Burak Baykara

Anxiety correlates to decreased blood and prefrontal cortex IGF-1 levels in streptozotocin induced diabetes

It is well known that diabetes mellitus may cause neuropsychiatric disorders such as anxiety disorders. Diabetes may also cause reduced IGF-1 (insulin like growth factor-1) levels in brain and blood. The purpose of the present study was to investigate the relationship between diabetes induced anxiety and IGF-1 levels in diabetic rats. The anxiety levels of rats were assessed 2 weeks after intraperitoneal injection of streptozotocin. Diabetic rats had higher levels of anxiety, as they spent more time in closed branches in elevated-plus-maze-test and less time in the center cells of open-field-arena. Prefrontal cortex (PFC) IGF-1 levels and neuron numbers were decreased and apoptosis was increased in diabetic rats. Blood IGF-1 levels decreased in a time dependent fashion following streptozotocin injection while blood corticosterone levels increased. They had higher malondialdehyde levels and lower superoxide dismutase enzyme activity. Oxidative stress may negatively affect blood and PFC tissue IGF-1 levels. Reduction in IGF-1 may cause PFC damage, which may eventually trigger anxiety in diabetic rats. Therapeutic strategies that increase blood and brain tissue IGF-1 levels may be promising to prevent psychiatric sequelae of diabetes mellitus.

Increased hippocampal volumes in lithium treated adolescents with bipolar disorders: A structural MRI study

BACKGROUND Structural neuroimaging studies in bipolar disorder (BD) have consistently identified several anatomical abnormalities in many brain areas related to mood regulation. Hippocampus is one of the key components of emotional regulatory networks in the brain. Evidence about hippocampal changes in BD is quite limited and inconsistent particularly for adolescent onset BD. It is aimed to compare hippocampus volumes of euthymic BD-I adolescents with healthy controls using structural MRI. METHODS Hippocampal volumes of seventeen youths between 13 and 19 age period with DSM-IV BD (seven boys) and twelve healthy comparison subjects (five boys) were compared using structural MRI. Differences in hippocampal volumes between groups were tested. RESULTS There was no significant difference between the right and left hippocampus volumes of patients with BD and the control group. However boys tended to have significantly larger right hippocampal volumes than girls both in BD and control group. Right hippocampal volumes were enlarged in lithium treated bipolar patients. This enlargement is not related to sex. LIMITATIONS Future, longitudinal follow-up studies need large enough sample sizes of both sexes and a sex-matched healthy comparison group to sort out developmental, gender and medication influences on brain structures over time in BD. CONCLUSIONS Lithium treatment in adolescent-onset BD has a significant effect on hippocampus volumes.

Decreased Right Hippocampal Volumes and Neuroprogression Markers in Adolescents with Bipolar Disorder

Objectives: The aim of the present study was to assess differences and correlations between the hippocampal volumes (HCVs), serum nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF) levels in adolescents with bipolar disorder (BP) compared to healthy controls. Methods: Using structural magnetic resonance imaging, we compared HCVs of 30 patients with euthymic BP who were already enrolled in a naturalistic clinical follow-up. For comparison, we enrolled 23 healthy controls between the ages of 13 and 19. The boundaries of the hippocampus were outlined manually. The BDNF and NGF serum levels were measured with the sandwich ELISA. Results: The groups did not differ in the right or left HCVs or in the NGF or BDNF serum levels. However, negative correlations were found between the right HCVs and the duration of the disorder and medication and positive correlations were found between the duration of the medications and the NGF and BDNF levels in the patient group. Additionally, positive correlations were found between the follow-up period and left normalized HCVs in both the BP and lithium-treated groups. Conclusions: The right HCVs may vary with illness duration and the medication used to treat BP; NGF and BDNF levels may be affected by long-term usage. Further research is needed to determine whether these variables and their structural correlates are associated with clinical or functional differences between adolescents with BP and healthy controls.

Correlations between amygdala volumes and serum levels of BDNF and NGF as a neurobiological markerin adolescents with bipolar disorder.

BACKGROUND The amygdala is repeatedly implicated as a critical component of the neurocircuitry regulating emotional valence. Studies have frequently reported reduced amygdala volumes in children and adolescents with bipolar disorder (BD). Brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF) play critical roles in growth, differentiation, maintenance, and synaptic plasticity of neuronal systems in adolescent brain development. The aim of the present study was to assess amygdala volumesand its correlation with serum levels of NGF and BDNF in euthymic adolescents with BD and healthy controls. METHODS Using structural MRI, we compared the amygdala volumes of 30 euthymic subjects with BD with 23 healthy control subjects aged between 13 and 19 years during a naturalistic clinical follow-up. The boundaries of the amygdala were outlined manually. Serum BDNF and NGF levels were measured using sandwich-ELISA and compared between the study groups. RESULTS The right or left amygdala volume did not differ between the study groups.The right and left amygdala volumes were highly correlated with levels of BDNF in the combined BD group and the valproate-treated group.Both R and L amygdala volumes were correlated with BDNF levels in healthy controls. The left amygdala volumes were correlated with BDNF levels in the lithium-treated group. LIMITATIONS This cross-sectional study cannot inform longitudinal changes in brain structure. Further studies with larger sample sizes are needed to improve reliability. CONCLUSIONS The correlations between amygdala volumes and BDNF levels might be an early neuromarker for diagnosis and/or treatment response in adolescents with BD.

Increased hexosaminidase activity in antipsychotic-induced extrapyramidal side effects: Possible association with higher occurrence in bipolar disorder patients

Dystonic movements and Parkinsonism are frequently seen in gangliosidoses and these conditions have been reported to modify dopaminergic plasticity. We investigated whether the activity of hexosaminidase, a type-two ganglioside (GM2) degrading enzyme, correlates with drug-induced extrapyramidal system (EPS) side effects in psychiatric patients. We compared hexosaminidase activity in the lymphocytes of 29 EPS-positive patients, 13 EPS-negative patients, and 30 healthy volunteers. The activities of A and B isoforms of hexosaminidase were higher in EPS-positive patients than EPS-negative patients and healthy controls. Multivariate analysis suggested an interaction with increased B isoform activity and EPS side effects in female bipolar disorder patients. Higher levels of hexosaminidase enzyme activity may explain the frequent occurrence of antipsychotic-induced extrapyramidal side effects in mood disorder patients.

The role of serotonin and serotonin 2A receptor in the anxiety due to traumatic brain injury in immature rats

Objective: The aim of this study is to investigate the relationship between anxiety due to traumatic brain injury (TBI) and prefrontal cortex serotonin (5-HT) and 5-HT2A receptor in immature rats. Methods: Seven days old rats were subjected to traumatic brain injury model. They were divided into five groups. 1-Sham; 2-TBI group; 3-TBI followed by 14 days of administration of essitalopram (selective serotonin reuptake inhibitors; SSRI) (10 mg/kg) group (TBI+SSRI); 4-TBI and cyproheptadine (nonspecific serotonin receptor antagonist; A) (5 mg/kg) given by gastric gavage one hour prior to behavioral tests (TBI+A); 5-TBI followed by 14 days of essitalopram (SSRI) and cyproheptadine (A) given 1 hour prior to behavioral tests (TBI+SSRI+A). Elevated T-maze test and open field test applied to all groups and then blood corticosterone, prefrontal cortex tissue 5-HT and 5-HT2A receptor quantities measured. Prefrontal cortex neuron density histologically evaluated. Results: In the TBI group, the time spent in the peripheral cells, the time spent in the elevated T-maze closed arms, and serum corticosterone levels found to increase as a result of anxiety. Neuronal density decreased in prefrontal cortex. SSRI treatment reduced the time spent on the closed arms in the elevated T-maze test. SSRI decreased serum corticosterone levels and increased neuronal density. Tissue serotonin levels decreased in all groups exposure to TBI compared to sham group. 5-HT2A receptor levels were higher in the TBI and A group. Conclusion: SSRIs showed anxiolytic effect for anxiety, secondary to TBI in immature rats.

Allele frequencies of dopamine D4 receptor gene (DRD4) and Catechol-O-methyltransferase (COMT) Val158Met polymorphism are associated with methylphenidate response in adolescents with attention deficit/hyperactivity disorder: a case control preliminary study

ABSTRACT OBJECTIVES: In this study, it was aimed to analyse the relationship between clinical improvement in adolescents with attention deficit/hyperactivity disorder (ADHD) and the presence of allele frequencies of dopamine D4 receptor (DRD4), and Val158Met polymorphism of catechol-O-methyltransferase (COMT) genes. METHODS: Thirty-four adolescents (age range, 13–18 years) with ADHD participated in this study. Thirty-two patients were males and two were females. Du Paul ADHD Rating Scale-Clinician version (ARS) and Clinical Global Impression-severity of impairment (CGI-S) were used for the evaluation of symptom severity. Fifty healthy age-matched adolescents were recruited as controls. RESULTS: When the groups with (n = 9) and without (n = 25) 7-repeat alleles for DRD4 were considered, there was a statistically significant decrease of DuPaul ARS total and hyperactivity scores in those treated with OROS-methylphenidate. When the Val/Met allele-positive group for COMT gene (n = 17) was compared with the Val/Val allele-positive group (n = 13) and Met/Met allele-positive group (n = 4), there was a statistically significant decrease of ARS total scores, ARS attention scores, and CGI scores in adolescents with ADHD treated with OROS-MPH. CONCLUSIONS: Specific data from further studies with a larger sample sizes would provide more insights to replicate the current findings.

Broad autism phenotype: theory of mind and empathy skills in unaffected siblings of children with autism spectrum disorder

ABSTRACT OBJECTIVE: Difficulties in social communication is core syptoms of autism spectrum disorder (ASD), and it is often present in first-degree relatives in varying degrees. However, these subclinical autistic traits, which are thought to be related to genetic susceptibility factors, may be heterogeneous in family members. This prospective, the aim of this study was to compare unaffected siblings of children with ASD in terms of theory of mind, empathy skills, and broad autism phenotype (BAP). METHODS: Fourty-one children who were diagnosed Autistic Disorder, Asperger Disorder and Pervasive Developmental Disorder-not otherwise specified according to Diagnostic and Statistical Manual of Mental Disorders, 4th Edition and their unaffected siblings and 43 controls of typically developing children were included. The Schedule for Affective Disorders and Schizophrenia for School-age Children – Present and Lifetime Version was conducted all children with the aim of excluding a psychiatric diagnosis. False-belief tasks and Emotion Recognition Scales were used to evaluate theory of mind and empathy skills. The Social Communication Questionnaire was administered by the clinician in order to evaluate subthreshold autistic symptoms. RESULTS: Unaffected siblings of ASD children exhibited worse performance in theory of mind and emotion recognition tasks. Additionally, these children had more autistic symptoms and there was a correlation with autism symptoms and social cognition tasks. DISCUSSION: In compatible with BAP, the results indicated that the siblings of children with ASD showed a neurocognitive profile associated with ASD at a slight level, and they had more subsyndromal autism symptoms compared with healthy children. The findings also indicated that there was a weakness in skills of empathy and theory of mind ability of siblings of ASD.

Genetic imaging study with [Tc-99m] TRODAT-1 SPECT in adolescents with ADHD using OROS-methylphenidate

Aim: To examine theeffects on the brain of 2‐month treatment withamethylphenidate extended‐release formulation (OROS‐MPH) using [Tc‐99m] TRODAT‐1SPECT in a sample of treatment‐naïve adolescents with Attention Deficit/Hyperactivity Disorder (ADHD). In addition, to assess whether risk alleles (homozygosity for 10‐repeat allele at the DAT1 gene were associated with alterations in striatal DAT availability. Methods: Twenty adolescents with ADHD underwent brain single‐photon emission computed tomography (SPECT) scans with [Tc‐99m] TRODAT‐1 at baseline and two months after starting OROS‐MPH treatment with dosages up to 1 mg/kg/day. Severity of illness was estimated using the Clinical Global Impression Scale (CGI‐S) and DuPaul ADHD Rating Scale‐Clinician version (ARS) before treatment,1 month and 2 months after initiating OROS‐MPH treatment. Results: Decreased DAT availability was found in both the right caudate (pretreatment DAT binding: 224.76 ± 33.77, post‐treatment DAT binding: 208.86 ± 28.75, p = 0.02) and right putamen (pre‐treatment DAT binding: 314.41 ± 55.24, post‐treatment DAT binding: 285.66 ± 39.20, p = 0.05) in adolescents with ADHD receiving OROS‐MPH treatment. Adolescents with ADHD who showed a robust response to OROS‐MPH (n = 7) had significantly greater reduction of DAT density in the right putamen than adolescents who showed less robust response to OROS‐MPH (n = 13) (p = 0.02). However, between‐group differences by treatment responses were not related with DAT density in the right caudate. Risk alleles (homozygosity for the 10‐repeat allele of DAT1 gene) in the DAT1 gene were not associated with alterations in striatal DAT availability. Conclusion: Two months of OROS‐MPH treatment decreased DAT availability in both the right caudate and putamen. Adolescents with ADHD who showed a robust response to OROS‐MPH had greater reduction of DAT density in the right putamen. However,our findings did not support an association between homozygosity for a 10‐repeat allele in the DAT1 gene and DAT density, assessedusing[Tc‐99m] TRODAT‐1SPECT. HighlightsMethylphenidate decreased DAT availability in both right caudate and putamen.Robust response to Methylphenidate greatly reduced DAT density in right putamen.No relation between homozygosity of 10‐repeat allele in DAT1 gene and DAT density was observed.

Are language features and emotion regulation related to maternal depression in autism and language delay

Language and communication are very important in child social, emotional and cognitive development. Delay in language is usually the first complaint for children diagnosed with autism spectrum disorder (ASD) or developmental language delay (DLD). This study evaluated language features and emotion regulation skills in children diagnosed with ASD and DLD and their association with maternal depression.