Behavioral Disinhibition Research Articles

Amygdala Atrophy as an Early Manifestation of Alzheimer’s Disease (S39.005)

<h3>Objective:</h3> To investigate whether structural changes in the amygdala occur during the earliest stages of Alzheimer’s disease (AD). <h3>Background:</h3> Neuropsychiatric symptoms are common early manifestations of AD, suggesting that the amygdala may be an early target of AD pathology. While prior studies have investigated amygdala atrophy in AD, little is known about amygdala atrophy during the earliest stages of AD including the preclinical stage. <h3>Design/Methods:</h3> This retrospective cross-sectional study included subjects from the Alzheimer’s Disease Neuroimaging Initiative with age≥50, 3T 3D T1-weighted magnetic resonance imaging (MRI) scans, and cerebrospinal fluid (CSF) AD biomarkers. Clinical Dementia Rating (CDR) of 0 was defined as cognitively normal. Positive AD pathology was based on previously established CSF criteria. 466 subjects met all inclusion criteria (112 cognitively normal with negative CSF biomarkers (CN), 38 preclinical AD (PAD), 106 early mild cognitive impairment (EMCI), 100 late mild cognitive impairment (LMCI), and 110 AD dementia). Total amygdala volumes were assessed and normalized to intracranial volume (FreeSurfer v7.2). Multiple linear regression analysis adjusting for appropriate covariates was conducted to determine associations between amygdala volume and CSF AD biomarkers or neuropsychiatric measures. <h3>Results:</h3> Amygdala volumes were significantly lower with worsening disease severity (CN &gt; PAD &gt; EMCI &gt; LMCI &gt; AD dementia, p &lt;0.001). Amygdala volumes were correlated with CSF amyloid-beta42 (β=0.28653, p &lt;0.001), total tau (β=−0.8881, p &lt;0.001) and phosphorylated tau181 (β=−7.558, p &lt;0.001) levels. Moreover, Neuropsychiatric Inventory (NPI) disinhibition and aberrant motor behavior scores were negatively correlated with the amygdala volume (NPI disinhibition, β=−28.556, p &lt;0.05; NPI aberrant motor, β=−57.427, p &lt;0.05). <h3>Conclusions:</h3> Lower amygdala volumes were seen in the early stages of AD that worsened with increasing clinical severity. Furthermore, amygdala volumes were associated with CSF AD biomarkers and neuropsychiatric symptoms. These findings support amygdala atrophy as an early target of AD pathology. <b>Disclosure:</b> Miss Al-Ani has nothing to disclose. Ms. Tao has nothing to disclose. Jonathan Dyke, 673 has nothing to disclose. Gloria Chiang has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Life Molecular Imaging. The institution of Gloria Chiang has received research support from NIH/NIA. Gloria Chiang has received personal compensation in the range of $500-$4,999 for serving as a Invited Speaker for CME with Horizons CME. Dr. Ishii has stock in Regeneron Pharmaceuticals. The institution of Dr. Ishii has received research support from NIH. The institution of Dr. Ishii has received research support from BrightFocus Foundation. The institution of Dr. Ishii has received research support from Alzheimer’s Association. Dr. Ishii has received personal compensation in the range of $0-$499 for serving as a Author/Contributor with Relias Media.

Associations between eating in the absence of hunger and executive functions in adolescents with binge-eating disorder: An experimental study

Eating in the absence of hunger (EAH) is one of the key behavioral features of binge-eating disorder (BED) in youth. Although preliminary evidence revealed that adolescent BED co-occurs with deficits in executive functions (EFs), it is unclear whether EFs are related to EAH. Thus, this study experimentally examined whether deficits in EFs predict EAH in adolescents with and without BED. Adolescents (12–20 years) with BED (n = 28) and age-, sex-, and weight-matched controls (n = 28) underwent an EAH paradigm in the laboratory, where they were offered snacks ad libitum after having established satiety during a lunch meal. Cognitive interference, cognitive flexibility, decision making, and EFs in daily life were assessed by neuropsychological tests and self- and parent-report. The BED group showed a significantly higher food intake in gram during the EAH trial than controls with medium effect, but no significant group differences in EFs emerged. Dysfunctional decision making in terms of risky decision making, but no other EFs, predicted increased EAH (g, kcal) in the total sample. Although increases in risky decision making over adolescence are well known, this study uniquely revealed that general decision-making abilities driven by short-term reward may account for disinhibited eating behavior. Interventions targeting decision making with focus on reward sensitivity should be evaluated for their efficacy in preventing and reducing disinhibited eating behavior in adolescents.

Impulsivity dimensions and their associations with disinhibited and actual eating behaviour

BackgroundPrevious research has suggested that there is an association between impulsivity, assessed via self-report measures and behaviourally, and disinhibited eating patterns, but it remains unclear which specific dimension of impulsivity is the most salient in this relationship. Furthermore, it remains uncertain whether any such associations would extend to actual eating behaviours and food consumption. Aims: The present study aimed to examine whether impulsivity, assessed both behaviourally and via self-report, is associated with self-reported disinhibited and actual eating behaviour in a controlled eating task. Method70 women from a community sample (aged 21–35) completed the Disinhibition subscale of the Three Factor Eating Questionnaire (TFEQ), the Barratt Impulsiveness Scale (BIS-11), the Matching Familiar Figures Task (MFFT-20), and a behavioural food consumption task. ResultsBivariate correlational analyses revealed significant associations between self-report measure of impulsivity, the scores on the MFFT-20 (assessing reflection impulsivity), and self-report measure of disinhibited eating. All these measures were associated with overall food consumption in a taste task, with reflection impulsivity, that is poor ability to reflect on information before making a decision, having the strongest association with the amount of food consumed. Self-reported impulsivity was most strongly associated with disinhibited eating. Partial correlations controlling for BMI and age did not diminish any significant correlations within these relationships. ConclusionsSignificant associations between both trait and behavioural (reflection) impulsivity, and self-reported disinhibited eating and actual eating behaviour were demonstrated. The implications of these findings on uncontrolled eating patterns in real life are discussed.

Orbitofrontal syndrome in an offender incarcerated for aggravated kidnapping, rape and death of a minor

Orbitofrontal syndrome is characterized by disinhibition, impulsiveness, transgression of social norms and sometimes thedevelopment of criminal behavior. This is the case of an 18-year-old male offender incarcerated for kidnapping, rape andhomicide of a minor. He was evaluated through interviews and the use of the Eysenck personality questionnaire (Form B), Raven’s progressive matrices (RPM), Rey–Osterrieth complex figure (Form A), Differences perception test (FACES-R), Stroop color and word test (SCWT), Mini-Mental state examination (MMSE) and Aggression questionnaire (AGQ). The research subject showed age-appropriate speech, language and vocabulary, and had neither physical problems nor attention, language, writing, reading, praxis, calculation, perception and memory disorders. The results highlight a higher-than-average intelligencequotient, optimal cognitive skills, melancholic temperament with depressive thoughts, introverted personality with lowenvironmental sensitivity, poor social skills, self-absorption and avoidance. Additionally, perfectionist tendencies, suddenemotional changes, difficulty changing behavioral patterns, impulsiveness and disinhibition, all of which are characteristicsof orbitofrontal syndrome. Finally, the research highlights the use of psychometric tests and neuropsychological evaluationsfor the diagnosis of orbitofrontal syndrome. Said tests and evaluations are necessary for the proper management of offendersincarcerated in prisons and/or detention centers who do not have access to neuroimaging; moreover, they may be used to design strategic intervention programs.

The oral presentation of secondary syphilis among men: the evolving interplay between syphilis, HIV and prophylactic strategies

Syphilis has been intricately linked with HIV because of shared transmission pathways and because these infections promote each other’s transmission. In addition, HIV infection may change the clinical presentation and management of syphilis lesions. Initially, the HIV epidemic had improved safe sex practices among men who have sex with men (MSM), but subsequent effective treatment and prophylaxis strategies, have resulted in behavioural disinhibition and a resurgence of syphilis. Here, we report on three cases of oral secondary syphilis and explore the relationship between oral syphilis and sexual practices, HIV and prophylactic measures that MSM employ. Three men, who presented to the University of Pretoria Oral Health Centre (UPOHC), complaining of oral lesions, were diagnosed by histopathology with secondary syphilis. The clinical appearance of the lesions, HIV status, treatment and prophylaxis employed by the men were documented. The clinical presentation, sexual practices, HIV status and prophylactic measures among these men differed and demonstrate the complexity of oral secondary syphilisdiagnosis and management.Syphilis presents variably in the oral cavity, and this may be linked to the sexual practices and HIV status of the patient.

Early prenatal and late prenatal escitalopram exposure differentially impacts behavioral flexibility and anxiety-related behaviors in adulthood

Selective serotonin reuptake inhibitors (SSRIs) are medications commonly used by pregnant women. While SSRIs have been considered safe during pregnancy, there is limited understanding of the long-term consequences of prenatal SSRI exposure on adult behavioral processes. Recent human studies have demonstrated prenatal exposure to some SSRIs in humans may increase susceptibility to autism spectrum disorder (ASD) and developmental delays. While escitalopram is one of the most effective antidepressants, it is also one of the newer available SSRIs, resulting in less information on its safety profile during pregnancy. The current study administered escitalopram (0 or 10 mg/kg, s.c.) to nulliparous female Long-Evans rats for the first (G1–10) or last half (G11–20) of the gestational period. Young adult male and female offspring were subsequently tested on a battery of behavioral tasks consisting of probabilistic reversal learning task, open field conflict, marble burying and social approach tasks. Results demonstrate that escitalopram exposure during the first half of pregnancy resulted in reduced anxiety-like behavior (disinhibition) on the modified open field and enhanced flexibility on the probabilistic reversal learning task. Exposure to escitalopram later in pregnancy resulted in an increase in marble burying behavior, but no differences were found with the other measures. These results suggest that exposure to escitalopram during the first half of prenatal development can have long lasting changes on adult behavior demonstrating better behavioral flexibility and lower anxiety-like behavior compared to non-exposed controls.

Oxidative stress as a shared mechanisms for different prenatal stressors: long-term effects on adolescent male and female mouse offspring

IntroductionStressful experiences in utero can produce physiological changes which become embedded biological traces affecting fetal brain development and ultimately leading to increased vulnerability for psychiatric disorders.ObjectivesWe hypothesized that stressors as diverse as maternal obesity and maternal psychophysical stress might disrupt fetal programming resulting in long-lasting effects on offspring brain development by acting through shared oxidative stress (OS)-mediated mechanisms.MethodsWe compared a mouse model (C57Bl/6N) of maternal high-fat diet (HFD) consumption (13 weeks, until delivery) to prenatal restraint stress (PNS) repeatedly administered during the last week of pregnancy. To counteract the negative effects of both stressors, the antioxidant N-acetyl-cysteine (NAC, 1 g/kg) was administered to female breeders for 8 weeks until delivery. Emotionality was assessed in adolescent male and female offspring through the elevated-plus-maze (EPM). Moreover, hippocampal gene expression levels of Brain-Derived-Neurotrophic-Factor (Bdnf ), Nuclear factor erythroid 2–related factor 2 (Nrf-2) and Kelch-like ECH-associated protein 1 (Keap-1) were measured, by qPCR, as markers of brain plasticity and antioxidant capacity.ResultsPrenatal exposure to both HFD and PNS enhanced behavioral disinhibition, increasing time spent in the open arms of the EPM and decreasing the frequency of risk-assessment behaviors, especially in female offspring. Moreover, both prenatal stressors led to decreased Bdnf (in females) and Nrf-2 levels, and disrupted Keap-1 levels. Prenatal NAC was able to counteract these effects on the brain.ConclusionsOur data support the hypothesis of a “funnel effect” model explaining how different prenatal stressors result in long-term negative effects on the adolescent offspring, increasing risk assessment behaviors and affecting brain plasticity and antioxidant defenses. The beneficial preventive effects of NAC suggest that OS may be a common mechanism, playing a pivotal role in fetal programming of mental disorders. ERANET-NEURON-JTC-2018-Mental Disorders-“EMBED” and Bando Ricerca Indipendente ISS 2021-2023; MOMINFLAM. Unique signatures underlying placental-fetal brain crosstalk in maternal obesity to F Cirulli.Disclosure of InterestNone Declared

Psychiatric manifestations of dengue fever- a case report from Pakistan

A 29-year-old male presented to Aga Khan University Hospital with complaints of fever, body-aches, vomiting and one episode of gum bleeding. A Dengue antigen test done prior to presentation was positive. He was admitted for medical management. During hospital stay, the patient developed manic symptoms including over-talkativeness, expansive mood, disinhibited behavior, excessive planning, paranoia and aggression. He remained oriented to time, place and person and neurological examination was unremarkable. He was managed with anti-psychotics and benzodiazepines, and his psychiatric symptoms improved with improvement in his medical condition. This case highlights the possibility of psychiatric manifestations occurring in context of a dengue infection.

Sexual Stimuli Cause Behavioral Disinhibition in Both Men and Women, but Even More So in Men

In our society men are considered more impulsive than women, especially in the violent and sexual domain. This correlation of sex and impulsivity might trace back to enhanced male impulsivity in general or a domain specific effect of emotions on impulsivity. The evidence for sex differences in the interaction of emotional or sexual stimuli and impulsivity has been relatively inconclusive so far. In this study, we investigated the effects of various emotional stimuli on responsivity in a Go/No-Go task. Participants had to respond quickly to a visual cue and withhold their response to another visual cue, while different emotional pictures were presented in the background, including sexual stimuli, non-sexual positive stimuli and negative stimuli. Both men (N = 37) and women (N = 38) made most commission errors in the sexual condition, indicating a disinhibiting effect in both genders. On top of this, men made even more commission errors than women, specifically in the sexual condition and not in other conditions. Men rated sexual stimuli as more positive, but did not differ from women in arousal ratings and pupil dilation. These findings may partly indicate increased impulsive behavior under sexual arousal in men, most likely driven by enhanced approach motivation due to more positive value but not higher arousal of sexual stimuli. The results are consistent with the theory of evolutionarily based concealment of sexual interest in women.

Heightened motor impairment as a protective factor against heavy drinking in individuals with high alcohol-induced disinhibition.

Behavioral disinhibition and motor impairment are both acutely elevated following alcohol consumption, and individual differences in sensitivity to alcohol-induced increases in these effects are associated with drinking habits. Specifically, high alcohol-induced disinhibition and low motor impairment have been identified as separate markers for alcohol-related problems. This study tested the degree to which alcohol-induced disinhibition and motor impairment jointly predict heavy drinking. We hypothesized that heavier drinkers would exhibit a combination of high sensitivity to alcohol-induced disinhibition and low sensitivity to its motor impairing effect. Data from three studies were aggregated to comprise a sample of 96 young adults. Participants' motor coordination (grooved pegboard) and behavioral disinhibition (cued go/no-go) were assessed following consumption of 0.65 g/kg alcohol and a placebo during separate sessions. As BAC was ascending, alcohol increased motor impairment and disinhibition compared to placebo. Combined effects at this time of alcohol on motor impairment and disinhibition predicted typical drinking habits. Specifically, a combination of high sensitivity to alcohol's disinhibiting effect and low sensitivity to its motor impairing effect was associated with heavy drinking. As BAC was descending, only reduced sensitivity to motor impairment remained as a predictor of heavy drinking. The findings suggest that although motor impairment following alcohol consumption is associated with certain negative outcomes (e.g., increased risk for physical injury and motor vehicle accidents), such heightened motor impairment from alcohol may actually serve as a protective factor against the excessive drinking that can accompany the disinhibiting effect of alcohol.

Sleep quality, emotional and behavioral disturbances, and eating behavior in adolescents with obesity: a network analysis-based model

To attempt to identify persistent associations between sleep quality, symptoms of emotional and behavioral disturbances, and characteristics of eating behavior in obese adolescents based on a network analysis. The study included 194 adolescents, aged 12-17 years (76 girls, 118 boys), with a confirmed diagnosis of obesity due to excess calories (ICD-10 code E66.0). Sleep quality was studied on the basis of the Adolescent Sleep Wake Scale (ASWS), emotional and behavioral disturbances were assessed with the Achenbach Youth Self-Report for Ages 11-18 (YSR), eating behavior - with the Dutch Eating Behavior Questionnaire (DEBQ). Network analysis was used to identify the most significant and stable associations between the studied indicators. The association of poor sleep quality with manifestations of disinhibited behavior in the form of violations of the rules of behavior, aggressiveness, and impaired attention was revealed. Positive correlations between the manifestations of disinhibited behavior (primarily, rule-breaking behavior) and emotional eating behavior, which, in turn, had a positive relationship with external and a negative relationship with restrictive eating behavior, were noted. The disinhibited adolescent behavior is linked with uncontrolled food intake, which can contribute to the development of obesity. Impaired sleep quality, symptoms of emotional and behavioral disorders, and eating disorders in obese adolescents present a stable and specific clinical pattern that should be taken into account when justifying therapy.

Mapping behavioural, cognitive and affective transdiagnostic dimensions in frontotemporal dementia.

Two common clinical variants of frontotemporal dementia are the behavioural variant frontotemporal dementia, presenting with behavioural and personality changes attributable to prefrontal atrophy, and semantic dementia, displaying early semantic dysfunction primarily due to anterior temporal degeneration. Despite representing independent diagnostic entities, mounting evidence indicates overlapping cognitive-behavioural profiles in these syndromes, particularly with disease progression. Why such overlap occurs remains unclear. Understanding the nature of this overlap, however, is essential to improve early diagnosis, characterization and management of those affected. Here, we explored common cognitive-behavioural and neural mechanisms contributing to heterogeneous frontotemporal dementia presentations, irrespective of clinical diagnosis. This transdiagnostic approach allowed us to ascertain whether symptoms not currently considered core to these two syndromes are present in a significant proportion of cases and to explore the neural basis of clinical heterogeneity. Sixty-two frontotemporal dementia patients (31 behavioural variant frontotemporal dementia and 31 semantic dementia) underwent comprehensive neuropsychological, behavioural and structural neuroimaging assessments. Orthogonally rotated principal component analysis of neuropsychological and behavioural data uncovered eight statistically independent factors explaining the majority of cognitive-behavioural performance variation in behavioural variant frontotemporal dementia and semantic dementia. These factors included Behavioural changes, Semantic dysfunction, General Cognition, Executive function, Initiation, Disinhibition, Visuospatial function and Affective changes. Marked individual-level overlap between behavioural variant frontotemporal dementia and semantic dementia was evident on the Behavioural changes, General Cognition, Initiation, Disinhibition and Affective changes factors. Compared to behavioural variant frontotemporal dementia, semantic dementia patients displayed disproportionate impairment on the Semantic dysfunction factor, whereas greater impairment on Executive and Visuospatial function factors was noted in behavioural variant frontotemporal dementia. Both patient groups showed comparable magnitude of atrophy to frontal regions, whereas severe temporal lobe atrophy was characteristic of semantic dementia. Whole-brain voxel-based morphometry correlations with emergent factors revealed associations between fronto-insular and striatal grey matter changes with Behavioural, Executive and Initiation factor performance, bilateral temporal atrophy with Semantic dysfunction factor scores, parietal-subcortical regions with General Cognitive performance and ventral temporal atrophy associated with Visuospatial factor scores. Together, these findings indicate that cognitive-behavioural overlap (i) occurs systematically in frontotemporal dementia; (ii) varies in a graded manner between individuals and (iii) is associated with degeneration of different neural systems. Our findings suggest that phenotypic heterogeneity in frontotemporal dementia syndromes can be captured along continuous, multidimensional spectra of cognitive-behavioural changes. This has implications for the diagnosis of both syndromes amidst overlapping features as well as the design of symptomatic treatments applicable to multiple syndromes.

Behavioural disinhibition in frontotemporal dementia investigated within an ecological framework

Disinhibition is a core symptom in behavioural variant frontotemporal dementia (bvFTD) particularly affecting the daily lives of both patients and caregivers. Yet, characterisation of inhibition disorders is still unclear and management options of these disorders are limited. Questionnaires currently used to investigate behavioural disinhibition do not differentiate between several subtypes of disinhibition, encompass observation biases and lack of ecological validity.In the present work, we explored disinhibition in an original semi-ecological situation, by distinguishing three categories of disinhibition: compulsivity, impulsivity and social disinhibition. First, we measured prevalence and frequency of these disorders in 23 bvFTD patients and 24 healthy controls (HC) in order to identify the phenotypical heterogeneity of disinhibition. Then, we examined the relationships between these metrics, the neuropsychological scores and the behavioural states to propose a more comprehensive view of these neuropsychiatric manifestations. Finally, we studied the context of occurrence of these disorders by investigating environmental factors potentially promoting or reducing them.As expected, we found that patients were more compulsive, impulsive and socially disinhibited than HC. We found that 48% of patients presented compulsivity (e.g., repetitive actions), 48% impulsivity (e.g., oral production) and 100% of the patients group showed social disinhibition (e.g., disregards for rules or investigator). Compulsivity was negatively related with emotions recognition. BvFTD patients were less active if not encouraged in an activity, and their social disinhibition decreased as activity increased. Finally, impulsivity and social disinhibition decreased when patients were asked to focus on a task.Summarising, this study underlines the importance to differentiate subtypes of disinhibition as well as the setting in which they are exhibited, and points to stimulating area for non-pharmacological management.

"Sensitivity to the disinhibiting effect of alcohol: The role of trait impulsivity and sex differences": Clarification.

Higher trait impulsivity is associated with more impulsive responding on certain behavioral measures of disinhibition. Additionally, behavioral disinhibition is acutely elevated following alcohol consumption. The present study examined the possibility that trait impulsivity may predict individual differences in sensitivity to the disinhibiting effect of alcohol. Specifically, the present study tested the hypothesis that those with elevated trait impulsivity also experience heightened sensitivity to the disinhibiting effect of alcohol, which might further compound their tendency toward impulsive action. To test this hypothesis, data from six studies were aggregated to comprise a sample of 190 young adults. Participants completed the Barratt Impulsiveness Scale-11 (BIS-11), and behavioral disinhibition was assessed using a cued go/no-go task following consumption of 0.65 g/kg alcohol and a placebo. Alcohol increased disinhibition overall, but higher impulsivity did not predict increased sensitivity to alcohol-induced disinhibition. In men, higher levels of trait impulsivity predicted heightened disinhibition in the unintoxicated state following placebo, but this relationship was not present in women. These findings suggest significant sex differences in the relationship between trait impulsivity and disinhibition. This sex difference may explain inconsistent research findings in studies assessing links between trait and behavioral measures of impulsivity. The data also point to trait impulsivity and sensitivity to alcohol-induced disinhibition as independent constructs. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Sensitivity to the disinhibiting effect of alcohol: The role of trait impulsivity and sex differences.

To test this hypothesis, data from six studies were aggregated to comprise a sample of 190 young adults. Participants completed the Barratt Impulsiveness Scale-11 (BIS-11), and behavioral disinhibition was assessed using a cued go/no-go task following consumption of 0.65 g/kg alcohol and a placebo. Alcohol increased disinhibition overall, but higher impulsivity did not predict increased sensitivity to alcohol-induced disinhibition. In men, higher levels of trait impulsivity predicted heightened disinhibition in the unintoxicated state following placebo, but this relationship was not present in women. These findings suggest significant sex differences in the relationship between trait impulsivity and disinhibition. This sex difference may explain inconsistent research findings in studies assessing links between trait and behavioral measures of impulsivity. The data also point to trait impulsivity and sensitivity to alcohol-induced disinhibition as independent constructs. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Clinical Profiles of Persons Who Progress to Cognitive Impairment in the Alzheimer’s Prevention Initiative (API) ADAD Colombia Trial

AbstractBackgroundIn Colombia, 13 pathogenic variants of presenilin 1 (PSEN1) causing Autosomal Dominant Alzheimer’s Disease (ADAD) have been identified. Some cases have atypical presentations, with variability in the age of onset and course of the disease. We characterized clinical profiles of cognitively unimpaired PSEN1 E280A mutation carriers who progress to MCI or dementia in the API ADAD Colombia Trial.MethodThe API ADAD Colombia Trial enrolled 252 cognitively unimpaired 30–60 year‐old participants into a 5‐8‐year double‐blind placebo controlled randomized prevention trial with a common close design. About 1/3 of participants were PSEN1 E280A mutation carriers who were randomized to the investigational anti‐oligomeric amyloid‐β antibody therapy crenezumab, 1/3 were mutation carriers who were randomized to placebo, and 1/3 were non‐carriers from the same kindred who were randomized to placebo. Trial results are pending. We used standardized procedures to blindly assess clinical features of participants who progressed to MCI and/or dementia during the trial, reviewed by an independent progression adjudication committee (PAC), to confirm the first instance of clinical progression.ResultDuring the trial 45 participants had an initial progression to MCI due to AD and 2 to dementia due to AD confirmed by the PAC. Among the 45 adjudicated with MCI due to AD, 32 subsequently progressed to dementia (30 due to AD and 2 due to other causes as determined by the site clinicians by consensus). The mean age onset of MCI was 45 (range 36–60 years) and of dementia was 47 (range 36–62 years). Three participants developed dementia before 40 years and one participant at 62 years. At the time of MCI, 43 participants had a predominantly amnesic profile, one had a predominantly behavioral disinhibition, and one had a Capgras syndrome, severe aggression and myoclonus. One participant developed severe global aphasia two years after the onset of dementia; two of the participant’s first‐degree relatives had language impairment in conjunction with MCI; one developed primary progressive logopenic aphasia.ConclusionSome persons with ADAD have an atypical clinical presentation. Additional studies are needed to clarify the biological changes, genetic/environmental risk factors, clinical course and response to treatment in these individuals.

The pattern of cortical thickness underlying disruptive behaviors in Alzheimer's disease.

Disruptive behaviors, including agitation, disinhibition, irritability, and aberrant motor behaviors, are commonly observed in patients with Alzheimer's disease (AD). However, the neuroanatomical basis of these disruptive behaviors is not fully understood. To confirm the differences in cortical thickness and surface area between AD patients and healthy controls and to further investigate the features of cortical thickness and surface area associated with disruptive behaviors in patients with AD. One hundred seventy-four participants (125 AD patients and 49 healthy controls) were recruited from memory clinics at the Peking University Institute of Sixth Hospital. Disruptive behaviors, including agitation/aggression, disinhibition, irritability/lability, and aberrant motor activity subdomain scores, were evaluated using the Neuropsychiatry Inventory. Both whole-brain vertex-based and region-of-interest-based cortical thickness and surface area analyses were automatically conducted with the CIVET pipeline based on structural magnetic resonance images. Both group-based statistical comparisons and brain-behavior association analyses were performed using general linear models, with age, sex, and education level as covariables. Compared with healthy controls, the AD patients exhibited widespread reduced cortical thickness, with the most significant thinning located in the medial and lateral temporal and parietal cortex, and smaller surface areas in the left fusiform and left inferior temporal gyrus. High total scores of disruptive behaviors were significantly associated with cortical thinning in several regions that are involved in sensorimotor processing, language, and expression functions. The total score of disruptive behaviors did not show significant associations with surface areas. We highlight that disruptive behaviors in patients with AD are selectively associated with cortical thickness abnormalities in sensory, motor, and language regions, which provides insights into neuroanatomical substrates underlying disruptive behaviors. These findings could lead to sensory, motor, and communication interventions for alleviating disruptive behaviors in patients with AD.

Brain region-specific synaptic function of FUS underlies the FTLD-linked behavioural disinhibition.

Synaptic dysfunction is one of the earliest pathological processes that contribute to the development of many neurological disorders, including Alzheimer's disease and frontotemporal lobar degeneration. However, the synaptic function of many disease-causative genes and their contribution to the pathogenesis of the related diseases remain unclear. In this study, we investigated the synaptic role of fused in sarcoma, an RNA-binding protein linked to frontotemporal lobar degeneration and amyotrophic lateral sclerosis, and its potential pathological role in frontotemporal lobar degeneration using pyramidal neuron-specific conditional knockout mice (FuscKO). We found that FUS regulates the expression of many genes associated with synaptic function in a hippocampal subregion-specific manner, concomitant with the frontotemporal lobar degeneration-linked behavioural disinhibition. Electrophysiological study and molecular pathway analyses further reveal that fused in sarcoma differentially regulates synaptic and neuronal properties in the ventral hippocampus and medial prefrontal cortex, respectively. Moreover, fused in sarcoma selectively modulates the ventral hippocampus-prefrontal cortex projection, which is known to mediate the anxiety-like behaviour. Our findings unveil the brain region- and synapse-specific role of fused in sarcoma, whose impairment might lead to the emotional symptoms associated with frontotemporal lobar degeneration.

Third Ventricular Colloid Cyst - An Organic Cause of Mania: A Case Report

Background: Psychiatric manifestations due to space-occupying lesions, although not uncommon, are generally misdiagnosed, leading to an unfavorable outcomes. Colloid cyst is a slow-growing, benign tumor in the anterior part of the third ventricle, which frequently presents with neurological complaints like headache and gait disturbances. However, a patient with colloid cyst may also present to the OPD with a spectrum of psychiatric symptoms. Case Report: We here report a middle-aged man who was brought to the OPD with symptoms of pervasive irritability and disinhibited behavior for three months, along with complaints of increased activity, reduced sleep and appetite, suspicious about wife, family members and neighbors. Patient had frequent episodes of headache in the past 3 months associated with nausea, restlessness for which neuroimaging was advised, which showed a hyper-dense lesion in the third ventricle. Patient was referred to neurosurgery and was operated for the same. Post-operatively, family members reported improvement in his behavior. Conclusion: A detailed systemic evaluation for any neurological causes of organic causes or atypical picture of psychiatric conditions is of extreme necessity. There is a dire need for liaison of psychiatrists with neurophysicians and neurosurgeons to attain betterment in patients in both physical as well as psychological aspects, especially in psychiatric diagnosis with organic causes.

Motor, cognitive and behavioural profiles of C9orf72 expansion-related amyotrophic lateral sclerosis

IntroductionAmyotrophic lateral sclerosis (ALS) individuals carrying the hexanucleotide repeat expansion (HRE) in the C9orf72 gene (C9Pos) have been described as presenting distinct features compared to the general ALS population (C9Neg). We aim to identify the phenotypic traits more closely associated with the HRE and analyse the role of the repeat length as a modifier factor.MethodsWe studied a cohort of 960 ALS patients (101 familial and 859 sporadic cases). Motor phenotype was determined using the MRC scale, the lower motor neuron score (LMNS) and the Penn upper motor neuron score (PUMNS). Neuropsychological profile was studied using the Italian version of the Edinburgh Cognitive and Behavioral ALS Screen (ECAS), the Frontal Behavioral Inventory (FBI), the Beck Depression Inventory-II (BDI-II) and the State-Trait Anxiety Inventory (STAI). A two-step PCR protocol and Southern blotting were performed to determine the presence and the size of C9orf72 HRE, respectively.ResultsC9orf72 HRE was detected in 55/960 ALS patients. C9Pos patients showed a younger onset, higher odds of bulbar onset, increased burden of UMN signs, reduced survival and higher frequency of concurrent dementia. We found an inverse correlation between the HRE length and the performance at ECAS ALS-specific tasks (P = 0.031). Patients also showed higher burden of behavioural disinhibition (P = 1.6 × 10–4), lower degrees of depression (P = 0.015) and anxiety (P = 0.008) compared to C9Neg cases.ConclusionsOur study provides an extensive characterization of motor, cognitive and behavioural features of C9orf72-related ALS, indicating that the C9orf72 HRE size may represent a modifier of the cognitive phenotype.