Association of GABRG3, GABRB3, HTR2A gene variants with autism spectrum disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental and neurobehavioral disorder characterized by impaired social communication, repetitive and restricted patterns of behavior, activity, or interest, and altered emotional processing. Reported prevalence is 4 times higher in men and it has increased in recent years. Immunological, environmental, epigenetic, and genetic factors play a role in the pathophysiology of autism. Many neurochemical pathways and neuroanatomical events are effective in determining the disease. It is still unclear how the main symptoms of autism occur because of this complex and heterogeneous situation. In this study, we focused on gamma amino butyric acid (GABA) and serotonin, which are thought to contribute to the etiology of autism; it is aimed to elucidate the mechanism of the disease by investigating variant changes in the GABA receptor subunit genes GABRB3, GABRG3 and the HTR2A gene, which encodes one of the serotonin receptors. 200 patients with ASD between the ages of 3-9 and 100 healthy volunteers were included in the study. Genomic DNA isolation was performed from peripheral blood samples taken from volunteers. Genotyping was performed using the RFLP method with PCR specific for specific variants. Data were analyzed with SPSS v25.0 program. According to the data obtained in our study; In terms of HTR2A (rs6313 T102C) genotypes, the homozygous C genotype carrying frequency in the patient group and the homozygous T genotype carrying frequency in the GABRG3 (rs140679 C/T) genotypes were found to be significantly higher in the patient group compared to the control group (*p: 0.0001, p: 0.0001). It was determined that the frequency of individuals with homozygous genotype was significantly higher in the patient group compared to the control group and having homozygous genotypes increased the disease risk approximately 1.8 times. In terms of GABRB3 (rs2081648 T/C) genotypes, it was determined that there was no statistically significant difference in the frequency of carrying homozygous C genotype in the patient group compared to the control group (p: 0.36). According to the results of our study, we think that the HTR2A (rs6313 T102C) polymorphism is effective in modulating the empathic and autistic characteristics of individuals, and that the HTR2A (rs6313 T102C) polymorphism is more distributed in the post-synaptic membranes in individuals with a higher number of C alleles. We believe that this situation can be attributed to the spontaneous stimulatory distribution of the HTR2A gene in the postsynaptic membranes because of T102C transformation. In genetically based autism cases, carrying the point mutation in the rs6313 variant of the HTR2A gene and the C allele and the point mutation in the rs140679 variant of the GABRG3 gene and accordingly carrying the T allele provide a predisposition to the disease.

Prevalence and clinical/molecular characteristics of PTEN mutations in Turkish children with autism spectrum disorders and macrocephaly.

BACKGROUND: Phosphatase and tensin homolog (PTEN) germline mutations are associated with cancer syndromes (PTEN hamartoma tumor syndrome; PHTS) and in pediatric patients with autism spectrum disorder (ASD) and macrocephaly. The exact prevalence of PTEN mutations in patients with ASD and macrocephaly is uncertain; with prevalence rates ranging from 1% to 17%. Most studies are retrospective and contain more adult than pediatric patients, there is a need for more prospective pediatric studies. METHODS: We recruited 131 patients (108 males, 23 females) with ASD and macrocephaly between the ages of 3 and 18 from five child and adolescent psychiatry clinics in Turkey from July 2018 to December 2019. We defined macrocephaly as occipito-frontal HC size at or greater than 2 standard deviations (SD) above the mean for age and sex on standard growth charts. PTEN gene sequence analysis was performed using a MiSeq next generation sequencing (NGS) platform, (Illumina). CONCLUSION: PTEN gene sequence analyses identified three pathogenic/likely pathogenic mutations [NM_000314.6; p.(Pro204Leu), (p.Arg233*) and novel (p.Tyr176Cys*8)] and two variants of uncertain significance (VUS) [NM_000314.6; p.(Ala79Thr) and c.*10del]. We also report that patient with (p.Tyr176Cys*8) mutation has Grade 1 hepatosteatosis, a phenotype not previously described. This is the first PTEN prevalence study of patients with ASD and macrocephaly in Turkey and South Eastern Europe region with a largest homogenous cohort. The prevalence of PTEN mutations was found 3.8% (VUS included) or 2.29% (VUS omitted). We recommend testing for PTEN mutations in all patients with ASD and macrocephaly.

Neutrophil-lymphocyte and platelet-lymphocyte ratios among adolescents with bipolar disorder: A preliminary study.

We aimed to evaluate the neutrophil lymphocyte and platelet lymphocyte ratios among euthymic adolescents with bipolar disorder (BD) type I. Thirty-six adolescents with BD and 30 healthy controls were included in the study. The diagnosis was made by experienced physicians using the Kiddie and Young Adult Schedule for Affective Disorders and Schizophrenia Present and Lifetime Version and the affective module of Washington University in St. Louis Kiddie and Young Adult Schedule for Affective Disorders and Schizophrenia-Present State and Lifetime. Blood samples were taken during euthymia, which was defined as Young Mania Rating Scale and Hamilton Depression Rating Scale scores below 7. There was no significant difference in neutrophil lymphocyte ratio and platelet lymphocyte ratio between the patient and control group. Considering the literature, we may speculate that in the early stages, euthymia is associated with a lower inflammatory response, and prolongation of BD causes increased inflammatory processes predominant even in euthymia. In pediatric BD, further studies that assess neutrophil lymphocyte ratio and platelet lymphocyte ratio during different mood episodes and that identify neutrophil lymphocyte ratio and platelet lymphocyte ratio changes during the course of the disease will clarify the role of inflammation in the etiology of pediatric BD.

An Overview of a Hospital-Based Child Advocacy Center's Experience from Turkey.

The purpose of the present study was to investigate sociodemographic variables, features of sexual abuse (SA), and first psychiatric evaluation results of abused children, and to analyze the relation of the psychiatric evaluation results to the children's age and gender, type and duration of abuse, abuser-child relationship, and marital status of the children's parents, at one of the most experienced Child Advocacy Centers (CACs) in Turkey. All data were obtained from reports prepared by child and adolescent psychiatrists. The sample of this study consists of 436 child sexual abuse (CSA) cases who admitted Izmir CAC between April 2014 and November 2015. The statistical analyses yielded significant relations between psychiatric symptoms and chronic abuse, the gender of the children, and type of abuse. Suicidal ideation and behaviors due to sexual abuse (SA) were also examined. According to our results, it is fair to say that children exposed to SA benefit from immediate psychiatric help because of their vulnerability for psychiatric disorders due to abuse. In this context, CACs are very important multidisciplinary establishments to determine children's multiple needs to ease their trauma with collaborative teamwork. Psychiatric evaluation should be part of this multidisciplinary context.

Infant colic or early symptom of autism spectrum disorder?

BACKGROUND: Gastrointestinal (GI) disorders are common in autism spectrum disorder (ASD). Infant colic (IC), the functional GI disorder of infancy, has not been evaluated in this patient group. The aim of this study was therefore to determine the rate of IC in ASD and investigate a possible association between ASD and IC. METHODS: The subjects consisted of 100 ASD patients (mean age, 6.6 ± 3.5 years) and 100 healthy controls (mean age, 5.3 ± 2.8 years). The parents were questioned using the diagnostic criteria for infant colic for clinical research purposes defined in Rome IV to diagnose IC, retrospectively. The sample size was estimated using a maximum type I error probability of 5% (alpha) and a type II error of 20%. RESULTS: The rate of IC was 16% and 17% in the ASD group and control group, respectively (P ˃ 0.05). Excessive crying with late onset and long duration in infants was defined as persistent crying. The rate of persistent crying was significantly higher in the ASD group than in the control group (32% vs 9%, P < 0.001). The relative risk of persistent crying was 4.40 in ASD. The likelihood of being misdiagnosed with IC in this group was 78%. CONCLUSION: The rate of IC is not increased in patients with ASD, but infants with excessive crying should be very thoroughly evaluated before being diagnosed with IC. In particular, persistent crying in infants (i.e. excessive crying with late onset and long duration) may be an early symptom of ASD.

[Executive Functions in Frontal Lob Syndrome: A Case Report]. / Frontal Lob Sendromunda Yönetici Islevler: Bir Olgu Sunumu.

Prefrontal cortex in frontal lobe (FL) is the center of executive functions (EF). FL damage can lead to executive dysfunction by influencing frontal-subcortical circuits (dorsolateral, orbitofrontal, ventromedial). Damage to the dorsolateral prefrontal cortex (DLPFC) can lead to deterioration in EF, whereas damage to the orbitofrontal cortex (OFC) can lead to personality changes with the characteristic of disinhibition and irritability. In addition, damage to the anterior cingulate cortex/medial prefrontal cortex (ACC/MPFC) can result in decreased spontaneity. Neuropsychological tests are important components in the assessment of EF including goal-directed behavior, decision-making, risk assessment, making plans for the future, setting of priorities and order of our actions. Clinical conditions affecting frontal-subcortical connections outside of the FL can also lead to executive dysfunctions and frontal lobe syndrome (FLS). This case report is about an adolescent patient diagnosed as FLS. The clinical symptoms, assessment and treatment processes of this case are discussed in this report. The case is a 15-year-old boy that was admitted to our clinic with behavioral problems, which began after a car accident three years ago. Magnetic resonance imaging (MRI) of the brain indicated hyperintense signal increase in periventricular deep white matter that is associated with traumatic brain damage. Neuropsychological tests results (Stroop, Wisconsin Card Sorting Test, Serial Digit Learning Test, Line Orientation Test, Verbal Memory Processes Scale) have demonstrated impairment in cognitive flexibility, verbal fluency, setting priority, inappropriate response inhibition, sustained attention, planning, problem solving, organization skills and subcortical memory functions. We thought that cognitive and behavioral symptoms of this case were associated with the dysfunctions of frontal-subcortical circuits, independent of an obvious frontal lesion. FLS for the patients with sudden-onset behavioral and cognitive problems after head traumas should be kept in mind in differential diagnosis, even in the absence of an obvious frontal lesion.

Serum Brain-derived Neurotrophic Factor Levels among Euthymic Adolescents with Bipolar Disorder Type I.

INTRODUCTION: Bipolar disorder (BD) has been increasingly associated with abnormalities in neuroplasticity and cellular resilience in brain regions that are involved in mood and that affect regulation. Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family that regulates neuroplasticity. The aims of the current study were to compare serum BDNF levels in euthymic adolescents with BD type I with those in controls and to investigate the relationship between clinical variables and serum BDNF levels in adolescents with BD type I. METHODS: Twenty-five adolescents diagnosed with BD type I and 17 healthy control subjects within the age range of 15-19 years were recruited. Diagnoses were made by two experienced research clinicians using the Kiddie and Young Adult Schedule for Affective Disorders and Schizophrenia Present and Lifetime Version and the affective module of Washington University in St. Louis Kiddie and Young Adult Schedule for Affective Disorders and Schizophrenia-Present State and Lifetime. Blood samples were taken during euthymia, which was defined as Young Mania Rating Scale and Hamilton Depression Rating Scale scores below 7. RESULTS: The comparison of BDNF serum levels between the case and healthy control groups revealed no significant differences. In the case group, BDNF levels were significantly lower in patients being currently treated with lithium. CONCLUSION: Similar to normal BDNF levels in adult patients with BD, the normal BDNF serum levels that we found in the euthymic state in adolescents and early adulthood may be related to the developmental brain stage in our study group. It may also show a common neurobiological basis of pediatric and adult BD. Further investigations evaluating BDNF levels in different mood states could help identify the role of BDNF in the underlying pathophysiology of BD.