Behavioral Disinhibition Research Articles

Advancing Gene Discovery for Substance Use Disorders Using Additional Traits Related to Behavioral Disinhibition.

Substance use disorders (SUDs) frequently co-occur with each other and with other traits related to behavioral disinhibition, a spectrum of outcomes referred to as externalizing. Nevertheless, genome-wide association studies (GWAS) typically study individual SUDs separately. This single-disorder approach ignores genetic covariance between SUDs and other traits and may contribute to the relatively limited genetic discoveries to date. To identify the most effective model for capturing genetic relationships between SUDs and externalizing phenotypes, optimizing the detection of genetic influences on SUDs while maintaining specificity. We used Genomic SEM to estimate SNP effects on a broad factor representing liability to externalizing and SUDs, on factors representing liability to behavioral disinhibition and SUDs separately, and on residualized SUDs. Subsequent gene-based, tissue expression, and polygenic score (PGS) analyses were used to compare the ability of these alternative approaches to identify genetic influences on SUDs. This study was carried out from May 2023 - September 2024. We used GWAS summary statistics based on samples of European ancestry from previous studies of externalizing and SUD phenotypes in the main multivariate GWAS ( N > 2.2 million). We used two independent samples to estimate polygenic associations, a family-based sample enriched for substance use problems (COGA; N = 7,530) and a population-based sample representative of the United States, (All of Us; N = 77,442). N/A. Across the three factors (Externalizing; SUDs; Behavioral Disinhibition) and four residualized SUDs (alcohol, tobacco, opioid, and cannabis), we compared the number, putative function, previous associations of significant genomic risk loci and genes, and variance explained by polygenic scores in substance use outcomes. We identified genomic risk loci and genes uniquely associated with Externalizing that are relevant to the neurobiology of substance use. Genes identified for residual SUDs were involved in substance-specific processes (e.g., metabolism). The Externalizing PGS accounted for the most variance in substance outcomes relative to the PGS for the other factors and residual PGS appeared to capture substance specific signals. Our findings suggest that modeling both a broad genetic liability to externalizing behaviors and substance-specific liabilities enhances the detection of genetic effects related to SUDs and explains more variance in substance use outcomes. Question: Can we advance gene discovery for substance use disorders (SUDs) by incorporating information about correlated outcomes related to behavioral disinhibition?Findings: Combining genetic effects common to SUDs and behavioral disinhibition in a multivariate genome-wide association study of > 2.2 million individuals identified 708 genomic risk loci and accounted for more variance in SUD phenotypes compared with modeling each set of phenotypes separately.Meaning: SUDs and behavioral dysregulation are influenced by a common set of common variants; modeling their joint contributions improves power for genetic discovery and polygenic prediction.

Prodromal symptoms of a first manic episode: a qualitative study to the perspectives of patients with bipolar disorder and their caregivers’

BackgroundDiagnosing bipolar disorder (BD) is challenging, and adequate treatment is of major importance to minimalize the consequences of the illness. Early recognition is one way to address this. Although in clinical research the prodromal phase of BD is gaining interest, the perspective of patients with BD and their caregivers on prodromal symptoms is still lacking. The aim of this study is to gain insights in prodromal symptoms of patients with BD and their caregivers before the onset of a first manic episode.MethodsA qualitative research method was used to investigate prodromal symptoms one year prior to a first manic episode. In-depth interviews were conducted with patients with BD type I and their caregivers. Only patients with a first manic episode in the previous five years were included.ResultsThe prodromal symptoms from patients’ and caregivers’ perspectives could be clustered into seven themes, with underlying subthemes: behavior (increased activity, destructive behavior, disinhibited behavior, inadequate behavior, changes in appearance), physical changes (changes in sleep, physical signals, differences in facial expression), communication (reciprocity, process, changes in use of social media), thought (process and content), cognition (changes in attention and concentration, forgetfulness), emotions (positive emotions, more intense emotions, mood swings), and personality (more pronounced manifestation of existing personality traits).ConclusionPatients with bipolar I disorder and their caregivers described subsyndromal manic features one year prior to a first manic episode. In addition, they recognized mood lability, physical changes and more pronounced manifestation of existing personality traits. The results of this study confirm the presence of a prodromal phase. In clinical practice, monitoring of prodromal symptoms of BD can be useful in patients with depression, especially those with a familial risk of BD.

The 1888 dissertation of a female medical student, Ueber Character-Veränderungen des Menschen in Folge von Laesionen des Stirnhirns (On character changes of man as a consequence of lesions of the frontal lobe)

A case of brain injury with a transient syndrome of mainly disinhibited behaviour (Franz Binz) was the subject of the 1888 medical dissertation of Leonore Welt (∗1859 Chernivtsi, Ukraine; †1944 Geneva, Switzerland) which came to be discussed quite controversially. Although Binz was never fully forgotten, the similar “American crow-bar case” (Phineas Gage) attracted more interest. Welt’s study, in contrast, provides not only well-illustrated neuropathological findings but also more detailed clinical data. Here, the clinical report and sections of its analysis are translated from the German original. Through comparison with similar cases, Welt proposed the straight gyrus (gyrus rectus) as the main area responsible. The transient nature of the behavioural alteration was taken as indicating a peculiar disease process at that location. She stressed that disinhibited behaviour suggests fronto-orbital lesions, but that the conclusion is not to be reversed. She had noted the absence of symptoms in the majority of similarly situated injuries: normal behaviour thus being no proof of an intact fronto-orbital region. Along with two sisters, Rosa Welt-Straus (1856–1938) and Sara Welt-Kakels (1860–1943), Leonore Gourfein-Welt was among the first females from then Austria to graduate in medicine – against considerable resistance. After her thesis work, she turned to practising ophthalmology in Geneva.

Development and preliminary validation of a modified Food Craving Inventory for Pregnancy (FCI-P) in U.S. military active-duty Service women

Food cravings during pregnancy are highly common, yet no measure of cravings has been validated among pregnant women. The current study evaluated the psychometric properties of the Food Craving Inventory (FCI) for use during pregnancy. U.S. military active-duty Service women (N = 192; 29.5 ± 3.8 years old; 44% Army, 36% Air Force, 15% Navy, and 4% Marine Corps) were recruited from the community at 12–27 weeks' gestation. Participants completed a modified version of the FCI validated for adults with binge-eating disorder, which included 13 additional items assessing cravings for foods that women commonly report experiencing during pregnancy (e.g., pickles, sour cream, hot or spicy wings). Additional measures also assessed disinhibited eating behaviors (i.e., loss of control eating and emotional eating). A series of confirmatory factor analyses were conducted to examine model fit for a four-factor structure of: (1) the FCI validated for binge-eating disorder (excluding the pregnancy-oriented food items) and (2) the FCI modified for pregnancy (with the pregnancy-oriented food items added). The previously validated four-factor structure of the FCI for binge-eating disorder demonstrated poor model fit in the current sample of pregnant women. After examining the structure of the FCI modified for pregnancy, several items were removed due to high cross-loading across multiple subscales. The resulting 16-item, four-factor (Fats, Sweets, Carbohydrates, Spicy/Strong foods) FCI for pregnancy (FCI-P) demonstrated generally good model fit (CFI = .95, TLI = .94, SRMR = .04, RMSEA = .09) and good-to-excellent internal consistency (Cronbach's alphas: .83-.96). Convergent validity was supported by significant correlations between the FCI-P scores and the disinhibited eating behavior scores (ps < .001). Results highlight the importance of psychometrically evaluating eating-related measures for use during pregnancy to appropriately capture the potentially unique experiences of the perinatal period.

Association Between Hypothalamic Volume and Metabolism, Cognition, and Behavior in Patients With Amyotrophic Lateral Sclerosis.

Dysfunction of energy metabolism, cognition, and behavior are important nonmotor symptoms of amyotrophic lateral sclerosis (ALS), negatively affecting survival and quality of life, but poorly understood. Neuroimaging is ideally suited to studying nonmotor neurodegeneration in ALS, but few studies have focused on the hypothalamus, a key region for regulating energy homeostasis, cognition, and behavior. We evaluated, therefore, hypothalamic neurodegeneration in ALS and explored the relationship between hypothalamic volumes and dysregulation of energy metabolism, cognitive and behavioral changes, disease progression, and survival. Patients with ALS and population-based controls were included for this cross-sectional and longitudinal MRI study. The hypothalamus was segmented into 5 subregions and their volumes were calculated. Linear (mixed) models, adjusted for age, sex, and total intracranial volume, were used to compare hypothalamic volumes between groups and to analyze associations with metabolism, cognition, behavior, and disease progression. Cox proportional hazard models were used to investigate the relationship of hypothalamic volumes with survival. Permutation-based corrections for multiple hypothesis testing were applied to all analyses to control the family-wise error rate. Data were available for 564 patients with ALS and 356 controls. The volume of the anterior superior subregion of the hypothalamus was smaller in patients with ALS than in controls (β = -0.70 [-1.15 to -0.25], p = 0.013). Weight loss, memory impairments, and behavioral disinhibition were associated with a smaller posterior hypothalamus (β = -4.79 [-8.39 to -2.49], p = 0.001, β = -10.14 [-15.88 to -4.39], p = 0.004, and β = -12.09 [-18.83 to -5.35], p = 0.003, respectively). Furthermore, the volume of this subregion decreased faster over time in patients than in controls (β = -0.25 [0.42 to -0.09], p = 0.013), and a smaller volume of this structure was correlated with shorter survival (hazard ratio = 0.36 [0.21-0.61], p = 0.029). We obtained evidence for hypothalamic involvement in ALS, specifically marked by atrophy of the anterior superior subregion. Moreover, we found that atrophy of the posterior hypothalamus was associated with weight loss, memory dysfunction, behavioral disinhibition, and survival, and that this subregion deteriorated faster in patients with ALS than in controls. These findings improve our understanding of nonmotor involvement in ALS and could contribute to the identification of new treatment targets for this devastating disease.

Mouse parasubthalamic Crh neurons drive alcohol drinking escalation and behavioral disinhibition.

Corticotropin-releasing factor (CRF, encoded by Crh) signaling is thought to play a critical role in the development of excessive alcohol drinking and the emotional and physical pain associated with alcohol withdrawal. Here, we investigated the parasubthalamic nucleus (PSTN) as a potential source of CRF relevant to the control of alcohol consumption, affect, and nociception in mice. We identified PSTN Crh neurons as a neuronal subpopulation that exerts a potent and unique influence on behavior by promoting not only alcohol but also saccharin drinking, while PSTN neurons are otherwise known to suppress consummatory behaviors. Furthermore, PSTN Crh neurons are causally implicated in the escalation of alcohol and saccharin intake produced by chronic intermittent ethanol (CIE) vapor inhalation, a mouse model of alcohol use disorder. In contrast to our predictions, the ability of PSTN Crh neurons to increase alcohol drinking is not mediated by CRF1 signaling. Moreover, the pattern of behavioral disinhibition and reduced nociception driven by their activation does not support a role of negative reinforcement as a motivational basis for the concomitant increase in alcohol drinking. Finally, silencing Crh expression in the PSTN slowed down the escalation of alcohol intake in mice exposed to CIE and accelerated their recovery from withdrawal-induced mechanical hyperalgesia. Altogether, our results suggest that PSTN Crh neurons may represent an important node in the brain circuitry linking alcohol use disorder with sweet liking and novelty seeking.

Partitioning the Genomic Components of Behavioral Disinhibition and Substance Use (Disorder) Using Genomic Structural Equation Modeling.

Externalizing behaviors encompass manifestations of risk-taking, self-regulation, aggression, sensation-/reward-seeking, and impulsivity. Externalizing research often includes substance use (SUB), substance use disorder (SUD), and other (non-SUB/SUD) "behavioral disinhibition" (BD) traits. Genome-wide and twin research have pointed to overlapping genetic architecture within and across SUB, SUD, and BD. We created single-factor measurement models-each describing SUB, SUD, or BD traits-based on mutually exclusive sets of European ancestry genome-wide association study (GWAS) statistics exploring externalizing variables. We then assessed the partitioning of genetic covariance among the three facets using correlated factors models and Cholesky decomposition. Even when the residuals for indicators relating to the same substance were correlated across the SUB and SUD factors, the two factors yielded a large correlation (rg=0.803). BD correlated strongly with the SUD (rg=0.774) and SUB (rg=0.778)factors. In our initial decompositions, 33% of total BD variance remained after partialing out SUD and SUB. The majority of covariance between BD and SUB and between BD and SUD was shared across all factors, and, within these models, only a small fraction of the total variation in BD operated via an independent pathway with SUD or SUB outside of the other factor. When only nicotine/tobacco, cannabis, and alcohol were included for the SUB/SUD factors, their correlation increased to rg=0.861; in corresponding decompositions, BD-specific variance decreased to 27%. Further research can better elucidate the properties of BD-specific variation by exploring its genetic/molecular correlates.

Serine racemase deletion alters adolescent social behavior and whole-brain cFos activation.

Neurodevelopmental disorders (NDDs) can cause debilitating impairments in social cognition and aberrant functional connectivity in large-scale brain networks, leading to social isolation and diminished everyday functioning. To facilitate the treatment of social impairments, animal models of NDDs that link N- methyl-D-aspartate receptor (NMDAR) hypofunction to social deficits in adulthood have been used. However, understanding the etiology of social impairments in NDDs requires investigating social changes during sensitive windows during development. We examine social behavior during adolescence using a translational mouse model of NMDAR hypofunction (SR-/-) caused by knocking out serine racemase (SR), the enzyme needed to make D-serine, a key NMDAR coagonist. Species-typical social interactions are maintained through brain-wide neural activation patterns; therefore, we employed whole-brain cFos activity mapping to examine network-level connectivity changes caused by SR deletion. In adolescent SR-/- mice, we observed disinhibited social behavior toward a novel conspecific and rapid social habituation toward familiar social partners. SR-/- mice also spent more time in the open arm of the elevated plus maze which classically points to an anxiolytic behavioral phenotype. These behavioral findings point to a generalized reduction in anxiety-like behavior in both social and non-social contexts in SR-/- mice; importantly, these findings were not associated with diminished working memory. Inter-regional patterns of cFos activation revealed greater connectivity and network density in SR-/- mice compared to controls. These results suggest that NMDAR hypofunction - a potential biomarker for NDDs - can lead to generalized behavioral disinhibition in adolescence, potentially arising from disrupted communication between and within salience and default mode networks.

Neural indices of heritable impulsivity: Impact of the COMT Val158Met polymorphism on frontal beta power during early motor preparation

Studies of COMT Val158Met suggest that the neural circuitry subserving inhibitory control may be modulated by this functional polymorphism altering cortical dopamine availability, thus giving rise to heritable differences in behaviors. Using an anatomically-constrained magnetoencephalography method and stratifying the sample by COMT genotype, from a larger sample of 153 subjects, we examined the spatial and temporal dynamics of beta oscillations during motor execution and inhibition in 21 healthy Met158/Met158 (high dopamine) or 21 Val158/Val158 (low dopamine) genotype individuals during a Go/NoGo paradigm. While task performance was unaffected, Met158 homozygotes demonstrated an overall increase in beta power across regions essential for inhibitory control during early motor preparation (∼100 ms latency), suggestive of a global motor “pause” on behavior. This increase was especially evident on Go trials with slow response speed and was absent during inhibition failures. Such a pause could underlie the tendency of Met158 allele carriers to be more cautious and inhibited. In contrast, Val158 homozygotes exhibited a beta drop during early motor preparation, indicative of high response readiness. This decrease was associated with measures of behavioral disinhibition and consistent with greater extraversion and impulsivity observed in Val homozygotes. These results provide mechanistic insight into genetically-determined interindividual differences of inhibitory control with higher cortical dopamine associated with momentary response hesitation, and lower dopamine leading to motor impulsivity.

Prevalence of substance and hazardous alcohol use and their association with risky sexual behaviour among youth: findings from a population-based survey in Zimbabwe

ObjectivesHazardous drinking (HD) and substance use (SU) can lead to disinhibited behaviour and are both growing public health problems among Southern African youths. We investigated the prevalence of SU and...

Mental health among centenarians living in Switzerland.

Given the increasing number of people achieving exceptionally long lifespans, there is an urgent need for a better understanding of mental health in centenarians. This study aimed to understand the prevalence of mental health conditions-depressive symptoms, anxiety, sleep disturbances, disinhibition, and aberrant motor behaviour-among centenarians in Switzerland. Data were collected from N = 169 participants via telephone interviews or paper questionnaires, either directly from centenarians or through proxy informants. Half the data were collected during a period when protective measures were imposed due to the COVID-19 pandemic, and half were collected after the measures were lifted. Mental health conditions were prevalent in our sample, particularly depressive symptoms (44.51%) and anxiety (42.17%). Significant positive associations were found between depressive symptoms and anxiety, and between disinhibition and aberrant motor behaviour. Furthermore, we identified statistical predictors for the occurrence of mental health conditions. Notably, institutionalised living increased the odds of depressive symptomatology, while those with higher education levels or an absence of cognitive impairment experienced more sleep disturbances. Finally, cognitive impairment was linked to increased disinhibition and aberrant motor behaviour. The high prevalence of mental health conditions underscores the need for proactive mental health care strategies in advanced old age. Moreover, it is vital to consider the interconnected nature of mental health conditions and to prioritise vulnerable groups, such as centenarians in institutional settings.

Differential diagnosis between frontotemporal dementia and bipolar disorder, review and case report

IntroductionDementia can present with psychiatric symptoms even before the cognitive impairment, which makes difficult to establish an adequate diagnosis. There have described symptoms of this type in vascular dementia, frontotemporal dementia, Alzheimer disease and Lewy bodies dementia. Frontotemporal dementia has a prevalence of 9-20% and it`s the third in frequency among degenerative dementia. It appears before the age of 65 years old and is more common in men. Two variants have been described, linguistic and behavioral. The behavioral one has usually an initial psychiatric presentation, with behavioral disorders, disinhibition and personality changes. Therefore it`s important to make an adequate differential diagnosis with late onset bipolar disorder.ObjectivesTo review about frontotemporal dementia and its differential diagnosis with late onset bipolar disorder.MethodsWe carry out a literature review about frontotemporal dementia and its differential diagnosis with late onset bipolar disorder, accompanied by a clinical description of one patient with behavioral disturbance and language disorder.Results A 59-year-old female was admitted to the short-term hospitalization unit from the emergency department due to behavior disorder. She had no relevant personal or familiar psychiatric history up to two years before when she received diagnosis of bipolar disorder. She presented behavioral disorganization, psychomotor restlessness, verbal aggressiveness, verbiage, insomnia and decreased intake. Psychopathological examination became difficult due to her language disorder since she presented an incoherent speech with paraphasias and loss of the common thread. Neurological study guided diagnosis to frontotemporal dementia even though they left the psychopharmacological treatment to our discretion. Olanzapine 5 mg twice a day was initiated, and behavioral improvement was observed. However, the patient maintained a significant functional impairment.ConclusionsPsychiatric presentation is frequent in dementia, even before cognitive failures which makes essential an exhaustive differential diagnosis. It`s important to consider the diagnosis of frontotemporal dementia in those patients who debut with behavioral disturbance in the 50s. Psychopharmacological treatment is only symptomatic so functional recovery should not be expected.Disclosure of InterestNone Declared

Neurexin1α knockout in rats causes aberrant social behaviour: relevance for autism and schizophrenia.

Genetic and environmental factors cause neuropsychiatric disorders through complex interactions that are far from understood. Loss-of-function mutations in synaptic proteins like neurexin1α have been linked to autism spectrum disorders (ASD) and schizophrenia (SCZ), both characterised by problems in social behaviour. Childhood social play behaviour is thought to facilitate social development, and lack of social play may precipitate or exacerbate ASD and SCZ. To test the hypothesis that an environmental insult acts on top of genetic vulnerability to precipitate psychiatric-like phenotypes. To that aim, social behaviour in neurexin1α knockout rats was assessed, with or without deprivation of juvenile social play. We also tested drugs prescribed in ASD or SCZ to assess the relevance of this dual-hit model for these disorders. Neurexin1α knockout rats showed an aberrant social phenotype, with high amounts of social play, increased motivation to play, age-inappropriate sexual mounting, and an increase in general activity. Play deprivation subtly altered later social behaviour, but did not affect the phenotype of neurexin1α knockout rats. Risperidone and methylphenidate decreased play behaviour in both wild-type and knockout rats. Amphetamine-induced hyperactivity was exaggerated in neurexin1α knockout rats. Deletion of the neurexin1α gene in rats causes exaggerated social play, which is not modified by social play deprivation. This phenotype therefore resembles disinhibited behaviour rather than the social withdrawal seen in ASD and SCZ. The neurexin1α knockout rat could be a model for inappropriate or disinhibited social behaviour seen in childhood mental disorders.

Associations of social and cognitive-behavioral variables with disinhibited eating and anxiety: An ecological momentary assessment study.

Among adolescents, disinhibited eating and anxiety commonly co-occur. Precision intervention approaches targeting unique mechanistic vulnerabilities that contribute to disinhibited eating and anxiety may therefore be helpful. However, the effectiveness of such interventions hinges on knowledge of between- and within-person associations related to disinhibited eating, anxiety, and related processes. A sample of 39 adolescent females (12-17 years) with elevated anxiety and above-average weight (BMI %ile ≥ 75th) completed measures of theoretically driven social and cognitive-behavioral variables, disinhibited eating, and anxiety via ecological momentary assessment over 7 days. Data were analyzed using mixed-effects models. Between-person differences in social stressors were linked to emotional eating, eating in the absence of hunger, and anxiety, whereas between-person differences in negative thoughts were associated with all disinhibited eating variables and anxiety. Between-person differences in avoidance were not related to any outcome. Additionally, between-person differences in social stressors and negative thoughts-as well as within-person deviations (from person-average levels) of social stressors, negative thoughts, and avoidance-were associated with anxiety. In turn, between-person differences in anxiety predicted eating in the absence of hunger and emotional eating, and within-person deviations in anxiety were associated with emotional eating at any given time point. Findings support elements of both the interpersonal and cognitive-behavioral models of disinhibited eating. Differential trigger effects on anxiety, both at the between- and within-person levels, and significant associations between anxiety and all eating-related outcomes, highlight the potential utility of interventions targeting individual differences in sensitivity to anxiety triggers. Findings provide support for the interpersonal and cognitive-behavioral models of disinhibited eating, highlighting anxiety as a salient vulnerability and potential mechanistic factor underlying disinhibited eating. Social, cognitive, and behavioral variables were differentially related to anxiety across participants, suggesting potential for future intervention tailoring and intervention selection based on adolescents' sensitivity to anxiety as a trigger for disinhibited eating behavior.

Reduced progranulin increases tau and α-synuclein inclusions and alters mouse tauopathy phenotypes via glucocerebrosidase

Comorbid proteinopathies are observed in many neurodegenerative disorders including Alzheimer’s disease (AD), increase with age, and influence clinical outcomes, yet the mechanisms remain ill-defined. Here, we show that reduction of progranulin (PGRN), a lysosomal protein associated with TDP-43 proteinopathy, also increases tau inclusions, causes concomitant accumulation of α-synuclein and worsens mortality and disinhibited behaviors in tauopathy mice. The increased inclusions paradoxically protect against spatial memory deficit and hippocampal neurodegeneration. PGRN reduction in male tauopathy attenuates activity of β-glucocerebrosidase (GCase), a protein previously associated with synucleinopathy, while increasing glucosylceramide (GlcCer)-positive tau inclusions. In neuronal culture, GCase inhibition enhances tau aggregation induced by AD-tau. Furthermore, purified GlcCer directly promotes tau aggregation in vitro. Neurofibrillary tangles in human tauopathies are also GlcCer-immunoreactive. Thus, in addition to TDP-43, PGRN regulates tau- and synucleinopathies via GCase and GlcCer. A lysosomal PGRN–GCase pathway may be a common therapeutic target for age-related comorbid proteinopathies.

Анализ четырехфакторной модели симптомов аутизма у детей 3–6 лет

&lt;p&gt;The work is devoted to the empirical analysis of age shifts within the framework of the factor model of autism for preschool children. In the 2020&amp;ndash;2022 studies, we obtained a factor model of autism and identified 4 vectors of autism &amp;mdash; typical subtypes of ASD in 3&amp;ndash;4 years old children. Among them are: 1) difficulties in establishing emotional contact, expressing one's emotions and decoding other people's emotions in the context of social interaction; 2) sensory disintegration; 3) impairments in verbal and nonverbal communication and social skills; 4) hyperactivity, including excessive movements, motor disinhibition and restless behavior. It should be emphasized that the first three vectors correspond to the core symptoms of ASD in accordance with the DSM-5. While the hyperactivity factor goes beyond the main symptoms of ASD. In this paper, a comparative analysis of the severity and stability of symptoms was carried out within the framework of a 4-factor model of autism for 3&amp;ndash;4 and 5&amp;ndash;6-year-old children with autism. Sensory and communication impairments have been found to decrease with age, however, emotional impairments and hyperactivity remain at a high level. The theoretical foundations of emotional disorders and hyperactivity in children with ASD are analyzed in detail. Brief practical recommendations are presented for effective early intervention in order to improve the potential trajectory of development of preschool children with ASD.&lt;/p&gt;

Frontotemporal disorders: the expansive panoply of syndromes and spectrum of etiologies.

Frontotemporal lobe disorders (FTD) are amongst the most common brain neurodegenerative disorders. Their relatively covert, frequently subtle presentations and diverse etiologies, pose major challenges in diagnosis and treatments. Recent studies have yielded insights that the etiology in the majority are due to environmental and sporadic causes, rather than genetic in origin. To retrospectively examine the cognitive and behavioral impairments in the veteran population to garner the range of differing syndrome presentations and etiological subcategories with a specific focus on frontotemporal lobe disorders. The design is a retrospective, observational registry, case series with the collection of epidemiological, clinical, cognitive, laboratory and radiological data on people with cognitive and behavioral disorders. Inclusion criteria for entry were veterans evaluated exclusively at Orlando VA Healthcare System, neurology section, receiving a diagnosis of FTD by standard criteria, during the observation period dated from July 2016 to March 2021. Frontotemporal disorders (FTD) were delineated into five clinical 5 subtypes. Demographic, cardiovascular risk factors, cognitive, behavioral neurological, neuroimaging data and presumed etiological categories, were collected for those with a diagnosis of frontotemporal disorder. Of the 200 patients with FTD, further cognitive, behavioral neurological evaluation with standardized, metric testing was possible in 105 patients. Analysis of the etiological groups revealed significantly different younger age of the traumatic brain injury (TBI) and Gulf War Illness (GWI) veterans who also had higher Montreal Cognitive Assessment (MOCA) scores. The TBI group also had significantly more abnormalities of hypometabolism, noted on the PET brain scans. Behavioral neurological testing was notable for the findings that once a frontotemporal disorder had been diagnosed, the four different etiological groups consistently had abnormal FRSBE scores for the 3 principal frontal presentations of (i) abulia/apathy, (ii) disinhibition, and (iii) executive dysfunction as well as abnormal Frontal Behavioral Inventory (FBI) scores with no significant difference amongst the etiological groups. The most common sub-syndromes associated with frontotemporal syndromes were the Geschwind-Gastaut syndrome (GGS), Klüver-Bucy syndrome (KBS), involuntary emotional expression disorder (IEED), cerebellar cognitive affective syndrome (CCA), traumatic encephalopathy syndrome (TES) and prosopagnosia. Comparisons with the three principal frontal lobe syndrome clusters (abulia, disinhibition, executive dysfunction) revealed a significant association with abnormal disinhibition FRSBE T-scores with the GGS. The regression analysis supported the potential contribution of disinhibition behavior that related to this complex, relatively common behavioral syndrome in this series. The less common subsyndromes in particular, were notable, as they constituted the initial overriding, presenting symptoms and syndromes characterized into 16 separate conditions. By deconstructing FTD into the multiple sub-syndromes and differing etiologies, this study may provide foundational insights, enabling a more targeted precision medicine approach for future studies, both in treating the sub-syndromes as well as the underlying etiological process.

Clinical heterogeneity of sleep quality, emotional and behavioral characteristics, and eating habits in adolescents with obesity: A cluster analysis.

This study aims to examine the role of sleep quality, emotional and behavioral characteristics, and eating behavior in adolescents with obesity by means of cluster analysis. One hundred ninety-four adolescents (78 girls, 116 boys) aged 12-17 (mean 14.3 ± 2.7) with obesity (ICD-10 code E 66.0) entered the study. The Adolescent Sleep Wake Scale was used to evaluate sleep quality. The Achenbach Youth Self-Report for Ages 11-18 questionnaire was used to evaluate emotional and behavioral disturbances. The Dutch Eating Behavior Questionnaire was used to assess maladaptive eating. k-Means cluster analysis was used to clarify heterogeneity. Four clusters were identified: the first included anxious, depressed, socially withdrawn adolescents with thought problems and somatic complaints, non-aggressive, obedient, and having mean values on the sleep quality scale, inclined to restrict their food consumption. The second consisted of rule-breaking youngsters with poor sleep quality, reluctant to restrict their food consumption. The third comprised subjects with the highest values on the sleep quality and lowest values on emotional and behavioral problems, aimed at restricting food consumption. The fourth comprised adolescents with obvious signs of emotional disorders, poorest sleep quality, disinhibited behavior, and emotional and external eating. No statistically significant difference was found between the clusters in sex distribution. Patient allocation to the second or fourth cluster was associated with significantly higher body mass index values, as opposed to the reference third cluster. Conclusion: There is significant variation in teenagers with obesity who have divergent psychological profiles, which should be taken into account. What is Known: • Patients with obesity present with different clinical characteristics. What is New: • Adolescents with obesity may be partitioned into clusters described in terms of emotional, behavioral patterns, including sleep characteristics, and maladaptive eating habits.

Behavioral disinhibition in stroke.

Post-stroke behavioral disinhibition (PSBD) is common in stroke survivors and often presents as impulsive, tactless or vulgar behavior. However, it often remains undiagnosed and thus untreated, even though it can lead to a longer length of stay in a rehabilitation facility. The proposed study will aim to evaluate the clinical, neuropsychological and magnetic resonance imaging (MRI) correlates of PSBD in a cohort of stroke survivors and describe its 12-month course. This prospective cohort study will recruit 237 patients and will be conducted at the Neurology Unit of the Prince of Wales Hospital. The project duration will be 24 months. The patients will be examined by multiple MRI methods, including diffusion-weighted imaging, within 1 week after stroke onset. The patients and their caregivers will receive a detailed assessment at a research clinic at 3, 9 and 15 months after stroke onset (T1, T2 and T3, respectively). The disinhibition subscale of the Frontal Systems Behavior Scale (FrSBe) will be completed by each subject and caregiver, and scores ≥65 will be considered to indicate PSBD.A stepwise logistic regression will be performed to assess the importance of lesions in the regions of interest (ROIs), together with other significant variables identified in the univariate analyses. For patients with PSBD at T1, the FrSBe disinhibition scores will be compared between the groups of patients with and without ROI infarcts, using covariance analysis. The demographic, clinical and MRI variables of remitters and non-remitters will be examined again at T2 and T3 by logistic regression. This project will be the first MRI study on PSBD in stroke survivors. The results will shed light on the associations of lesions in the orbitofrontal cortex, anterior temporal lobe and subcortical brain structures with the risk of PSBD. The obtained data will advance our understanding of the pathogenesis and clinical course of PSBD in stroke, as well as other neurological conditions. The findings are thus likely to be applicable to the large population of patients with neurological disorders at risk of PSBD and are expected to stimulate further research in this field.

A Case of Creutzfeldt–Jakob disease with psychiatric presentation

ABSTRACT Creutzfeldt–Jakob disease (CJD) belongs to the group of fatal neurodegenerative disorders known as prion diseases. We are going to describe the case of a 54-year-old married man who initially presented with rapidly progressive cognitive decline along with behavioral symptoms and was subsequently diagnosed with probable CJD. He presented with 1½ months history of disinhibited behavior, decreased social interaction, persecutory ideas, food refusal, and decreased sleep along with cognitive decline. On examination, the patient had myoclonus and ataxia. Routine blood investigations, serological tests, and autoimmune and paraneoplastic profiles were normal. Injection haloperidol 2.5 mg intramuscular for behavioral symptoms was given with no improvement. The cerebrospinal fluid study revealed positive results for 14-3-3 protein. The patient was diagnosed with probable CJD and subsequently passed away within 1 month of presentation. Thus, CJD should be kept in the differential diagnosis of patients with cognitive decline and persistent behavioral symptoms despite standard psychiatric treatment.