Polymorphisms in ERBB4 and TACR1 associated with dry mouth in clozapine-treated patients.

BACKGROUND: Sialorrhea is a common and uncomfortable adverse effect of clozapine, and its severity varies between patients. The aim of the study was to select broadly genes related to the regulation of salivation and study associations between sialorrhea and dry mouth and polymorphisms in the selected genes. METHODS: The study population consists of 237 clozapine-treated patients, of which 172 were genotyped. Associations between sialorrhea and dry mouth with age, sex, BMI, smoking, clozapine dose, clozapine and norclozapine serum levels, and other comedication were studied. Genetic associations were analyzed with linear and logistic regression models explaining sialorrhea and dry mouth with each SNP added separately to the model as coefficients. RESULTS: Clozapine dose, clozapine or norclozapine concentration and their ratio were not associated with sialorrhea or dryness of mouth. Valproate use (p = 0.013) and use of other antipsychotics (p = 0.015) combined with clozapine were associated with excessive salivation. No associations were found between studied polymorphisms and sialorrhea. In analyses explaining dry mouth with logistic regression with age and sex as coefficients, two proxy-SNPs were associated with dry mouth: epidermal growth factor receptor 4 (ERBB4) rs3942465 (adjusted p = 0.025) and tachykinin receptor 1 (TACR1) rs58933792 (adjusted p = 0.029). CONCLUSION: Use of valproate or antipsychotic polypharmacy may increase the risk of sialorrhea. Genetic variations in ERBB4 and TACR1 might contribute to experienced dryness of mouth among patients treated with clozapine.

Genetic Polymorphisms Associated With Constipation and Anticholinergic Symptoms in Patients Receiving Clozapine.

BACKGROUND: Clozapine impairs gastrointestinal motility owing to its anticholinergic and antiserotonergic properties. This commonly leads to constipation and potentially to more severe complications such as bowel obstruction and ischemia. The aim of this study was to determine whether genetic variations in the genes encoding muscarinic and serotonergic receptors (CHRM2, CHRM3, HTR2, HTR3, HTR4, and HTR7) explain the variations in incidence of constipation and anticholinergic symptoms during clozapine treatment. Genes associated with opiate-induced constipation were also included in this analysis (TPH1, OPRM1, ABCB1, and COMT). PROCEDURES: Blood samples from 176 clozapine-treated, Finnish, white patients with schizophrenia were genotyped. Constipation and anticholinergic symptoms were rated using the Liverpool University Neuroleptic Side Effect Rating Scale self-report questionnaire. In total, 192 single-nucleotide polymorphisms (SNPs) were detected and grouped to formulate a weighted genetic-risk score (GRS). RESULTS: No significant associations between individual SNPs or GRSs and constipation or laxative use were observed. A GRS of 19 SNPs in CHRM2, CHRM3, HTR3C, HTR7, ABCB1, OPRM1, and TPH1 was associated with anticholinergic symptoms in a generalized linear univariate model, with body mass index, clozapine monotherapy, and GRS as explaining variables (permuted P = 0.014). Generalized linear univariate model analysis performed on the opiate-induced constipation-associated SNPs and a single CHRM3 SNP revealed an association between anticholinergic symptoms and a score of 8 SNPs (adjusted P = 0.038, permuted P = 0.002). CONCLUSIONS: Two GRSs are able to predict the risk of anticholinergic symptoms in patients receiving clozapine and possibly an increased risk of gastrointestinal hypomotility.

BDNF and NRG1 polymorphisms and temperament in selective serotonin reuptake inhibitor-treated patients with major depression.

OBJECTIVE: We investigated the separate effects of and possible interactions between the functional polymorphisms of brain-derived neurotrophic factor (BDNF) rs11030101, BDNF rs61888800, and neuregulin-1 (NRG1) rs3924999 and NRG1 rs6994992 on change of temperament scores in a clinical sample of subjects with major depression (MDD), who received selective serotonin reuptake inhibitor treatment for a period of 6 weeks. METHODS: The study population consisted of 98 Finnish individuals with MDD. They were assessed by the 107-item Temperament and Character Inventory temperament questionnaire (version IX) and the Montgomery-Åsberg Depression Rating Scale (MADRS). In general linear univariate models (GLM) for novelty seeking (NS) or reward dependence (RD) change age, gender, MADRS score change and BDNF and NRG1 genotypes were used as explaining explanatory variables. RESULTS: Mean comparisons between corresponding temperament dimensions and genotypes showed significant differences between NS change and BDNF rs61888800 T-carrying status (mean difference: GG 0.30, GT/TT 2.47, p=0.022, t-test) and between RD change and NRG1 rs3924999 A-carrying status (mean difference: GG 1.21, GA/AA -0.33, p=0.003). In GLM models for NS change the significant predictors comprised BDNF rs61888800 T-carrying status, age and MADRS score change (model 1), and additionally NRG1 rs6994992 T-carrying status (model 2). For RD change the predictors included NRG1 rs3924999 A-carrying status, age and MADRS score change (model 1) and additionally gender (model 2). CONCLUSION: According to the current results both BDNF and NRG1 are associated with temperament traits during depression. These results warrant further studies regarding the impact of this association on depression recovery.

Histaminergic gene polymorphisms associated with sedation in clozapine-treated patients.

Sedation is a common adverse effect of clozapine treatment, which may be partly related to clozapine binding to histamine receptors in the central nervous system. The objective of this study was to investigate whether single nucleotide polymorphisms (SNPs) in the histaminergic system are associated with sedation in clozapine-treated patients. The study population comprised 237 clozapine-treated, Finnish, Caucasian patients that were diagnosed with schizophrenia and 176 were genotyped using Illumina HumanCoreExome-12 BeadChip. Sedation levels were assessed using self-rating questions from the Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS). The relationships between 55 different SNPs in the histaminergic system and adverse sedation effects were examined. SNPs were analyzed separately, and in groups, to formulate a genetic risk score (GRS). A permutation test was performed to avoid type I errors. Eight linked SNPs (r2 = 1) in the HNMT gene were also associated with sedation according to the GLM, adjusted for age, gender and BMI (false-discovery-rate-adjusted p = 0.013). An association on a trend level between a GRS of four different SNPs (recessive histamine N-methyltransferase HNMT rs2737385, additive histamine receptor H1 rs1552498, dominant HRH1 rs17034063 and recessive amine oxidase, copper containing 1 AOC1 rs6977381) and sedation was found (permuted p-value = 0.066) in a generalized linear model (GLM) incorporating age, gender and body mass index (BMI; adjusted R2 = 0.22). Polymorphisms in genes encoding histamine receptors or enzymes related to histamine metabolism may explain individual variation in sedative effects experienced during clozapine treatment.

Anxiety Disorders and Temperament-an Update Review.

PURPOSE OF REVIEW: The review focused on associations between temperament dimensions and clinical features in different anxiety disorders, likewise in obsessive-compulsive disorder in clinical samples of adults. A literature search was conducted in the Medline and PsycINFO databases covering the years 2010-2016. A systematic review and grading of the level of evidence for an association between temperament dimension scores and clinical features in each disorder were performed. RECENT FINDINGS: Twenty papers reporting 18 different studies were included. Five of the papers focused on panic disorder (PD), five on social anxiety disorder (SAD), three on post-traumatic stress disorder (PTSD), one on generalized anxiety disorder (GAD), three on obsessive-compulsive disorder (OCD), and an additional three papers on several anxiety disorders. The review consolidates the finding that trait anxiety, especially as assessed by Cloninger's model or the five-factor model, is a phenomenon common to all anxiety disorders and OCD. More follow-up studies including large samples are needed to differentiate the dimensional profiles of trait anxiety in specific disorders.

Resistin as an inflammatory marker in patients with schizophrenia treated with clozapine.

BACKGROUND: Schizophrenia is associated with excess cardiovascular comorbidity and mortality related to lifestyle factors, such as lack of physical activity, poor diet, and smoking. The prevalence of metabolic syndrome is increased among patients with schizophrenia, with the highest rates among patients on clozapine treatment. Smoking, obesity, physical inactivity, airway inflammation and obstruction, and adipose tissue and inflammatory marker activation are related in systemic inflammation. Low-grade inflammation is also associated with schizophrenia. Adipokine resistin is a biomarker involving several acute and chronic inflammatory states. However, the inflammatory role of resistin is so far inconclusive and studies in schizophrenia are scanty. AIMS: The aim of the present study was to explore the role of serum resistin as an inflammatory marker in patients with schizophrenia on clozapine treatment. METHODS: Associations between serum levels of resistin and some other selected cytokines/adipokines (adiponectin, leptin, adipsin, IL-6, IL-1Ra, TNF-α, hs-CRP) and metabolic markers in 190 patients with schizophrenia on clozapine treatment were studied using a cross-sectional study design. RESULTS: Among male patients especially, smokers had higher levels of resistin than non-smokers, and among smokers resistin levels were associated with IL-1Ra and hs-CRP levels. In the whole patient group levels of resistin associated with levels of IL-1Ra, and among male patients with low HDL-cholesterol. CONCLUSIONS: Resistin is a biomarker of systemic inflammation associated with smoking among patients with schizophrenia on clozapine treatment. Resistin might have a role as a marker of cardiovascular comorbidity.

INSIG2 polymorphism and weight gain, dyslipidemia and serum adiponectin in Finnish patients with schizophrenia treated with clozapine.

AIM: To investigate INSIG2's association with obesity, weight change and serum lipid profile during clozapine treatment. MATERIALS & METHODS: Subjects with schizophrenia (n = 190) were genotyped, identifying seven SNPs. Genetic risk scores (GRSs) were calculated to adiponectin, high-density lipoprotein cholesterol, triglycerides and weight gain. RESULTS: In the model for weight gain, SNPs rs12151787, rs17047733 and rs10490626 were selected. Explanatory variables were BMI (p = 5.05 × 10-5), age (p = 0.003) and GRS (p = 2.81 × 10-5, p = 0.0002 after permutation). No GRS resulted for adiponectin or high-density lipoprotein cholesterol. Rs2161829 and rs10490620 were selected for triglycerides; this GRS was insignificant after permutation. CONCLUSION: INSIG2 plays a role in weight gain and obesity during clozapine treatment.

[Diagnosis and drug therapy of anxiety disorders in primary health care]. / Ahdistuneisuushäiriöiden diagnostiikka ja lääkehoito perusterveydenhuollossa.

Generalized anxiety disorder, panic disorder and social phobia are common in primary health care patients. They may, however, be difficult to identify, since the patients seek medical attention primarily because of somatic symptoms. Anxiety disorders cause suffering, impair functional capability and are frequently accompanied by excessive use of healthcare services. These disorders are often accompanied by comorbid depression, which must be taken into consideration in the therapy. They are treated with psychotherapy, drug treatment or combination thereof. SSRI and SNRI drugs are the first-line choice of medication.

SERT and NET polymorphisms, temperament and antidepressant response.

BACKGROUND: The genetic variations in norepinephrine transporter (NET) and serotonin transporter (SERT) genes have been associated with personality traits, several psychiatric disorders and the efficacy of antidepressant treatment. AIMS: We investigated the separate effects and possible interactions between NET T-182C (rs2242446) and SERT 5-HTTLPR (rs4795541) polymorphisms on selective serotonin reuptake inhibitors (SSRI) treatment response and temperamental traits assessed by the Temperament and Character Inventory (TCI) in a clinical sample of subjects with major depressive disorder (MDD). METHODS: Our sample of 97 patients with major depression completed the 107-item TCI temperament questionnaire (version IX) at the initial assessment of the study and after 6 weeks of follow-up. All subjects received selective SSRI medications. Temperament dimension scores at baseline ( 1 ) and endpoint ( 2 ) during antidepressant treatment were analyzed between NET and SERT genotypes. RESULTS: SS-genotype of 5-HTTLPR was associated with higher baseline Persistence scores than SL- or LL-genotype. A corresponding but weaker association was found at endpoint. No differences were found between 5-HTTLPR genotypes and other temperament dimensions and 5-HTTLPR genotypes had no effect on treatment response. CONCLUSIONS: Our results suggest that the SS-genotype of 5-HTTLPR is associated with Persistence scores in patients with MDD. Higher Persistence could be viewed as a negative trait when recovering from stress and its association with short and "weaker" S-allele may be related to less efficient serotonin neurotransmission, possibly resulting in less effective coping strategies on a behavioral level.

Factors associated with subjective side-effects during clozapine treatment.

OBJECTIVE: Clozapine is associated with subjectively unpleasant or clinically serious side-effects, which may affect treatment adherence. The aims of the study were to explore the association of clozapine+ norclozapine serum concentration and other factors with subjective side-effects in schizophrenia patients. METHODS: In this cross-sectional study, 237 patients with a diagnosis of schizophrenia, schizo-affective or other non-organic psychoses completed the Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS), a self-report scale measuring side-effects of antipsychotics and a clinical questionnaire. Clozapine+ norclozapine serum concentration of 190 patients was measured. Of the patients 80 (33.7%) were on antipsychotic combination therapy. RESULTS: Higher clozapine+ norclozapine concentrations were associated with the depression-anxiety factor of LUNSERS and antipsychotic combination treatments were associated with sympatichotonia-tension factor. Younger patients reported sedation more often than older patients. CONCLUSION: According to the present results, high clozapine concentrations were associated with depression-anxiety symptoms, but the causality remains unknown.

Polymorphism in alpha 2A adrenergic receptor gene is associated with sialorrhea in schizophrenia patients on clozapine treatment.

OBJECTIVE: Clozapine-induced sialorrhea (CIS) is a common, inconvenient and socially stigmatizing adverse effect. The pathophysiology of CIS may be related to the effect of clozapine on the muscarinic and adrenergic receptors as well as the disruption of the circadian rhythms. The aim of this study was to find out if polymorphisms in muscarinic M1 and M3 receptor genes (CHRM1 and CHRM3), adrenoceptor alpha 2A gene (ADRA2A) or clock circadian regulator gene (CLOCK) are associated with CIS. METHODS: Two hundred and thirty-seven clozapine-treated Finnish schizophrenia patients were genotyped for CHRM1, CHRM3, CLOCK and ADRA2A polymorphisms, and their salivary dysfunction was assessed with two questions. Twenty-six of these patients had previously been on medication to treat CIS. Comparisons of the genotypes between patients with excessive versus non-excessive salivation were analysed. Genotype distributions between patients and control group and haplotypes were also studied. RESULTS: CHRM1, CHRM3 and CLOCK polymorphisms and haplotypes were not associated with CIS. ADRA2A (rs1800544) genotype was associated with CIS (p = 0.029). In patients with CIS, CC genotype (n = 103) was more common than in G-allele carriers (n = 79) (p = 0.013, OR 2.13, 95% CI: 1.17-3.88). No differences were found in the distributions of genotypes between patients and controls. CONCLUSIONS: ADRA2A genotype was associated with CIS.

Meta-analysis of anxiety disorders and temperament.

BACKGROUND: The aims of the present study were to explore whether symptoms in different anxiety disorders are associated with Cloninger's model temperament dimensions novelty seeking (NS), harm avoidance (HA), reward dependence and persistence compared with control subjects in clinical samples of adults or late adolescents. METHOD: Literature search in the following databases: Cochrane Library, PubMed (Medline), Web of Science, Psycinfo and PsycArticles. Systematic review, grading the level of evidence and meta-analysis for each disorder by comparing the temperament dimension scores between patient and control samples in single studies. RESULTS: A total of 40 papers fulfilled the inclusion criteria. Meta-analyses were conducted on a total of 24 studies focusing on panic disorder (PD), social anxiety disorder (SAD) and obsessive-compulsive disorder (OCD). The primary finding was a constant and clinically marked positive association between the HA temperament dimension and symptoms of PD, SAD and OCD, with a most marked effect in SAD, and a moderate effect in OCD and PD. Second, less marked and clinically marginal associations between NS score and SAD and OCD (negative associations), but no associations with PD were observed. The meta-analyses revealed heterogeneity between the results of individual studies, especially in the analyses including SAD and OCD. CONCLUSIONS: PD, SAD and OCD share a marked and state-dependent avoidant behavioral pattern, which is common for all anxiety disorders. However, PD showed a different pattern of arousal to novel stimuli from that of SAD and OCD. The findings are state dependent and based on cross-sectional studies.

Smoking and weight among patients using clozapine.

BACKGROUND: Both obesity and smoking are common in schizophrenia patients taking clozapine, causing cardiovascular disease and premature deaths. METHODS: Two hundred and thirty-seven patients with schizophrenia or related psychoses treated with clozapine completed the Liverpool University Neuroleptic Assessment Scale (LUNSERS) and a questionnaire including current height, weight, changes therein and smoking status. AIMS: The aim of this study was to analyze weight and weight change in smoking and non-smoking patients taking clozapine. A possible interaction between obesity and smoking was explored. RESULTS: No association was found between weight change and smoking status during clozapine treatment. There was no significant difference in body mass index (BMI) between non-smokers and smokers. In the analysis of covariance (ANCOVA) with BMI as the dependent variable, the best fitting model comprised age, sex, intensity of sedation, and reported amount of smoking as explanatory variables (ηp(2)= 0.116; P = 0.029; power = 0.750). None of the explanatory proportions of any single factor was significant. CONCLUSIONS: Estimated according to reported weight gain and BMI, no difference was found between smoking and non-smoking clozapine-treated patients. Number of cigarettes smoked explained BMI if age and sex were taken into account. This result is in line with the findings of some general population studies, where heavy smoking has been associated with a greater risk of obesity.

Cytokine and adipokine alterations in patients with schizophrenia treated with clozapine.

Metabolic syndrome is associated with both schizophrenia and antipsychotic medication, especially clozapine, with alterations in inflammatory cytokines and adipokines. However, the data in this field is heterogeneous and the sample sizes of the patients are limited. In this study we assessed the serum levels of cytokines/adipokines IL-6, IL-1Ra, hs-CRP and adiponectin, and components of metabolic syndrome in 190 patients with treatment resistant schizophrenia treated with clozapine. Substantial metabolic comorbidity was found in this patient group; overweight/obesity, smoking, hypertriglyceridemia, low HDL-cholesterol, high HOMA-IR, low adiponectin levels, elevated hs-CRP levels and elevated IL-1Ra levels. Elevated IL-1Ra levels are associated with insulin resistance, obesity and hypertriglyceridemia. Low adiponectin levels were associated with hypertriglyceridemia, low HDL cholesterol and high glucose, and in male patients also with obesity and high IL-1Ra levels. After controlling for confounding factors age and smoking, levels of IL-1Ra and hs-CRP associated with obesity, and the levels of IL-6 associated with obesity in female patients. We conclude that there are partly gender dependent cytokine and adipokine alterations in patients with schizophrenia on clozapine treatment associated with metabolic comorbidity. The genetic background of these cytokine alterations needs to be further investigated.

A cluster model of temperament as an indicator of antidepressant response and symptom severity in major depression.

OBJECTIVE: Not enough is known about which patients suffering from major depressive disorder benefit from antidepressant drug treatment. Individual temperament is relatively stable over a person's lifespan and is thought to be largely biologically predefined. We assessed how temperament profiles are related to depression and predict the efficacy of antidepressant treatment. METHODS: We recruited one hundred Finnish outpatients (aged 19 to 72) suffering from major depressive disorder, of whom 86 completed the 6-week study. We assessed their temperament features with the Temperament and Character Inventory and used cluster analysis to determine the patient's temperament profile. We also categorized the patients according to the vegetative symptoms of major depressive disorder. RESULTS: There was an association between skewed temperament profile and severity of major depressive disorder, but the temperament profiles alone did not predict antidepressant treatment response. Those with higher baseline vegetative symptoms score had modest treatment response. Our model with baseline Montgomery Åsberg Depression Rating Scale (MADRS) vegetative symptoms, age and temperament clusters as explanatory variables explained 20% of the variance in the endpoint MADRS scores. CONCLUSION: The temperament clusters were associated both with severity of depression and antidepressive treatment response of depression. The effect of the temperament profile alone was modest but, combined with vegetative symptoms of depression, their explanatory power was more marked suggesting that there could be an association of these two in the biological basis of MDD.

CYP1A2 polymorphism -1545C > T (rs2470890) is associated with increased side effects to clozapine.

BACKGROUND: Cytochrome P450 1A2 gene (CYP1A2) polymorphisms have been suggested to be associated with increased side effects to antipsychotics. However, studies on this are scarce and have been conducted with either various antipsychotics or only in small samples of patients receiving clozapine. The aim of the present study was to test for an association between the CYP1A2 -1545C > T (rs2470890) polymorphism and side effects in a larger sample of patients during long-term clozapine treatment. METHODS: A total of 237 patients receiving clozapine treatment completed the Liverpool University Neuroleptic Side-Effect Rating Scale (LUNSERS) assessing clozapine-induced side effects. Of these patients, 180 completed the questionnaire satisfactorily, agreed to provide a blood sample, and were successfully genotyped for the polymorphism. RESULTS: The TT genotype of CYP1A2 polymorphism -1545C > T (rs2470890) was associated with significantly more severe side effects during clozapine treatment (p = 0.011). In a subanalysis, all seven types of side effects (sympathicotonia-tension; depression-anxiety; sedation; orthostatic hypotension; dermal side effects; urinary side effects; and sexual side effects) appeared numerically (but insignificantly) more severely among TT carriers. In addition, use of mood stabilizers was more common among patients with the TT genotype (OR = 2.63, p = 0.004). CONCLUSIONS: This study has identified an association between the CYP1A2 polymorphism -1545C > T (rs2470890) and the occurrence of more severe clozapine side effects. However, these results should be regarded as tentative and more studies of larger sample sizes will be required to confirm the result.

Association between vitamin b12 levels and melancholic depressive symptoms: a Finnish population-based study.

BACKGROUND: An association between vitamin B12 levels and depressive symptoms (DS) has been reported in several epidemiological studies. The purpose of this study was to evaluate vitamin B12 levels in population-based samples with melancholic or non-melancholic DS as the relationship between vitamin B12 levels and different subtypes of DS has not been evaluated in previous studies. METHODS: Subjects without previously known type 2 diabetes, aged 45-74 years were randomly selected from the National Population Register as a part of the Finnish diabetes prevention programme (FIN-D2D). The study population (N = 2806, participation rate 62%) consisted of 1328 men and 1478 women. The health examinations were carried out between October and December 2007 according to the WHO MONICA protocol. The assessment of DS was based on the Beck Depression Inventory (BDI, cut-off ≥10 points). A DSM-IV- criteria based summary score of melancholic items in the BDI was used in dividing the participants with DS (N = 429) into melancholic (N = 138) and non-melancholic DS (N = 291) subgroups. In the statistical analysis we used chi-squared test, t-test, permutation test, analysis of covariance, multivariate logistic regression analysis and multinomial regression model. RESULTS: The mean vitamin B12 level was 331±176 pmol/L in those without DS while the subjects with non-melancholic DS had a mean vitamin B12 level of 324 ± 135 pmol/L, and those with melancholic DS had the lowest mean vitamin B12 level of 292±112 pmol/L (p < 0.001 after adjusted for age, sex, use of antidepressive medication and chronic diseases sum index). The adjusted difference of vitamin B12 levels between the non-melancholic and the melancholic group was 33 pmol/L (95%CI 8 to 57, p = 0.008). Melancholic DS and vitamin B12 levels showed an independent linearly inverse association. The relative risk ratio (RRR) for melancholic DS was 2.75 (95%CI 1.66 to 4.56) in the lowest vitamin B12 level tertile versus the highest (p for linearity <0.001) when those without DS formed the reference group. The RRR in the non-melancholic subgroup was nonsignificant. CONCLUSIONS: The vitamin B12 level was associated with melancholic DS but not with non-melancholic DS.

TPH1 A218C polymorphism and temperament in major depression.

BACKGROUND: In major depression, one of the candidate genes possibly affecting the risk and severity of symptoms has been found to be tryptophan hydroxylase (TPH1). Variation in treatment response to antidepressive agents according to TPH1 genotype has also been found in several studies. However, the relationship between temperament and TPH1 genotype in major depression is poorly understood, as only one study has been published so far. There are no earlier studies on the interaction between temperament traits, antidepressive medication response and TPH1 genotype. This interaction was studied in 97 subjects with major depression treated for six weeks with selective serotonine reuptake inhibitors. METHODS: Temperament dimensions Harm Avoidance (HA), Novelty Seeking (NS), Reward Dependence (RD) and Persistence (P) scores at baseline (1) and endpoint (2) were rated with the Temperament and Character Inventory (TCI) and compared between TPH1 A218C genotypes. Multivariate analysis of co-variance (MANCOVA) was used to analyze the interaction between the TPH1 genotype, treatment response and the different temperament dimensions at baseline and endpoint. In the analysis model, treatment response was used as a covariate and TPH1 genotype as a factor. A post hoc analysis for an interaction between remission status and TPH1 A218C genotype at endpoint HA level was also performed. RESULTS: The number of TPH1 A-alleles was associated with increasing levels in NS1 and NS2 scores and decreasing levels in HA1 and HA2 scores between TPH1 A218C genotypes. In the MANCOVA model, TPH1 genotype and treatment response had an interactive effect on both HA1 and HA2 scores, and to a lesser degree on NS2 scores. Additionally, an interaction between remission status and TPH1 A218C genotype was found to be associated with endpoint HA score, with a more marked effect of the interaction between CC genotype and remission status compared to A-allele carriers. CONCLUSIONS: Our results suggest that in acute depression TPH1 A218C polymorphism and specifically the CC genotype together with the information on remission or treatment response differentiates between different temperament profiles and their changes.

BDNF polymorphism rs11030101 is associated with the efficacy of electroconvulsive therapy in treatment-resistant depression.

The aim of the present study was to test for a possible association between two brain-derived neurotrophic factor (BDNF) polymorphisms (rs11030101 and rs61888800) and the efficacy of electroconvulsive therapy (ECT) [change in Montgomery-Åsberg Depression Rating Scale (MADRS)]. So far, there are no studies investigating an association between these polymorphisms and the efficacy of ECT. The patient sample included 119 patients with treatment-resistant major depressive disorder who were treated with ECT. BDNF polymorphism rs11030101, but not rs61888800, was associated with a change in the MADRS score. Patients with the TA genotype of rs11030101 were less likely to benefit from ECT compared with patients with the TT genotype (P=0.041). The finding suggests an association between BDNF polymorphism rs11030101 and the efficacy of ECT. Further studies with larger samples will be required to confirm this finding.

No support for a role for BDNF gene polymorphisms rs11030101 and rs61888800 in major depressive disorder or antidepressant response in patients of Finnish origin.

Brain-derived neurotrophic factor (BDNF) is suggested to play a role in the aetiology of major depression and in the antidepressant response in patients with major depression. Several BDNF gene polymorphisms have been investigated in the above-mentioned context. The aim of the present study was to examine the role of two BDNF gene polymorphisms (rs11030101 and rs61888800) in relation to the response to selective serotonin reuptake inhibitor medication in 106 patients of Finnish origin suffering from major depression. The secondary objective was to evaluate the association of these two BDNF polymorphisms in major depression, as we also had a control population of 386 healthy individuals. We did not find any significant differences in the distribution of these two BDNF gene polymorphisms in our patient population in relation to remission or response to treatment with selective serotonin reuptake inhibitor. Also, there were no significant differences between the patients and the controls.