRI of the orbits and sinuses was reported to show enophthalmos of no obvious cause. Around the same time, she was also referred to dermatology for an enlarging patch of alopecia over the right frontoparietal scalp. Autoimmune screening blood tests including ANA, ENA, dsDNA and centromere were negative. Scalp biopsy was inconclusive but was most in keeping with old alopecia areata. She was treated with intralesional steroids and had a partial response. It was only by 2021 that PRS with LSCS was recognised as the cause of her symptoms. We can be confident that her neuroinflammation is an extracutaneous manifestation, which occurred early on when cutaneous signs were subtle. Discussion PRS is a rare, acquired disorder characterised by progressive unilateral atrophy of facial skin, soft tissue, muscles, and underlying bony structures. LSCS is a subtype of linear scleroderma that occurs on the forehead or frontoparietal scalp. PRS and LSCS commonly coexist, and it is debated whether they are on a spectrum of the same disease. Both usually occur in childhood or adolescence, and adult-onset disease is very rare. The diagnoses are clinical and there are no specific diagnostic tests. Both are associated with neurological involvement, including seizures, headaches, focal neurological deficits and neuropsychiatric changes. Usually, the cutaneous lesion develops months to years before the onset of neurological symptoms. Our patient had noticed subtle changes in her appearance at least five years before her presentation in 2015. Neuroimaging abnormalities are predominately ipsilateral to the cutaneous lesions but may rarely be contralateral. Key learning points Given that adult-onset PRS and LSCS are very rare, there may be a lack of awareness of the conditions amongst adult physicians. This can lead to diagnostic delay. This case highlights that PRS and LSCS are not just conditions of the skin and connective tissues and that neurological involvement is a frequent extracutaneous manifestation. This case is also a reminder of the importance of a thorough examination of the skin, especially when the diagnosis is unclear.

Social investigation and social novelty in zebrafish: Roles of salience and novelty

Social preference tests can be used to analyze variables that influence and modify social behaviors, and to investigate effects of substances such as medications, drugs, and hormones. They may become important tools for finding a valid model to study neuropsychiatric changes and to study human neurodevelopmental processes that have been impaired by social events. While a preference for conspecifics has been shown for different species, social novelty has been used as a model for anxiety-like behavior in rodents. The goal of this research was to understand the roles of stimulus salience (numerousness) and novelty in social investigation and social novelty tests in zebrafish (Danio rerio Hamilton 1822). We used a sequential design, in which animals are exposed first to a social investigation test (with dichotomous presentation of novel conspecifics vs. empty tank) and then to a social novelty test (with dichotomous presentation of the already known conspecific and a novel conspecific). In experiment 1, animals were presented to either 1 or 3 (vs. an empty tank) conspecifics as stimuli. In experiment 2, animals were presented to 1 vs. 3 conspecifics as stimuli. In experiment 3, animals were observed in the social investigation and social novelty tests for 3 consecutive days. The results showed equivalence between 1 or 3 conspecifics in the social investigation and social novelty tests, although animals were able to discriminate between different shoal sizes. These preferences do not change with repeated test exposure, suggesting novelty to be a minor contributor to social investigation and social novelty in zebrafish.