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.

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.

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.

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.

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.

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.

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.

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.

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.

New alterations at potentially regulated regions of the Glial Derived Neurotrophic Factor gene in bipolar disorder.

INTRODUCTION: Glial Derived Neurotrophic Factor (GDNF) plays an important role in the survival and differentiation of neurons. We examined 5'upstream and 3' untranslated region of the GDNF gene by PCR amplification and direct sequencing to explore the effect of alteration in the potentially regulated part of GDNF in bipolar disorder. MATERIALS AND METHODS: Sixty-six patients with bipolar disorder, 27 first degree relatives of these patients and 56 healthy volunteers were screened for mutations and polymorphisms in GDNF gene. RESULTS: Seven previously reported polymorphisms and additional three novel allele variants of GDNF were detected. Association test of rs2075680 C>A SNP showed significant difference between patients and healthy subjects with higher allele frequency in healthy subjects performing Chi-square test. However, there was no significant difference after multiple test corrections between groups. There were no significant differences in association test of rs2075680 C>A SNP between first degree relatives and healthy volunteers/patients. rs142426358 T>C SNP was seen only in one patient with an early age of illness onset. New T>A alterations were found in chromosome locations 5:37812784 and 5:37812782 in two male bipolar disorder patients with age of illness onset 12 and 24 years. LIMITATIONS: The sample size was relatively small. DISCUSSION: Our study proposes the suggestive association between polymorphisms in the potential regulatory sites of GDNF and bipolar disorder.

Alterations in BDNF (brain derived neurotrophic factor) and GDNF (glial cell line-derived neurotrophic factor) serum levels in bipolar disorder: The role of lithium.

OBJECTIVE: Brain-derived neurotrophic factor (BDNF) has been consistently reported to be decreased in mania or depression in bipolar disorders. Evidence suggests that Glial cell line-derived neurotrophic factor (GDNF) has a role in the pathogenesis of mood disorders. Whether GDNF and BDNF act in the same way across different episodes in bipolar disorders is unclear. METHOD: BDNF and GDNF serum levels were measured simultaneously by enzyme-linked immunosorbent assay (ELISA) method in 96 patients diagnosed with bipolar disorder according to DSM-IV (37 euthymic, 33 manic, 26 depressed) in comparison to 61 healthy volunteers. SCID- I and SCID-non patient version were used for clinical evaluation of the patients and healthy volunteers respectively. Correlations between the two trophic factor levels, and medication dose, duration and serum levels of lithium or valproate were studied across different episodes of illness. RESULTS: Patients had significantly lower BDNF levels during mania and depression compared to euthymic patients and healthy controls. GDNF levels were not distinctive. However GDNF/BDNF ratio was higher in manic state compared to euthymia and healthy controls. Significant negative correlation was observed between BDNF and GDNF levels in euthymic patients. While BDNF levels correlated positively, GDNF levels correlated negatively with lithium levels. Regression analysis confirmed that lithium levels predicted only GDNF levels positively in mania, and negatively in euthymia. LIMITATIONS: Small sample size in different episodes and drug-free patients was the limitation of thestudy. CONCLUSION: Current data suggests that lithium exerts its therapeutic action by an inverse effect on BDNF and GDNF levels, possibly by up-regulating BDNF and down-regulating GDNF to achieve euthymia.

Prevalence and risk factors of depression among community dwelling elderly.

Depression in the elderly is associated with increased morbidity and mortality. The purpose of this study was to determine the prevalence and risk factors of depression among community-dwelling older population in an urban setting in Turkey. This cross-sectional study was conducted among 482 elderly individuals 65 years and over in an urban area. Cluster sampling method was used for sample size. Depression in the elderly had been diagnosed by a clinical interview and Geriatric Depression Scale. Data were collected by door-to-door survey. Chi square test was used for statistical analysis. P value, which was calculated by the results of chi square test and coefficient of phi (φ), below 0.05 was included in the analysis of logistic regression. Depression was significantly associated with female gender, being single or divorced, lower educational status, low income, unemployment, and lack of health insurance. However, logistic regression analysis revealed higher depression rates in the elderly with chronic obstructive pulmonary disease, psychiatric disease, cerebrovascular disease, low income and being dependent. Depression is common among community-dwelling older people in an urban area of Izmir, Turkey. Older adults living in community should be cautiously screened to prevent or manage depression.

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.

Treatment-induced manic switch in the course of unipolar depression can predict bipolarity: cluster analysis based evidence.

BACKGROUND: Antidepressants are known to induce manic switch in patients with depression. Treatment-induced mania is not considered as bipolar disorder in DSM IV. The aim of this study was to assess whether clinical characteristics of patients with unipolar depression with a history of treatment-induced mania were similar to those of patients with bipolar disorder. METHOD: The study included 217 consecutive patients with DSM-IV mood disorders, diagnosed as: bipolar disorder type I (BP-I, n = 58) or type II (BP-II, n = 18) whose first episodes were depression, recurrent (unipolar) major depressive disorder with a history of antidepressant treatment-induced mania (switchers = sUD; n = 61) and without such an event (rUD; n = 80). First, the groups were compared with regard to clinical features and course specifiers using variance and chi-square analysis. Variables that differed significantly between the four groups were included in two-step cluster analysis to explore naturally occurring subgroups in all diagnoses. Subsequently, the relationship between the naturally occurring clusters and pre-defined DSM-IV diagnoses were investigated. RESULTS: Two-step cluster analysis revealed two different naturally occurring groups. Higher severity of depressive episodes, with higher rate of melancholic features, higher number of hospitalization and suicide attempts were represented in one cluster where switchers (77%), bipolar I (94.8%) and II (83.3%) patients clustered together. CONCLUSION: The findings of this study confirm that treatment-induced mania is a clinical phenomenon that belongs within the bipolar spectrum rather than a coincidental treatment complication, and that it should be placed under "bipolar disorders" in future classification systems. LIMITATIONS: The study includes the limitations of any naturalistic retrospective study.

Disturbance in long distance gamma coherence in bipolar disorder.

The aim of this study was to investigate long distance event-related gamma (28-48 Hz) coherence in mania before and after valproate monotherapy. Gamma coherence in response to visual oddball paradigm in ten medication-free, manic patients was studied before and after six weeks of valproate monotherapy in comparison to ten controls. Inter-hemispheric F(3)-F(4), C(3)-C(4), T(3)-T(4), T(5)-T(6), P(3)-P(4), O(1)-O(2) and intra-hemispheric F(3)-P(3), F(4)-P(4), F(3)-T(5), F(4)-T(6), F(3)-O(1), F(4)-O(2), C(3)-O(1), C(2)-O(4) electrode pairs were included in the analysis. Repeated measures ANOVA revealed a significant difference between groups with regard to pre-treatment coherence values (p: 0.018). The coherence to the target stimuli at the right fronto-temporal location was significantly reduced by 35.41% in the patients compared to controls (p: 0.003). Patients showed significantly lower pre-treatment coherence values in response to non-target stimuli compared to controls at the right fronto-temporal (28.51%, p: 0.004), right fronto-occipital (23.71%, p: 0.024), and right centro-occipital (25.69%, p: 0.029) locations. After six weeks of valproate monotherapy, manic symptoms improved significantly. Post-treatment change in target and non-target coherence values was statistically non-significant. EEG coherence is a measure of functional connectivity in the brain. Event-related gamma oscillations are essential for brain electrical activity. The results show that acute mania presents right sided long distance connectivity disturbance, thus pointing to the potential importance of measuring oscillatory responses in the search for consistent neurobiological markers in such a complicated condition as bipolar disorder.

[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.

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.