Elevated serum nitric oxide and superoxide dismutase in euthymic bipolar patients: impact of past episodes.

Nitric oxide (NO) has been implicated to play a role in the pathogenesis of many neuropsychiatric disorders. NO level was found high in acute manic inpatients. In this study, we aimed to assess NO level and activity of the antioxidant enzyme, superoxide dismutase (SOD), in euthymic bipolar patients. Twenty-seven patients with bipolar disorder (BD) in euthymic phase, and 20 healthy volunteers were included in this study. A semi-structured form was used to note social, demographic and clinical parameters of the patients. NO level and SOD activity were studied in the serum samples obtained from the patients and controls. The mean serum NO level in BD was significantly higher than in controls. Mean serum SOD activity was found to be elevated in patients with BD compared to controls. Total number of the manic episodes correlated with NO levels, but not with SOD activity. In conclusion, the number of manic episodes is positively associated with NO levels. NO and SOD appear to have a pathophysiological role in BD, especially in Type I euthymic phase, and may be considered an available trait marker for BD.

Long-acting Injectable Risperidone Use in an 11-Years-Old Bipolar Child.

Early-onset bipolar disorder is difficult for child psychiatrists in terms of both diagnosis and treatment. The proper diagnostic evaluation is negatively impacted by the atypical clinical manifestation and rapid cycling pattern of the disease, together with common comorbidity with attention-deficit hyperactivity disorder and anxiety disorder. In addition to poor insight, nonadherence to treatment, poor family coping skills, and insufficient child psychiatric inpatient units make clinicians unsuccessful in following up and treating such patients. Risperidone is a commonly used atypical antipsychotic it has been approved for the treatment of manic and mixed episodes of bipolar disorder even in 10-17-year-old patients, and it is commonly used. It has a long-acting injectable formulation. Studies on its long-acting form in younger children are limited. In this case presentation, the diagnostic procedure in an 11-year old child with bipolar disorder will be presented. Long-acting injectable risperidone use in the case of nonadherence to treatment and observed side effects will be discussed.

Association between Ala-9Val polymorphism of Mn-SOD gene and schizophrenia.

Reactive oxygen species (ROS) have been suggested to play an important role in physiopathology of schizophrenia. The major intracellular antioxidant enzymes, copper-zinc superoxide dismutase in the cytoplasm and manganese superoxide dismutase (Mn-SOD) in the mitochondria, rapidly and specifically reduce superoxide radicals to hydrogen peroxide. Polymorphisms in the genes encoding antioxidant enzymes should therefore result in predisposition to schizophrenia. The present study was performed to assess whether there is a genetic association between a functional polymorphism (Ala-9Val) in the human Mn-SOD gene in schizophrenic patients (n=153) and healthy controls (n=196) using a PCR/RFLP method. Significant differences in the genotypic distribution between schizophrenics and controls were observed. Genotypic distribution with 14 (9.2%) Ala/Ala, 106 (69.3%) Ala/Val and 33 (21.6%) Val/Val subjects in schizophrenia was different from those of controls with 46 (23.5%), 83 (42.3%) and 67 (34.2%), respectively (p<0.0001). When the patients with schizophrenia were divided into the subgroups as disorganized, paranoid and residual, there was a significant difference in genotypic distribution among the subgroups (chi2=11.35, df=4, p=0.023). This association between -9Ala Mn-SOD allele and schizophrenia suggests that -9Ala variant may have a contribution in the physiopathogenesis of schizophrenia. Further investigations are warranted in larger populations with other susceptible genes that might be associated with schizophrenia.

Psychiatric comorbidity distribution and diversities in children and adolescents with attention deficit/hyperactivity disorder: a study from Turkey.

OBJECTIVE: We aimed to determine distribution and diversities of psychiatric comorbidities in children and adolescents with attention deficit/hyperactivity disorder (ADHD) in terms of age groups, sex, and ADHD subtype. MATERIALS AND METHODS: The sample included 6-18 year old children and adolescents from Turkey (N=108; 83 boys, 25 girls) diagnosed with ADHD. All comorbid diagnoses were determined based on the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version assessment. RESULTS: 96.3% of the cases were found to have at least one psychiatric comorbid diagnosis. The most frequent psychiatric comorbid disorder was oppositional defiant disorder (69.4%) followed by anxiety disorders (49%) and elimination disorders (27.8%). Disruptive behavior disorders were more common in ADHD-combined type. Depression and anxiety disorders were more common in girls. Separation anxiety disorder and elimination disorder were more common in children, whereas depression, bipolar disorder, obsessive-compulsive disorder, and social phobia were more common in the adolescents. CONCLUSION: According to our results, when a diagnostic tool was used to assess the presence of comorbid psychiatric disorders in children and adolescents diagnosed with ADHD, almost all cases had at least one comorbid diagnosis. Therefore, especially in the clinical sample, ADHD cases should not be solely interpreted with ADHD symptom domains, instead they should be investigated properly in terms of accompanying psychiatric disorders.

A 5-year-old boy with recurrent mania successfully treated with carbamazepine.

In the present paper the clinical symptomatology and treatment of childhood mania that was first seen in a child at 5 years of age and which re-emerged at age 7, is reported. The patient presented at the child and adolescent psychiatric outpatient clinic of Istanbul Medical University with the typical symptoms of mania such of hyperactivity, euphoria, irritability, dangerous and risky behavior, decreased sleep, and age-inappropriate sexual behavior. He was treated with carbamazepine safely and effectively without any major side-effects. Clinical phenomenology and treatment of the condition are discussed with relevant literature.

No evidence for an association between the T102C and 1438 G/A polymorphisms of the serotonin 2A receptor gene in attention deficit/hyperactivity disorder in a Turkish population.

Disturbances in the serotonergic neurotransmission system have been implicated in the etiology of attention deficit/hyperactivity disorder (ADHD). As the importance of genetic factors is well established, genes encoding for proteins of the serotonergic pathway are important candidates to unravel the underlying genetic contribution. We previously demonstrated that the polymorphisms of the serotonin transporter gene promoter and regions of variable number of tandem repeats were involved in the pathogenesis of ADHD. The purpose of this study was to examine the relationship between ADHD and two polymorphisms (T102C and 1438 G/A) in the 5-HT2A gene in a sample of Turkish children. Using the PCR technique, these polymorphisms were assessed in 70 patients with ADHD and in 100 healthy controls. There was no significant difference between the frequencies of the T, C, G and A alleles of both groups. No association was found between the studied polymorphisms of the 5-HT2A gene and ADHD in this sample consisting of Turkish children. Overall, our results suggest that the investigated 5-HT2A polymorphisms are not major susceptibility factors in the etiology of ADHD.

Reliability and validity of the Turkish version of the adolescent dissociative experiences scale.

The Adolescent Dissociative Experiences Scale (A-DES) is designed to measure dissociation in adolescents. The present study aimed to assess the reliability, validity, and psychometric characteristics of the Turkish version of the A-DES. The Turkish version of the A-DES was administered to 20 patients with a dissociative disorder, 24 patients with post-traumatic stress disorder (PTSD), 31 patients with anxiety disorder, 31 patients with mood disorder, 24 patients with attention deficit-hyperactivity disorder (ADHD), and 201 non-clinical participants. The internal consistency and the test-retest correlation of the A-DES were excellent. The mean total score of A-DES was 6.2 in dissociative disorder, 3.9 in PTSD, 2.1 in anxiety disorder, 2.4 in mood disorder, 2.5 in ADHD groups and 2.4 in non-clinical participants. There was a statistically significant difference between dissociative patients and other diagnostic groups on the A-DES total score. The good psychometric characteristics of the A-DES among Turkish participants support its cross-cultural validity.

Pathophysiological role of nitric oxide and adrenomedullin in autism.

Several studies indicate that nitric oxide (NO) is involved in the aetiopathogenesis of many neuropsychiatric disorders such as schizophrenia, bipolar disorder, depression, Alzheimer's disease, Hungtington disease and stroke. Although it has not been investigated yet, several recent studies proposed that NO may have a pathophysiological role in autism. Adrenomedullin (AM), a recently discovered 52-amino acid peptide hormone, induces vasorelaxation by activating adenylate cyclase and also by stimulating NO release. AM immune reactivity is present in the brain consistent with a role as a neurotransmitter. It has been stated that NO and AM do function in the regulation of many neurodevelopmental processes. We hypothesized that NO and AM activities have been affected in autistic patients and aimed to examine these molecules. Twenty-six autistic patients and 22 healthy control subjects were included in this study. AM and total nitrite (a metabolite of NO) levels have been measured in plasma. The mean values of plasma total nitrite and AM levels in the autistic group were significantly higher than control values, respectively (p < 0.001, p = 0.028). There is no correlation between total nitrite and AM levels (r = 0.11, p = 0.31). Certainly, this subject needs much further research investigating autistic patients in earlier periods of life and with subtypes of the disorder.

The role of the arginine-nitric oxide pathway in the pathogenesis of bipolar affective disorder.

There is a reciprocal regulation of arginase and nitric oxide synthase (NOS) in L-arginine-metabolizing pathways. Nitric oxide (NO) may be involved in some psychiatric disorders like schizophrenia, depression and bipolar affective disorder (BPAD). To our knowledge, there is no study in the literature in which the role of arginase, an important part of the arginine regulatory system affecting NOS activity, was investigated in BPAD. This study aims to investigate arginase, manganese (Mn) and total nitrite levels (a metabolite of NO) and their relationship to the arginine-NO pathway in patients with BPAD. Arginase activities, Mn and total nitrite levels were measured in plasma from forty-three patients with BPAD (Type one) and thirty-one healthy control subjects. Plasma arginase activities and Mn were found to be significantly lower and total nitrite level higher in patients with BPAD compared with controls. Our results suggest that the arginine-NO pathway is involved in the pathogenesis of BPAD.

Is the arginine-nitric oxide pathway involved in the pathogenesis of schizophrenia?

The reciprocal regulation of arginase and nitric oxide synthase (NOS) in L-arginine-metabolizing pathways has been demonstrated. There are various evidences of the role of the nitric oxide (NO) in several neuropsychiatric disorders including schizophrenia. However, there is no study which has investigated the role of arginase as an important part of the arginine regulatory system affecting NOS activity in schizophrenia. This study aims to investigate arginase, manganese (Mn) and total nitrite levels (a metabolite of NO) and their relationship to the arginine-NO pathway in patients with schizophrenia. Arginase activities, Mn and total nitrite levels were measured in plasma from 46 patients with schizophrenia and 32 healthy control subjects. Plasma arginase activities and Mn were found to be significantly lower and total nitrite level higher in patients with schizophrenia compared with controls. Our results suggest that the arginine-NO pathway is involved in the pathogenesis of schizophrenia.

Suicide attempt and self-mutilation among Turkish high school students in relation with abuse, neglect and dissociation.

A questionnaire consisting of items about abuse, neglect, self-mutilation and suicide attempt and the Turkish Version of the Dissociative Experiences Scale were given to 862 high school students. The rates of suicide attempt and self-mutilative behaviors were 10.1% and 21.4%, respectively. Abused or neglected groups (34.3%) had 7.6-fold higher suicide attempts and 2.7-fold higher self-mutilation behaviours. The logistic regression model showed that each type of trauma and dissociation contributed to suicide attempts and self-mutilation, but dissociation was the most powerful. Suicidal and self-destructive adolescents should precisely be evaluated for abuse, neglect and dissociation in clinical practice.

Possible role of nitric oxide and adrenomedullin in bipolar affective disorder.

Nitric oxide (NO) has been implicated to play a role in the pathogenesis of depressive disorders. Adrenomedullin (AM) induces vasorelaxation by activating adenylate cyclase and also by stimulating the release of NO. AM immune reactivity is present in the brain, consistent with a role as neurotransmitter. Therefore, it is suggested that these two molecules may play a role together in the brain. We aimed to examine AM and NO in bipolar affective disorder (BPAD). Forty-four patients with BPAD and 21 healthy control subjects were included in this study. DSM-IV diagnosis of bipolar affective disorder (type I, manic episodes) was independently established by two psychiatrists and the Turkish version of the Bech-Rafaelson Mania Scale was administered. Also, a semistructured form was used to ascertain several sociodemographic and clinical variables of the patients. AM and NO were studied in plasma. The mean value of plasma NO levels in the BPAD group of 46.58 +/- 13.97 micromol/l was significantly higher than that of controls (31.81 +/- 8.14 micromol/l) (z = -4.15, p = 0.000). Mean plasma AM levels were found to be increased in patients with BPAD (35.13 +/- 5.26 pmol/l) compared to controls (16.22 +/- 3.02 pmol/l) (z = -6.16, p = 0.000). AM levels of BPAD patients were approximately 2-fold higher than controls. AM levels were positively correlated with the duration of hospitalization for the current episode and negatively correlated with the total duration of illness. Both NO and AM may have a pathophysiological role in BPAD (type I, manic episodes) and the clinical symptomatology and prognosis of BPAD.