DNA Methylation of BDNF Gene in Schizophrenia.

BACKGROUND Although genetic factors are risk factors for schizophrenia, some environmental factors are thought to be required for the manifestation of disease. Epigenetic mechanisms regulate gene functions without causing a change in the nucleotide sequence of DNA. Brain-derived neurotrophic factor (BDNF) is a neurotrophin that regulates synaptic transmission and plasticity. It has been suggested that BDNF may play a role in the pathophysiology of schizophrenia. It is established that methylation status of the BDNF gene is associated with fear learning, memory, and stressful social interactions. In this study, we aimed to investigate the DNA methylation status of BDNF gene in patients with schizophrenia. MATERIAL AND METHODS The study included 49 patients (33 male and 16 female) with schizophrenia and 65 unrelated healthy controls (46 male and 19 female). Determination of methylation pattern of CpG islands was based on the principle that bisulfite treatment of DNA results in conversion of unmethylated cytosine residues into uracil, whereas methylated cytosine residues remain unmodified. Methylation-specific PCR was performed with primers specific for either methylated or unmethylated DNA. RESULTS There was no significant difference in methylated or un-methylated status for BDNF promoters between schizophrenia patients and controls. The mean duration of illness was significantly lower in the hemi-methylated group compared to the non-methylated group for BDNF gene CpG island-1 in schizophrenia patients. CONCLUSIONS Although there were no differences in BDNF gene methylation status between schizophrenia patients and healthy controls, there was an association between duration of illness and DNA methylation.

Increased oxidative stress and oxidative DNA damage in non-remission schizophrenia patients.

Increasing evidence shows that oxidative stress plays a role in the pathophysiology of schizophrenia. But there is not any study which examines the effects of oxidative stress on DNA in schizophrenia patients. Therefore we aimed to assess the oxidative stress levels and oxidative DNA damage in schizophrenia patients with and without symptomatic remission. A total of 64 schizophrenia patients (38 with symptomatic remission and 26 without symptomatic remission) and 80 healthy volunteers were included in the study. 8-hydroxydeoxyguanosine (8-OHdG), total oxidant status (TOS) and total antioxidant status (TAS) were measured in plasma. TOS, oxidative stress index (OSI) and 8-OHdG levels were significantly higher in non-remission schizophrenic (Non-R-Sch) patients than in the controls. TOS and OSI levels were significantly higher in remission schizophrenic (R-Sch) patients than in the controls. TAS level were significantly lower and TOS and OSI levels were significantly higher in R-Sch patients than in Non-R-Sch patients. Despite the ongoing oxidative stress in patients with both R-Sch and Non-R-Sch, oxidative DNA damage was higher in only Non-R-Sch patients compared to controls. It is suggested that oxidative stress can cause the disease via DNA damage, and oxidative stress plays a role in schizophrenia through oxidative DNA damage.

Phenprobamate dependence: a case report.

Phenprobamate (3-phenylpropylcarbamate) is a centrally acting muscle relaxant with mild sedative and anticonvulsant effects. Muscle relaxants can enhance and prolong the effect of narcotic drugs and enable to obtain same effect with a smaller amount of alcohol or illicit substance. Almost all of the centrally acting muscle relaxants have varying sedative effects on which their abuse potential mainly depends. Data related to abuse of carisoprodol, meprobamate, baclofen takes place in the literature. However, to our knowledge this is the first case report about abuse of and tolerance to phenprobamate. We aimed to attract attention to important points of prescribing drugs that have abuse potential like in our case who was using up to 16000 mg/day phenprobamate.

Post-traumatic stress disorder among Syrian refugees in Turkey: a cross-sectional study.

OBJECTIVE: Refugees have had major challenges to meet their health care needs throughout history especially in war zones and natural disaster times. The health care needs of Syrian refugees have been becoming an increasingly important issue. We aimed to examine the prevalence of post-traumatic stress disorder (PTSD) and explore its relation with various socioeconomic variables among Syrian refugees, who sought asylum in Turkey. METHODS: This cross-sectional study was conducted in a tent city. Sample size calculation yielded 352 and the participants of the study were determined randomly. Experienced and native Arabic speaking, psychiatrist evaluated the participants. RESULTS: The frequency of PTSD was 33.5%. Through the binary logistic regression analysis, we calculated that the probability of having PTSD among Syrian refugees in our sample was 71%, if they had the following features: with female gender; being diagnosed with psychiatric disorder in the past; having a family history of psychiatric disorder; and experiencing 2 or more traumas. CONCLUSIONS: The findings of our study suggest that PTSD among Syrian refugees in Turkey might be an important mental health issue in refugee camps especially among female refugees, who were exposed to 2 or more traumatic events and had a personal or family history of psychiatric disorder.

Are oxidative stress markers useful to distinguish schizoaffective disorder from schizophrenia and bipolar disorder?

OBJECTIVE: Schizoaffective disorder is a disease with both affective and psychotic symptoms. In this study, we aimed to compare oxidative metabolism markers of schizoaffective disorder, bipolar disorder and schizophrenic patients. Furthermore, we also aimed to investigate whether schizoaffective disorder could be differentiated from schizophrenia and bipolar disorder in terms of oxidative metabolism. METHODS: Total oxidant status (TOS) and total antioxidant status (TAS) were measured in the blood samples that were collected from schizoaffective patients (n = 30), bipolar disorder patients (n = 30) and schizophrenic patients (n = 30). Oxidative stress index (OSI) was calculated by dividing TOS by TAS. RESULTS: TOS and OSI were found to be higher in patients with schizoaffective disorder compared with those in schizophrenia and bipolar disorder patients. TAS was not significantly different between the groups. CONCLUSION: Schizoaffective disorder was found to be different from bipolar disorder and schizophrenia in terms of oxidative parameters. This result may indicate that schizoaffective disorder could differ from bipolar disorder and schizophrenia in terms of biochemical parameters. Increased TOS levels observed in schizoaffective disorder may suggest poor clinical course and may be an indicator of poor prognosis.

New molecule in the etiology of schizophrenia: urotensin II.

AIMS: Urotensin II (U-II) is a cyclic peptide that was first isolated from the caudal neurosecretory system of goby fish. U-II receptors were detected in the vascular endothelium, brain and kidney cortex. Urotensin is by far the most powerful vasoconstrictor identified. U-II molecules were previously isolated from the brain of rats and were shown to have an impact on rat behavior. The aim of the present study was to measure the level of U-II molecule in schizophrenia patients and to investigate whether the U-II level is associated with the etiology of schizophrenia. METHODS: Forty schizophrenia patients who were followed at Gaziantep University Faculty of Medicine Department of Psychiatry Psychotic Disorders Unit and 40 healthy volunteers were enrolled in this study. Blood samples were taken from the antecubital vein after 12-h fasting. U-II level was measured on ELISA. RESULTS: The U-II level in schizophrenia patients was significantly higher than in the control group. U-II level was not different with regard to gender in either group. U-II level was not different between subgroups of schizophrenia. No significant correlation was found between U-II level, Positive and Negative Syndrome Scale and Clinical Global Impression-Severity scale scores. CONCLUSION: U-II level was higher in schizophrenia patients, indicating that U-II level may be related to the etiology of the disease.

Effective treatment of catatonia by combination of benzodiazepine and electroconvulsive therapy.

OBJECTIVE: Catatonia, a motor dysregulation syndrome, can emerge in numerous psychiatric disorders, mainly in schizophrenia and mood disorders, and metabolic and endocrine disorders such as infections, toxic states, epilepsy, and traumatic brain injury. In our study, we aimed to investigate demographic, clinical, and treatment-related characteristics of catatonic patients managed in our inpatient clinic. METHODS: The medical records of 57 patients diagnosed to have catatonia according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, criteria who were admitted to the inpatient psychiatry clinic of the Gaziantep University School of Medicine between 1 January, 2003, and 31 December, 2011, were retrospectively reviewed. RESULTS: In patients with catatonia, mood disorders (63.2%) were found to be the most common underlying or primary disease, whereas mutism (47.4%) was found to be the most common catatonic symptom. There was a comorbid medical condition in 9 patients (15.8%). Patients underwent an average of 9.00 electroconvulsive therapy (ECT) sessions. Among 57 patients with catatonia, catatonic symptoms were resolved in 57 patients (100%) by benzodiazepine and ECT. CONCLUSIONS: In our study, full recovery was achieved in catatonia by benzodiazepine plus ECT combination. As a result, we recommend combined ECT and benzodiazepine for catatonia.

Electroconvulsive therapy in pregnant patients.

OBJECTIVES: In this study, the aim was to evaluate the clinical characteristics of patients that received electroconvulsive therapy (ECT) during pregnancy due to psychiatric disorders, evaluate the safety and efficacy of ECT in pregnant women, and evaluate the overall status of mothers and babies during the postpartum period. METHODS: The study included 33 patients who were admitted as inpatients with the indication of ECT due to pregnancy and concurrent psychiatric disorders. RESULTS: Upon ECT administration, a complete response to treatment was seen in 84.21% of patients with major depression (n=16), a partial response to treatment in 15.78% of patients (n=3), a complete response to treatment in 91.66% of patients with bipolar disorder (n=11), a partial response to treatment in 8.33% of the patients(n=1), and a full response to treatment in 50% of patients with schizophrenia (n=1) and a partial response to treatment in 50% of patients with schizophrenia (n=1) were obtained. We had after birth information of 27 infants from total 33. It was learned that two of them had disease, one was stillbirth and 24 of them did not have any health problems. CONCLUSIONS: ECT administration during pregnancy to treat psychiatric disorders was found to be an effective treatment method. No risk of preterm birth in mothers treated with ECT during pregnancy was detected.

No effect of antidepressant treatment on elevated serum ceruloplasmin level in patients with first-episode depression: a longitudinal study.

BACKGROUND AND AIMS: Ceruloplasmin, an acute phase reactant with antioxidant capacity, has been found to be increased in some psychiatric disorders like schizophrenia and obsessive compulsive disorder. However, studies in depression are very scarce. We undertook this study determine the serum ceruloplasmin levels of depressive patients before and after treatment, to compare them with those of healthy control subjects, and to assess any possible association of ceruloplasmin and treatment response. METHODS: Nineteen (8 male, 11 female) patients with major depressive disorder and 40 (17 male, 23 female) healthy control subjects were included in the study. The patients received naturalistic antidepressant treatment for 8 weeks after diagnosis. Serum ceruloplasmin levels and Hamilton Depression Rating Scale (HAM-D) scores of the patients were measured before and after their antidepressant treatment. Blood collection for ceruloplasmin measurement was done only once for healthy control subjects. RESULTS: Patients' ceruloplasmin levels before and after antidepressant treatment were significantly higher than control subjects (t = 7.569, p <0.001 and t = 6.764, p <0.001, respectively). Despite clinical improvement, ceruloplasmin did not show any significant change after treatment in patients with depression (t = -1.163, p = 0.260) and remained higher than levels of control subjects. No correlation was found between HAM-D score, presence of response, and ceruloplasmin levels. CONCLUSIONS: Compared to healthy control subjects, ceruloplasmin level seemed to be higher in patients with depression and remained high, despite acute antidepressant treatment. Improvement in clinical measurements of depression after antidepressant treatment was not reflected as significant alterations in serum ceruloplasmin levels.

Evaluation of total oxidative status in adult attention deficit hyperactivity disorder and its diagnostic implications.

Adult Attention Deficit Hyperactivity Disorder (A-ADHD) is one of the psychiatric disorders which awareness is growing. The exact causes of A-ADHD are still unknown. In addition to neurochemical and neuroanatomic disorders, genetic and environmental factors are discussed in its etiology. In our study, we aimed to evaluate the oxidative status of A-ADHD patients and investigate whether oxidative metabolites can be used as diagnostic tools or not in A-ADHD. Blood samples were taken from enrolled 50 A-ADHD patients and 31 controls in appropriate way and Total Antioxidative Status (TAS), Total Oxidative Status (TOS), and Oxidative Stress Index (OSI) were studied in Harran University Biochemistry Labs. Results were compared between groups and ROC curve was drawn in order to evaluate diagnostic performances. Patients' TAS, TOS and OSI were significantly higher than controls. There was not a significant difference between comorbid cases and only A-ADHD patients in terms of measured values. A-ADHD can be predicted for TOS over 9.8575 µmol H(2)O(2) Eqv./L level with 86% positive predictive value and %100 negative predictive value. In A-ADHD, oxidative balance is impaired. High antioxidant levels may be compensatory against the oxidant increase. Oxidative parameters may be used in A-ADHD diagnosis.

Gender differences with respect to psychiatric comorbidity in obstructive sleep apnea syndrome.

OBJECTIVES: Psychiatric disorders are common in obstructive sleep apnea syndrome (OSAS); however, interrelating factors influencing psychiatric comorbidity (PC) in OSAS are unclear. The aim of this study is to investigate gender related differences with PC in OSAS. METHODS: Data of patients diagnosed as OSAS in University of Gaziantep from January 2006 to January 2010 were retrospectively evaluated. Polysomnographic data were recorded with Viasys Sleep Screen (Viasys Healthcare, Germany). Patients younger than 18 years old were excluded. RESULTS: PC was present in 53.1% of OSAS patients. The rate of male subjects with PC was 42.6%; however, 76.26% of females had PC (P = 0.00). Age (P = 0.00) and body mass index (BMI) (P = 0.00) were higher in patients with PC. Ferritin levels were lower in patients with PC (P = 0.00). Male subjects with PC were older and had lower sleep efficiency and longer rapid eye movement latency than males without PC. BMI was the only contributory factor to PC in female subjects. CONCLUSION: PC in OSAS is common, especially in females. Apnea hypopnea index does not seem to influence probability of PC.

How is electrocardiogram influenced by electroconvulsive therapy in males and females?

OBJECTIVES: We aimed to investigate and compare the P duration and P dispersion (Pd) between male and female patients with a primary diagnosis of chronic schizophrenia disorder before and after the electroconvulsive therapy (ECT) period. METHODS: We obtained electrocardiograms of 50 healthy young volunteers which included 25 female (group F, n = 25) and 25 male patients (group M, n = 25). We measured minimum and maximum P wave durations (Pmin, Pmax) and Pd in milliseconds. Electrocardiography was performed before electroconvulsive therapy (ECT) and immediately after the ECT period after awakening. A 12-lead surface electrocardiogram was obtained from each subject in the supine position. RESULTS: The post-ECT P duration was significantly longer than the pre-ECT P duration in groups F and M (P = 0.01 and P = 0.008, respectively). The post-ECT Pd was significantly longer than the pre-ECT Pd in groups F and M (P = 0.0001 in both groups). A higher correlation (r) in group M was observed between the pre-ECT Pd and post-ECT P duration than in group F (r = 0.538, P = 006 in group M; r = 0.349, P = 08 in group F). There was no significant difference between the groups regarding hemodynamics. CONCLUSIONS: Electroconvulsive therapy in both sexes may influence atrial conduction as evidenced by the significantly prolonged Pmax and Pd in patients with a primary diagnosis of schizophrenia disorder.

Oxidative imbalance in bipolar disorder subtypes: a comparative study.

OBJECTIVE: The oxidants are related with the membrane-associated pathologies in the central nervous system and may have an important role in neuropsychiatric disorders. Several studies were performed on the effects of free radicals in bipolar disorder. However, there are no studies investigating the effects of free radicals both in the subtypes of BD (Bipolar disorders I and II) and in antidepressant induced mania (AIM). In this study, we aimed to investigate the status of oxidative metabolism in BD and its subtypes. METHODS: 94 bipolar patients (BD I-II and AIM) diagnosed according to DSM IV and as control group 41 healthy subjects were included to the study. The total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI) were examined in the properly obtained plasma samples of subjects and healthy controls included in the study. RESULTS: The patients' TAS, TOS and OSI were significantly higher than the controls. TAS is negatively correlated with the number of previous total episodes in BD I. The BD I group appeared to have higher TOS compared to BD II group. CONCLUSIONS: Oxidative balance is impaired in bipolar disorder. Antioxidant levels may be increased compensatorily in response to increased oxidant levels. Another important result of our study was that in the comparison of the three disease subtypes BD I group was found to have higher TOS compared to the BD II group. This finding is compatible with the literature on BD I and may be associated with the more severe course of BD I.

Oxidative imbalance in adult attention deficit/hyperactivity disorder.

OBJECTIVE: There are few studies evaluating the biochemical basis of adult attention deficit/hyperactivity disorder (A-ADHD). In the present study, we evaluated whether nitric oxide (NO), an oxidant, level and superoxide dismutase (SOD), an antioxidant, activity are associated with A-ADHD or not. METHODS: Twenty A-ADHD patients from Gaziantep University Sahinbey Research Hospital, Psychiatry Clinic, diagnosed according to The Turkish version of Adult ADD/ADHD DSM IV-Based Diagnostic Screening and Rating Scale by two psychiatrists (H.A.S. and S.S.), and twenty-one healthy volunteer controls were included. Blood samples were collected; NO levels and SOD activities were measured. RESULTS: The mean NO levels in patients were significantly higher than those of controls and SOD activity of patients was significantly lower than controls. CONCLUSIONS: Remarkable high levels of oxidant NO, and low SOD activities suggest an oxidative imbalance in A-ADHD. This is the first study evaluating the oxidative metabolism in A-ADHD.

Quetiapine and ziprasidone as adjuncts in treatment-resistant obsessive-compulsive disorder: a retrospective comparative study.

BACKGROUND AND OBJECTIVE: While serotonin reuptake inhibitors (SRIs) are first-line pharmacological agents in the treatment of obsessive-compulsive disorder (OCD), 40-60% of patients with the disorder do not respond to these agents. This suggests that other neurotransmitters may play a role in OCD. In this regard, there has been particular interest in the dopaminergic system, with various antipsychotic drugs having been used as adjunctive therapy for refractory OCD. The aim of this study was to compare the efficacy of quetiapine and ziprasidone as adjuncts for treatment-resistant OCD. METHODS: A total of 24 OCD patients treated with either quetiapine (n = 15) or ziprasidone (n = 9) as adjunctive therapy to high-dose SRI treatment were included in this retrospective evaluation. Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and Clinical Global Impression (CGI) scale scores were used to evaluate baseline clinical status and clinical improvement at 1, 2, 3 and 6 months of follow-up. RESULTS: Clinical improvement was established in 80% of the quetiapine group and in 44.4% of the ziprasidone group with an overall mean improvement rate on the Y-BOCS scale of 66.7%. Both Y-BOCS and CGI mean scores were higher in the ziprasidone group at 2, 3 and 6 months follow-up than in the quetiapine group. CONCLUSIONS: In the first reported study of its role in this setting, ziprasidone was found to be less effective than quetiapine in the treatment of refractory OCD.

Role of oxidative and antioxidative parameters in etiopathogenesis and prognosis of panic disorder.

Free radicals have been implicated in some psychiatric disorders. This study aimed to investigate the role of oxidative and antioxidative parameters in etiopathogenesis and prognosis of panic disorder (PD), using novel methods for measurement of total oxidant and antioxidant statuses. Nineteen PD patients and 40 healthy subjects were recruited. Both total antioxidant status and oxidative stress index, and ceruloplasmin levels of PD patients were significantly higher in PD patients. Total oxidant status and oxidative stress index decreased after treatment. This study suggests an oxidative imbalance in PD and treatment can reverse overall oxidative imbalance.

Oxidative imbalance in obsessive compulsive disorder patients: a total evaluation of oxidant-antioxidant status.

OBJECTIVES: Various psychological, social, genetic, biochemical, factors are to be involved in the etiology of OCD. Some molecules of free radicals are also found to play role in OCD. To the best of our knowledge, there has been no study, regarding the role of free radicals in the pathogenesis of OCD, from a general antioxidant aspect of view. Therefore, in this present cross-sectional study, we aimed to assess whether antioxidant-oxidant status is associated with OCD and can be used or not as a biological marker regarding that disorder. METHODS: 37 OCD patients diagnosed according to DSM-IV and as control group forty healthy subjects were included to the study. Venous blood samples were collected once. The total oxidant status, antioxidant status and oxidative stress index of the plasma were measured using a novel automated colorimetric measurement method. RESULTS: There was not a significant difference between only OCD and all patients in all measures (TOS: Z = - 1.453, p = 0.521; TAS: Z = - 0.151, p = 0.880; OSI: Z = - 0.679 p = 0.497). TAS levels were both higher than controls in only OCD groups and all patients (Z = - 5.538, p < 0.001 and Z = - 6.394, p < 0.001 respectively). TOS and OSI of both patient groups were significantly lower than controls (TOS: Z = - 5.131, p < 0.001; OSI: Z = - 5.105, p < 0.001 and TOS: Z = - 5.979, p < 0.001; OSI: Z = - 5.862, p < 0.001). In only OCD group, illness duration was correlated with TOS and OSI (r(0) = 0.44, p = 0.023, n = 26 and r(0) = 0.44, p = 0.026, n = 26 respectively) but not with TAS. CONCLUSION: Our study found an overall oxidative imbalance shifted towards antioxidant side in OCD which may be due to either a rebound phenomenon or chronicity of the condition.

The course of nitric oxide and superoxide dismutase during treatment of bipolar depressive episode.

BACKGROUND AND AIMS: Studies have already pointed out a possible pathophysiological role of oxidative and antioxidative molecules in bipolar disorder. We aimed to evaluate the activity and levels of antioxidant superoxide dismutase (SOD), and oxidant nitric oxide (NO), in bipolar I depressive episode (BD-DE) patients in a prospective design. METHOD: 30 BD-DE patients, diagnosed according to DSM IV, and 30 healthy volunteer controls were included. The serum levels of NO and SOD have been studied when admitted to hospital (1st) and on the 30th days. Clinical outcome was measured by Hamilton Depression Scale (HAM-D). The patients were allowed to have their treatments. One patient was dropped out due to insufficient sampling. RESULTS: As in the previous studies, NO 1st day levels were significantly higher in patients and SOD 1st day activity was significantly low (p<0.01). NO levels significantly decreased (p<0.01) and normalized, as SOD activity significantly increased but did not reach to the controls' levels (p<0.01) on the 30th day. CONCLUSION: Despite normalized NO levels, persistent low SOD activity might point out an oxidative imbalance in BD-DE. Chronic low SOD activity may be associated with incapacity of coping with oxidative stress. This research connotes the probable oxidative imbalance in BD-DE and discusses that phenomenon within the continuum of the disease state.

Malondialdehyde levels in adult attention-deficit hyperactivity disorder.

OBJECTIVE: To evaluate the biochemical basis of adult attention-deficit hyperactivity disorder (A-ADHD), we compared lipid peroxidation status in the plasma of A-ADHD patients, and that of control subjects without A-ADHD by quantifying the levels of malondialdehyde (MDA), an end product of fatty acid oxidation. We aimed to examine the association between MDA and A-ADHD. METHOD: The study comprised 20 A-ADHD patients from Gaziantep University Sahinbey Research Hospital Psychiatry Clinic, diagnosed by 2 psychiatrists (H.A.S. and S.S.) according to the Turkish version of the adult ADD/ADHD DSM-IV-Based Diagnostic Screening and Rating Scale, and 21 healthy volunteers. Malondialdehyde levels were measured in plasma samples of both study groups. RESULTS: The mean (standard deviation [SD]) MDA levels in patients (2.44 [0.84] nmol/mL) were significantly higher than those of control subjects (0.36 [0.20] nmol/mL) (t=11.013, df=39, p<0.01). MDA levels were correlated with overall number of criteria met (n=20, p=0.01, Ro=0.56) and total hyperactivity/impulsivity score (n=20, p=0.02, Ro=0.51). CONCLUSION: The fact that MDA levels were increased in A-ADHD could be an indication of increased oxidative stress in this disease. We suggest that such changes may have a pathological role in A-ADHD. This is the first study evaluating the MDA levels in A-ADHD, and our findings may provide a scientific guide for the further clinical enzymologic and biochemical studies on this disorder.