Relationship between Serum Bilirubin Levels and Metabolic Syndrome in Patients with Schizophrenia Spectrum Disorders.

OBJECTIVE: We investigated the relationship between serum bilirubin levels and metabolic syndrome (MetS), and the longitudinal effects of baseline serum bilirubin concentrations on MetS in patients with schizophrenia spectrum disorders undergoing atypical antipsychotics. METHODS: The sample of this study consisted of 131 patients with schizophrenia spectrum disorders. Waist circumference, blood pressure, and levels of triglycerides, high-density lipoprotein cholesterol, fasting glucose, and insulin were evaluated at baseline and at month six. Serum bilirubin levels were measured at baseline. Serum bilirubin levels of the patients with and without MetS criteria were compared. We also compared patients with high and low bilirubin levels (upper and lower 50th percentiles of serum bilirubin levels) in terms of MetS criteria, MetS frequency, and course of MetS. RESULTS: Serum direct bilirubin levels were more consistently related to MetS and MetS-related variables. The waist circumference and triglyceride criteria for MetS were significantly related to low serum direct bilirubin at baseline; waist circumference and fasting glucose criteria, and insulin resistance were associated with low serum direct bilirubin at follow-up. MetS diagnosis and the presence of the waist circumference criterion were more frequent at the baseline and the follow-up in low bilirubin group. At the end of the follow-up period, the rate of reverse MetS was significantly higher in the high bilirubin group. CONCLUSION: Our results have suggested that serum direct bilirubin levels showed a more reliable and stable relationship with abdominal obesity for MetS components.in patients with schizophrenia spectrum disorders using antipsychotics. Further studies are required.

Evaluation of Oxidative Status in Patients Treated with Electroconvulsive Therapy.

OBJECTIVE: Electroconvulsive therapy (ECT) is used in the treatment of many psychiatric diseases and this therapy may be effective on antioxidant defence system. In this study, we aimed to evaluate the effects of ECT on oxidative stress. METHODS: Fourteen major depression, 11 schizophrenia and 8 bipolar affective disorder patients diagnosed and received ECT treatment, and 37 healthy volunteers enrolled in the study. ECT was applied to all patients. Before ECT, after the first and last ECTs, serum samples were obtained. Serum total antioxidant status (TAS), total oxidant status (TOS), and calculated oxidative stress index (OSI) were measured in patients before and after ECTs. RESULTS: TOS values before ECT were higher in major depression (p=0.005) and schizophrenia (p=0.001) groups compared to the control group. TAS values were lower in major depression (p=0.0001), schizophrenia (p=0.004), bipolar affective disorder (p=0.004) groups compared to the controls. Also OSI values were higher in major depression (p=0.0001), schizophrenia (p=0.001), bipolar affective disorder (p=0.009) groups compared to healthy group. After the last ECT, TOS values were significantly lower compared to TOS values before ECT in major depression (p=0.004) and schizophrenia patients (p=0.004). TAS values after the first ECT were higher compared to values before ECT in major depression patients (p=0.004). After last ECT, OSI values were significantly lower compared to before ECT in schizophrenia patients (p=0.006). CONCLUSION: As a result, it can be said that ECT did not increase oxidative stress. However, further studies with more patients are needed.

Brain-Derived Neurotrophic Factor Gene Val66Met Polymorphism Is a Risk Factor for Attention-Deficit Hyperactivity Disorder in a Turkish Sample.

OBJECTIVE: Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that negatively affects different areas of life. We aimed to evaluate the associations between the Val66Met polymorphism of brain-derived neurotrophic factor (BDNF) and ADHD and to assess the effect of the BDNF polymorphism on the neurocognitive profile and clinical symptomatology in ADHD. METHODS: Two hundred one ADHD cases and 99 typically developing subjects (TD) between the ages of 8 and 15 years were involved in the study. All subjects were evaluated using a complete neuropsychological battery, Child Behavior Checklist, the Teacher's Report Form (TRF) and the DSM-IV Disruptive Behavior Disorders Rating Scale-teacher and parent forms. RESULTS: The GG genotype was significantly more frequent in the patients with ADHD than in the TD controls, and the GG genotype was also significantly more frequent in the ADHD-combined (ADHD-C) subtype patients than in the TDs. However, there were no significant associations of the BDNF polymorphism with the ADHD subtypes or neurocognitive profiles of the patients. The teacher-assessed hyperactivity and inattention symptom count and the total score were higher, and the appropriately behaving subtest score of the TRF was lower in the GG genotypes than in the GA and AA (i.e., the A-containing) genotypes. CONCLUSION: We found a positive association between the BDNF gene Val66Met polymorphism and ADHD, and this association was observed specifically in the ADHD-C subtype and not the ADHD-predominantly inattentive subtype. Our findings support that the Val66Met polymorphism of BDNF gene might be involved in the pathogenesis of ADHD. Furthermore Val66Met polymorphism of BDNF gene may be more closely associated with hyperactivity rather than inattention.

miR-181b-5p, miR-195-5p and miR-301a-3p are related with treatment resistance in schizophrenia.

The aim of the study was to determine the differences between expression levels of certain miRNAs, as their association with schizophrenia has been well presented in the literature, and to investigate their relation to treatment resistance in schizophrenic patients. Three groups were formed: 1) treatment-resistant group, 2) treatment responsive group and 3) healthy control group. Expression levels of miRNAs from peripheric blood samples were determined by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). We investigated the roles of 29 schizophrenia-related miRNAs in schizophrenia treatment and their potentials to be considered as indicators. Among these miRNAs, only miR-181b-5p, miR-195-5p and miR-301a-3p expressions were found to be significantly different between the treatment-resistant group and the group responding well to the treatment. miRNAs may cause resistance by silencing the receptor genes of the drugs used for schizophrenia treatment. miR-181b-5p, miR-195-5p and miR-301a-3p may be candidate indicators that can be used to reveal resistance against schizophrenia treatment.

The impact of synapsin III gene on the neurometabolite level alterations after single-dose methylphenidate in attention-deficit hyperactivity disorder patients.

OBJECTIVE: To investigate the neurometabolite level changes according to synapsin III gene rs133945G>A and rs133946C>G polymorphisms by using magnetic resonance spectroscopy (MRS) in patients with attention-deficit hyperactivity disorder (ADHD). METHODS: Fifty-seven adults diagnosed with ADHD were recruited for the study. The participants were examined by single-voxel (1)H MRS when medication naïve and 30 minutes after oral administration of 10 mg methylphenidate (Mph). Those who had been on a stimulant discontinued the medication 48 hours before MRS imaging. Spectra were taken from the anterior cingulate cortex, dorsolateral prefrontal cortex, striatum, and cerebellum, and N-acetylaspartate (NAA), choline, and creatine levels were examined. For genotyping of the synapsin III gene polymorphisms, DNA was isolated from peripheral blood leukocytes. The effects of age, sex, and ADHD subtypes were controlled in the analyses. RESULTS: After a single dose of Mph, choline levels increased significantly in the striatum of rs133945G>A polymorphism-GG genotypes (P=0.020) and NAA levels rose in the anterior cingulate cortex of rs133946C>G polymorphism-CG genotypes (P=0.014). Both rs133945G>A and rs133946C>G polymorphisms were found to statistically significantly affect the alteration of NAA levels in response to Mph in dorsolateral prefrontal cortex with two-way repeated measure of analysis of variance. Post hoc comparisons revealed a significant difference between CG and GG genotypes of rs133946C>G polymorphisms after Bonferroni adjustment (P=0.016). CONCLUSION: Synapsin III gene polymorphisms may be affecting the changes in neurometabolite levels in response to Mph in adult ADHD patients. Future studies are needed to confirm our findings.

White matter alterations related to attention-deficit hyperactivity disorder and COMT val(158)met polymorphism: children with valine homozygote attention-deficit hyperactivity disorder have altered white matter connectivity in the right cingulum (cingulate gyrus).

INTRODUCTION: In this article, the COMT gene val(158)met polymorphism and attention-deficit hyperactivity disorder (ADHD)-related differences in diffusion-tensor-imaging-measured white matter (WM) structure in children with ADHD and controls were investigated. PATIENTS AND METHODS: A total of 71 children diagnosed with ADHD and 24 controls aged 8-15 years were recruited. Using diffusion tensor imaging, COMT polymorphism and ADHD-related WM alterations were investigated, and any interaction effect between the COMT polymorphism and ADHD was also examined. The effects of age, sex, and estimated total IQ were controlled by multivariate analysis of covariance (MANCOVA). RESULTS: First, an interaction between the COMT val(158)met polymorphism and ADHD in the right (R) cingulum (cingulate gyrus) (CGC) was found. According to this, valine (val) homozygote ADHD-diagnosed children had significantly lower fractional anisotropy (FA) and higher radial diffusivity (RD) in the R-CGC than ADHD-diagnosed methionine (met) carriers, and val homozygote controls had higher FA and lower RD in the R-CGC than val homozygote ADHD patients. Second, met carriers had higher FA and axial diffusivity in the left (L)-uncinate fasciculus and lower RD in the L-posterior corona radiata and L-posterior thalamic radiation (include optic radiation) than the val homozygotes, independent of ADHD diagnosis. Third, children with ADHD had lower FA in the L-CGC and R-retrolenticular part of the internal capsule than the controls, independent of the COMT polymorphism. CONCLUSION: Significant differences reported here may be evidence that the COMT gene val(158)met polymorphism variants, as well as ADHD, could affect brain development. ADHD and the COMT polymorphism might be interactively affecting WM development in the R-CGC to alter the WM connectivity in children with val homozygote ADHD.

The Effect of Single Dose Methylphenidate on Neurometabolites according to COMT Gene Val158Met Polymorphism in the Patient with Attention Deficit Hyperactivity Disorder: A Study Using Magnetic Resonance Spectroscopy.

OBJECTIVE: Attention deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. Thus, the present study aimed to determine the effects of a single dose of methylphenidate (Mph) on neurometabolite levels according to polymorphisms of the catechol-O-methyltransferase (COMT) gene. METHODS: This study evaluated the neurometabolite levels including N-acetylaspartate (NAA), creatine (Cr), and choline (Cho) of ADHD patients, before and after treatment with Mph (10 mg) according to the presence of COMT polymorphisms. The spectra were obtained from the dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), cerebellum, and striatum. RESULTS: The NAA levels of the val/val and val genotype carriers (val/val and val/met genotypes) increased in the DLPFC and ACC, respectively, following Mph treatment. The NAA/Cr ratio was lower in the DLPFC of val carriers than in the met/met genotype carriers prior to Mph administration. The Cho levels of the val/met genotype and val carriers increased in the striatum following Mph treatment. Following Mph treatment, the Cr levels of the met/met genotype carriers were higher than those of the val/met genotype and val carriers. Additionally, after Mph treatment, there was a significant increase in Cr levels in the DLPFC of the met/met genotype carriers but a significant decrease in such levels in the striatum of val/val genotype carriers. CONCLUSION: These findings suggest that polymorphisms of the COMT gene can account for individual differences in neurochemical responses to Mph among ADHD patients. Therefore, further studies are needed to fully characterize the effects of the Val158met polymorphism of the COMT gene on treatment outcomes in patients with ADHD.

Increased urinary 6-hydroxymelatoninsulfate levels in attention deficit hyperactivity disorder diagnosed children and adolescent.

There are some studies in attention deficit hyperactivity disorder (ADHD) which note altered circadian rhythms, suggesting abnormalities in melatonin physiology. In order to better characterize the possible melatonin alteration in ADHD, in this study we aimed to detect daytime, nighttime and 24 h levels of 6-hydroxymelatoninsulfate (6-OH MS) in the patients diagnosed with ADHD. Twenty-seven patients between 6 and 16 years-old, who had been diagnosed initially with ADHD, but without other physical and psychiatric disease history and who had not taken psychotropic pharmacotherapy for six months, plus 28 healthy volunteer controls, were included in the study. Urine samples were collected during the whole 24 h cycle, daytime and nighttime separately to assess the time-dependent excretion of the 6-OH MS, which is the main urine metabolite of melatonin. The Enzyme-Linked Immunosorbent Assay (ELISA) method was used for measuring the urine 6-OH MS level. Daytime (15.4 (8.9-24.8) ng/ml vs 6.9 (2.5-15.9) ng/ml, p=0.002), nighttime (102.9 (65.3-197.7) ng/ml vs 61.5 (37.2-114.4) ng/ml, p=0.012) and 24 h (54.1 (34.6-83.9) ng/ml vs 27.3 (14.3-48.9) ng/ml, p=0.000) 6-OH MS levels median (25p-75p) were found to be significantly higher in the ADHD group. After adjustment for age and sex, there was a statistically significant difference between the ADHD group (59.8 ± 4.9) and control group (33.8 ± 4.8) in 24-h 6-OH MS levels (F(1, 51)=13.673, p=.001, partial η2=.211). There was no relationship between 6-OH MS levels and Conners Parent Rating Scale short form subscale scores for the ADHD group. These findings indicate that melatonin production is increased in ADHD cases. Further research is needed to determine and thereby understand the mechanisms underlying the higher melatonin production, to assess the impact of altered melatonin on the pathophysiology of ADHD.

Practice of Acute and Maintenance Electroconvulsive Therapy in the Psychiatric Clinic of a University Hospital from Turkey: between 2007 and 2013.

OBJECTIVE: Electroconvulsive therapy (ECT) can be given as the form of acute, continuation or maintenance ECT according to the process of administration. We report our 7 years' observation with acute and maintenance ECT in a university hospital in Turkey. METHODS: The medical records of the hospitalized patients treated with acute or maintenance ECT between the years 2007 and 2013 was retrospectively analyzed. The sociodemographic characteristics, diagnosis, data of ECT and the co-administered psychotropic drugs were recorded. The frequency of ECT was calculated by identifying the total number of the hospitalized patients during the study period from the hospital records. RESULTS: A total number of 1,432 female and 1,141 male patients hospitalized in a period of 7 years, with a total number of 111 patients treated with ECT. The ratio of ECT was 4%, maintenance/acute ECT 11%. For acute ECT, affective disorders (65.3%) and psychotic disorders (21.6%) were among the leading diagnoses. Maintenance ECT, the diagnosis was; 6 affective disorders, 4 psychotic disorders and 1 obsessive compulsive disorder. There was a significant difference between the patients receiving acute and maintenance ECT in terms of age, duration of illness, and number of previous hospitalizations and ECTs. CONCLUSION: The percentage of patients treated with acute ECT is lower in our institution than that in many other institutions from our country. Acute and maintenance ECT should be considered as an important treatment option particularly for patients with long disease duration, a high number of hospitalizations and a history of benefiting from previous ECTs.

Treatment response, safety, and tolerability of paliperidone extended release treatment in patients recently diagnosed with schizophrenia.

OBJECTIVE: This study was designed to explore the efficacy and tolerability of oral paliperidone extended release (ER) in a sample of patients who were switched to flexible doses within the crucial first 5 years after receiving a diagnosis of schizophrenia. METHODS: Patients were recruited from 23 countries. Adults with nonacute but symptomatic schizophrenia, previously unsuccessfully treated with other oral antipsychotics, were transitioned to paliperidone ER (3-12 mg/day) and prospectively treated for up to 6 months. The primary efficacy outcome for patients switching for the main reason of lack of efficacy with their previous antipsychotic was at least 20% improvement in Positive and Negative Syndrome Scale (PANSS) total scores. For patients switching for other main reasons, such as lack of tolerability, compliance or 'other', the primary outcome was non-inferiority in efficacy compared with the previous oral antipsychotic. RESULTS: For patients switching for the main reason of lack of efficacy, 63.1% achieved an improvement of at least 20% in PANSS total scores from baseline to endpoint. For each reason for switching other than lack of efficacy, efficacy maintenance after switching to paliperidone ER was confirmed. Statistically significant improvement in patient functioning from baseline to endpoint, as assessed by the Personal and Social Performance scale, was observed (p < 0.0001). Treatment satisfaction with prior antipsychotic treatment at baseline was rated 'good' to 'very good' by 16.8% of patients, and at endpoint by 66.0% of patients treated with paliperidone ER. Paliperidone ER was generally well tolerated, with frequently reported treatment-emergent adverse events being insomnia, anxiety and somnolence. CONCLUSIONS: Flexibly dosed paliperidone ER was associated with clinically relevant symptomatic and functional improvement in recently diagnosed patients with non-acute schizophrenia previously unsuccessfully treated with other oral antipsychotics.

Association of adult attention deficit hyperactivity disorder subtypes and response to methylphenidate HCL treatment: A magnetic resonance spectroscopy study.

The effects of methylphenidate (MPH) treatment on N-acetyl aspartate (NAA), choline and creatine are being examined in individuals with different subtypes of attention deficit hyperactivity disorder (ADHD). Sixty ADHD subjects were included into the study aging between 18 and 60 years. Levels of NAA, creatine and choline in anterior cingulate cortex, cerebellum, striatum and dorsolateral prefrontal cortex were measured with magnetic resonance spectroscopy. Then, 10mg oral MPH was given to the subjects and the same metabolite levels were measured after an interval of 30min. Distribution of the patients according to the ADHD subtypes was as follows: 21 of them (35.0%) were in the inattentive type, 11 of them (18.3%) were in the hyperactive type and 28 of them were (46.7%) in the combined type. Changes of brain metabolite levels after MPH were found not to be statistically significantly different between the subtypes. The increase of choline levels after MPH compared to the levels of choline before MPH in striatum in the combined type patients were statistically significant. No clear association was found between ADHD subtypes and changes of brain metabolites with use of MPH in adult ADHD.

Association of microRNA biogenesis pathway gene variants and alcohol dependence risk.

Alcohol dependence (AD) is a neuropsychiatric disorder to which both genetic and environmental factors contribute. Especially, multiple genetic factors are promising to explain the etiology of AD. microRNAs (miRNAs) are members of a family of noncoding small RNAs, which are thought to be responsible for the altered gene expression in neuropsychiatric disorders. We hypothesized that single nucleotide polymorphisms (SNPs) in the miRNA biogenesis pathway may result in dysregulation of miRNA levels inside the cell. The aim of this study was to test an association between miRNA biogenesis gene variants and AD risk. Real-time polymerase chain reaction genotyping experiment was conducted on DNA samples from 123 alcohol-dependent patients and 135 healthy controls. We found that AGO1 rs595961 (χ(2) = 9.066, p = 0.003; odds ratio [OR] = 0.459, 95% confidence interval [CI]: 0.275-0.768) and AGO2 rs4961280 (χ(2) = 4.111, p = 0.043; OR = 0.590, 95% CI: 0.353-0.986) G alleles have significantly altered the risk for AD, and also there is a significant association of GEMIN4 rs910924 (χ(2) = 5.291, p = 0.021; OR = 1.913, 95% CI: 1.094-3.344) T allele with the risk for AD. We also found statistically significant difference in AGO1 rs595961 (χ(2) = 11.139, p = 0.001) and DGCR8 rs1640299 (χ(2) = 13.001, p = 0.002) genotype frequencies between case-control groups. This is the first study to investigate the effects of SNPs in the miRNA biogenesis pathway on AD risk. In conclusion, we identified a significant association of miRNA biogenesis genes with altered AD risk, and these results could be a guide to research on the role of miRNAs in AD in the future.

Association of SNAP-25 Gene Ddel and Mnll Polymorphisms with Adult Attention Deficit Hyperactivity Disorder.

OBJECTIVE: The synaptosomal-associated protein of 25 kDa (SNAP-25) gene is a presynaptic plasma membrane protein and an integral component of the vesicle docking and fusion machinery mediating secretion of neurotransmitters. Previously, several studies reported association between SNAP-25 and attention deficit hyperactivity disorder (ADHD). We investigated whether these SNAP-25 polymorphisms (MnlI T/G and DdelI T/C) were also associated with ADHD in the Turkish population. METHODS: Our study comprised unrelated 139 subjects who met DSM-IV criteria for ADHD and 73 controls and all were of Turkish origin. Genetic analyses were performed and patients were evaluated with Wender-Utah Rating Scale and Adult ADD/ADHD DSM IV-Based Diagnostic Screening and Rating Scale. RESULTS: SNAP-25 DdelI polymorphism was not associated with ADHD but there was a statistically significant difference between ADHD patients and controls for SNAP-25 MnlI polymorphism. For SNAP-25 MnlI polymorphism patients with G/G genotype of the SNAP-25 gene MnlI polymorphism had higher Wender-Utah scores and higher scores in the 1st and 3rd parts of adult ADD/ADHD Scale. CONCLUSION: We detected a significant association of the MnlI polymorphism in our ADHD sample which was similar to previous findings. Our study also revealed that SNAP-25 MnlI polymorphism was also associated with symptom severity of ADHD. This study is also, the first report on the association of SNAP-25 with ADHD in the Turkish population.

Association of VAMP-2 and Syntaxin 1A Genes with Adult Attention Deficit Hyperactivity Disorder.

OBJECTIVE: The etiology of attention deficit hyperactivity disorder (ADHD) has not been entirely clarified yet. Structural and metabolic differences at the prefrontal striatal cerebellary system and the interaction of gene and environment are the main factors that thought to play roles in the etiology. Genetic investigations are performed especially about the dopamine pathways and receptors. In this study; it was aimed to investigate the association of the synaptobrevin-2 (VAMP-2) gene Ins/Del polymorphism and syntaxin 1A gene intron 7 polymorphism, which take place in encoding presynaptic protein, with adult ADHD. METHODS: One hundred thirty-nine patients, having ADHD aging between 18 and 60 years and 106 healthy people as controls were included into the study. DNA samples were extracted from whole blood and genetic analysis were performed. RESULTS: A significant difference was determined between ADHD and VAMP-2 Ins/Del polymorphism and syntaxin 1A intron 7 polymorphism according to the control group. These polymorphisms were found not to be associated with subtypes of ADHD. CONCLUSION: It is supposed that synaptic protein genes together with dopaminergic genes might have roles in the etiology of ADHD.

Association of synapsin III gene with adult attention deficit hyperactivity disorder.

It was aimed to investigate the association of the synapsin III gene -196 G> A and -631 C>G polymorphisms that takes place in an encoding presynaptic protein, with adult attention deficit hyperactivity disorder (ADHD). One hundred thirty-nine patients having adult ADHD and 106 controls were included in the study. DNA samples were extracted from whole blood and genetic analyses were performed. A significant difference was determined between ADHD and synapsin III gene -631 C>G polymorphism compared to the control group. No significant difference was determined between ADHD and synapsin III gene -196 G>A polymorphism. These polymorphisms were found not to be associated with subtypes of ADHD. It is supposed that synaptic protein genes together with dopaminergic genes might have roles in the etiology of ADHD.

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.

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.

Synaptosomal-associated protein 25 gene polymorphisms and antisocial personality disorder: association with temperament and psychopathy.

OBJECTIVE: The molecular genetic of personality disorders has been investigated in several studies; however, the association of antisocial behaviours with synaptosomal-associated protein 25 (SNAP25) gene polymorphisms has not. This association is of interest as SNAP25 gene polymorphism has been associated with attention-deficit hyperactivity disorder and personality. METHODS: We compared the distribution of DdeI and MnII polymorphisms in 91 young male offenders and in 38 sex-matched healthy control subjects. We also investigated the association of SNAP25 gene polymorphisms with severity of psychopathy and with temperament traits: novelty seeking, harm avoidance, and reward dependence. RESULTS: The MnII T/T and DdeI T/T genotypes were more frequently present in male subjects with antisocial personality disorder (APD) than in sex-matched healthy control subjects. The association was stronger when the frequency of both DdeI and MnII T/T were taken into account. In the APD group, the genotype was not significantly associated with the Psychopathy Checklist-Revised scores, measuring the severity of psychopathy. However, the APD subjects with the MnII T/T genotype had higher novelty seeking scores; whereas, subjects with the DdeI T/T genotype had lower reward dependence scores. Again, the association between genotype and novelty seeking was stronger when both DdeI and MnII genotypes were taken into account. CONCLUSION: DdeI and MnII T/T genotypes may be a risk factor for antisocial behaviours. The association of the SNAP25 DdeI T/T and MnII T/T genotypes with lower reward dependence and higher novelty seeking suggested that SNAP25 genotype might influence other personality disorders, as well.

Association among SNAP-25 gene DdeI and MnlI polymorphisms and hemodynamic changes during methylphenidate use: a functional near-infrared spectroscopy study.

OBJECTIVE: To investigate the interaction of treatment-related hemodynamic changes with genotype status for Synaptosomal associated protein 25 (SNAP-25) gene in participants with attention deficit hyperactivity disorder (ADHD) on and off single dose short-acting methylphenidate treatment with functional near-infrared spectroscopy (fNIRS). METHOD: A total of 15 right-handed adults and 16 right-handed children with DSM-IV diagnosis of ADHD were evaluated. Ten milligrams of short-acting methylphenidate was administered in a crossover design. RESULTS: Participants with SNAP-25 DdeI T/T genotype had decreased right deoxyhemoglobin ([HHb]) with treatment. SNAP-25 MnlI genotype was also associated with right deoxyhemoglobin ([HbO2]) and [HHb] changes as well as left [HHb] change. When the combinations of these genotypes were taken into account, the participants with [DdeI C/C or T/C and MnlI G/G or T/G] genotype had increased right [HHb] with MPH use whereas the participants with [DdeI T/T and MnlI T/T] or [DdeI T/T and MnlI G/G or T/G] genotypes had decreased right prefrontal [HHb]. CONCLUSIONS: These results suggested that SNAP-25 polymorphism might be associated with methylphenidate induced brain hemodynamic changes in ADHD participants.