Glial cell-derived neurotrophic factor gene polymorpisms affect severity and functionality of bipolar disorder.

Glial cell-derived neurotrophic factor and other neurotrophins have important role in the development of mental disorders. Here, we aimed to assess the effects of Single nucleotide polymorphisms at potentially regulated regions of GDNF on severity and functionality of bipolar disorder and GDNF serum levels in bipolar disorder patients and healthy volunteers. Severity and functionality of bipolar disorder were evaluated using the Clinical Global Impression and Global Assessment of Functioning scales in sixty-six bipolar disorder patients. The GDNF serum levels obtained from bipolar disorder patients and healthy volunteers who had been already reported SNPs information by our group. GAF scales were lower and GDNF serum levels were higher in Bipolar disorder patients with T/A genotype at 5:37812784 and 5:37812782 compared to patients with T/T genotype. There were significant difference in severity and functionality scores, but not in GDNF serum levels, between patients with G/G and G/A genotype of rs62360370 G > A SNP.rs2075680 C > A and rs79669773 T > C SNPs had no effect on bipolar disorder severity and functionality scores and GDNF serum levels. The results suggest that some SNPs of GDNF have potential association with severity and functionality of bipolar disorder. In addition, except two SNPs, none of GDNF SNPs had association with GDNF serum levels.

Mutation/SNP analysis in EF-hand calcium binding domain of mitochondrial Ca[Formula: see text] uptake 1 gene in bipolar disorder patients.

Calcium signaling is important for synaptic plasticity, generation of brain rhythms, regulating neuronal excitability, data processing and cognition. Impairment in calcium homeostasis contributed to the development of psychiatric disorders such as bipolar disorder (BP). MCU is the most important calcium transporter in mitochondria inner membrane responsible for influx of Ca[Formula: see text]. MICU1 is linked with MCU and has two canonical EF hands that are vital for its activity and regulates MCU-mediated Ca[Formula: see text] influx. In the current study, we aimed to investigate the role of genetic alteration of EF hand calcium binding motifs of MICU1 on the development of BP. We examined patients with BP, first degree relatives of these patients and healthy volunteers for mutations and polymorphisms in EF hand calcium binding motifs of MICU1. The result showed no SNP/mutation in BP patients, in healthy subjects and in first degree relatives. Additionally, alignment of the EF hand calcium binding regions among species (Gallus-gallus, Canis-lupus-familiaris, Bos-taurus, Mus-musculus, Rattus-norvegicus, Pan-troglodytes, Homosapiens and Danio-rerio) showed exactly the same amino acids (DLNGDGEVDMEE and DCDGNGELSNKE) except in one of the calcium binding domain of Danio-rerio that there was only one difference; leucine instead of Methionine. Our results showed that the SNP on EF-hand Ca[Formula: see text] binding domains of MICU1 gene had no effect in phenotypic characters of BP patients.

A Preliminary Observation of Increased Glial Cell Line-Derived Neurotrophic Factor in Manic Switch due to Electroconvulsive Treatment in Depressive Patients.

OBJECTIVE: Neurotrophic factors are known to be involved in the pathogenesis of mood disorders. However, the precise neurobiology underlying relapse into depression or switch to mania under antidepressant treatment is not fully understood. Evidence suggests the role of neuroplasticity in these processes. METHOD: Brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor (GDNF) serum levels were measured concomitantly during electroconvulsive treatment (ECT) in 30 depressive patients (25 patients with unipolar, 5 with bipolar depression), including those who relapsed into depression (n = 6) or switched to mania (n = 3) within 1 to 4 weeks after the end of the ECT, and in 33 healthy volunteers. RESULTS: Despite significant decrease in depression scores, the levels of brain-derived neurotrophic factor did not significantly change during the ECT, also in the patients who relapsed into depression or switched to mania. However, GDNF levels were lower in the ECT responders compared with pre-ECT levels (z = -2.203; P = 0.01) and increased in manic switch compared with the ECT responders (z = -2.761; P = 0.001) (Cohen d = -1.75; effect size r = -0.66) and healthy controls as well (P = 0.044). CONCLUSIONS: Our data suggest the role of GDNF in manic switch and the involvement of glial system in the pathogenesis of mood disorders.

Female vulnerability for thyroid function abnormality in bipolar disorder: role of lithium treatment.

BACKGROUND: Previous studies have provided evidence of subtle thyroid hormone metabolism abnormalities in patients with mood disorders. Although these studies are informative, the precise role of the hypothalamic-pituitary-thyroid axis in bipolar disorder, especially in women, remains unclear. We sought to further corroborate thyroid function in patients with bipolar disorder in comparison to patients with other psychiatric, as well as non-psychiatric, diagnoses. METHODS: In this retrospective, cross-sectional, naturalistic study, serum thyroid-stimulating hormone (TSH) levels in a total sample of 3,204 patients were compared. The study sample included patients with bipolar disorder (n = 469), unipolar depression (n = 615), and other psychiatric diagnoses (n = 999), patients from endocrinology clinics (n = 645), and patients from dermatology clinics (n = 476). Analyses were completed using two different normal ranges for TDH: a high normal range (0.4-5.0 µIU/mL) and a low normal range (0.3-3.0 µIU/mL). RESULTS: Patients with bipolar disorder showed significantly higher serum TSH levels compared to all other groups. In women, the rate of above normal range TSH was highest in patients with bipolar disorder for both high (5.0 µIU/mL; 12.1%) and low (3.0 µIU/mL; 30.4%) upper normal limits. In patients with bipolar disorder, serum TSH levels did not differ significantly between different mood states. In the lithium-treated patients (n = 240), a significantly lower percentage of women (55.9%) compared to men (71.2%) fell within the 0.3-3.0 µIU/mL normal TSH window (p = 0.016). For the high normal range (0.4-5.0 µIU/mL), serum lithium levels above 0.8 mmol/L were associated with a significantly lower proportion of female patients (59.2%) falling within the normal range than male patients (88.9%). Non-lithium treatment was not associated with a gender difference. CONCLUSIONS: Our findings show a higher rate of TSH abnormality in patients with bipolar disorder, particularly those taking lithium, compared to those with other psychiatric and medical conditions. Lithium-associated thyroid dysregulation occurs more frequently in female patients. Using the low normal range TSH values at follow-up can increase sensitivity in recognizing hyperthyroidism in lithium-treated female patients, and help in preventing the development of subclinical hypothyroidism and an adverse course of illness.

Can risk-taking be an endophenotype for bipolar disorder? A study on patients with bipolar disorder type I and their first-degree relatives.

Risk-taking behavior and impulsivity are core features of bipolar disorder. Whether they are part of the inherited aspect of the illness is not clear. We aimed to evaluate risk-taking behavior as a potential endophenotype for bipolar disorders, and its relationship with impulsivity and illness features. The Balloon Analogue Risk Task (BART) and Barratt Impulsiveness Scale-11 (BIS-11) were used to assess risk-taking behavior and impulsivity respectively in 30 euthymic bipolar I patients (BD), their 25 asymptomatic first-degree relatives (BD-R), and 30 healthy controls (HC). The primary BART outcome measure was the behavioral adjustment score (number of pumps after trials where the balloon did not pop minus the number of pumps after trials where the balloon popped). BD (p < .001) and BD-R (p = .001) had similar and significantly lower adjustment scores than HC. Only BD scored significantly higher on BIS-11 total (p = .01) and motor (p = .04) subscales than HC. Neither the BART, nor impulsivity scores associated with illness features. A limitation of this study is medicated patients and a heterogeneous BD-R were included. Riskiness may be a candidate endophenotype for bipolar disorder as it appears independently from illness features, presents similarly in BD and BD-R groups and differs from impulsivity.

Brain-derived neurotrophic factor in bipolar disorder: Associations with age at onset and illness duration.

Bipolar disorder (BD) is a heterogeneous disorder that contains neurodevelopmental differences. Defining homogeneous subgroups of BD patients by using age at onset (AAO) as a specifier may promote the classification of biomarkers. This study compares peripheral BDNF levels between pediatric and adult BD patients to investigate the associations between BDNF levels, AAO, and illness duration. We enrolled two groups of euthymic patients, those with pediatric BD (n = 39) and those with adult BD (n = 31), as well as a group of healthy controls (HCs) (n = 90). Participants were assessed using clinical measures and BDNF serum levels were obtained using ELISA. We observed that BDNF levels were comparable between adult BD and HCs, but were clearly lower in pediatric BD than in HCs. In adult BD with AAO ≥30 years, BDNF levels were significantly higher than in adult BD with AAO <30 years. In pediatric BD, patients with prepubertal-onset had higher BDNF levels than those with pubertal-onset. BDNF levels demonstrated the accuracy of being able to distinguish pediatric BD from healthy controls in a receiver operating characteristic (ROC) curve analysis (area under the curve [AUC] = 0.792). In adult BD, higher BDNF levels were associated with later disease onset, but this was not the case in pediatric BD. Finally, reduced BDNF levels were associated with illness duration in adult BD. The findings indicate that BDNF levels in BD patients are associated with AAO. BDNF may, therefore, potentially serve as a developmental marker in BD, when AAO is taken into account.

[Do general practitioners diagnose and treat patients with alcohol use problems?]. / Pratisyen Hekimler Alkol Kullanim Sorunlari Olan Hastalari Taniyor ve Tedavi Ediyorlar Mi?

AIM: To determine the primary health care working general practitioners' knowledge, attitude and behavior towards alcohol use disorders. METHOD: In this descriptive and cross-sectional study 135 general practitioners (GPs) completed the questionnaire. RESULTS: Pre and post graduate education on alcohol use disorders is low (25.4 % and 11.7% respectively). Most of the GPs do not know the levels of risky alcohol use, screening tests, and biochemical markers. The mean knowledge score is 6.67+/-1.70. Most GPs think that alcohol use disorders are not an important issue in primary health care (57%), they do not have time to deal with patients' alcohol problems (74.1%), it is difficult to diagnose risky alcohol users without clear symptoms (91.1%), patients do not follow advice on alcohol use (85.2%), and physicians themselves are tolerant towards alcohol (71.1%). Half of the GPs reported that they find it difficult to talk about alcohol use with patients and think that patients may be angered by alcohol consumption questions. Mean attitude score is 4.44+/-2.15. Most of the GPs reported that they would ask questions about alcohol use to their patients (91.7%) and declare that the patients' problems were related to alcohol (90.2%). More than half of them reported that they would refer the patient to a specialist or an alcohol treatment center (58.5%). The mean behavior score is 5.96+/-1.46. CONCLUSION: In our country it is clear that more education and support for GPs is needed due to their important role in intervention for alcohol use problems.

Neurocognitive functioning during symptomatic states and remission in bipolar disorder and schizophrenia: A comparative study.

Aims Patients with bipolar disorder present milder cognitive impairment in comparison to patients with schizophrenia. Psychotic symptoms are associated with poorer cognitive functioning in both disorders. We aim to compare cognitive dysfunction between bipolar disorder and schizophrenia across symptomatic and remitted states. Methods An extensive cognitive battery was used to assess bipolar disorder patients (32 in manic episodes with psychotic features, 44 in euthymia), patients with schizophrenia (41 symptomatic, 39 remitted), and 55 healthy controls. A global cognitive factor and six neurocognitive domain factors were identified using principal component analyses. Results Global cognition components differed according to both illness and remission status; working memory differed according to remission status regardless of diagnosis; verbal fluency differed according to diagnosis regardless of remission status. An omnibus F test revealed that the remission state had a significant impact on processing speed in schizophrenia. Conclusion Our data suggest that both disorders are associated with state dependent (i.e., global cognition and working memory) and diagnosis dependent (i.e., global cognition and verbal fluency) neurocognitive dysfunctions. Processing speed was exclusively influenced by symptomatic states of schizophrenia.

Reliability and validity of revised Turkish version of Mini Mental State Examination (rMMSE-T) in community-dwelling educated and uneducated elderly.

OBJECTIVE: To evaluate the reliability and validity of the revised Turkish version of Mini Mental State Examination (rMMSE-T) in educated and uneducated community-dwelling elderly, to re-organize the present Turkish version of MMSE and to determine cut-off point of the revised test. METHODS: This cross-sectional and analytical study involved totally 490 elderly subjects selected by cluster sampling method. Receiver operating characteristic (ROC) analysis, kappa analysis and Cronbach's alpha coefficients were used for statistical analysis. RESULTS: Areas under ROC curve in educated and uneducated elderly were found as 0.953 and 0.907. Cut-off point of 22/23 of rMMSE-T in educated elderly had the highest sensitivity (90.9), specificity (97.0) and positive likelihood ratio (30.3), whereas cut-off point of 18/19 of the test in uneducated elderly had the highest sensitivity (82.7), specificity (92.3) and positive likelihood ratio (10.7). The Cronbach's alpha values of the rMMSE-T for educated and uneducated elderly were higher than 0.7 (sign of good internal consistency of the test). A significant correlations between intrarater and interrater test-retest in educated elderly subjects were observed (0.966 (p = 0.000); 0.855 (p = 0.000), respectively), and also in uneducated elderly (0.988 (p = 0.000); 0.934 (p = 0.000), respectively). Kappa value of the test in educated and uneducated elderly showed a perfect agreement interraters (1.000) and a substantial agreement in intraraters (1.000, 0.784; 0.826, 0.656, respectively). CONCLUSION: rMMSE-T had a high reliability and validity. It will be more appropriate to use the revised test and the new cut-off point for the diagnosis and screening of dementia among community-dwelling Turkish elderly population.

Cortical thickness and surface area as an endophenotype in bipolar disorder type I patients and their first-degree relatives.

OBJECTIVES: So far, few studies have investigated cortical thickness (CT) and surface area (SA) measures in bipolar disorder type I (BDI) in comparison to a high genetic risk group such as first-degree relatives (FR). This study aimed to examine CT and SA differences between BDI, FR and healthy controls (HC). METHODS: 3D T1 magnetic resonance images were acquired from 27 euthymic BDI patients, 24 unaffected FR and 29 HC. CT and SA measures were obtained with FreeSurfer version 5.3.0. Generalized estimating equations were used to compare CT and SA between groups. Group comparisons were repeated with restricting the FR group to 17 siblings (FR-SB) only. RESULTS: \Mean age in years was 36.3 ±â€¯9.5 for BDI, 32.1 ±â€¯10.9 for FR, 34.7 ±â€¯9.8 for FR-SB and 33.1 ±â€¯9.0 for HC group respectively. BDI patients revealed larger SA of left pars triangularis (LPT) compared to HC (p = .001). In addition, increased SA in superior temporal cortex (STC) in FR-SB group compared to HC was identified (p = .0001). CONCLUSIONS: Our result of increased SA in LPT of BDI could be a disease marker and increased SA in STC of FR-SB could be a marker related with resilience to illness.

Brain oscillatory responses in patients with bipolar disorder manic episode before and after valproate treatment.

BACKGROUND: GABA/Glutamatergic dysfunction and neural circuits which regulate cognitive processing are involved in the underlying pathology of bipolar disorder. Event related oscillatory neuroelectrical activity reflects integrative brain functioning, different frequency bands representing different cognitive functions. METHODS: Event Related Potentials to visual odd-ball paradigm in ten manic/hypomanic medication free, DSM-IV bipolar patients were measured before and after six weeks of valproate monotherapy in comparison to ten sex and age matched healthy controls. Different frequency band responses were obtained by digital filtration of ERPs. Young mania rating scale (YMRS) was used to assess clinical response. Repeated measures ANOVA, Wilcoxon and Mann Whitney U tests were used for statistical analysis. RESULTS: Patients showed significantly higher baseline occipital beta (18-30 Hz) (p: 0.014) response than healthy controls. They were devoid of the occipito-frontal alpha (8-13 Hz) dominance presented by the control group. Occipital beta response reduced significantly (p: 0.009) and became similar to controls after treatment. Post-treatment alpha responses were significantly lower than baseline in anterior temporal (p: 0.038) and occipital (p: 0.027) locations. Healthy controls displayed a significantly increased frontal alpha response at the second assessment but the patients did not. Mean YMRS score reduced significantly compared to baseline at the end of six weeks (p: 0.004). CONCLUSIONS: Alpha response is the universal operator in the brain. Increased occipital beta response in mania may be compensatory to the dysfunctional alpha operation. Its reduction after valproate may be through modulation of glutamatergic and GABAergic mechanisms and indicate medication's corrective effect on the underlying pathogenesis.

Event related oscillations in euthymic patients with bipolar disorder.

Bipolar disorder involves dysfunction in gamma amino butyric acid (GABA)/glutamatergic systems and neural circuits that regulate cognitive processing. Valproate, a mood stabilizing anticonvulsant, modulates GABA/glutamate and shows neuroprotective effect. Electroencephalographic oscillatory activity assessment is an alternative brain imaging technique with high time resolution. It presents integrative brain functioning. We aimed to assess the oscillatory responses of patients with bipolar disorder in euthymic state of bipolar disorder and the changes after treatment with valproate. Event related potentials to visual odd-ball paradigm in 10 euthymic medication free, bipolar patients were measured before and after 6 weeks of valproate monotherapy and compared with sex- and age-matched healthy controls. Delta frequency bands, as representative of signal detection and decision-making, were obtained by digital filtering. At baseline, patients showed higher delta responses to target stimuli in all but significantly left frontal channels in comparison to controls. After 6 weeks of treatment, delta responses decreased significantly in central frontal (Fz) (p: 0.028), left frontal (F3) (p: 0.028), left (T3) (p: 0.015), right anterior (T4) (p: 0.011), and left posterior temporal (T5) (p: 0.011) channels compared to baseline and became no different to the controls, which did not differ between two assessments. The findings point to a diffuse increase in low frequency electrical activity which was prominent in the left frontal location in euthymic patients with bipolar disorder. Reduction of the electrical activity of the left frontal and bilateral anterior temporal areas with treatment may be through modulation of glutamatergic and GABAergic mechanisms and indicative of valproate's neuroprotective effect.

Increased hexosaminidase activity in antipsychotic-induced extrapyramidal side effects: possible association with higher occurrence in bipolar disorder patients.

Dystonic movements and Parkinsonism are frequently seen in gangliosidoses and these conditions have been reported to modify dopaminergic plasticity. We investigated whether the activity of hexosaminidase, a type-two ganglioside (GM2) degrading enzyme, correlates with drug-induced extrapyramidal system (EPS) side effects in psychiatric patients. We compared hexosaminidase activity in the lymphocytes of 29 EPS-positive patients, 13 EPS-negative patients, and 30 healthy volunteers. The activities of A and B isoforms of hexosaminidase were higher in EPS-positive patients than EPS-negative patients and healthy controls. Multivariate analysis suggested an interaction with increased B isoform activity and EPS side effects in female bipolar disorder patients. Higher levels of hexosaminidase enzyme activity may explain the frequent occurrence of antipsychotic-induced extrapyramidal side effects in mood disorder patients.

DNA redox modulations and global DNA methylation in bipolar disorder: Effects of sex, smoking and illness state.

DNA redox modulations and methylation have been associated with bipolar disorder (BD) pathophysiology. We aimed to investigate DNA redox modulation and global DNA methylation and demethylation levels in patients with BD during euthymia, mania or depression in comparison to non-psychiatric controls. The roles of sex and smoking as susceptibility factors for DNA redox modulations and global DNA methylation and demethylation were also explored. Levels of 5-methylcytosine (5-mC), 5-hydroxymethylcytosine (5-hmC) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were assessed in DNA samples of 75 patients with DSM-IV BD type I (37 euthymic, 18 manic, 20 depressive) in comparison to 60 non-psychiatric controls. Levels of 5-mC and 5-hmC were assessed using Dot Blot as a screening process, and verified using ELISA. Levels of 8-OHdG were assessed using ELISA. The levels of 8-OHdG significantly differed among non-psychiatric control, euthymia, mania and depression groups [F (3,110) = 2.771, p = 0.046], whereas there were no alterations in the levels of 5-hmC and 5-mC. Linear regression analyses revealed the significant effects of smoking (p = 0.031) and sex (p = 0.012) as well as state of illness on the levels of 8-OHdG (p = 0.025) in patients with BD. Our results suggest that levels of 8-OHdG may be affected by sex, illness states and smoking in BD.

Oxidatively-induced DNA damage and base excision repair in euthymic patients with bipolar disorder.

Oxidatively-induced DNA damage has previously been associated with bipolar disorder. More recently, impairments in DNA repair mechanisms have also been reported. We aimed to investigate oxidatively-induced DNA lesions and expression of DNA glycosylases involved in base excision repair in euthymic patients with bipolar disorder compared to healthy individuals. DNA base lesions including both base and nucleoside modifications were measured using gas chromatography-tandem mass spectrometry and liquid chromatography-tandem mass spectrometry with isotope-dilution in DNA samples isolated from leukocytes of euthymic patients with bipolar disorder (n = 32) and healthy individuals (n = 51). The expression of DNA repair enzymes OGG1 and NEIL1 were measured using quantitative real-time polymerase chain reaction. The levels of malondialdehyde were measured using high performance liquid chromatography. Seven DNA base lesions in DNA of leukocytes of patients and healthy individuals were identified and quantified. Three of them had significantly elevated levels in bipolar patients when compared to healthy individuals. No elevation of lipid peroxidation marker malondialdehyde was observed. The level of OGG1 expression was significantly reduced in bipolar patients compared to healthy individuals, whereas the two groups exhibited similar levels of NEIL1 expression. Our results suggest that oxidatively-induced DNA damage occurs and base excision repair capacity may be decreased in bipolar patients when compared to healthy individuals. Measurement of oxidatively-induced DNA base lesions and the expression of DNA repair enzymes may be of great importance for large scale basic research and clinical studies of bipolar disorder.

Is the Ultimate Treatment Response Predictable with Early Response in Major Depressive Episode?

INTRODUCTION: New evidence suggests that the efficacy of antidepressants occurs within the first weeks of treatment and this early response predicts the later response. The purpose of the present study was to investigate if the partial response in the first week predicts the response at the end of treatment in patients with major depressive disorder who are treated with either antidepressant medication or electroconvulsive therapy. METHODS: Inpatients from Dokuz Eylül University Hospital with a major depressive episode, treated with antidepressant medication (n=52) or electroconvulsive therapy (ECT) (n=48), were recruited for the study. The data were retrospectively collected to decide whether a 25% decrease in the Hamilton Depression Rating Scale (HDRS) score at the first week of treatment predicts a 50% decrease at the third week using validity analysis. In addition, the effects of socio-demographic and clinical variables on the treatment response were assessed. RESULTS: A 25% decrease in the HDRS score in the first week of treatment predicted a 50% decrease in the HDRS score in the third week with a 78.3% positive predictive value, 62.1% negative predictive value, 62.1% sensitivity, and 78.3% specificity for antidepressant medications and an 88% positive predictive value, 52.2% negative predictive value, 66.7% sensitivity, and 80% specificity for ECT. The number of previous hospitalizations, comorbid medical illnesses, number of depressive episodes, duration of illness, and duration of the current episode were related to the treatment response. CONCLUSION: Treatment response in the first week predicted the response in the third week with a high specificity and a high positive predictive value. Close monitoring of the response from the first week of treatment may thus help the clinician to predict the subsequent response.

A double-blind controlled study of adjunctive treatment with risperidone in schizophrenic patients partially responsive to clozapine: efficacy and safety.

BACKGROUND: Several open trials and case studies have reported beneficial effects following the addition of risperidone for partial responders to clozapine. The purpose of this study was to carry out a placebo-controlled, randomized, double-blind trial of the efficacy, safety, and tolerability of adjunctive treatment with risperidone in patients with schizophrenia partially responsive to clozapine. METHOD: In this 6-week double-blind study, 30 patients with DSM-IV schizophrenia who had partial response to clozapine despite being treated for a mean of 32 months were randomly assigned to risperidone (N = 16) up to 6 mg/day or placebo (N = 14). Efficacy assessments included the Positive and Negative Syndrome Scale (PANSS), the Calgary Depression Scale, the Clinical Global Impressions-Severity of Illness scale, the Global Assessment of Functioning scale, and the Quality of Life Scale. A variety of safety and tolerability measures were also obtained. Data were collected between November 2001 and July 2003. RESULTS: Significant improvement was noted in both groups on a variety of measures of psychopathology, but there was significantly greater improvement in the placebo-treated patients on the primary outcome measure, the PANSS positive symptom subscale. There were no significant differences between the treatment groups regarding extrapyramidal symptoms, weight gain, vital signs, serum clozapine levels, and QTc interval. The only side effect significantly more severe in risperidone-treated compared to placebo-treated patients was sedation. The patients treated with risperidone developed significant increases in plasma prolactin levels. CONCLUSION: Adjunctive risperidone treatment in schizophrenia patients partially responsive to clozapine does not significantly improve psychopathology or quality of life compared to placebo in a 6-week period.

Lithium-induced alterations in nucleoside triphosphate levels in human brain: a proton-decoupled 31P magnetic resonance spectroscopy study.

We examined how lithium's demonstrated effects on various cellular processes in human brain would be reflected in the (31)P magnetic resonance spectra of living human beings with respect to brain high-energy phosphate metabolites. Eight healthy volunteers received a baseline (31)P magnetic resonance spectroscopy (MRS) scan, after which they received lithium carbonate, 900 mg/day, for 14 days. Follow-up MRS scans were obtained on day 7 and on day 14. We detected a lithium-induced decrease in alpha-, beta-, gamma- and total nucleoside triphosphate NTP levels with chronic administration of lithium. On day 7, significant decreases were noted in gamma-NTP (14%) and total NTP (11%) levels. There was a trend for a decrease in beta-NTP (11%) levels. On day 14, significant decreases were noted in alpha-NTP (7%) and total NTP (8%) levels. There was a trend for a decrease in beta-NTP (16%) levels. Lithium caused a 25% reduction in inorganic phosphate (P(i)) levels on day 14. The theoretical relevance of the lithium-induced alterations on brain high-energy phosphates to the lithium-induced modifications of neuroplasticity is discussed.

[Factorial structure, validity, and reliability of the Turkish temperament and character inventory]. / Mizaç ve Karakter Envanteri'nin Türkçe Formunun Faktör Yapisi, Geçerlik ve Güvenilirligi.

OBJECTIVE: To assess the factorial structure, reliability and validity of the Turkish version of the Temperament and Character Inventory (TCI), a 240-item, self-report, paper-and-pencil test, and true-false format inventory based on Cloninger's psychobiological model of personality. It measures the four higher-order temperament dimensions and three character dimensions. METHOD: Using samples consisting of 470 healthy volunteers and 544 psychiatric patients, psychometric features were explored. RESULTS: The internal consistency of the scales was good (Cronbach alpha coefficients between 0.68 and 0.84), but weak for Reward dependence (0.55) and Persistence (0.56). The factor structures of the temperament and character dimensions, explored separately, were in agreement with the hypothesized constructs, except for the scales NS1 (Novelty Seeking 1 = exploratory excitability) and SD4 (Self-directedness 4 -- self-acceptance). The present study also confirmed that the TCI scales were weakly related among themselves. On the whole, psychiatric patients had higher harm avoidance and lower self-directedness, persistence, cooperativeness, and self-transcendence scores than the normal subjects. Gender differences were also found for different dimensions. CONCLUSION: The findings of this study suggest that the TCI can be applied in the investigation of psychiatric and normal populations.

Neuroanatomical correlates of genetic risk for bipolar disorder: A voxel-based morphometry study in bipolar type I patients and healthy first degree relatives.

BACKGROUND: Bipolar disorder (BD) is a highly heritable mental illness which is associated with neuroanatomical abnormalities. Investigating healthy individuals at high genetic risk for bipolar disorder may help to identify neuroanatomical markers of risk and resilience without the confounding effects of burden of illness or medication. METHODS: Structural magnetic resonance imaging scans were acquired from 30 euthymic patients with BD-I (BP), 28 healthy first degree relatives of BD-I patients (HR), and 30 healthy controls (HC). Data was analyzed using DARTEL for voxel based morphometry in SPM8. RESULTS: Whole-brain analysis revealed a significant main effect of group in the gray matter volume in bilateral inferior frontal gyrus, left parahippocampal gyrus, left lingual gyrus and cerebellum, posterior cingulate gyrus, and supramarginal gyrus (alphasim corrected (≤0.05 FWE)). Post-hoc t-tests showed that inferior frontal gyrus volumes were bilaterally larger both in BP and HR than in HC. BP and HR also had smaller cerebellar volume compared with HC. In addition, BP had smaller left lingual gyrus volume, whereas HR had larger left parahippocampal and supramarginal gyrus volume compared with HC. LIMITATIONS: This study was cross-sectional and the sample size was not large. All bipolar patients were on medication, therefore we were not able to exclude medication effects in bipolar group in this study. CONCLUSIONS: Our findings suggest that increased inferior frontal gyrus and decreased cerebellar volumes might be associated with genetic predisposition for bipolar disorder. Longitudinal studies are needed to better understand the predictive and prognostic value of structural changes in these regions.