Possible Effects of Copper and Ceruloplasmin Levels on Auditory Event Potentials in Boys with Attention Deficit Hyperactivity Disorder.

INTRODUCTION: The aims of the present study were to investigate the relationship between levels of plasma copper (Cu) and ceruloplasmin (Cp) and amplitudes and latencies of P1, N2, and P3 in the parietal and frontal areas of children with attention deficit hyperactivity disorder (ADHD) as well as to compare these Cu levels and event-related potentials (ERPs) indices in controls. METHODS: Boys (n=41) with ADHD were divided into two subgroups according to a median split of plasma Cu and Cp levels, separately. ERP indices from the parietal and frontal regions were recorded in children with ADHD and 24 normal boys (control group) using an auditory oddball paradigm. RESULTS: Parietal P3 latency was significantly longer, and parietal P3 amplitude, frontal P3 amplitude, and frontal N2 amplitudes were smaller in children with ADHD than in controls (all p values <0.017). Parietal P1 and frontal P1 latencies were significantly shorter in the higher Cu group than in the lower Cu group (both p values <0.017). Decreased latency of parietal P1 was dependent on plasma levels of Cu (p<0.05). Frontal N2 and parietal N2 amplitudes were significantly lower in the ADHD group with lower Cp levels than in the ADHD group with higher Cp levels (both p values <0.017). Decreased frontal N2 and parietal N2 amplitudes were dependent on plasma levels of Cp (both p values <0.05). CONCLUSION: Plasma Cu and Cp levels may have an effect on ERPs in ADHD, thus indicating the existence of effects on information processing. Cu levels may have a negative effect on the neuronal encoding of sound, whereas Cp levels may have a positive effect on the processes of cognitive control, conflict monitoring, and stimulus discrimination in children with ADHD.

Salivary alpha amylase levels in youths with anxiety disorders.

It is suggested that salivary alpha-amylase (sAA) may be a marker of sympathoadrenal medullary system activity. Thus, it can be a possible relationship sAA and anxiety disorders. The aim of this study is to investigate sAA in children and adolescents with anxiety disorders and healthy controls. Thirty drug-free youths, aged 8-16 years, who were diagnosed as any anxiety disorders and 36 healthy controls with similar socio-demographic characteristics were included in this study. The sAA was found to be significantly increased in anxiety group compared to control group. However, there was no correlation between sAA and any anxiety scores of the scales. Present study suggested that anxiety disorders in youths may be associated with increased autonomic activity.

Follow-up study of children whose mothers were treated with transcranial magnetic stimulation during pregnancy: preliminary results.

OBJECTIVES: The purpose of this study is to determine the impact of repetitive transcranial stimulation (rTMS) treatment during pregnancy on neurodevelopment of children. MATERIALS AND METHODS: Women who were treated with rTMS during pregnancy and delivered liveborn children between 2008 and 2013 were selected. A control group consisted of children whose mothers had a history of untreated depression during their pregnancy (N = 26). Early developmental characteristics of all the children in the study were evaluated, and their developmental levels were determined using the Ankara Developmental Screening Inventory. RESULTS: The mean age of the children in the rTMS treatment group was 32.4 months (range 16-64 months), and that of the untreated group was 29.04 (range 14-63 months). Jaundice (N = 2) and febrile convulsion (N = 1) were the reported medical conditions in the children of the rTMS-treated group; jaundice (N = 3) and low birth weight (N = 1) were reported in the untreated group. In the rTMS group, mothers' perception of delay in language development was observed, but there were not any statistically significant differences in the prevalence rate compared with the untreated group (OR = 0.38; 95% CI 0.0860-1.6580). CONCLUSIONS: Our results suggest that rTMS exposure during pregnancy is not associated with poorer cognitive or motor development outcomes in children aged 18-62 months. Although language development as reported by the mothers was found to be poorer than expected in the rTMS-treated group, the delay was found to be similar to the language delay observed in offspring of untreated mothers, as reported in previous studies of prenatal depression treated with selective serotonin reuptake inhibitors.

From Poster Presentation to Publication: National Congress of Child and Adolescent Psychiatry.

INTRODUCTION: The aims of this study were as follows: 1) to determine publication rate, time to publication, and study design of poster presentations accepted at the National Congress of Child and Adolescent Psychiatry (NCCAP) and converted to publication and the degree of first author in a published article and journal index and 2) to investigate the relationship of these data with each other. METHODS: The poster presentations of four congresses organized between 2005 and 2008 were investigated separately. The presentations were screened by taking into account the title and the first and second author in English and Turkish languages via PubMed and Google Academic databases. Published studies, time between presentation and publishing date, study design, degree of first author, and journal index of these studies were recorded. RESULTS: Fifty-four (25.2%) of 214 poster presentations were published in international and national peer-reviewed journals. Of the published articles, 74.1% (n=40) were research type and 61.1% (n=33) were found in the Science Citation Index (SCI) and Science Citation Index-Expanded (SCI-E) peer-reviewed journals. The first author in 42.6% (n=23) of published articles were assistant professors. The average time between presentation and publishing date was 30.72±18.89 months. Statistical differences were not determined between publication rate and study design; between time to publication and study type/study design, degree of first author, and journal index; and between journal index and study design and degree of first author (p>0.05). It was found that research articles were published significantly more by teaching staff than experts and other researchers (p<0.05). CONCLUSION: Compared with literature data, it was found that the time to publication was longer while the publication rate was similar for poster presentations in our congresses. Based on these results, it is important to create necessary conditions and encourage the researchers to publish the poster presentations presented in NCCAP.

Therapeutic drug monitoring: perspectives of psychiatrists in Turkey.

OBJECTIVES: Although the medical and economic implications of therapeutic drug monitoring have been intensely discussed over the past years, little is known about the experiences and attitudes of psychiatrists in their clinical practice. The aim of this study was to investigate psychiatrists' daily practice with therapeutic drug monitoring in Turkey. METHODS: A nation-wide cross-sectional survey among adult and child psychiatry specialist psychiatrists in Turkey was conducted. RESULTS: We found that 98.4% (n = 380) of the study participants used TDM in clinical practice and 1.6% (n = 6) did not. However, TDM use is limited to mood stabilizers (lithium 96.3%, valproate 97.6%) to a great extent. Only a small number of psychiatrists perform TDM for other psychotropic drugs, e.g., clozapine 2.4%, tricyclic antidepressants 1.3%, benzodiazepines 1.1%, and selective serotonin reuptake inhibitors 0,8%. CONCLUSIONS: Most of the psychiatrists in Turkey have a positive attitude toward use of therapeutic drug monitoring although there is also a considerable difficulty to reach services for the therapeutic drug monitoring of psychotropics other than mood stabilizers.

Plasma Methylphenidate Levels in Youths With Attention Deficit Hyperactivity Disorder Treated With OROS Formulation.

BACKGROUND: There are limited studies investigating the relationship between oral release osmotic system-methylphenidate (OROS-MPH) doses and plasma methylphenidate (MPH) concentrations in children and adolescents. The aim of this study was to investigate the relationship between the doses of OROS-MPH and the plasma levels of the drug. We also examined the effects of the other drugs including aripiprazole, risperidone, fluoxetine, and sertraline on the levels of the MPH in the plasma. METHODS: The files of 100 attention deficit hyperactivity disorder (ADHD) subjects (76 male, 24 female) who were diagnosed as ADHD according to the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition criteria, were screened. The ages of subjects were between 6 and 18 years (mean = 11.5 ± 3.8 years). Plasma MPH levels were determined by high-performance liquid chromatography-tandem mass spectrometry assay. RESULTS: Daily mean OROS-MPH dose used in ADHD children was 0.7 ± 0.2 mg/kg (range: 0.3-1.3 mg/kg). The mean plasma OROS-MPH was 11.6 ± 7.3 ng/mL (range: 0.5-43.4 ng/mL). There was no group difference in the mean plasma MPH and dose-related MPH levels between the groups that used any additional drug including aripiprazole (n = 25), risperidone (n = 10), fluoxetine (n = 16), sertraline (n = 10), and did not use these drugs (P > 0.05). There was a positive correlation between the OROS-MPH doses (mg/kg) and the blood MPH levels (Pearson correlation = 0.40; P < 0.001). The plasma levels of MPH were found to be less than 13 ng/mL in 65% of the subjects. CONCLUSIONS: Our findings point to the fact that plasma levels of MPH show a wide range of changes at similar doses, correlate positively with the doses and, as expected, are not affected by using risperidone, sertraline, fluoxetine, and aripiprazole. Therapeutic drug monitoring may help to optimize MPH dose in patients not responding to treatment or in those experiencing serious side effects, but not in routine clinical practice. The presence of intermediate dose formulations such as 45-mg tablets for OROS-MPH may contribute to the optimization.

Effect of valproate on the plasma concentrations of aripiprazole in bipolar patients.

OBJECTIVE: There is very limited documentation available on the effects of valproate co-medication on the pharmacokinetics of aripiprazole in a naturalistic setting. The aim of the present study was to investigate the effect of co-medication with valproate on serum concentrations of aripiprazole in bipolar disorder patients in a clinical setting. METHOD: Plasma samples of bipolar disorder patients (n = 69) on a stable dose of aripiprazole 20 mg/day were analyzed by a liquid chromatography-mass spectrometry method in a routine therapeutic drug monitoring setting. Therapeutic drug monitoring was done for the entire study group before and after valproate co-administration. RESULTS: We observed a statistically significant difference between the aripiprazole monotherapy and aripiprazole-valproate combination with respect to total aripiprazole plasma levels (p < 0.01). However, no statistically significant differences were noted in aripiprazole levels between the first week and the second week of valproate co-administration. CONCLUSION: In conclusion, concurrent treatment with valproate resulted in changes in the total aripiprazole plasma levels by 23%. But a lower total aripiprazole concentration during co-medication with valproate, caused by protein binding displacement, is reported being clinically insignificant in previous studies. The results from these studies are important in order to clarify clinical safety and efficacy.

Mean platelet volume in children with attention deficit hyperactivity disorder.

The mean platelet volume (MPV), the accurate measure of platelet size, is considered a marker and determinant of platelet function. MPV can be a potentially useful prognostic biomarker in patients with cardiovascular disease. After reviewing literature, we hypothesized that attention deficit hyperactivity disorder (ADHD) in childhood may be a risk factor for coronary heart disease (CHD) in adulthood. The aim of this study was investigation of MPV and platelet count (PLT) in children with ADHD and healthy subjects. The MPV and the PLT were measured in 70 children with ADHD (aged 6-16 years), and compared with 41 healthy controls. The MPV was found to be significantly increased in ADHD group compared to control group (p=.006). There was no significant difference in the PLT between groups (p>.05). To our knowledge, this was the first study of investigating the levels of MPV and PLT in children with ADHD. Although significance and cause of increased MPV level in ADHD remain unclear in present study, further studies are warranted to investigate relationships among MPV, ADHD in childhood and CHD in adulthood.

Dental injuries in autistic patients.

PURPOSE: The purpose of this study was to assess the incidence of traumatic dental injury among Turkish children and young adults with autism and compare this to the general population of Turkish children and young adults without autism. METHODS: This study was comprised of 186 children and young adults (138 males and 48 females), 93 with autism (autistic group, or AG) and 93 without autism (control group, or CG). Dental injuries were classified according to drawings and texts based on the WHO classification system, as modified by Andreasen and Andreasen. RESULTS: The rate of injury was higher among the AG (23%) than the CG (15%). The difference between the 2 groups, however, was not statistically significant (P<.19). The most common type of dental injury was enamel fracture. The rate of enamel fracture was higher in the CG (59%) than in the AG (33%), and the distribution of types of traumatic injury differed significantly between the AG and CG (P>.01). CONCLUSIONS: There were no significant differences in the rates of traumatic dental injuries among children and young adults with and without autistic disorder. The most frequently injured teeth were the permanent maxillary central incisors, and the frequency of injury to these teeth differed significantly (P>.01) between AG (56%) and CG (91%). The most common type of dental injury, enamel fracture, was more common in CG (59%) than AG (33%). The distribution of types of traumatic dental injuries differed significantly between the 2 groups (P>.01).

Chromium, cadmium, and lead levels in urine of children with autism and typically developing controls.

Although potentially harmful effects of heavy metals are well known, limited numbers of studies exist regarding their relationship with autism. The aim of this study was to investigate urine levels of some heavy metals such as of chromium (Cr), cadmium (Cd), and lead (Pb) in children with autism and healthy subjects. Urine levels of Cr, Cd, and Pb were measured by atomic absorption spectrometry in 30 children with autism and compared with 20 healthy controls. Urine Cd and Pb levels were found as significantly decreased in children with autism compared to healthy subjects (p < 0.05). On the other hand, urine Cr levels were significantly higher in children with autism than healthy subjects (p < 0.05). This study suggested that autism may be associated with significant decrease in excretion rate of Cd and Pb and a significant increase excretion rate in the levels of Cr in the urine. These results have indicated that further studies are warranted for investigation of possible roles of heavy metals in autism.

Potential effects of zinc on information processing in boys with attention deficit hyperactivity disorder.

PURPOSE: The aims of the present study were to investigate the relationship between plasma zinc levels and amplitudes and latencies of P1, N2, and P3 in parietal and frontal areas in children with ADHD, and to compare these zinc levels and event-related potentials (ERPs) indices with controls. METHODS: 28 boys with ADHD were divided into two groups according to plasma zinc levels: low zinc group (N=13, zinc level <80 microg/dL) and zinc non-deficient group (N=15, zinc level >or=80 microg/dL). ERP indices from parietal and frontal brain regions were recorded in children with ADHD and in 24 normal boys by using an auditory oddball paradigm. Plasma zinc levels were measured by an atomic absorption spectrophotometer. RESULTS: The plasma zinc levels were significantly lower in both ADHD groups (means are 65.8 microg/dL in low zinc group and 89.5 microg/dL in zinc non-deficient group) than controls (mean: 107.8 microg/dL; both p values <0.017). In ADHD compared to controls, the amplitudes of P3 in frontal and parietal regions were significantly lower, and the latency of P3 in parietal region was significantly longer (all p values <0.017). In low zinc ADHD group compared to zinc non-deficient ADHD group, the latencies of N2 in frontal and parietal region were significantly shorter (all p values <0.017). In addition, there was a medium but significant positive correlation between plasma zinc levels and amplitude and latency of frontal N2 wave in ADHD. CONCLUSIONS: These results can suggest that plasma zinc levels might have an effect on information processing in ADHD children, and lower zinc levels seem to affect N2 wave. Since N2 wave changes may reflect a different inhibition process, further studies are warranted to investigate the effect of zinc on inhibitory process in children with ADHD, and in low zinc and non-deficient ADHD groups.

Morphology of the orbitofrontal cortex in first-episode schizophrenia: relationship with negative symptomatology.

Different studies have documented OFC abnormalities in schizophrenia, but it is unclear if they are present at disease onset or are a consequence of disease process and/or drug exposure. The evaluation of first-episode, drug-naïve subjects allows us to clarify this issue. Magnetic resonance imaging was performed on 43 first-episode, antipsychotic-naïve schizophrenia patients and 53 healthy comparison subjects matched for age, gender, race, and handedness. Gray matter OFC volumes were measured blind to the diagnoses. As compared to controls, patients had greater volumes in left total OFC (p=0.048) and left lateral OFC (p=0.037). Severity of negative symptoms (anhedonia, flattened affect, and alogia) positively correlated with both the left lateral (Spearman's, rho=0.37, p=0.019; rho=0.317, p=0.041; r=0.307, p=0.048, respectively) and the left total OFC (Spearman's, rho=0.384, p=0.014; rho=0.349, p=0.023; rho=0.309, p=0.047, respectively). The present results suggest that first-episode, antipsychotic-naïve schizophrenia subjects exhibit increased OFC volumes that correlate with negative symptoms severity. The OFC, through extensive and complex interconnections with several brain structures with putative role in pathophysiology of schizophrenia including amygdala, hippocampus, thalamus, DLPFC, and superior temporal lobe, may mediate schizophrenia symptoms such as blunting of emotional affect and impaired social functioning. Although the specific neuropathological mechanisms underlying structural abnormalities of the OFC remain unclear, increased OFC volumes might be related to deviations in neuronal migration and/or pruning. Future follow-up studies examining high-risk individuals who subsequently develop schizophrenia at different stages of disease could be especially instructive.

Magnetic resonance imaging study of the orbitofrontal cortex in autism.

The orbitofrontal cortex is involved in multiple psychologic functions, such as emotional and cognitive processing, learning, and social behavior. These functions are variably impaired in individuals with autism. The present study examined the size of the orbitofrontal cortex, and its medial and lateral subdivisions, using magnetic resonance imaging (MRI) scans obtained from 40 non-mentally retarded individuals with autism and 41 healthy controls. No differences were observed between the two groups on any of the orbitofrontal cortex measurements. However, when compared with controls, a smaller right lateral orbitofrontal cortex was observed in children and adolescents with autism, whereas a larger right lateral orbitofrontal cortex was found in adult patients. Interestingly, a positive relationship was found in the patient group between circumscribed interests and all orbitofrontal cortex structures. The present study suggests the absence of global volumetric abnormalities in the orbitofrontal cortex in autism and indicates that the functional disturbances in this structure might not be related to anatomic alterations.

[Plasma zinc and copper levels in boys with oppositional defiant disorder]. / Karsi Olma Karsi Gelme Bozuklugunda Plazma Cinko ve Bakir Düzeyleri.

OBJECTIVE: Oppositional defiant disorder consists of negativistic, hostile, or defiant behavior, created in one of three domains of functioning (academic, occupational, or social), and lasting at least six months. Alterations in zinc and copper levels of plasma in animals and humans are associated with behavioral and cognitive abnormalities. The aim of this study is to compare plasma zinc and copper levels between children with oppositional defiant disorder (ODD) and controls. METHOD: Plasma zinc and copper levels were measured in 21 boys with ODD having a mean age of 8.6 +/- 2.0 years and in 24 healthy boys having a mean age of 8.3 +/- 2.1 years by atomic absorption spectrophotometry. An ODD diagnosis was made according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). About 61% of the children with ODD had comorbid attention deficit hyperactivity disorder. RESULTS: Plasma zinc was significantly lower in ODD children compared to the controls (p < .05). No significant difference in plasma copper measurements was found between the two groups (p >.05). CONCLUSION: The results of the present study suggested that the plasma copper level in boys with ODD did not differ from that in normal subjects. Although ODD children had a lower plasma zinc level than normal subjects, the mean plasma zinc level was within the normal range for the population. Further studies investigating the Zn and Cu metabolism in ODD are needed.

Anatomic evaluation of the orbitofrontal cortex in major depressive disorder.

BACKGROUND: The orbitofrontal cortex (OFC) plays a major role in neuropsychologic functioning including exteroceptive and interoceptive information coding, reward-guided behavior, impulse control, and mood regulation. This study examined the OFC and its subdivisions in patients with MDD and matched healthy control subjects. METHODS: Magnetic resonance imaging (MRI) was performed on 31 unmedicated MDD and 34 control subjects matched for age, gender, and race. Gray matter volumes of the OFC and its lateral and medial subdivisions were measured blindly. RESULTS: The MDD patients had smaller gray matter volumes in right medial [two-way analysis of covariance F(1,60) = 4.285; p =.043] and left lateral OFC [F(1,60) = 4.252; p =.044]. Left lateral OFC volume correlated negatively with age in patients but not in control subjects. Male, but not female patients exhibited smaller left and right medial OFC volumes compared with healthy control subjects of the same gender. CONCLUSIONS: These findings suggest that patients with MDD have reduced OFC gray matter volumes. Although this reduction might be important in understanding the pathophysiology of MDD, its functional and psychopathologic consequences are as yet unclear. Future studies examining the relationship between specific symptomatic dimensions of MDD and OFC volumes could be especially informative.

Clinical characteristics of depressive symptoms in children and adolescents with major depressive disorder.

OBJECTIVE: Very few studies have compared the symptoms of major depressive disorder (MDD) and rates of comorbid psychiatric disorders between depressed children and adolescents. The aim of this study was to reproduce and extend these findings. METHOD: The Kiddie Schedule for Affective Disorders and Schizophrenia, present version (KSADS-P) was administered to parents (about their children) and in face-to-face interviews with 916 subjects aged 5.6 to 17.9 years with MDD (DSM criteria) (715 adolescents and 201 children; 348 male and 568 female). The subjects were consecutive referrals to an outpatient mood and anxiety disorders clinic. RESULTS: Depressed adolescents had significantly more hopelessness/helplessness, lack of energy/tiredness, hypersomnia, weight loss, and suicidality compared with children (p values < or = .001). In comparison with children, adolescents had significantly more substance abuse and less comorbid separation anxiety disorder and attention-deficit/hyperactivity disorder (p values < or = .001). Depressed female adolescents had significantly more suicidality than depressed male adolescents (p < or = .001). There were no other sex differences between males and females. The symptoms of depressed adolescents grouped into 3 factors (endogenous, negative cognitions/suicidality, and appetite/weight), whereas the symptoms in children grouped into 2 factors (endogenous/negative cognitions/suicidality and appetite/weight). CONCLUSIONS: These results provide further evidence for the continuity of MDD from childhood to adolescence.

Measurement of the orbitofrontal cortex: a validation study of a new method.

The orbital frontal cortex (OFC) plays a critical role in the pathophysiology of several neuropsychiatric disorders. Few morphometric neuroimaging studies have examined the OFC using different methodologies and have reported discrepant values. Substantial variability in gyri and sulci across individuals as well as unclear landmarks underline the difficulties in obtaining accurate and reliable measurements. We propose a new geometrical method for measuring the OFC taking into account individual brain variability. The OFC was defined by using the intercommissural line and the inferior edge of the frontal lobe as the main landmarks. The medial and lateral subdivisions of OFC were also separately measured using the olfactory sulcus as the boundary to distinguish between them. After resampling and refitting, 10 scans were independently traced by two trained researchers using BRAINS software. Talairach coordinates were identified on each scan from the OFC and surrounding adjacent brain regions to assess the validity of this method. Brain regions were assigned using Talairach Daemon system. OFC volumes were comparable with those previously reported. Sensitivity and specificity for OFC gray matter were 87.6 and 84.8%, respectively. Intraclass coefficients (ICCs) for gray, white, and total OFC were 0.995, 0.994, and 0.997, respectively. ICCs for OFC medial and lateral subdivisions ranged between 0.996 and 0.998. This method appears to be a valid method for measuring the OFC with excellent reliability. This uncomplicated approach is easy to apply and has the potential to be a valuable alternative to the previously published methods.