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Objective: Alcoholism is associated with genetic variants of genes related to alcohol metabolizing enzymes, dopaminergic, gamma-aminobutyric acidergic, glutamatergic, opioid, cholinergic, and serotonergic systems. Neurpeptide Y system and Neurexins were shown to be associated with alcohol dependence. Recent studies identified new genetic polymorphisms related to endogenous cannabinoid system, neuropetide Y and neurexin. In the present study, we aimed to investigate the association of Neurpeptide Y LEU7PRO rs16139 and neurexin 3 gene rs760288 polymorphisms with alcohol dependence in patients with alcohol dependence and healthy control subjects. Methods: 123 patients who were diagnosed with alcohol dependence according to the DSM-IV criteria and 159 healthy volunteers were included in the study. Blood samples were used to investigate polymorphisms. The genotyping of the neurexin 3 gene rs760288 and the neuropetide Y gene Leu7Pro rs16139 polymorphisms was performed using TaqMan SNP Genotyping Assays Real-Time PCR System. Results: Of the 2 genetic polymorphisms investigated in the present study, we detected association between and neurexin 3 gene rs760288 polymorphisms with alcohol dependence. Conclusions: Neurexin gene polymorphisms might be an important factor in development of alcohol addiction. © 2016, Cukurova Univ Tip Fakultesi Psikiyatri Anabilim Dali. All rights reserved.

Objective: The effects of certain genetic alterations in the brain function of patients with attention deficit hyperactivity disorder (ADHD) remain unclear and, in fact, there is a limited amount of data in this field. For example, the relationship between the SNAP-25 polymorphism and brain metabolites in response to methylphenidate (MPH) has yet to be investigated. Thus, the present study aimed to determine the relationship between changes in creatine (Cr), choline (Cho), and N-acetyl aspartate (NAA) levels in the prefrontal cortex (PFC) and anterior cingulate cortex (ACC) of adults with ADHD and the SNAP-25 gene polymorphism following the use of MPH. Patients and Methods: The present study assessed 60 patients between 18 and 60 years of age who were diagnosed with ADHD according to criteria from the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV). Genetic analyses were carried out using blood samples obtained from the ADHD patients and included a detailed clinical evaluation for the SNAP-25 gene polymorphism. The NAA, Cr, and Cho levels in the ACC and PFC were measured using magnetic resonance spectroscopy (MRS). Following the evaluation, 10 mg of oral MPH was given to the patients, and the same metabolite levels were measured after 30 minutes. Results: The levels of NAA, Cr, and Cho in the PFC and ACC of patients with the SNAP-25 Ddel and Mnll polymorphism genotypes did not significantly differ before and after the administration of MPH. However, in patients with the SNAP-25 Ddel polymorphism T/T genotype and the Mnll polymorphism G/G genotype, there was a significant increase in NAA levels in the ACC after MPH treatment compared with before MPH treatment. Conclusion: The present results suggest that the SNAP-25 Ddel and Mnll polymorphisms might be associated with MPH-related changes in NAA levels in the ACC.

Barlas IO, Semiz U, Erdal ME, Algül A, Ay OI, Ateş MA, Camdeviren H, Basoglu C, Herken H. Association between dopamine beta hydroxylase gene polymorphism and age at onset in male schizophrenia. Objectives: The heterogeneity of schizophrenia mainly results from variations in clinical expressions of the disease, such as age at onset, gender differences in onset of illness, symptoms and response to antipsychotic treatment. Enhanced sensitisation of dopamine pathways in males, having consistently an earlier onset, might be implicated as disease modifiers for schizophrenia in males. Methods: In this study, we performed a case (n = 87)-control (n = 100) association study between the DBH5'-ins/del and DBH-444g/a polymorphisms of the DBH gene and also compared the level of psychotic symptoms between patients with different DBH genotypes/haplotypes with respect to antipsychotic therapeutic response and gender difference. Results: No significant differences between allele and genotype and haplotype frequencies at either groups (p < 0.05). When the age is considered in patient group, a significant difference was observed between patients with ID genotype and with II genotype (p = 0.018). Patients with ID genotype have been diagnosed as schizophrenics in early ages when compared to II genotype carriers. We also found a significant difference between II and ID genotype (p = 0.007) when the gender had taken into account, showing that the ID genotype carriers had an early onset to schizophrenia. Conclusions: This association was more significant in male schizophrenia patients than females. Thus, this finding may constitute a novel biological support for the prior finding that onset of schizophrenia varies with gender. The results also showed that critical genetic vulnerability may be associated with the presence or absence of the ID genotype of DBH5'-ins/del. © 2011 John Wiley & Sons A/S.

Objective: Catechol-O-Methyltransferase (COMT) enzyme plays an important role in dopamine metabolism. Three different genotypes have been defined, one resulting from a valine (val)→methionine (met) amino acid change due to a guanine→adenine nucleotide change at codon 108/158 of the COMT gene, while the other two genotypes are formed by alleles containing val (heat-resistant, high activity) and met (heat-sensitive, low activity). This functional polymorphism in the COMT gene causes an alteration in the enzyme activity, where the enzyme activity is reduced 4 times in genotypes related to low enzyme activity. In schizophrenic patients, alterations in the amounts and efficiency of dopamine are known to be related to the clinical symptoms and cognitive functions. This study aimed to investigate the effects of COMT Val158Met functional polymorphisms on clinical symptoms, executive functions related to prefrontal functions, and attention and verbal memory in schizophrenic patients. Method: Schizophrenic patients in remission, who were followed up at the Psychosis Clinics of Pamukkale University Faculty of Medicine, Department of Psychiatry between the years of 2007- 2009, were included in the study. The Brief Psychiatric Rating Scale (BPRS), the Scale for Assessment of Positive Symptoms (SAPS), and theScale for Assessment of Negative Symptoms (SANS), were used to evaluate the patients. Neuropsychological evaluation included the Wisconsin Card Sorting Test (WCST) for executive functions, the Verbal Memory Processes Test (VMPT) for verbal memory and the Stroop Test (ST) for attention tasks. COMT enzyme Val158Met polymorphisms were defined from the isolated DNA of the patients by Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) analysis, as defined in literature. Results: A total of 42 patients (16 female, 26 male) were included in the study. The patients were grouped into high-level enzyme activity (Val/Val) and low-level enzyme activity (Val/Met and Met/Met) groups, according to their COMT Val158Met functional polymorphisms, and statistical analysis was carried out accordingly. Patients with Val/Val polymorphism had lower SANS scores, while the number of conceptual level responses, the percentage of conceptual level responses, and the failure to maintenance set scores at WCST were lower compared to those with the met allele. No difference was determined between the two groups in the scores on the SAPS and BPRS, and on the performance of the Stroop Test and the VPMT. Conclusion: We measured lower levels of negative symptoms in patients with high enzyme activity compared to those with low enzyme activity. There was no difference in executive functions assessed with the WCST in scores related to perseveration, while the patients with high enzyme activity presented a better performance in the fields related to working memory. Although the small subject number of the study represents a serious limitation, these results suggest that COMT Val158Met polymorphism has a limited effect on clinical symptoms and executive functions, but no effect on attention level and memory in schizophrenia.

Backgrounds: Although several studies have tested the association between bipolar disorder (BD) and the Val108 (H, high-activity allele)/158Met (L, low-activity allele) polymorphism of the catechol-O-methyltransferase (COMT) gene, most of the results showed no significant association. However, an association between the H or L allele and bipolar disorder (BD), particularly, between L allele and rapid-cycling form has been reported; it has also been suggested that the variation in the COMT gene modifies the course of BD and there is a tendency for the L allele amongst the female patients. In this study, the researchers aimed to evaluate the association between BD and COMT gene H/L polymorphism considering the influence of gender in a group of Turkish patients. Method: One hundred and thirty-five BD patients (71 male and 64 female) and 171 controls were included. Polymerase chain reaction-based endonuclease digestion method was used. Results: Genotypic distribution in patients and controls were in Hardy-Weinberg equilibrium. No significant difference was found in genotypic and allelic frequencies between patients and controls. However, female patients had H allele more frequently than male patients and female healthy controls. Females had more depressive and less manic episodes than males. Number of total episodes was associated with H allele in all patients. Conclusion: Distribution of COMT genetic polymorphism was not significantly different between the patients and controls. However, it has been found an association of H allele with female patients and number of episodes among all patients. © 2011 Elsevier GmbH. All rights reserved.

Objective: Although attention-deficit hyperactivity disorder (ADHD) was perceived as a disorder of childhood, it is now recognized as a chronic condition persisting into adulthood. The aim of this study was to explore the frequency of comorbidity in adults with ADHD. Methods: 80 ADHD patients between 16 and 60 years of age and 80 controls were recruited to the study. The groups were compared in terms of socio-demographic characteristics and diagnosis based on SCID-I and SCID-II. Results: The groups were identical regarding socio-demographic characteristics such as age, gender, education and marital status. The frequency of generalized anxiety disorder, major depression, dysthymia, somatoform disorder, antisocial and borderline personality disorders was significantly higher in ADHD group compared to the control group. Conclusion: We found that adult ADHD was an important risk factor for psychiatric comorbidity throughout lifetime. It is clear that misdiagnosis of comorbid disorders in ADHD patients may cause worsening of the symptoms and treatment resistance. Further studies on this topic may help us to better understand the course of adult ADHD and its treatment. © Archives of Neuropsychiatry.

Objective: Considering the suggested association of tryptophan hydroxylase gene 1 (TPH1) polymorphism with some psychiatric disorders and studies concerning serotonin's effect on TPH 1 gene, brain and the neurotransmitter monoamines, as well as the studies performed on the serotonin levels in cerebrospinal fluid of bipolar patients, we aimed to investigate the frequencies and distribution of TPH 1 gene 218 A>C (rs1800532) polymorphism; A/A, A/C and C/C genotypes in bipolar patients and healthy control subjects for the first time in Turkish population (1-2). Methods: One hundred and sixteen adult patients who applied to the Mood Disorders Unit of Psychiatry Department, Medical School of Gaziantep University, and diagnosed with bipolar disorder (BD) according to DSM-IV diagnostic criteria were included in the study. One hundred and fifty healthy volunteers, a hospital staff at Gaziantep University, were involved as the control group. Results: In female patients, the frequency of A/A genotype was found to be higher than in the females in the control group. No significant difference was detected between patient and control groups in terms of age and gender distribution. The distribution of A/A, A/C and C/C genotypes were similar in patient and control groups. Conclusion: The distribution of TPH1 gene 218 A>C polymorphism was found to be significantly different between female patients and females in the control group. This result can be explicated as being one of the possible reasons for different course of bipolar disorder in male and female patients. © Archives of Neuropsychiatry.

Objective: Antipsychotic induced weight gain is a major problem for second generation antipsychotics which may lead to diabetes and metabolic syndrome. Recent studies were mentioning that genetic factors might be relevant in antipsychotic induced weight gain. Aim of this study is evaluation of the association between IRS-1 Glyp972Arg polymorphism and olanzapine induced weight gain. Methods: Total of 95 patients whom were diagnosed as schizophrenia by DSM-IV criteria were included to study. Body weight, body mass index and blood glucose levels of all patients were checked at the beginning and six weeks after olanzapine treatment. Blood for DNA analysis were obtained from patients and analyzed as mentioned in literature. Data were evaluated with descriptive methods and Mann Whitney U test was used for comparison of two groups. Results: Eighty and four of patients had Glycine/Glycine and 11 patients had Glycine/Arginine genotype of IRS-1 Gly972Arg polymorphism. Despite the patients with Glycine/Glycine polymorphism gained more weight than patients with Glycine/Arginine polymorphism, the difference between Glycine/Glycine and Glycine/Arginine groups for weight change and body mass index change wasn't statistically significant. Conclusion: Our results showed no statistical relationship between the IRS-1 Gly972Arg polymorphism and olanzapine induced weight gain. However exploration of the other IRS genotypes and the antipsychotic-induced body weight change may help in the understanding of the mechanisms of antipsychotic-induced body weight gain.

It is hypothesized that molecular components of dopaminergic system, especially the dopamine D3 receptor gene (DRD3), may play a crucial role in the pathophysiology of schizophrenia, because it is abundant in the limbic system of the brain and it binds antipsychotic drugs. Several groups attempted to find an association between a serine-to-glycine polymorphism of the DRD3 gene (Ser9Gly) and schizophrenia; however, the results were inconsistent. In this study, we aimed to investigate the relationship of the Serine/Glycine polymorphism of the DRD3 gene with therapeutic response to clozapine treatment between Turkish schizophrenia patients (N = 92) and healthy controls (N = 100). Genotype groups were comparable in BPRS, SAPS, SANS analysis of response to clozapine. Our results suggest that an association between the Ser/Gly polymorphism of DRD3 gene and response to clozapine in Turkish schizophrenia patients is unlikely to exist. © 2008 Wiley-Liss, Inc.

Purpose: We sought to investigate whether the volume of the corpus callosum would be abnormally smaller in schizophrenic subjects using Cavalieri method. Methods: In schizophrenic patients (n=17) and in healthy volunteers (n=11) volume of the corpus callosum were estimated using the magnetic resonance images (MRI). A detailed systematic series of sagittal MRI of the entire brain was obtained in each subject. All estimations were done according to Cavalieri method by a modified point counting probe placed on surface areas of corpus callosum slices. Results: The mean volume of the corpus callosum was 4671,34 mm3 and 6677,15 mm3 in the female schizophrenics and controls, respectively. The mean volumes of the corpus callosurn were 5033.46 mm3 and 5663.52 mm3 in the male schizophrenics and controls, respectively. A statistically significant difference was found between corpus callosum volumes of the schizophrenic patients and controls. There was no correlation between corpus callosum volume and BPRS, SANS and SAPS. Conclusion: Corpus callosum volume was significantly reduced in schizophrenic group. Evidence of reduced interhemispheric communication in schizophrenia may be important in explaining the associations between the abnormalities of midline brain structures with the psychiatric illness. © Universitätsverlag Ulm GmbH 2008.

Background: There has been much evidence in recent years that free oxygen radicals and nitric oxide (NO) may play an important role in the pathophysiology of neuropsychiatric disorders. In this study, we aimed to investigate whether NO, xanthine oxidase (XO), superoxide dismutase (SOD), and adenosine deaminase (ADA) levels are associated with major depression (MD) and to evaluate the impact of antidepressant treatments on NO, SOD, ADA and XO levels in MD. Methods: Thirty-six patients who were diagnosed as MD according to DSM-IV criteria and 20 healthy controls were included. The serum levels of NO, XO, SOD, and ADA were measured by spectrophotometric methods both in patients and controls. Patients were treated with antidepressant drugs for 8 weeks. All patients were assessed by Hamilton Depression Rating Scale (HDRS) both before and after antidepressant treatment. Results: ADA and XO levels of the patients were significantly higher than the controls. SOD level of the patients was significantly lower than the controls. Although NO levels of the patients were higher than the controls, the difference was not statistically significant. There was no correlation between HDRS and the parameters studied (SOD, ADA, XO, and NO) of the patients. After 8 weeks of antidepressant treatment, ADA and SOD activities were increased, whereas NO and, XO levels decreased significantly. Conclusions: ADA, XO, and SOD activity may have a pathophysiological role in MD and may predict prognosis of MD. Activity of these enzymes may be used to monitor effects of the antidepressant treatment. © 2007 IMSS.

Objective: Suicide is one of the most important public health problems. Suicide, which needs to be discussed as a part of preventive mental health, has a wide range of causes. Temperament is genetic and structural behavioral characteristics that individuals have in their nature and cannot change for a whole-of-life. On the other hand, character is discussed as a concept, which is affected by education and environmental factors and can change in the course of time. In this study, we aimed to determine the discriminating personality characteristic of suicide attempters compared to healthy control subjects. Methods: Attempted suicide cases (n=69) who applied to Gaziantep University, Medicine Faculty, Emergency Service between May 2003 and August 2005 and who were asked to be assessed as psychiatrically were assessed according to DSM-IV diagnosis criterion and Tempera-ment and Character Inventory (TCI-240 items), Beck Depression Inventory (BDI), and Beck Hopelessness Scale (BHS) were employed to these cases and personality profiles were compared to control group including age and gender matched individuals who do not have any lifetime history of mental disorders (n=77) Results: Suicide attempters showed higher scores in harm avoidance, self-transcendence and lower scores in self-directedness, cooperativeness, and reward dependence when compared to controls. Beck hopelessness scale is positively correlated with harm avoidance score and reward dependence, persistence, self-directedness, cooperativeness scores negatively correlated in suicide group. In attempted suicide group, when we compared TCI scores within genders, responsibility scores was higher in men whereas, fear of uncertainty, virtuousness, and mercifulness subscores were higher in women. As for control group sentimentality, attachment and empathy subscores were higher in women. Conclusion: Temperament and character features of suicide attempters show significant differences compared with healthy control group. Determining personality profile among suicide attempters may be useful in employing different treatment approaches. (Anatolian Journal of Psychiatry 2008; 9:232-237)

Objective: Ceruloplasmin is a protein in the human serum that is synthesized by hepatocytes, but extrahepatic gene expression in the brain, lung, spleen, and testis has also been reported. Ceruloplasmin contains approximately 95% of serum copper and it carries copper from liver to numerous tissues. Ceruloplasmin level reflects largely the copper concentration of the serum. However, ceruloplasmin has also an antioxidant function that is known as the acute phase reactant. Additionally, ceruloplasmin has a role in the oxidation of serotonin, epinephrine, and norepinephrine. Abnormalities in ceruloplasmin levels have been associated with several neurodegenerative diseases. Moreover, the alteration of plasma ceruloplasmin levels has been linked to schizophrenia and its some clinical characteristics including acute or chronic phase, the length of the disease or whether the patients on treatment or not. However, there exists a controversy on relationship between the plasma level of ceruloplasmin and schizophrenia. There are number of reports on the increased or decreased and/or normal level of plasma ceruloplasmin in association with schizophrenia, These differences may have been originated from the usage of different measurement methods, clinical situations, and ethnobiological differences. In the present study, we aimed to investigate the association between plasma ceruloplasmin level and schizophrenic in Turkish patients. Methods: 60 patients (36 women and 24 men, mean of age 31.93 +/- 9.37 years, range 19-55) that were diagnosed as schizophrenia according to DSM-IV were induced for this study at the Psychotic Disorders Unit, Department of Psychiatry, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey. The control group consisted of 40 healthy subjects in similar age and gender (23 women, 17 men). Venous blood samples were collected from the left forearm into heparinized tubes The blood samples were centrifuged and the plasma was removed, Erel's ceruloplasmin measurement method that is based on the enzymatic oxidation of ferrous ions to ferric ions was used. SPSS Windows program 13.0 was applied for statistical analysis. Results: Plasma ceruloplasmin levels of schizophrenic patients were significantly higher than the healthy controls (p < 0.001), In addition, female patients had higher ceruloplasmin levels than male patients (p < 0.001), while there was no statistically significant difference between women and men in the control group. There was no association between the ceruloplasmin levels and the age, the duration of illness, smoking, schizophrenia subtypes, symptom severity, and antipsychotic therapy. Conclusions: The study suggests that ceruloplasmin may play a role in pathophysiology of schizophrenic, Moreover, female patients having a higher level of ceruloplasmin than those of male patients that is first time reported in the literature. However, further studies are needed to clarify the higher level of ceruloplasmin in schizophrenia and to reveal the importance of the gender differences in ceruloplasmin levels in schizophrenia.