Behavioral Dysregulation Research Articles

Abstract 18334: Altered in-vivo Placental Microstructure Predicts Adverse Neurodevelopmental Outcomes in Toddlers With Congenital Heart Disease

Introduction: Pregnancies complicated by fetal congenital heart disease (CHD) are at risk for disrupted placenta function; placental insufficiency, in turn, is a risk factor that may adversely impact offspring neurodevelopment. However, the relationship between altered in-vivo placenta function and infant neurobehavioral outcomes in CHD is unknown. Hypothesis: We hypothesized that altered in-vivo placenta microstructural diffusion in CHD would be associated with impaired infant neurodevelopment. Methods: We prospectively recruited women with pregnancies complicated by CHD diagnosis and low-risk pregnancies. Women underwent an MRI on a GE 1.5T scanner at 20-39 gestational weeks. T2w sequence and pulsed gradient spin echo were acquired for placenta volume and diffusion kurtosis measures. Bayley-III and Infant-Toddler Social and Emotional Assessment were completed at around 18 months. Generalized estimating equation was used to examine the association between placenta measures and infant outcomes, adjusting for potential confounders. Results: We enrolled 236 mother/baby dyads (111 CHD; 125 controls) who underwent 394 MRIs (175 CHD; 219 controls). Forty-seven had single-ventricle (SV) CHD and 64 had two-ventricle (2V) CHD. In CHD, 32 subjects died, and 71 infants had neurodevelopment testing at a mean age of 20 months. Placenta diffusion coefficient (dki_d), reflecting tissue cellularity, was higher in CHD vs controls (p=0.009). In CHD, placenta diffusional kurtosis (dki_k), reflecting tissue heterogeneity, was lower in neonates who died pre-operatively vs those who survived (p=0.05). Compared to 2V CHD, pregnancies with SV fetuses had lower placenta dki_k and trending higher placenta dki_d. In CHD, higher placenta dki_d was associated with poorer language skills (p=0.05) while lower placenta dki_k was associated with higher behavioral dysregulation (p=0.03). Conclusions: We report for the first time disturbances in placenta microstructural diffusion in CHD. We also demonstrate that altered placenta diffusion was associated with impaired language and behavioral dysregulation in CHD toddlers. These data suggest that altered placenta microstructure may be an important biomarker for later neurodevelopmental dysfunction in CHD.

Case report: Neuropsychological assessment in a patient with 4H leukodystrophy

Objective: POLR3-HLD or 4H leukodystrophy is an autosomal recessive disorder characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism, and caused by variants in POLR3A, POLR3B, POLR1C, or POLR3K genes. Neurological and non-neurological clinical features and disease severity vary. While previous studies reference variable cognition, this is the first report of 4H detailing a comprehensive neuropsychological assessment. Method: The current study presents a 20-year-old, English-speaking, right-handed, non-Hispanic White female with 12 years of education with genetically confirmed 4H POLR3B-related leukodystrophy without hormonal replacement treatment. Results: At age 4, developmental delays, ataxia, hearing loss, and abnormal dentition were present. Imaging, endocrinology, and neurologic examinations revealed hypomyelination, reduced cerebellar volume, delayed bone age density, osteopenia, and evidence of adrenarche without signs of true puberty. Neuropsychological assessment at age 20 revealed global cognitive impairment with intellectual, attention, verbal memory retrieval, construction, executive (e.g. processing speed, sustained attention) and math computation deficits, along with behavioral dysregulation. Conclusion: We present the first detailed neuropsychological assessment of a patient with 4H leukodystrophy. The neuropsychological assessment revealed cognitive and behavioral dysexecutive deficits aligning with hypomyelination observed on imaging. Further longitudinal studies are needed to shed light on the neurobehavioral presentation associated with this disorder to assist care providers, patients, and their families.

Bioelectric Reprogramming of the Bone Marrow Niche in Acute Myeloid Leukemia

Background. A large body of evidence indicates that cancer is not comprised solely of malignant cells, but that it represents part of a complex network of transformed and non-transformed cells, including mesenchymal stromal cells (MSCs), immune, nervous, endothelial, stem cells and fibroblasts that, together with soluble mediators, make up the tumor microenvironment. More recently, molecular mechanisms underlying a novel system of developmental control have been described to define the role of bioelectric gradients. Differences in endogenous resting membrane potential (V mem) of non-neural cells have importance in cell-cell interactions and regulation or dysregulation in embryogenesis, regeneration patterns, and cell behavior, especially proliferation and differentiation. Recently, the same issues have been suggested to be related to cancer where abnormal depolarization of resting V mem is associated to neoplastic cells and the role of ion channels conductivity in cancer initiation and progression deserves great attention in tumor microenvironment remodeling and therapy response. Methods and results. We characterized MSCs derived from bone marrow (BM) of pediatric acute myeloid leukemia patients (AML-MSCs) and identified significant changes in ion channel expression profile, including the Voltage-gated L-type calcium channel CaV1.2. We investigated the role of CaV1.2 and documented a reduced expression of CaV1.2 channel in 14 primary AML-MSCs (<53% by flow cytometry, p<0.001) mediating more frequent spontaneous calcium oscillations with higher amplitude than those found in MSCs derived from healthy donors (h-MSCs) (21% and 7%, respectively, p<0.05). Measurement of V mem by patch clamp and a fluorescent potential-sensitive probe DiBAC revealed that AML-MSCs showed a more depolarized V mem (-14.7 mV) with respect to h-MSCs (-30.5 mV, p<0.01). We hypothesized that depolarization may play a role in the AML-MSCs gene expression and functional reprogramming. Hence, we exposed h-MSCs to AML blasts demonstrating that MSCs V mem depolarized (-11.8 mV, n=10), resembling the AML-MSCs V mem, with a concomitant decrease of CaV1.2 channel expression level (<44% by flow cytometry, p<0.01). We treated h-MSCs with depolarizing pharmacological agents (ouabain and potassium gluconate) finding that the pharmacological-induced V mem depolarization promotes a pro-leukemia cell phenotype like the AML-MSCs. Briefly, MSCs exhibited higher proliferation level (ouabain, 2.5-fold; Kgluc, 1.9-fold, p<0.05), higher release of IL-6 (1.7-fold average, p<0.05), lower immunomodulatory potential and reduced the CaV1.2 levels (<35% by flow cytometry, p<0.05) with respect to untreated h-MSCs. On the contrary, we treated AML-MSCs with hyperpolarizing agents (lubiprostone and ivermectin), which reverted their phenotype to that of h-MSCs, including lower proliferation level (ivermectin -1.9-fold, p<0.05), higher immunomodulatory potential, and higher CaV1.2 levels (1.8-fold by flow cytometry, p<0.05) with respect to untreated AML-MSCs, suggesting that depolarization is reversible and that by modeling MSCs V mem we can restore an healthy stroma within the BM niche. We transduced AML-MSCs with a CaV1.2 expressing lentiviral vector (namely re-AML-MSCs, n=7) inducing a stable hyperpolarized V mem and documented that their gene expression profile reverted toward the h-MSCs profile. Finally, we observed that re-AML-MSCs propagated their acquired bioelectrical state to the contiguous AML-MSCs establishing a healthy bio-electric field. Conclusions. We demonstrated an unprecedented AML niche bioelectrical code that governs the state of MSCs, demonstrating that the contact with AML blasts is the driving force inducing the h-MSCs V mem depolarization shift and the acquisition of pro-leukemia functions. In addition, we unveiled CaV1.2 channels as a key player in this process and postulated that rewriting the bioelectric code of the patient' AML-MSCs, through the restoration of voltage-dependent calcium channel CaV1.2 activity, could be a strategy to restore their healthy phenotype. These findings provide the biological rationale to evaluate the potential of novel MSCs gene or pharmacological therapies that could both disadvantage AML progression and restore a permissive BM niche.

Opponent intrinsic brain network connectivity profiles associated with posttraumatic fear and dysphoria symptoms in trauma-exposed refugees.

Resting-state functional magnetic resonance imaging (rsfMRI) studies report functional alterations in the connectivity between intrinsic brain networks in posttraumatic stress disorder (PTSD), but PTSD heterogeneity is rarely considered. Evidence points to fear (e.g., reexperiencing) and dysphoria (e.g., withdrawal) symptom factors as important in PTSD presentations, including relating to variable emotion dysregulation patterns. This study, therefore, tested how fear and dysphoria posttraumatic symptoms were differentially associated with core network connectivity and emotion dysregulation behaviors in a large group of trauma-exposed refugees. A final sample of 77 trauma-exposed participants completed a rsfMRI scan. Independent component analysis identified active networks and functional network connectivity (FNC) between networks was assessed. Fear and dysphoria posttraumatic symptoms were partially correlated with FNCs, and linear regression models examined relationships with self-reported difficulties in emotion regulation. Twenty-three active networks were identified, eight being in the networks of interest (p < .05 false discovery rate-corrected). Fear and dysphoria symptoms were specifically related to connectivity patterns between two subnetworks of the default mode network (DMN). Fear symptoms were negatively associated with anterior dorsomedial DMN (admDMN) and temporoparietal DMN (tpDMN) connectivity; whereas dysphoria symptoms were positively associated with admDMN-tpDMN connectivity. Additionally, admDMN-tpDMN connectivity was positively predicted by goal-directed emotion dysregulation but negatively predicted by poor emotional clarity. Fear and dysphoria posttraumatic symptoms showed opponent associations with admDMN and tpDMN connectivity, potentially reflecting patterns of under- and overemotion dysregulation associated with these symptom profiles respectively. Findings highlight the importance of considering posttraumatic heterogeneity when constructing neural models of PTSD. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

30 Examining the Bilingual Advantage in Executive Functioning in ADHD: A Retrospective Study

Objective:Several studies have found a bilingualism advantage on executive functioning tasks like cognitive flexibility, inhibitory control, switching, and working memory in typically developing populations. (Grote et al., 2015, Foy &amp; Mann, 2014). However, some studies have found deficits in inhibitory control and switching for bilingual individuals with Attention Deficit/Hyperactivity Disorder (ADHD) compared to monolingual individuals and control groups (Bialystok et al., 2017, Mor et al., 2015). They suggest that this disadvantage is due to the burden of managing two language systems which perpetuates the executive dysfunction seen in ADHD. The current study aims to examine if there is a bilingualism advantage in other aspects of executive function, including inhibitory control, planning, problem solving, switching, and working memory among children and adults diagnosed with ADHD.Participants and Methods:The medical records of 170 patients evaluated in an outpatient neuropsychology clinic from 20182022 were reviewed. Sixty participants diagnosed with ADHD, between the ages of 6 and 46 (61.67% male), comprised the final sample. Forty-one were monolingual and 19 were bilingual or multilingual. Language status was based upon patient or parental report. Outcomes on various direct and indirect measures of executive function were examined.Results:Linear regression models, adjusting for age and sex, revealed a significant bilingual advantage on the following measures: Wechsler Intelligence Scale for Children- Fifth Edition (WISC-V) and Wechsler Adult Intelligence Scale - Fourth Edition (WAIS-IV) Digit Span Backwards and Digit Span Sequencing, WISC-V Picture Span, and Behavior Rating Inventory of Executive Function, 2nd Edition (BRIEF-2) Parent-Report Emotion Regulation Index (ERI). There were no significant differences in scores between monolinguals and bilinguals on the following measures: Delis-Kaplan Executive Function System (D-KEFS) Color-Word Interference Inhibition versus Combined Naming Contrast Score and Inhibition/Switching versus Inhibition Contrast Score, D-KEFS Trail Making Number-Letter Switching versus Combined Number Sequencing and Letter Sequencing Contrast Score, A Developmental Neuropsychological Assessment, 2nd Edition (NEPSY-2) Naming versus Inhibition Contrast Score and Switching versus Inhibition Contrast Score, Wisconsin Card Sort Task Learning to Learn Index, BRIEF-2 Parent-rated Behavioral Regulation Index (BRI), Cognitive Regulation Index(CRI), and Global Executive Composite(GEC), BRIEF-2 Self-rated BRI, ERI, CRI, and GEC, or BRIEF Adult Version BRI, Metacognitive Index, and GEC.Conclusions:Bilingual status is associated with stronger auditory and visual working memory among people with ADHD, but not with stronger inhibitory control, switching, planning, or problem solving skills. At the same time, there were no significant differences between monolingual and bilingual ADHD patients on BRIEF parent- or self-rated behavioral or cognitive dysregulation. Our results suggest that bilingualism may confer an advantage in some aspects of executive function among a population with weak attention and executive function skills more broadly. Furthermore, we did not find any type of disadvantage for those who are bilingual. Future studies should examine whether lower parental ratings of emotion dysregulation among ADHD patients who are bilingual are due to bilingual children’s better ability to adapt to different situations or cultural differences in parenting practices.

Sex Differences in the Relationship between Chronotype and Eating Behaviour: A Focus on Binge Eating and Food Addiction.

Men are more likely than women to have subthreshold overeating disorders. Lifestyle plays a role as a determinant, while chronotype is an emerging factor. Chronotype explains the natural preferences of wakefulness and activity throughout the day: evening chronotypes (E-Types), those most productive in the evening, have been linked with unhealthy dietary patterns and a higher propensity to substance addiction than morning types (M-Types). We carried out a cross-sectional study on 750 overweight or obese adults (70% females, 48 ± 10 years, BMI 31.7 ± 5.8 kg/m2). The Binge-Eating Scale, the Yale Food Addiction Scale 2.0 (YFAS 2.0), the reduced Morningness-Eveningness Questionnaire (rMEQ), and the MEDAS questionnaire were used to assess binge eating, food addiction, chronotype, and adherence to the Mediterranean diet, respectively. No differences in BES binge-eating and FA food-addiction scores occurred between chronotypes, but we found significant interactions between sex × rMEQ score. While women showed the same prevalence for binge eating and food addiction across all chronotypes, binge eating and food addiction risk increased with reducing rMEQ score in men, indicating that being male and E-Type increases the risk association of binge eating and/or food addiction prevalence. chronotype is associated with binge eating and food addiction in men, emphasizing the link between chronobiology and sex differences as determinants in appetite and eating behaviour dysregulation and in overweight and obesity.

Influence of aerobic exercise on inhibitory control of executive functions in children with hemiplegic cerebral palsy: A randomized controlled trial

Objective This study investigates the influence of aerobic exercise training on inhibitory control of executive functions in children with hemiplegic cerebral palsy. Design Single-blind randomized controlled trial. Setting Outpatient Physical Therapy Clinic. Participants Children aged 7–11 with left-sided hemiplegic cerebral palsy with emotional and behavioral dysregulation evidenced by scores >28 on Paediatric Symptom Checklist and GMFCS I or II (n = 60). Intervention Participants were randomly allocated into two equal groups. The control group received standard-of-care physical therapy for 1 h, and the aerobic exercise group received standard-of-care physical therapy for 30 min and moderate-intensity continuous exercise on a bicycle ergometer for 30 min. All groups received treatment three times a week for 12 weeks. Main Measures The Eriksen Flanker test and Stroop Color–Word test were used to assess inhibitory control of executive function at the baseline and after 12 weeks. Results Differences between pre- and post-treatment values in the exercise group showed significant improvement in Flanker response accuracy and Stroop response accuracy (p = 0.001) and significant decreases in Flanker congruent reaction time and Stroop congruent reaction time (p < 0.05). However, there were no significant differences between both groups in Flanker incongruent reaction time and Stroop incongruent reaction time (p > 0.05). Conclusions Aerobic exercise has a promising effect on inhibitory control of executive function in children with left-sided hemiplegic cerebral palsy.

Preschool-based mother-child emotional preparation program improves emotional connection, behavior regulation in the home and classroom: a randomized controlled trial

IntroductionBased on the theory that increasing emotional connection and reducing emotional stress between mother and child at home will reduce dysregulated behavior in the classroom, we tested a novel family-based school intervention aimed at facilitating mother-child emotional connection. This question has gained great importance following the COVID-19 pandemic, as child mental health has been declared a national emergency.MethodsSubjects were randomized into two groups; one (Control: n = 32) receiving the standard curriculum in a large community-based preschool education program, and another (MCEP) receiving the standard curriculum plus the Mother Child Emotional Preparation Program (MCEP: n = 30). Two to eight MCEP mother-child pairs participated in eight elective weekly 2-h group sessions over a 16-week period. During the 2-h sessions, the pairs were engaged in face to face calming sessions. At 6 months post-enrollment, we assessed mother-child emotional connection on the Welch Emotional Connection Screen (WECS). In addition, mothers and teachers completed validated questionnaires and instruments.ResultsWe found that the percentage of MCEP mother-child pairs who became emotionally connected at 6 months was five-fold higher than Control pairs (47.4%, vs. 8.3% p = 0.004, effect size = 0.44). Also at six months, MCEP children had fewer behavioral symptoms (p = 0.024)) (effect size &amp;gt;0.5); fewer autism symptoms (p = 0.048) (effect size = 0.53); fewer emotional symptoms (p = 0.01) (effect size &amp;gt;0.76); better personal, social skills (p = 0.045) (effect size = 0.51); better executive function (p = 0.032) (effect size = 0.59). Importantly, teachers reported MCEP children showed more improved behavior in the classroom, compared to controls.DiscussionThis trial was retrospectively registered in the clinicaltrial.gov registry (NCT02970565) on April 9, 2019.

Energy deficiency promotes rhythmic foraging behavior by activating neurons in paraventricular hypothalamic nucleus.

Dysregulation of feeding behavior leads to a variety of pathological manifestations ranging from obesity to anorexia. The foraging behavior of animals affected by food deficiency is not fully understood. Home-Cage system was used to monitor the behaviors. Immunohistochemical staining was used to monitor the trend of neuronal activity. Chemogenetic approach was used to modify neuronal activity. We described here a unique mouse model of foraging behavior and unveiled that food deprivation significantly increases the general activities of mice with a daily rhythmic pattern, particularly foraging behavior. The increased foraging behavior is potentiated by food cues (mouthfeel, odor, size, and shape) and energy deficit, rather than macronutrient protein, carbohydrate, and fat. Notably, energy deficiency increases nocturnal neuronal activity in paraventricular hypothalamic nucleus (PVH), accompanying a similar change in rhythmic foraging behavior. Activating neuronal activity in PVH enhances the amplitude of foraging behavior in mice. Conversely, inactivating neuronal activity in PVH decreases the amplitude of foraging behavior and impairs the rhythm of foraging behavior. These results illustrate that energy status and food cues regulate the rhythmic foraging behavior via PVH neuronal activity. Understanding foraging behavior provides insights into the underlying mechanism of eating-related disorders.

A - 167 Neuropsychological Correlates of Challenging Behavior in Moderate to Severe ABI.

Cognitive and behavioral changes, common after severe acquired brain injury (ABI), are important predictors of functional recovery, independence, and quality of life. The Overt Behavior Scale (OBS) is a standardized measure of challenging behaviors following ABI, and has been associated with pre-injury risk factors and psychosocial stressors. Information about the neuropsychological underpinnings of OBS scores is unknown, however. The current study is a preliminary analysis of relationships among OBS scores and neuropsychological data associated with behavioral dysregulation in adults with chronic moderate to severe ABI in a residential neurorehabilitation setting. Participants were 81 adults, ages 27-71 (SD = 10.46), 55 males, with average education of 12.6years, and average time since injury of 26.34 (SD = 13.35). Participants were administered neuropsychological tests (including NAB Screening Module Memory, Executive Functioning, and Attention Index and subtests, NAB Judgment, and Trails B). The OBS was administered by the psychology provider with input from the treatment team. Exploratory correlations examined the relationship between neuropsychological tests and OBS scores. Results found a significant relationship between the number of challenging behaviors on the OBS and NAB delayed story recall (p < 0.040, r = -0.266). Other correlations between OBS and the NAB and Trails B were not significant. The results raise the possibility that the OBS captures unique aspects of behavioral change that are not measured by traditional neuropsychological tests. Other possible explanations of the data include that the severity of cognitive impairment and physical limitations may be moderating factors, which will be examined in future studies.

Borderline personality disorder in mothers, maternal sensitivity, and infant social withdrawal: a study on clinical dyads referred to perinatal mental health units

ABSTRACT Behavioural, cognitive and emotional dysregulation related to parent borderline personality disorder (BPD) may have a major impact on parent–infant interactions. We investigated the ways in which infant social withdrawal and mother sensitivity may be associated to a BPD diagnosis in mothers. Two groups of clinic-referred mother–infant dyads were set up: one in which consulting mothers were diagnosed with BPD. Infant social withdrawal and maternal sensitivity were assessed during free-play interactions videotaped within a clinical setting. Mothers with BPD showed lower maternal sensitivity, while their infants displayed higher levels of social withdrawal behaviour when compared to dyads with no maternal psychiatric diagnosis. Infants of mothers with BPD appear at particular risk of adverse developmental outcomes from their very first months of life. Early interventions should concentrate on improving maternal interpretation and response to infant cues, such as identifying nonverbal behaviours and regulating the infant’s emotional states, and on promoting mentalization.

Cumulative risk factors for injuries and poisoning requiring hospital care in youth with prenatal substance exposure: A longitudinal controlled cohort study.

Aim: To investigate whether the youth with prenatal substance exposure (PSE) (aged 15-24 years, n = 615) had been in hospital care more often due to injuries and poisoning in comparison with unexposed matched controls (n = 1787). Methods: Data from medical records (exposure) and national health and social welfare registers (outcome and confounders) were combined and youths were monitored from birth until either outpatient or inpatient hospital care for injury or poisoning, death or the end of the study period (December 2016). Cox regression models were used in the analyses accounting for associated child and maternal risk factors. Results: Half (50.4%) of the exposed group and 40.6% of controls had been in hospital care due to injury or poisoning during the follow-up (p < 0.001). The difference between groups was diminished after controlling for postnatal child and maternal risk factors (hazard ratio [HR] = 0.88, 95% confidence interval [CI] 0.72-1.07, p > 0.05). Cumulative adversity, especially out-of-home care in combination with a diagnosed attention or behavioural dysregulation problem, posed the highest risk in both groups (exposed: HR = 1.65, 95% CI 1.24-2.19, p < 0.001; controls: HR = 1.84, 95% CI 1.33-2.56, p < 0.001). Conclusion: Hospital care for injury and poisoning is more common in youth with PSE, but this is largely explained by the related postnatal child and maternal factors. Long-term support to families with maternal substance abuse problems could prevent injury and poisoning among youth with PSE.

Non Suicidal Self-Injurious Behavior And Emotional Dysregulation Among College Students: Karnataka India

Background: It is necessary to understand that self-harm is the most common behavior in both suicide and non-suicidal self-injury (NSSI) though those are not interrelated. Both result in physical damage to better or cope, whereas behaviors related to suicide are undertaken to end the capacity to feel at all by ending one’s life. Aim: The aim of the study was to explore NSSI behavior and emotional dysregulation among college students and find relationship between NSSI behavior and emotional dysregulation. Methods: A descriptive cross-sectional survey was carried out and total 896 college students were selected by multistage cluster sampling method from one district of Karnataka, India. The data was collected using FASM and DERS tool. Results: The study revealed that 21.9% of the participants were found to have NSSI behavior. Participants were having both minor behavior (66.84%) and severe behavior (71.94%) of NSSI. Mean age of onset of NSSI behavior was 16.88 years. The present study found significant relationship between NSSI behavior and emotional dysregulation (t value: 4.19, p value: &lt;0.01). Participants were having emotional dysregulation with mean value of 100.32. International Journal of Scientific Research in Engineering and Management (IJSREM) Volume: 07 Issue: 10 | October - 2023 SJIF Rating: 8.176 ISSN: 2582-3930 © 2023, IJSREM | www.ijsrem.com DOI: 10.55041/IJSREM26329 | Page 2 Conclusion: The findings of the study show the need to increase the awareness and understanding of NSSIs and to plan targeted interventions among college youth. An information booklet on emotion regulation strategies was developed by the researcher to improve students’ knowledge and awareness. Keywords NSSI (Non-suicidal self-injury), Emotional dysregulation, FASM (Functional Assessment of Self-Mutilation) questionnaire, DERS (Difficulties in Emotional Regulation Scale)

30.4 Behavioral Dysregulation and Antipsychotics in Foster Care: Perspective From an Oversight Program

30.4 Behavioral Dysregulation and Antipsychotics in Foster Care: Perspective From an Oversight Program

Risk factors for behavioral and psychotic dysregulation at the epilepsy monitoring unit in patients with intracranial electrodes

ObjectiveAberrant behavior in patients with epilepsy (PWE) admitted to an epilepsy monitoring unit (EMU) can endanger their safety. We sought to identify predictive factors for post-ictal behavioral dysregulation and psychosis in patients with refractory epilepsy being monitored at an EMU. MethodsRetrospective data were gathered from electronic patient files of all patients with refractory epilepsy who underwent intracranial registration at our EMU. We assessed behavioral and psychotic dysregulations by reviewing clinical notes, administered emergency medication, and reports of injuries or casualties in patients and nurses. In addition, we compared patient demographic characteristics, clinical characteristics, and antiepileptic drug (AED) profiles between patients with and without behavioral and/or psychotic dysregulation. ResultsOut of 73 admissions, 23 patients (32%) experienced behavioral dysregulation, and five patients experienced psychosis (7%). Behavioral dysregulation was only significantly associated with a previous history of interictal or postictal psychosis. Psychotic dysregulation is significantly associated with a psychiatric history, including a history of agitation or psychosis, whether or not epilepsy-related. For both types of dysregulations, there was no relation with a pre-admission frequency of seizures, clustering of seizures during monitoring, or a temporal focus of seizures. We could not report a relationship between AED use, tapering, and the occurrence of dysregulation. ConclusionWe conclude that a psychiatric history, including a history of agitation and psychosis, is related to an increased risk of behavioral and psychotic dysregulation in patients undergoing invasive seizure monitoring at the EMU.

Characterizing subdomains of insistence on sameness in autistic youth.

Insistence on sameness (IS) encompasses a range of behavioral patterns, including resistance to change, routines, and ritualized behaviors, that can be present across social and non-social contexts. Given the breadth of behaviors encompassed by IS, it is important to determine whether this domain is best conceptualized and measured as uni- or a multi-dimensional construct. Therefore, the current study aimed to characterize the structure of IS and explore potentially distinct of patterns of associations between identified IS factors and relevant correlates, including age, sex, IQ, anxiety, social abilities, emotional and behavioral dysregulation, and sensory hypersensitivity. Exploratory graph analysis was conducted using the dimensional assessment of restricted and repetitive behaviors to examine the structure of IS in a sample 1892 autistic youth (Mage = 10.82, SDage = 4.14; range: 3-18 years; 420 females) recruited from the Simons Foundation Powering Autism Research for Knowledge cohort. Three distinct IS subdomains labeled as IS-Ritualistic/sameness, IS-Routines, and IS-Others (referring to IS behaviors during interactions with others)were identified. Generalized additive models demonstrated that each of the IS subdomains showed a unique pattern of association with key variables. More specifically, while sensory hypersensitivity was significantly associated with IS-Ritualistic/sameness and IS-Routines, it was not associated with IS-Others. Further, while emotional dysregulation was a unique predictor of IS-Ritualistic/sameness (but not IS-Routines or IS-Others), social interaction abilities were a unique predictor of IS-Routines (but not IS-Ritualistic/sameness or IS-Others). Current findings provide preliminary evidence that the IS may encompass several distinct subdomains.

International consensus recommendations for the identification and treatment of tuberous sclerosis complex-associated neuropsychiatric disorders (TAND)

BackgroundTuberous sclerosis complex (TSC) is associated with a wide range of physical manifestations for which international clinical recommendations for diagnosis and management have been established. TSC is, however, also associated with a wide range of TSC-Associated Neuropsychiatric Disorders (TAND) that are typically under-identified and under-treated yet associated with a profound burden of disease. The contemporary evidence base for the identification and treatment of TAND is much more limited and, to date, consensus recommendations for the diagnosis and management of TAND have also been limited and non-specific.MethodsThe TANDem project was launched with an international, interdisciplinary, and participatory consortium of 24 individuals, including TSC family representatives, from all World Health Organization (WHO) regions but one. One of the aims of the TANDem project was to generate consensus recommendations for the identification and treatment of TAND. At the time of this project, no internationally adopted standard methodology and methodological checklists existed for the generation of clinical practice recommendations. We therefore developed our own systematic procedure for evidence review and consensus-building to generate evidence-informed consensus recommendations of relevance to the global TSC community.ResultsAt the heart of the consensus recommendations are ten core principles surrounded by cluster-specific recommendations for each of the seven natural TAND clusters identified in the literature (autism-like, dysregulated behavior, eat/sleep, mood/anxiety, neuropsychological, overactive/impulsive, and scholastic) and a set of wraparound psychosocial cluster recommendations. The overarching recommendation is to “screen” for TAND at least annually, to “act” using appropriate next steps for evaluation and treatment, and to “repeat” the process to ensure early identification and early intervention with the most appropriate biological, psychological, and social evidence-informed approaches to support individuals with TSC and their families.ConclusionsThe consensus recommendations should provide a systematic framework to approach the identification and treatment of TAND for health, educational, social care teams and families who live with TSC. To ensure global dissemination and implementation of these recommendations, partnerships with the international TSC community will be important. One of these steps will include the generation of a “TAND toolkit” of “what to seek” and “what to do” when difficulties are identified in TAND clusters.

A central serotonin regulating gene polymorphism (TPH2) determines vulnerability to acute tryptophan depletion-induced anxiety and ventromedial prefrontal threat reactivity in healthy young men

Serotonin (5-HT) has long been implicated in adaptive emotion regulation as well as the development and treatment of emotional dysregulations in mental disorders. Accumulating evidence suggests a genetic vulnerability may render some individuals at a greater risk for the detrimental effects of transient variations in 5-HT signaling. The present study aimed to investigate whether individual variations in the Tryptophan hydroxylase 2 (TPH2) genetics influence susceptibility for behavioral and neural threat reactivity dysregulations during transiently decreased 5-HT signaling. To this end, interactive effects between TPH2 (rs4570625) genotype and acute tryptophan depletion (ATD) on threat reactivity were examined in a within-subject placebo-controlled pharmacological fMRI trial (n = 51). A priori genotype stratification of extreme groups (GG vs. TT) allowed balanced sampling. While no main effects of ATD on neural reactivity to threat-related stimuli and mood state were observed in the entire sample, accounting for TPH2 genotype revealed an ATD-induced increase in subjective anxious arousal in the GG but not the TT carriers. The effects were mirrored on the neural level, such that ATD specifically reduced ventromedial prefrontal cortex reactivity towards threat-related stimuli in the GG carriers. Furthermore, the ATD-induced increase in subjective anxiety positively associated with the extent of ATD-induced changes in ventromedial prefrontal cortex activity in response to threat-related stimuli in GG carriers. Together the present findings suggest for the first time that individual variations in TPH2 genetics render individuals susceptible to the anxiogenic and neural effects of a transient decrease in 5-HT signaling.

An Open-Label Study of Cranial Electrotherapy Stimulation on Behavioral Regulation in a Mixed Neurodevelopmental Clinical Cohort.

Individuals with neurodevelopmental disorders often report disturbances in the autonomic nervous system (ANS)-related behavioral regulation, such as sensory sensitivity, anxiety, and emotion dysregulation. Cranial electrotherapy stimulation (CES) is a method of non-invasive neuromodulation presumed to modify behavioral regulation abilities via ANS modulation. Here we examined the feasibility and preliminary effects of a 4-week CES intervention on behavioral regulation in a mixed neurodevelopmental cohort of children, adolescents, and young adults. In this single-arm open-label study, 263 individuals aged 4-24 who were receiving clinical care were recruited. Participants received at-home CES treatment using an Alpha-Stim® AID CES device for 20 minutes per day, 5-7 days per week, for four weeks. Before and after the intervention, a parent-report assessment of sensory sensitivities, emotion dysregulation, and anxiety was administered. Adherence, side effects, and tolerance of the CES device were also evaluated at follow-up. Results showed a 75% completion rate, an average tolerance score of 68.2 (out of 100), and an average perceived satisfaction score of 58.8 (out of 100). Additionally, a comparison between pre- and post-CES treatment effects showed a significant reduction in sensory sensitivity, anxiety, and emotion dysregulation in participants following CES treatment. Results provide justification for future randomized control trials using CES in children and adolescents with behavioral dysregulation. CES may be a useful therapeutic tool for alleviating behavioral dysregulation symptoms in children and adolescents with neurodevelopmental differences.

Anger dysregulation and non-suicidal self-injury during adolescence: A test of directionality.

Non-suicidal self-injury (NSSI) has been tied to several forms of emotional and behavioral dysregulation in adolescence, with less attention paid to regulation of anger. Most assume that anger dysregulation leads to engagement in NSSI, rather than the reverse. However, it is plausible that NSSI compromises adolescents' abilities to regulate their emotions, including anger, because it may reduce the development of alternative regulatory strategies and intensify negative emotions by reducing tolerance of distress. Using three waves of data from a sample of adolescents in 17 Swedish schools (n = 1,304 M age = 13.68, SD age = .67; 89% of Swedish origin; 58% girls), we examined the directionality of ties between NSSI and three forms of anger dysregulation: dysregulated expressions of anger, anger suppression, and low anger reflection. We also looked for differences in magnitude of paths and gender differences. Random-intercept cross-lagged panel models showed that NSSI predicted changes in all forms of anger dysregulation but found no support for the opposite direction. Gender differences were not evident. Results challenge directionality assumptions and support suggestions that adolescents' anger regulation degrades when they self-injure.