Severe Behavioral Disorders Research Articles

Precision Medicine in Angelman Syndrome.

Angelman syndrome (AS) is a rare neurogenetic disorder caused by a loss of function of UBE3A on the maternal allele. Clinical features include severe neurodevelopmental delay, epilepsy, sleep disturbances, and behavioral disorders. Therapy currently evolves from conventional symptomatic, supportive, and antiseizure treatments toward alteration of mRNA expression, which is subject of several ongoing clinical trials.This article will provide an overview of clinical research and therapeutic approaches on AS.

O-demethyl galantamine alters protein expression in cerebellum of 5xFAD mice.

Alzheimer's disease (AD), one of the most common health issues, is characterized by memory loss, severe behavioral disorders, and eventually death. Despite many studies, there are still no drugs that can treat AD or stop it from progressing. Previous in vitro tests showed that O-demethyl galantamine (ODG) might have therapeutic potential owing to its 10 times higher acetylcholinesterase inhibitory activity than galantamine (GAL). We aimed to assess the effect of ODG at the molecular level in a 12-month-old 5xFAD Alzheimer's mouse model. To this end, following the administrations of ODG and GAL (used as a positive control), protein alterations were investigated in the cortex, hippocampus, and cerebellum regions of the brain. Surprisingly, GAL altered proteins prominently in the cortex, while ODG exclusively exerted its effect on the cerebellum. GNB1, GNB2, NDUFS6, PAK2, and RhoA proteins were identified as the top 5 hub proteins in the cerebellum of ODG-treated mice. Reregulation of these proteins through Ras signaling and retrograde endocannabinoid signaling pathways, which were found to be enriched, might contribute to reversing AD-induced molecular changes. We suggest that, since it targets specifically the cerebellum, ODG may be further evaluated for combination therapies for AD.

Les aléas du suivi orthophonique chez l’adolescent avec autisme : les facteurs influençant sa (non) mise en œuvre

ObjectiveThis exploratory qualitative study aims to identify factors influencing orientation, access to speech therapy professionals and its maintenance in adolescents with autism. This was carried out by questioning them about their perceptions of the place and objectives of speech therapy concerning teenagers with autism spectrum disorders in a context where adolescents struggle to benefit from it. Sample and MethodEight child psychiatry professionals including four child psychiatrists, three speech therapists and a psychomotor-therapist took part. These semi-structured interviews have been analyzed using the Interpretative Phenomenological Analysis (IPA). ResultsThe perception of adolescents with ASD as carriers of severe behavioral disorders and unlikely to be e subject to significant clinical changes has an unfavorable influence on the indication for speech therapy at this age. In addition, the management of the shortages in speech therapy is done to the detriment of adolescents in order to prioritize the youngest. Speech therapy follow-ups are experienced as cumbersome with a lack of specific assessments and speech therapy tools for this age. DiscussionCommunication disorders are insufficiently assessed by prescribing professionals who have a more vague representation of the specificities of speech therapy work at this age. In the current situation of speech therapy shortage, speech therapists are torn between the desire to continue to follow an adolescent, whose development potential is not always perceived, and the moral and clinical obligation to take care of toddlers who are generally prioritized. ConclusionThese results reveal the need for more specific speech therapy assessments and tools for adolescents with autism to better target their communication needs and offer more appropriate care. Precise training on the issue of ASD in adolescence would make it possible to consider the diversity of needs and presentations of disorders at this age. Speech therapy monitoring of adolescents with autism raises questions about possible changes in the practice of speech therapy.

Pathways to epilepsy surgery in children with tuberous sclerosis complex-associated epilepsy

BackgroundPrevious studies showed the efficacy of epilepsy surgery in carefully selected children with epilepsy associated with tuberous sclerosis complex. However, how this selection is conducted, and the characteristics of the patients brought to surgery are still poorly described. By conducting a multicentric retrospective cohort study covering the practice of the last twenty years, we describe the paths leading to epilepsy surgery in children with epilepsy associated with tuberous sclerosis complex. MethodsWe identified 84 children diagnosed with tuberous sclerosis complex and epilepsy by matching two exhaustive registries of genetic diseases and subsequent medical records reviews within two French neuropediatric and epilepsy centers. Demographic, clinical, longitudinal, and diagnostic and surgical procedures data were collected. ResultsForty-six percent of the children were initially drug-resistant and 19% underwent resective surgery, most often before the age of four. Stereotactic electroencephalography was performed prior to surgery in 44% of cases. Fifty-seven and 43% of patients remained seizure-free one and ten years after surgery, respectively. In addition, 52% of initially drug-resistant patients who did not undergo surgery were seizure-free at the last follow-up. The number of anti-seizure medications required decreased in 50% of cases after surgery. Infantile spasms, intellectual disability, autism spectrum disorder or severe behavioral disorders were not contraindications to surgery but were associated with a higher rate of complications and a lower rate of seizure freedom after surgery. ConclusionDespite the assumption of complex multifocal epilepsy and practical difficulties in young children with tuberous sclerosis complex, successful surgery results are comparable with other populations of patients with drug-resistant epilepsy, and a spontaneous evolution to drug-sensitive epilepsy may occur in non-operated patients.

Psychiatric Residential Treatment Facilities for Child Behavioral Health Services in North Carolina Medicaid.

Psychiatric residential treatment facilities (PRTFs) are non-hospital inpatient treatment settings for children with severe be-havioral health disorders. PRTFs are a restrictive and costly form of care that can potentially be avoided with community-based behavioral health services. Statewide Medicaid enrollment and claims data for 2015-2022 were used to describe PRTF utilization in North Carolina. We examined annual episodes of care in PRTFs and compared trends before and during the COVID-19 public health emergency. From 2015 to 2022, 10,038 children insured by NC Medicaid entered a PRTF across 10,966 episodes of care. In the past five years (2018-2022), care in PRTFs resulted in Medicaid expenditures of over $550 million total, or over $100 million per year. In 2022, 42% of children who entered PRTFs were in foster care and 44% of children were placed in PRTFs outside of North Carolina. The analysis was limited to data collected for administrative purposes. Current trends indicate an ongoing overrepresentation of children in foster care placed in PRTFs and increased out-of-state PRTF placements. Coordinated efforts in future research, policy, and practice are needed to determine the cause of these trends and iden-tify solutions.

Integrating Structural and Experiential Family Therapy in Neurodivergent Families: A Case Study

Autism Spectrum Disorder (ASD) is widely regarded as the most severe childhood behavioral disorder. However, society’s lack of awareness regarding neurodevelopmental disorders, like autism, has led to a limited understanding of their profound impact on children and their families. Challenges include unique sensory experiences, communication and social interactions, strain on familial relationships, emotional toll on parents, and educational hurdles, which can significantly impact the well-being of individuals and their families. This case study explores the integration of Structural and Experiential Family Therapy in a neurodivergent family coping with ASD and Attention-Deficit/Hyperactivity Disorder (ADHD). Structural interventions focus on clarifying roles and redistributing caregiving responsibilities, addressing issues of communication, and power dynamics. Experiential interventions target emotion-focused techniques, empathy building, and cultural sensitivity training. This integration may promote lasting change in family dynamics and a call to empower parents within neurodivergent families through tailored interventions, contributing to a sustainable therapeutic approach.

Association between dementia diagnosis at dialysis initiation and mortality in older patients with end-stage kidney disease in South Korea.

The prevalence of dementia is 2- to 7-fold higher among patients with end-stage kidney disease (ESKD) than among the general population; however, its clinical implications in this population remain unclear. Therefore, this study aimed to determine whether comorbid dementia increases mortality among older patients with ESKD undergoing newly initiated hemodialysis. We analyzed data from the Korean Society of Geriatric Nephrology retrospective cohort, which included 2,736 older ESKD patients (≥70 years old) who started hemodialysis between 2010 and 2017. Kaplan-Meier survival and Cox regression analyses were used to examine all-cause mortality between the patients with and without dementia in this cohort. Of the 2,406 included patients, 8.3% had dementia at the initiation of dialysis; these patients were older (79.6 ± 6.0 years) than patients without dementia (77.7 ± 5.5 years) and included more women (male:female, 89:111). Pre-ESKD diagnosis of dementia was associated with an increased risk of overall mortality (hazard ratio, 1.503; p < 0.001), and this association remained consistent after multivariate adjustment (hazard ratio, 1.268; p = 0.009). In subgroup analysis, prevalent dementia was associated with mortality following dialysis initiation in female patients, those aged <85 years, those with no history of cerebrovascular accidents or severe behavioral disorders, those not residing in nursing facilities, and those with no or short-term hospitalization. A pre-ESKD diagnosis of dementia is associated with mortality following dialysis initiation in older Korean population. In older patients with ESKD, cognitive assessment at dialysis initiation is necessary.

A Comparative Review on Epilepsy and its Treatment Options

Today, people are confronted with various types of stress in everyday life and the majority of people around the world are affected by various neurological diseases. Epilepsy is one of the most common brain diseases that affects about 50 million people worldwide, 90% of whom come from developing countries. Genetic factors, brain infections, strokes, tumors, high fever and other diseases cause epilepsy. It places a heavy economic burden on the health system in countries where stigma and discrimination are found against patients and their families, especially in communities, workplaces, schools and homes. Many epilepsy patients suffer from severe emotional pain, behavioral disorders and extreme social isolation.

The phenotypic presentation of adult individuals with SLC6A1-related neurodevelopmental disorders.

SLC6A1 is one of the most common monogenic causes of epilepsy and is a well-established cause of neurodevelopmental disorders. SLC6A1-neurodevelopmental disorders have a consistent phenotype of mild to severe intellectual disability (ID), epilepsy, language delay and behavioral disorders. This phenotypic description is mainly based on knowledge from the pediatric population. Here, we sought to describe patients with SLC6A1 variants and age above 18 years through the ascertainment of published and unpublished patients. Unpublished patients were ascertained through international collaborations, while previously published patients were collected through a literature search. A total of 15 adult patients with SLC6A1 variants were included. 9/13 patients had moderate to severe ID (data not available in two). Epilepsy was prevalent (11/15) with seizure types such as absence, myoclonic, atonic, and tonic-clonic seizures. Epilepsy was refractory in 7/11, while four patients were seizure free with lamotrigine, valproate, or lamotrigine in combination with valproate. Language development was severely impaired in five patients. Behavioral disorders were reported in and mainly consisted of autism spectrum disorders and aggressive behavior. Schizophrenia was not reported in any of the patients. The phenotype displayed in the adult patients presented here resembled that of the pediatric cohort with ID, epilepsy, and behavioral disturbances, indicating that the phenotype of SLC6A1-NDD is consistent over time. Seizures were refractory in >60% of the patients with epilepsy, indicating the lack of targeted treatment in SLC6A1-NDDs. With increased focus on repurposing drugs and on the development of new treatments, hope is that the outlook reflected here will change over time. ID appeared to be more severe in the adult patients, albeit this might reflect a recruitment bias, where only patients seen in specialized centers were included or it might be a feature of the natural history of SLC6A1-NDDs. This issue warrants to be explored in further studies in larger cohorts.

Intrafamilial variability in SLC6A1-related neurodevelopmental disorders.

Phenotypic spectrum of SLC6A1-related neurodevelopmental disorders (SLC6A1-NDD) includes intellectual disability (ID), autistic spectrum disorders (ASD), epilepsy, developmental delay, beginning from early infancy or after seizure onset, and other neurological features such as hypotonia and movement disorders. Data on familial phenotypic heterogeneity have been rarely reported, thus in our study we aimed to investigate intrafamilial phenotypic variability in families with SLC6A1 variants. We collected clinical, laboratory and genetic data on 39 individuals, including 17 probands, belonging to 13 families harboring inherited variants of SLC6A1. Data were collected through an international network of Epilepsy and Genetic Centers. Main clinical findings in the whole cohort of 39 subjects were: (a) epilepsy, mainly presenting with generalized seizures, reported in 71% of probands and 36% of siblings or first/second-degree relatives. Within a family, the same epilepsy type (generalized or focal) was observed; (b) ID reported in 100% and in 13% of probands and siblings or first/second-degree relatives, respectively; (c) learning disabilities detected in 28% of the SLC6A1 carriers, all of them were relatives of a proband; (d) around 51% of the whole cohort presented with psychiatric symptoms or behavioral disorders, including 82% of the probands. Out of the 19 patients with psychiatric symptoms, ASD were diagnosed in 40% of them; (e) neurological findings (primarily tremor and speech difficulties) were observed 38.5% of the whole cohort, including 10 probands. Our families harbored 12 different SLC6A1 variants, one was a frameshift, two stop-gain, while the remaining were missense. No genotype-phenotype associations were identified. Our study showed that first-or second-degree relatives presented with a less severe phenotype, featuring mainly mild intellectual and/or learning disabilities, at variance with the probands who suffered from moderate to severe ID, generalized, sometimes intractable, epileptic seizures, behavioral and psychiatric disorders. These findings may suggest that a proportion of individuals with mild SLC6A1-NDD might be missed, in particular those with an older age where genetic testing is not performed. Further studies on intrafamilial phenotypic variability are needed to confirm our results and possibly to expand the phenotypic spectrum of these disorders and benefit genetic counseling.

Severe behavior disorders within Sturge-Weber Syndrome adimitted in child forensic psychiatric board. Case presentation

Severe behavior disorders within Sturge-Weber Syndrome adimitted in child forensic psychiatric board. Case presentation

Parent treatment of complex pica in a teen with autism

AbstractPica is a severe behavior disorder involving the persistent consumption of nonnutritive substances. Due to health complications and risks for fatality, designing effective behavioral treatments that are feasible for implementation by family members at home is imperative. This case report presents a parent‐conducted functional analysis and treatment evaluation of automatically maintained pica in a teenager with autism spectrum disorder. Initial treatment with a competing stimulus was effective when paired with response interruption and redirection. Although effective, this combination of treatment components required very close parental proximity and led to increases in untargeted body‐oriented pica (e.g., ingestion of skin, hair, and nails). Upon extending treatment to include the second topography of pica, both the originally targeted (object‐oriented) pica and body‐oriented pica decreased. Nonetheless, treatment effects were not sustained while fading parent proximity. The treatment was then augmented a third time with response cost. This final treatment package produced clinically significant reductions in all pica, facilitated parent proximity fading until the participant was alone, extended to their home, and maintained over a year of follow up.

Assessment of Psychosocial and Neonatal Risk Factors for Trajectories of Behavioral Dysregulation Among Young Children From 18 to 72 Months of Age

Emotional and behavioral dysregulation during early childhood are associated with severe psychiatric, behavioral, and cognitive disorders through adulthood. Identifying the earliest antecedents of persisting emotional and behavioral dysregulation can inform risk detection practices and targeted interventions to promote adaptive developmental trajectories among at-risk children. To characterize children's emotional and behavioral regulation trajectories and examine risk factors associated with persisting dysregulation across early childhood. This cohort study examined data from 20 United States cohorts participating in Environmental influences on Child Health Outcomes, which included 3934 mother-child pairs (singleton births) from 1990 to 2019. Statistical analysis was performed from January to August 2022. Standardized self-reports and medical data ascertained maternal, child, and environmental characteristics, including prenatal substance exposures, preterm birth, and multiple psychosocial adversities. Child Behavior Checklist caregiver reports at 18 to 72 months of age, with Dysregulation Profile (CBCL-DP = sum of anxiety/depression, attention, and aggression). The sample included 3934 mother-child pairs studied at 18 to 72 months. Among the mothers, 718 (18.7%) were Hispanic, 275 (7.2%) were non-Hispanic Asian, 1220 (31.8%) were non-Hispanic Black, 1412 (36.9%) were non-Hispanic White; 3501 (89.7%) were at least 21 years of age at delivery. Among the children, 2093 (53.2%) were male, 1178 of 2143 with Psychosocial Adversity Index [PAI] data (55.0%) experienced multiple psychosocial adversities, 1148 (29.2%) were exposed prenatally to at least 1 psychoactive substance, and 3066 (80.2%) were term-born (≥37 weeks' gestation). Growth mixture modeling characterized a 3-class CBCL-DP trajectory model: high and increasing (2.3% [n = 89]), borderline and stable (12.3% [n = 479]), and low and decreasing (85.6% [n = 3366]). Children in high and borderline dysregulation trajectories had more prevalent maternal psychological challenges (29.4%-50.0%). Multinomial logistic regression analyses indicated that children born preterm were more likely to be in the high dysregulation trajectory (adjusted odds ratio [aOR], 2.76; 95% CI, 2.08-3.65; P < .001) or borderline dysregulation trajectory (aOR, 1.36; 95% CI, 1.06-1.76; P = .02) vs low dysregulation trajectory. High vs low dysregulation trajectories were less prevalent for girls compared with boys (aOR, 0.60; 95% CI, 0.36-1.01; P = .05) and children with lower PAI (aOR, 1.94; 95% CI, 1.51-2.49; P < .001). Combined increases in PAI and prenatal substance exposures were associated with increased odds of high vs borderline dysregulation (aOR, 1.28; 95% CI, 1.08-1.53; P = .006) and decreased odds of low vs high dysregulation (aOR, 0.77; 95% CI, 0.64-0.92; P = .005). In this cohort study of behavioral dysregulation trajectories, associations were found with early risk factors. These findings may inform screening and diagnostic practices for addressing observed precursors of persisting dysregulation as they emerge among at-risk children.

The clinical and sleep manifestations in children with FOXG1 syndrome

FOXG1 syndrome is a rare neurodevelopmental disorder associated with severe cognitive dysfunction, autistic behavior, and early-onset hyperkinetic movement disorders. Patients have also been reported to experience sleep disturbances. However, these findings are mainly based on subjective caregivers' reports, and limited by small case numbers. Moreover, no studies using objective evaluation tools, such as actigraphy, have been reported. We analyzed the clinical and sleep manifestations of children with FOXG1 syndrome registered in the FOXG1 Research Foundation Patient Registry database. A total of 258 individuals with FOXG1 syndrome were included in this research. 132 (51.16%) had sleep disturbances. The more impaired of language acquisitions (absence of speech, OR: 3.99, 95%CI = 1.69-9.42, p = 0.002), hyperkinetic movement disorders (OR: 2.64, 95%CI = 1.34-5.20 p =0.005) and feeding difficulties (OR: 2.81, 95% CI = 1.52-5.19, p = 0.001) were significantly associated with an increase in odds of sleep disturbance after adjusting for age, sex, and antiepileptic drugs. We also performed sleep studies on six individuals with FOXG1 syndrome using The Children's Sleep Habits Questionnaire (CSHQ), the Sleep Disturbance Scale for Children (SDSC), and 7-day data from Actiwatch. The Pittsburgh Sleep Quality Index (PSQI) and 7-day data from Actiwatch were also used to evaluate the sleep condition of their parents. The CSHQ scores revealed bedtime resistance, sleep onset delay, sleep duration, sleep anxiety, night-waking, and parasomnia. Sleep-wake transition disorders and disorders of initiating and maintaining sleep were also suggested by the SDSC scores. The children's actigraphy revealed short sleep durations, impaired sleep efficiency, longer wake after sleep onset, and frequent night-waking. All caregivers reported significantly higher PSQI scores, mildly declined sleep efficiency, and shorter total sleep duration. Sleep disturbances, especially in initiating and maintaining sleep, are common in individuals with FOXG1 syndrome and their caregivers. Sleep disorders in patients with FOXG1 syndrome and their caregivers should be investigated.

Does intensive home treatment change treatment trajectories of psychiatric disorders?

IntroductionIntensive home treatment (IHT) for people experiencing a mental health crisis has been progressively established in many western countries as an alternative to in-ward admission. But is this a real alternative? We previously reported that patients treated in our IHT unit only differ from those voluntarily admitted to hospital in suicidal risk and severe behaviour disorders (not in other factors such as clinical severity) (Martín-Blanco et al., Rev Psiquiatr Salud Ment 2022;15:213-5). Now we are interested in disentangle if those patients who used to require inward management can be successfully treated at home.ObjectivesTo describe subsequent treatment trajectories of the first 1000 admissions to our IHT unit and to compare clinical characteristics among the different groups of trajectories.MethodsRetrospective cohort study. Subsequent treatment trajectories were collected from December 2016 to October 2022 and classified: absence, hospital, IHT, and mixed (hospital and IHT). Statistical significance was tested by means of ANOVA or Kruskal-Wallis test for quantitative variables (corrected for multiple comparisons) and chi-square tests for qualitative variables.Results Tables 1 shows the characteristics of the whole sample. Of the 1000 IHT admissions, 12.1% needed subsequent hospital admission(s), 12.7% IHT admission(s), and 9.3% mixed admission(s). There were no differences among these groups in median severity at IHT admission, but there were differences in the number of previous admissions (p=0.0001): the group with no subsequent admissions had less previous admissions than the other groups (pBonf&lt;0.0001), and the group with subsequent IHT admissions had less than the group with mixed admissions (pBonf=0.0123). There were differences between groups regarding distribution of diagnoses (p&lt;0.0001) (Fig. 1). When considering subsequent admissions by diagnosis, there were differences in severity at IHT admission (p=0.0068) and in number of previous hospitalizations (p&lt;0.0001) (Fig. 2).Table 1.Clinical characteristics of the whole sample (N=1000)meanSDAge (years)47.0717.02CGI-s at admission *54-5N%Sex (female)54854.8%Psychotic disorders46346.3%Affective disorder25725.7%Bipolar disorder12812.8%Other disorders15215.2%Hospital admission in the previous 5 years31331.3%CGI-s: clinical global impression - severity. * median and IQRImage:Image 2:ConclusionsPatients that used to require inward management can now be treated at home when suffering an acute episode. Therefore, IHT has changed treatment trajectories for some patients with psychiatric disorders.Disclosure of InterestNone Declared

Onychophagia Progressing to Extensive Finger Amputation: A Brief Review Addressing Severe Body-Focused Repetitive Behavior Disorder in an Adult

Individuals engaging in repetitive, persistent and intentional behaviors resulting in significant self-injury can, for many medical and psychiatric care providers, stir vexing questions as to how such behavior should be conceptualized and managed. Onychophagia (nail-biting), categorized as a Body-Focused Repetitive Behavior Disorder (BFRBD) in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition , is a common oral habit, observed in both children and adults. For most persons, the nail-biting is merely a cosmetic concern that does not attract clinical attention. Although more extreme forms of this behavior can manifest with moderate complications, we present an unusual case of an adult for whom persistent onychophagia progressed to significant injury to his hands due to recurrent osteomyelitis. Emerging research exploring the underpinnings of severe forms of BFRBDs are discussed. This case illuminates management challenges that can arise when clinicians fail to recognize the condition and highlights the need for early coordinated multidisciplinary intervention to mitigate the behavior and its sequelae longitudinally. [ Psychiatr Ann . 2023;53(3):145–148.]

Exploring Education Beyond Traditional Contexts: An Interview With Dr. Sarup Mathur

Dr. Sarup Mathur is the Ryan C. Harris Professor of Special Education in the Division of Educational Leadership at Arizona State University. She is nationally recognized as a leader in the fields of emotional and behavioral disorders and juvenile justice, particularly specializing in the areas of social skills and re-entry of adjudicated youth. She has been the co-editor of a yearly special issue of Education and Treatment of Children on severe behavior disorders of children and youth, is the former secretary and president of the Council for Exceptional Children’s Division of Emotional and Behavioral Health, and has enabled teachers in juvenile justice to support adjudicated youth by developing transitioning planning processes. She has written numerous scholarly articles, published and edited books, and has secured extensive grant funding to support the training of doctoral students specializing in working with adjudicated youth.

Prader-Willi syndrome: Symptoms and topiramate response in light of genetics.

Prader-Willi Syndrome (PWS) is a rare genetic condition, which affects one in 25,000 births and results in various phenotypes. It leads to a wide range of metabolic and endocrine disorders including growth delay, hypogonadism, narcolepsy, lack of satiety and compulsive eating, associated with mild to moderate cognitive impairment. Prognosis is especially determined by the complications of obesity (diabetes, cardiorespiratory diseases) and by severe behavioral disorders marked by impulsivity and compulsion. This heterogeneous clinical picture may lead to mis- or delayed diagnosis of comorbidities. Moreover, when diagnosis is made, treatment remains limited, with high interindividual differences in drug response. This may be due to the underlying genetic variability of the syndrome, which can involve several different genetic mutations, notably deletion or uniparental disomy (UPD) in a region of chromosome 15. Here, we propose to determine whether subjects with PWS differ for clinical phenotype and treatment response depending on the underlying genetic anomaly. We retrospectively included all 24 PWS patients who were referred to the Reference Center for Rare Psychiatric Disorders (GHU Paris Psychiatrie and Neurosciences) between November 2018 and July 2022, with either deletion (N = 8) or disomy (N = 16). The following socio-demographic and clinical characteristics were recorded: age, sex, psychiatric and non-psychiatric symptoms, the type of genetic defect, medication and treatment response to topiramate, which was evaluated in terms of eating compulsions and impulsive behaviors. We compared topiramate treatment doses and responses between PWS with deletion and those with disomy. Non-parametric tests were used with random permutations for p-value and bootstrap 95% confidence interval computations. First, we found that disomy was associated with a more severe clinical phenotype than deletion. Second, we observed that topiramate was less effective and less tolerated in disomy, compared to deletion. These results suggest that a pharmacogenomic-based approach may be relevant for the treatment of compulsions in PWS, thus highlighting the importance of personalized medicine for such complex heterogeneous disorders.

How COVID-19 Phases Have Impacted Psychiatric Risk: A Retrospective Study in an Emergency Care Unit for Adolescents.

Dramatic events during the COVID-19 pandemic have acutely impacted the psychosocial environment worldwide, with negative implications for mental health, particularly for more vulnerable children and adolescents with severe psychiatric illnesses. Some data suggest that the pandemic waves may have produced different psychopathological consequences, further worsening in the second phase of the pandemic, compared to those in the first lockdown, soon after March 2020. To test the hypothesis of a further worsening of psychiatric consequences of COVID-19 in the second lockdown compared to the first lockdown, we focused our analysis on a consecutive sample of youth referred to a psychiatric emergency unit for acute mental disorders in the time period between March 2019-March 2021. The sample, consisting of 241 subjects (123 males and 118 females, ranging in age from 11 to 17 years), was divided into three groups: Pre-Lockdown Group (PLG, 115 patients); First Lockdown Group (FLG, 65 patients); and Second Lockdown Group (SLG, 61 patients). Patients in the SLG presented more frequently with non-suicidal self-injuries (NSSIs), suicidal ideation, and suicidal behavior, while no significant differences in self-harm were found between PLG and FLG. Eating disorders were more frequent in both the FLG and SLG, compared to the PLG, while sleep problems were higher only in the SLG. Furthermore, patients in the SLG presented with more frequent psychological maltreatments and neglect, as well as with psychiatric disorders in the parents. Adverse traumatic experiences and internalizing disorders were significantly associated with an increased risk of suicidality. Intellectual disability was less represented from the PLG to SLG, and similarly, the rate of ADHD was lower in the SLG. No differences were found for the other psychiatric diagnoses. This information may be helpful for a better understanding and management of adolescents with severe emotional and behavioral disorders after the exposure to long-lasting collective traumas.

Teaching NeuroImage: Selectively Bright Inferior Cerebellum in Christianson Syndrome.

A 4-year-old boy presented with developmental delay (nonverbal and unable to walk or sit independently) and recurrent tonic-clonic seizures beginning at 1 month of age. EEG demonstrated underdeveloped background organization and intermittent focal right occipital slowing. Brain MRI revealed inferior cerebellar atrophy with T2-WI and FLAIR cortical hyperintensity (Figure). A SLC9A6 c.803+3_803+6del (intronic) pathogenic variant was detected, confirming a diagnosis of Christianson syndrome (CS). CS is characterized by severe cognitive dysfunction, behavioral disorder, seizures, ataxia, and microcephaly. The condition results from loss-of-function alterations affecting sodium Na+/H+ exchange enzymes. While some clinical features may overlap with Angelman syndrome (AS), inferior cerebellar atrophy is characteristic of CS. It is important to distinguish between the 2 diagnoses because the prognosis in CS is worse than that in AS.