Search

Individuals with depression differ substantially in their response to treatment with antidepressants. Specific predictors explain only a small proportion of these differences. To meaningfully predict who will respond to which antidepressant, it may be necessary to combine multiple biomarkers and clinical variables. Using statistical learning on common genetic variants and clinical information in a training sample of 280 individuals randomly allocated to 12-week treatment with antidepressants escitalopram or nortriptyline, we derived models to predict remission with each antidepressant drug. We tested the reproducibility of each prediction in a validation set of 150 participants not used in model derivation. An elastic net logistic model based on eleven genetic and six clinical variables predicted remission with escitalopram in the validation dataset with area under the curve 0.77 (95%CI; 0.66-0.88; p = 0.004), explaining approximately 30% of variance in who achieves remission. A model derived from 20 genetic variables predicted remission with nortriptyline in the validation dataset with an area under the curve 0.77 (95%CI; 0.65-0.90; p 0.001), explaining approximately 36% of variance in who achieves remission. The predictive models were antidepressant drug-specific. Validated drug-specific predictions suggest that a relatively small number of genetic and clinical variables can help select treatment between escitalopram and nortriptyline.

BACKGROUND: Strategies to dissect phenotypic and genetic heterogeneity of major depressive disorder (MDD) have mainly relied on subphenotypes, such as age at onset (AAO) and recurrence/episodicity. Yet, evidence on whether these subphenotypes are familial or heritable is scarce. The aims of this study are to investigate the familiality of AAO and episode frequency in MDD and to assess the proportion of their variance explained by common single nucleotide polymorphisms (SNP heritability).METHOD: For investigating familiality, we used 691 families with 2-5 full siblings with recurrent MDD from the DeNt study. We fitted (square root) AAO and episode count in a linear and a negative binomial mixed model, respectively, with family as random effect and adjusting for sex, age and center. The strength of familiality was assessed with intraclass correlation coefficients (ICC). For estimating SNP heritabilities, we used 3468 unrelated MDD cases from the RADIANT and GSK Munich studies. After similarly adjusting for covariates, derived residuals were used with the GREML method in GCTA (genome-wide complex trait analysis) software.RESULTS: Significant familial clustering was found for both AAO (ICC = 0.28) and episodicity (ICC = 0.07). We calculated from respective ICC estimates the maximal additive heritability of AAO (0.56) and episodicity (0.15). SNP heritability of AAO was 0.17 (p = 0.04); analysis was underpowered for calculating SNP heritability of episodicity.CONCLUSIONS: AAO and episodicity aggregate in families to a moderate and small degree, respectively. AAO is under stronger additive genetic control than episodicity. Larger samples are needed to calculate the SNP heritability of episodicity. The described statistical framework could be useful in future analyses.

Previous research has documented multiple chains of risk in the development of PTSD among war veterans. However, existing studies were mostly carried out in the West, while they also did not analyze specific symptom clusters of PTSD. The aim of this study was to examine the role of socio-demographic characteristics, war experiences and subjective quality of life in the prediction of three clusters of PTSD symptoms (i.e., avoidance, intrusion, hyperarousal). This study comprised 184 male participants who have survived war imprisonment during the Croatian Homeland War in the period from 1991 to 1995. The data was collected through several self-report measuring instruments: questionnaire on socio-demographic data, war experiences (Questionnaire on Traumatic Combat and War Experiences), subjective quality of life (WHO-Five Well-being Index), and PTSD symptoms (Impact of Events Scale - Revised). The level of three symptom clusters of PTSD was found to be moderate to high, as indicated by the scores on the IES-R. Results of the three hierarchical regression analyses showed the following: traumatic war experiences were significant predictors of avoidance symptoms ; traumatic war experiences and subjective quality of life were significant predictors of hyperarousal symptoms ; and traumatic war experiences, material status and subjective quality of life were significant predictors of intrusion symptoms. These findings support the widespread belief that the development of war-related PTSD is accounted for by multiple chains of risk, while traumatic war experiences seem to be the only predictor of all three symptom clusters. Future research should put more emphasis on specific PTSD symptom clusters when investigating the etiopathogenesis of this disorder among war- affected populations.

Objective Indirect evidence suggests that common genetic variation contributes to individual differences in antidepressant efficacy among individuals with major depressive disorder, but previous studies may have been underpowered to detect these effects. Method A meta-analysis was performed on data from three genome-wide pharmacogenetic studies (the Genome-Based Therapeutic Drugs for Depression [GENDEP] project, the Munich Antidepressant Response Signature [MARS] project, and the Sequenced Treatment Alternatives to Relieve Depression [STAR*D] study), which included 2, 256 individuals of Northern European descent with major depressive disorder, and antidepressant treatment outcomes were prospectively collected. After imputation, 1.2 million single-nucleotide polymorphisms were tested, capturing common variation for association with symptomatic improvement and remission after up to 12 weeks of antidepressant treatment. Results No individual association met a genome-wide threshold for statistical significance in the primary analyses. A polygenic score derived from a meta-analysis of GENDEP and MARS participants accounted for up to approximately 1.2% of the variance in outcomes in STAR*D, suggesting a weakly concordant signal distributed over many polymorphisms. An analysis restricted to 1, 354 individuals treated with citalopram (STAR*D) or escitalopram (GENDEP) identified an intergenic region on chromosome 5 associated with early improvement after 2 weeks of treatment. Conclusions Despite increased statistical power accorded by meta-analysis, the authors identified no reliable predictors of antidepressant treatment outcome, although they did identify modest, direct evidence that common genetic variation contributes to individual differences in antidepressant response.

Decreased platelet serotonin level is associated with fatigue and depression in Sjogren's syndrome.

Magnetic resonance spectroscopy (MRS) noninvasively provides information on the concentration of some cerebral metabolites in vivo. Among those measurable by proton magnetic resonance spectroscopy (1H-MRS), N-acetyl- aspartate (NAA) is decreased, and myo-inositol (ml) and choline (Cho) levels are increased in patients with Alzheimer's disease (AD). Donepezil, an acetylcholinesteraze inhibitor, has proven effect on cognitive symptoms in patients with AD. In previous studies, treatment response was associated with an increase of NAA and NAA/Cr in the parietal lobe and hippocampi. Correlation of longitudinal changes of 1H-MRS detectable metabolites in dorsolateral prefrontal cortex (DLPFC) with clinically observable changes is a poorly researched topic. The objective of this non-interventional study is to assess whether changes in 1H-MRS measurable metabolites correlate with clinical outcome after donepezil treatment. Twelve patients with mild to moderate AD were evaluated during 26 weeks of donepezil treatment. 1H-MRS parameters in DLPFC were assessed before and after 26 weeks of donepezil treatment. Cognition was assessed with Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-Cog). A significant increase in NAA/Cr ratio and significantly lower decrease in mI/Cr ratio were found in AD patients with positive treatment response. The results of this study indicate possible modest donepezil effect on prevention of neuronal functional deterioration in DLPFC which correlates with clinical outcome and point the use of 1HMRS as technique of help in assessment of drug effect.

Tremor, seizures, and psychosis as presenting symptoms in a patient with chronic lyme neuroborreliosis (LNB).

The results of this phase III, multicenter, randomized, double-blind, placebo-controlled clinical trial of Lu AA21004 in 560 adult patients with MDD, showed significant reduction in Hamilton Depression Rating Scale (HAM-D24) scores for all Lu AA21004 treatment groups (1 mg, 5 mg, 10 mg) compared with placebo after 8 weeks of treatment (p

A long‐time mortality of persons imprisoned in Serbian camps and prisons during the war in Croatia was observed. We gathered data about 6.237 prisoners. The prisoners were followed from their release from the camps to December 2006. Among the persons studied, men were more numerous than women (80, 86% to 19, 14%). Also, there were more soldiers (60, 11%), than civilians (39, 89%). Prisoners were released from camps or prisons at the average age of 37, 8 years, after they spent a mean period of 103 days in captivity. Over the above mentioned time period, 467 ex‐prisoners died. Average age at the time of death was 61, 9 years. The most common causes of death were ischemic heart disease, injuries, cerebrovascular disease, neoplasms and liver diseases. We found an inverse correlation between number of days spent in prison and the age of death. We conclude that population of ex‐prisoners differs significantly from general population in terms of age and causes of death.

Introduction: In studies of the neurobiological basis of psychotic disorders, schizoaffective disorder is sometimes included as part of schizophrenia patient group and sometimes as part of bipolar disorder patient group. Since most studies report hippocampal volume reduction in schizophrenia and not in bipolar disorder when analyzed without the inclusion of schizoaffective disorder patients, the aim of the study was to analyze hippocampal volume in schizoaffective disorder as a separate group. Materials and methods: Hippocampal lobe volumes were estimated using high resolution magnetic resonance imaging in 60 subjects, 15 subjects in each patient and in one healthy subjects' group. Results: Hippocampal volume in both hemispheres is statistically significantly reduced in schizophrenia and schizoaffective disorder compared to healthy control group. There is no statistically significant difference in hippocampal volume between bipolar disorder and healthy control group. Conclusion: Further studies are needed to compare other frequent neurobiological findings in schizophrenia, schizoaffective and bipolar disorder. Even though these psychotic disorders share many clinical features, their clinical differences may be substantiated by differences in structural neurobiological findings. In further studies these disorders should be analyzed separately. Key words: hippocampal volume, magnetic resonance imaging, shizoaffective disorder

Introduction: In a present pilot study, performed on 11 subjects, we studied proton magnetic resonance spectroscopy (1H‐MRS) changes in early to intermediate (3‐6 weeks) responders to antidepressant treatment with selective serotonin reuptake inhibitors (SSRIs). All subjects had diagnosis of major recurrent depression comorbid to posttraumatic stress disorder (PTSD). Subjects and methods: Magnetic spectroscopy was done in the region of dorsolateral prefrontal cortex on a 3T MRI‐unit. Participants were selected out of the larger sample due to an early response to antidepressant treatment within 3‐6 weeks, measured with Beck Depression Inventory (BDI). We measured levels of neuronal marker N‐acetyl‐ aspartate (NAA), choline (CHO) and creatine (CRE). Results: There was no difference in NAA/CRE ratios at the first and second spectroscopy (p=0, 514). However, CHO/CRE ratios showed different trend with mean value at the first spectroscopy of 1, 07 (sd=0, 12) while mean value at second was 1, 22 (sd=0, 08) with statistical significance with p‐ value of 0, 003. In conclusion, significant increase in choline to creatine ratio from the first to the second spectroscopy during the antidepressant treatment, compared to almost identical values of NAA to creatine ratio, suggests increased turnover of cell membranes as a mechanism of the early response to the antidepressant drug therapy.

The definite etiology of schizophrenia is still unknown, although there are many theories trying to explain it. It is considered that seasonality of schizophrenia could clarify the etiology of this illness. There are very few studies in differences in the birth seasonality regarding the type of schizophrenia but the results of these studies are inconsistent. Our research is conducted in the group of patients with the diagnosis of schizophrenia, who were born in the period between January, 1st 1950 and December, 31st 1960 and who were hospitalized in medical institutions in republic of Croatia by the year 1990. Data from Register of psychosis of the Croatian National Institute of Public Health and Central Bureau of Statistics were used. There were 3.257 subjects included in this study. Birth rate of schizophrenia patients with regards to the month of birth does not significantly deviate in paranoid, catatonic, hebephrenic, residual, simple, undifferentiated and other schizophrenia. In conclusion, we did not find any significant seasonality trends with regards to the different types of schizophrenia. However, we plan to expand the present study to younger persons and to persons hospitalized after 1990. Analysis of this new data will clarify present findings and perhaps shed some new light on this topic.

Limited potential of electroencephalogram (EEG), magnetic resonance images (MRI) and cerebrospinal fluid (CSF) test for 14-3-3 protein in the clinical diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) resulted in developments in diagnostic premortem tehniques. Recent studies provided evidence that magnetic resonance spectroscopy (MRS) and measurement of total- tau (T-tau) and phospho-tau (P-tau) may be useful to identify patients with CJD. We combined detected metabolic changes in the brain by MRS and measured T-tau and tau-pT181 by ELISA, and tau-pT231 by Westernblot in a patient with autopsy proven sCJD. Our results show that in contrast to negative CSF 14-3-3 protein, nonspecific EEG and MRI, MRS revealed metabolic alterations in regions of the brain that has appeared normal on MRI, and tau tests has shown measurable levels of phosphorylated and non-phosphorylated isoforms in CSF. We conclude that rapidly progressive dementia with negative 14-3-3 test and non-specific initial EEG and MRI must still be considered in the differential diagnosis of the sCJD. Combination of serial functional MRI along with MRS study and measurement of tau ratio could improve the early diagnosis of sCJD. The current case is the first attempt to study results of the use of MRS and tau tests in a case of sCJD with diagnostic dilemma.

The newest charactheristics of antidepressant response in phamacogentic trial was described.

U radu se raspravlja o sposobnosti osoba sa mentalnim poremećajima za davanje informiranog pristanka u biomedicinskim istraživanjima.

Response to the treatment with antidepressants escitalopram and nortryptiline in correlation between serotonin transporter polymorphisms was described.

Analiza po MKB-10 subtipovima

Catatonic schizphrenia has a shorter pre-hospitalisation interval than other types of schizophrenia

Sažetak dostavljen u pisanom obliku.