Cognitive functioning and clinical characteristics of children with non-syndromic orofacial clefts: A case-control study.

Introduction: The higher rate of neuropsychiatric disorders in individuals with non-syndromic orofacial clefts has been well documented by previous studies. Our goal was to identify children with non-syndromic orofacial clefts that are at risk for abnormal neurodevelopment by assessing their developmental history and present cognitive functioning. Materials and methods: A single-center, case-controlled study was carried out at the Department of Pediatrics of the University of Pécs in Hungary. The study consisted of three phases including questionnaires to collect retrospective clinical data and psychometric tools to assess IQ and executive functioning. Results: Forty children with non-syndromic oral clefts and 44 age-matched controls participated in the study. Apgar score at 5 min was lower for the cleft group, in addition to delays observed for potty-training and speech development. Psychiatric disorders were more common in the cleft group (15%) than in controls (4.5%), although not statistically significant with small effect size. The cleft group scored lower on the Continuous Performance Test. Subgroup analysis revealed significant associations between higher parental socio-economic status, academic, and cognitive performance in children with non-syndromic orofacial clefts. Analyzes additionally revealed significant associations between early speech and language interventions and higher scores on the Verbal Comprehension Index of the WISC-IV in these children. Discussion: Children with non-syndromic orofacial clefts seem to be at risk for deficits involving the attention domain of the executive system. These children additionally present with difficulties that affect cognitive and speech development. Children with non-syndromic orofacial clefts show significant skill development and present with similar cognitive strengths as their peers. Longitudinal studies with larger sample sizes are needed to provide more conclusive evidence on cognitive deficits in children with non-syndromic orofacial clefts at risk for neurodevelopmental difficulties.

Self-Harm in Children and Adolescents Who Presented at Emergency Units During the COVID-19 Pandemic: An International Retrospective Cohort Study.

OBJECTIVE: To compare psychiatric emergencies and self-harm at emergency departments (EDs) 1 year into the pandemic, to early pandemic and pre-pandemic, and to examine the changes in the characteristics of self-harm presentations. METHOD: This retrospective cohort study expanded on the Pandemic-Related Emergency Psychiatric Presentations (PREP-kids) study. Routine record data in March to April of 2019, 2020, and 2021 from 62 EDs in 25 countries were included. ED presentations made by children and adolescents for any mental health reasons were analyzed. RESULTS: Altogether, 8,174 psychiatric presentations were recorded (63.5% female; mean [SD] age, 14.3 [2.6] years), 3,742 of which were self-harm presentations. Rate of psychiatric ED presentations in March to April 2021 was twice as high as in March to April 2020 (incidence rate ratio [IRR], 1.93; 95% CI, 1.60-2.33), and 50% higher than in March to April 2019 (IRR, 1.51; 95% CI, 1.25-1.81). Rate of self-harm presentations doubled between March to April 2020 and March to April 2021 (IRR, 1.98; 95% CI, 1.68-2.34), and was overall 1.7 times higher than in March to April 2019 (IRR, 1.70; 95% CI, 1.44-2.00). Comparing self-harm characteristics in March to April 2021 with March to April 2019, self-harm contributed to a higher proportion of all psychiatric presentations (odds ratio [OR], 1.30; 95% CI, 1.05-1.62), whereas female representation in self-harm presentations doubled (OR, 1.98; 95% CI, 1.45-2.72) and follow-up appointments were offered 4 times as often (OR, 4.46; 95% CI, 2.32-8.58). CONCLUSION: Increased pediatric ED visits for both self-harm and psychiatric reasons were observed, suggesting potential deterioration in child mental health. Self-harm in girls possibly increased and needs to be prioritized. Clinical services should continue using follow-up appointments to support discharge from EDs. DIVERSITY & INCLUSION STATEMENT: One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. While citing references scientifically relevant for this work, we also actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our reference list. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.

Increased prevalence of minor physical anomalies in patients with epilepsy.

Our aim was to investigate the rate and topological profile of minor physical anomalies (MPAs) in adult patients with epilepsy with the use of the Méhes Scale, a comprehensive modern scale of dysmorphology. Consecutive epilepsy patients admitted for outpatient evaluation were included. Patients with comorbidities of neurodevelopmental origin (such as autism, severe intellectual disability, attention deficit hyperactivity disorder, schizophrenia, tic disorder, Tourette syndrome, bipolar disorder, specific learning disorder and specific language impairment) were excluded. All participants underwent physical examination with the use of the Méhes Scale for evaluation of MPAs, including 57 minor signs. The frequency and topological profile of MPAs were correlated to clinical patient data using Kruskal-Wallis, chi2 tests and logistic regression model. 235 patients were included, according to the following subgroups: acquired epilepsy (non-genetic, non-developmental etiology) [N = 63], temporal lobe epilepsy with hippocampal sclerosis (TLE with HS) [N = 27], epilepsy with cortical dysgenesis etiology [N = 29], cryptogenic epilepsy [N = 69] and idiopathic generalized epilepsy (IGE) [N = 47]. As controls, 30 healthy adults were recruited. The frequency of MPAs were significantly affected by the type of epilepsy [H(6) = 90.17; p < 0.001]. Pairwise comparisons showed that all patient groups except for acquired epilepsy were associated with increased frequency of MPAs (p < 0.001 in all cases). Furrowed tongue and high arched palate were more common compared to controls in all epilepsy subgroup except for TLE (p < 0.001 or p = 0.001 in all cases). A positive association was detected between the occurrence of MPAs and antiepileptic drug therapy resistance [Exp(B) = 4.19; CI 95% 1.37-12.80; p = 0.012]. MPAs are more common in patients with epilepsy, which corroborates the emerging concept of epilepsy as a neurodevelopmental disorder. Assessment of these signs may contribute to the clarification of the underlying etiology. Moreover, as increased frequency of MPAs may indicate pharmacoresistance, the identification of patients with high number of MPAs could allow evaluation for non-pharmacological treatment in time.

The Brain in Oral Clefting: A Systematic Review With Meta-Analyses.

Background: Neuroimaging of individuals with non-syndromic oral clefts have revealed subtle brain structural differences compared to matched controls. Previous studies strongly suggest a unified primary dysfunction of normal brain and face development which could explain these neuroanatomical differences and the neuropsychiatric issues frequently observed in these individuals. Currently there are no studies that have assessed the overall empirical evidence of the association between oral clefts and brain structure. Our aim was to summarize the available evidence on potential brain structural differences in individuals with non-syndromic oral clefts and their matched controls. Methods: MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, Web of Science and Embase were systematically searched in September 2020 for case-control studies that reported structural brain MRI in individuals with non-syndromic oral clefts and healthy controls. Studies of syndromic oral clefts were excluded. Two review authors independently screened studies for eligibility, extracted data and assessed risk of bias with the Newcastle-Ottawa Scale. Random effects meta-analyses of mean differences (MDs) and their 95% confidence intervals (95% CI) were performed in order to compare global and regional brain MRI volumes. Results: Ten studies from 18 records were included in the review. A total of 741 participants were analyzed. A moderate to high risk of bias was determined for the included studies. The cerebellum (MD: -12.46 cm3, 95% CI: -18.26, -6.67, n = 3 studies, 354 participants), occipital lobes (MD: -7.39, 95% CI: -12.80, -1.99, n = 2 studies, 120 participants), temporal lobes (MD: -10.53 cm3, 95% CI: -18.23, -2.82, n = 2 studies, 120 participants) and total gray matter (MD: -41.14 cm3; 95% CI: -57.36 to -24.92, n = 2 studies, 172 participants) were significantly smaller in the cleft group compared to controls. Discussion: There may be structural brain differences between individuals with non-syndromic oral clefts and controls based on the available evidence. Improvement in study design, size, methodology and participant selection could allow a more thorough analysis and decrease study heterogeneity.

Anti-Neuronal Autoantibodies (Cell Surface and Onconeural) and Their Association With Natural Autoantibodies in Synthetic Cannabinoid-Induced Psychosis.

Patients suffering from encephalitis may present psychiatric symptoms; however, the clinical relevance of anti-neuronal antibodies in patients experiencing a psychotic episode without encephalitis is still unclear. In this study, we examined the presence of anti-neuronal cell surface autoantibodies and onconeural autoantibodies in serum samples of 22 synthetic cannabinoid users presenting with psychosis. We found only two positive cases; however, seven patients had borderline results. Nonetheless, we found no significant correlation between anti-neuronal autoantibodies and the intensity of psychosis indicated by the Positive and Negative Syndrome Scale (PANSS) scores. The length of drug use and the combination of other drugs with synthetic cannabinoids have no significant effect on anti-neuronal autoantibody positivity. Nonetheless, the ratio of anti-citrate synthase (anti-CS) IgM and IgG natural autoantibodies was significantly lower (p = 0.036) in the anti-neuronal autoantibody-positive/borderline samples, than in the negative group. Interestingly, anti-CS IgM/IgG showed a significant negative correlation with PANSS-positive score (p = 0.04, r = -0.464). Our results demonstrated that anti-neuronal autoantibody positivity occurs in synthetic cannabinoid users, and the alteration of anti-CS IgM/IgG natural autoantibody levels points to immunological dysfunctions in these cases.

Increased Prevalence of Minor Physical Anomalies Among the Healthy First-Degree Relatives of Bipolar I Patients - Results With the Méhes Scale.

Minor physical anomalies are somatic markers of aberrant neurodevelopment, so the higher prevalence of these signs among the relatives of bipolar I patients can confirm minor physical anomalies as endophenotypes. The aim of the study was to evaluate the prevalence of minor physical anomalies in first-degree healthy relatives of patients with bipolar I disorder compared to normal control subjects. Using a list of 57 minor physical anomalies (the Méhes Scale), 20 first-degree unaffected relatives of patients with the diagnosis of bipolar I disorder and as a comparison 20 matched normal control subjects were examined. Minor physical anomalies were more common in the ear, head, mouth and trunk regions among the relatives of bipolar I patients compared to normal controls. By the differentiation of minor malformations and phenogenetic variants, we have found that both minor malformations and phenogenetic variants were more common among the relatives of bipolar I patients compared to the control group, while individual analyses showed, that one minor malformation (sole crease) and one phenogenetic variant (high arched palate) were more prevalent in the relative group. This is the first report in literature on the increased prevalence of minor physical anomalies among the first-degree unaffected relatives of bipolar I patients. The study support the concept, that minor physical anomalies can be endophenotypic markers of bipolar I affective disorder.

Maternal mosaicism underlies the inheritance of a rare germline AKT3 variant which is responsible for megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome in two Roma half-siblings.

Megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndrome is a developmental brain disorder characterized by an enlarged brain size with bilateral perisylvian polymicrogyria and a variable degree of ventriculomegaly. MPPH syndrome is associated with oromotor dysfunction, epilepsy, intellectual disability and postaxial hexadactyly. The molecular diagnosis of this disorder is established by the identification of a pathogenic variant in either AKT3, CCND2 or PIK3R2. Previously reported AKT3 variants are associated with various brain abnormalities and may lead to megalencephaly. MPPH syndrome is usually due to germline pathogenic AKT3 variants. Somatic mosaic pathogenic variants associated with hemimegalencephaly, which is similar to MPPH, have also been observed. A Hungarian Roma family with two half-siblings, which present with intellectual disability, dysmorphic features, epilepsy, brain malformations, and megalencephaly was studied. Whole exome sequencing (WES) analysis was performed. WES analysis revealed a heterozygous c.1393C > T p.(Arg465Trp) pathogenic missense AKT3 variant in both affected half-siblings. The variant was verified via Sanger sequencing and was not present in the DNA sample from the healthy mother, which was derived from peripheral blood, suggesting maternal germline mosaicism. In conclusion, this is the first report in which maternal germline mosaicism of a rare pathogenic AKT3 variant leads to autosomal dominantly inherited MPPH syndrome.

Energy Drink Consumption, Depression, and Salutogenic Sense of Coherence Among Adolescents and Young Adults.

The prevalence of energy drink consumption has increased in Hungary over the past 10-15 years. This study assesses the frequency, motivations, and adverse effects of energy drink consumption, and examines how the process of becoming a regular consumer is connected with sense of coherence and depression symptoms. A total of 631 high school and college students were assessed using the Depression Scale (BDS-13) and Sense of Coherence Scale (SOC-13). Logistic regression models were fit to test the effect of and links between factors influencing addiction to energy drink use. A total of 31.1% (95% CI: 27.4-34.7) of those surveyed consumed energy drinks, 24.0% of those affected consumed the energy drink with alcohol, 71.4% (95% CI: 64.7-77.3) experienced adverse effects following energy drink consumption, and 10.2% (95% CI: 6.7-15.2) experienced at least four symptoms simultaneously. The most common motivations of consumption were fatigue, taste, and fun. Obtained by multivariate logistic regression models, after adjustment for sex and age, SOC and tendency to depression had a significant influence on the respondents' odds of addiction. The tendency to depression increases the chances of addiction, while a strong sense of coherence diminishes the effects of depression. Young people in Hungary have been shown to consume energy drinks in quantities that are detrimental to their health. Complex preventive measures and programs are needed to address the problem. Families and educators should strive to instill a strong sense of coherence in children from an early age.

[Catatonia in childhood and adolescence - a brief review and case report].

The authors overview the clinical, epidemiological, pathophysiological and therapeutic aspects of catatonia in childhood and adolescence. They deal with the recent changes of the nosological position of the phenomenon, and emphasize the importance of specific therapeutic interventions.

Adaptation and validation of the Hungarian version of the Yale Food Addiction Scale for Children.

Background Childhood obesity proves to be an important public health issue, since it serves as a potential risk factor for multiple diseases. Food addiction could also serve as an important etiological factor. As childhood obesity plays a serious issue also in Hungary, we aimed to adapt and validate the Hungarian version of the Yale Food Addiction Scale for Children (H-YFAS-C). Methods A total of 191 children were assessed with the H-YFAS-C and the Eating Disorder Inventory (EDI). The following psychometric properties were analyzed: internal consistency, construct validity, convergent, and discriminant validity. Results A good construct validity was revealed by confirmatory factor analysis (RMSEA = 0.0528, CFI = 0.896, χ2 value = 279.06). Question 25 proved to have no significant effect on its group and was removed from further analyses. The Kuder-Richardson 20 coefficient indicated good internal consistency (K20 = 0.82). With the use of the eight EDI subscales, a good convergent and discriminant validity could be determined. Food addiction was diagnosed in 8.9% of children. The mean symptom count was 1.7 ± 1.2 (range: 0-7). Females were more often diagnosed with food addiction than males (p = .016; OR = 3.6, 95% CI: 1.2-10.6). BMI percentiles were significantly higher in children with diagnosed food addiction (p = .003). There proved to be no correlation between age and the occurrence of food addiction. Discussion and conclusion Our results show that H-YFAS-C is a good and reliable tool for addictive-like behavior assessment.

Minor physical anomalies and dermatoglyphic signs in affective disorders: A systematic review.

The increased prevalence of minor physical anomalies (MPAs) and the abnormalities of dermatoglyphic patterns may be physical manifestations of neurodevelopmental disruption in affective disorders. This paper aims to review the current state of knowledge on the frequency of MPAs and dermatoglyphic abnormalities in mood disorders. A MEDLINE, PsychInfo and Web of Science search was carried out to collect all publications on the frequency of MPAs and on dermatoglyphic traits in bipolar disorder and unipolar depression. 24 studies on MPAs, 19 on dermatoglyphics, and 5 dealing with both were found with discrepant findings. The relative contribution of neurodevelopmental retardation to the aetiology of affective disorders remains undetermined, the field is open for further research. Increased recognition of neurodevelopmental processes in the origin of affective disorders may allow for earlier and more effective intervention and prevention.

Minor physical anomalies in bipolar I and bipolar II disorders - Results with the Méhes Scale.

Minor physical anomalies (MPAs) are external markers of abnormal brain development, so the more common appearence of these signs among bipolar I and bipolar II patients can confirm the possibility of a neurodevelopmental deficit in these illnesses. The aim of the present study was to investigate the rate and topological profile of minor physical anomalies in patients with bipolar I and - first in literature - with bipolar II disorders compared to matched healthy control subjects. Using a list of 57 minor physical anomalies (the Méhes Scale), 30 bipolar I and 30 bipolar II patients, while as a comparison 30 matched healthy control subjects were examined. Significant differences were detected between the three groups comparing the total number of minor physical anomalies, minor malformations and phenogenetic variants and in the cases of the ear and the mouth regions. The individual analyses of the 57 minor physical anomalies by simultaneous comparison of the three groups showed, that in the cases of furrowed tongue and high arched palate were significant differences between the three groups. The results can promote the concept, that a neurodevelopmental deficit may play a role in the etiology of both bipolar I and bipolar II disorders.

Anti-N-methyl-D-aspartate receptor encephalitis and drug abuse - the probable role of molecular mimicry or the overstimulation of CB receptors in a 17-year-old adolescent - case report.

Anti-N-methyl-D-aspartate encephalitis is an autoimmune disorder characterized by autoantibodies produced against NMDA receptors. We report the case of a 17-year-old drug user teenager who presented with altered mental scale, psychiatric symptoms and autonomic dysfunction. In the background we diagnosed NMDA encephalitis. We supposed that synthetic cannabinoids/drugs may have lead to the of trigger NMDA encephalitis via the altered activation of the immune system and molecular mimicry mechanism.

[Yale Food Addiction Scale - review of literature].

INTRODUCTION: Food addiction is a condition presenting with a similar symptomatology to that of drug addiction, with an underlying individual sensitivity and special adaptation to certain foods, being consumed regularly. The concept of food addiction created one of the central issues in addiction research, owing to the pandemic spreading of obesity causing serious public health concerns. Development of an objective, standardized measuring tool of food addiction has become markedly necessary for both research and public health purposes. METHODS: Literature overview in the fields of food addiction and Yale Food Addiction Scale (1956-2016). RESULTS: For the establishment of food addiction diagnosis, the Yale Food Addiction Scale has become the most widely used method. It is an English questionnaire consisting of 25 questions, having been developed according to the 7 substance use disorder criteria in DSM-IV. The scale provides the possibility of diagnosis establishment, as well as measurement of food addiction severity. Development of the scale has given way to a number of new scientific results. The mean prevalence of food addiction is 19.7%, being more common in women, obese individuals, people >35 years and patients with already established eating disorders (binge eating disorder, bulimia). The most common symptom is the 'persistent desire or repeated unsuccessful attempts to quit'. A positive association has been recognized between food addiction symptomcount and the reward system dysfunction. CONCLUSION: The Yale Food Addiction Scale is a psychometrically valid, objective and standardized tool, being not only useful in addiction research but also helping in diagnosis establishment in clinical practice.

Minor physical anomalies are more common among the first-degree unaffected relatives of schizophrenia patients - Results with the Méhes Scale.

Minor physical anomalies are external markers of abnormal brain development,so the more common appearance of these signs among the relatives of schizophrenia patients can confirm minor physical anomalies as intermediate phenotypes. The aim of the present study was to investigate the rate and topological profile of minor physical anomalies in the first-degree unaffected relatives of patients with schizophrenia compared to matched normal control subjects. Using a list of 57 minor physical anomalies (the Méhes Scale), 20 relatives of patients with the diagnosis of schizophrenia and as a comparison 20 matched normal control subjects were examined. Minor physical anomalies were more common in the head and mouth regions among the relatives of schizophrenia patients compared to normal controls. By the differentiation of minor malformations and phenogenetic variants, we have found that only phenogenetic variants were more common in the relatives of schizophrenia patients compared to the control group, however individual analyses showed, that one minor malformation (flat forehead) was more prevalent in the relative group. The results can promote the concept, that minor physical anomalies can be endophenotypic markers of the illness.

[Genetic testing in hereditary spastic paraplegia]. / Herediter spasticus paraplegia genetikai vizsgálata.

INTRODUCTION: Hereditary spastic paraplegia is the overall term for clinically and genetically diverse disorders characterized with progressive and variable severe lower extremity spasticity. The most common causes of autosomal dominantly inherited hereditary spastic paraplegias are different mutations of the spastin gene with variable incidence in different ethnic groups, ranging between 15-40%. Mutations in the spastin gene lead to loss of spastins function, causing progressive neuronal failure, which results in axon degeneration finally. AIM: The molecular testing of spastin gene is available in the institution of the authors since January, 2014. The experience gained with the examination of the first eleven patients is described in this article. METHOD: After polymerase chain reaction, Sanger sequencing was performed to examine the 17 exons of the spastin gene. Multiplex ligation-dependent probe amplification was performed to detect greater rearrangements in the spastin gene. Eight of the patients were examined in the genetic counseling clinic of the authors and after detailed phenotype assessment spastin gene testing was obtained. The other three patients were referred to the laboratory from different outpatient clinics. RESULTS: Out of the 11 examined patients, four different pathogenic mutations were found in 5 patients. CONCLUSIONS: The first Hungarian data, gained with the examination of spastin gene are presented in this article. The five patients, in whom mutations were detected, represent 45.5% of all tested patients with hereditary spastic paraplegia, which is similar to those published in the international literature. Molecular testing and subsequent detailed genotype-phenotype correlations of the Hungarian patients may serve valuable new information about the disease, which later on may influence our therapeutic possibilities and decisions.

Minor physical anomalies are more common in schizophrenia patients with the history of homicide.

Minor physical anomalies may be external markers of abnormal brain development, so the more common appearance of these signs in homicidal schizophrenia might suggest the possibility of a more seriously aberrant neurodevelopment in this subgroup. The aim of the present study was to investigate the rate and topological profile of minor physical anomalies in patients with schizophrenia with the history of committed or attempted homicide comparing them to patients with schizophrenia without homicide in their history and to normal control subjects. Using a list of 57 minor physical anomalies, 44 patients with the diagnosis of schizophrenia were examined with the history of committed or attempted homicide, as a comparison 22 patients with the diagnosis of schizophrenia without the history of any kind of homicide and violence and 21 normal control subjects were examined. Minor physical anomalies are more common in homicidal schizophrenia patients compared to non-homicidal schizophrenia patients and normal controls, which could support a stronger neurodevelopmental component of etiology in this subgroup of schizophrenia. The higher rate of minor physical anomalies found predominantly in the head and mouth regions in homicidal schizophrenia patients might suggest the possibility of a more seriously aberrant brain development in the case of homicidal schizophrenia.

[Anti-N-methyl-D aspartate receptor encephalitis - guideline to the challenges of diagnosis and therapy]. / Anti-N-metil-D-aszpartát-receptor-encephalitis - útmutató a diagnosztikus és terápiás kihívásokhoz.

OBJECTIVE: Anti-N-methyl-D-Aspartate encephalitis is a recently diagnosed autoimmune disorder with increasing significance. During this disease antibodies are produced against the subunit of the NMDA receptor, which cause different symptoms, both psychiatric and neurological. The aim of this publication is to introduce this disease, to facilitate the diagnosis and to recommend therapeutical guideline. MATERIALS AND METHODS: In this review we summarized the relevant literature published between 2007 and 2015 giving emphasis on etiopathogenesis, diagnosis, differential diagnosis, treatment and prognosis. RESULTS: In the etiology an underlying tumor or a viral agent should be considered. During the disease we can discern 3 periods: first prodromal viral infections-like symptoms can be seen, 1-2 weeks later psychiatric symptoms, such as aggression, sleep and behavior disturbances appear. After that neurological symptoms (tonic-clonic convulsions, aphasia, catatonia, orofacial dyskinesia, autonom lability, altered mental state) are typical, and the patient's condition deteriorates. For the correct diagnosis it is necessary to detect antibodies against the NMDA receptor from the serum and the liquor. Steroids, immunoglobulins and plasmaheresis are the first-line therapies. If the disease is unresponsive, then as a second-line therapy anti-CD 20 (Rituximab) and cyclophosphamid can be useful. Most of the patients are improving without any neurological sequale with prompt detection and appropriate therapy. CONCLUSION: It is important to be familiar with the symptoms, diagnosis and therapy of this disease as a practicing clinician, especially as a psychiatrist or neurologist. 75 percentage of the patients are admitted to psychiatric departments first because of the leading symptoms. Autoimmune NMDA encephalitis is a reversible disease after early diagnosis and treatment.