A Delphi-method-based consensus guideline for definition of treatment-resistant depression for clinical trials.

Criteria for treatment-resistant depression (TRD) and partially responsive depression (PRD) as subtypes of major depressive disorder (MDD) are not unequivocally defined. In the present document we used a Delphi-method-based consensus approach to define TRD and PRD and to serve as operational criteria for future clinical studies, especially if conducted for regulatory purposes. We reviewed the literature and brought together a group of international experts (including clinicians, academics, researchers, employees of pharmaceutical companies, regulatory bodies representatives, and one person with lived experience) to evaluate the state-of-the-art and main controversies regarding the current classification. We then provided recommendations on how to design clinical trials, and on how to guide research in unmet needs and knowledge gaps. This report will feed into one of the main objectives of the EUropean Patient-cEntric clinicAl tRial pLatforms, Innovative Medicines Initiative (EU-PEARL, IMI) MDD project, to design a protocol for platform trials of new medications for TRD/PRD.

Genome-wide association study of panic disorder reveals genetic overlap with neuroticism and depression.

Panic disorder (PD) has a lifetime prevalence of 2-4% and heritability estimates of 40%. The contributory genetic variants remain largely unknown, with few and inconsistent loci having been reported. The present report describes the largest genome-wide association study (GWAS) of PD to date comprising genome-wide genotype data of 2248 clinically well-characterized PD patients and 7992 ethnically matched controls. The samples originated from four European countries (Denmark, Estonia, Germany, and Sweden). Standard GWAS quality control procedures were conducted on each individual dataset, and imputation was performed using the 1000 Genomes Project reference panel. A meta-analysis was then performed using the Ricopili pipeline. No genome-wide significant locus was identified. Leave-one-out analyses generated highly significant polygenic risk scores (PRS) (explained variance of up to 2.6%). Linkage disequilibrium (LD) score regression analysis of the GWAS data showed that the estimated heritability for PD was 28.0-34.2%. After correction for multiple testing, a significant genetic correlation was found between PD and major depressive disorder, depressive symptoms, and neuroticism. A total of 255 single-nucleotide polymorphisms (SNPs) with p < 1 × 10-4 were followed up in an independent sample of 2408 PD patients and 228,470 controls from Denmark, Iceland and the Netherlands. In the combined analysis, SNP rs144783209 showed the strongest association with PD (pcomb = 3.10 × 10-7). Sign tests revealed a significant enrichment of SNPs with a discovery p-value of <0.0001 in the combined follow up cohort (p = 0.048). The present integrative analysis represents a major step towards the elucidation of the genetic susceptibility to PD.

Precision psychiatry in clinical practice.

The treatment of depression represents a major challenge for healthcare systems and choosing among the many available drugs without objective guidance criteria is an error-prone process. Recently, pharmacogenetic biomarkers entered in prescribing guidelines, giving clinicians the possibility to use this additional tool to guide prescription and improve therapeutic outcomes. This marked an important step towards precision psychiatry, which aim is to integrate biological and environmental information to personalise treatments. Only genetic variants in cytochrome enzymes are endorsed by prescribing guidelines, but in the future polygenic predictors of treatment outcomes may be translated into the clinic. The integration of genetics with other relevant information (e.g., concomitant diseases and treatments, drug plasma levels) could be managed in a standardised way through ad hoc software. The overcoming of the current obstacles (e.g., staff training, genotyping and informatics facilities) can lead to a broad implementation of precision psychiatry and represent a revolution for psychiatric care.Key pointsPrecision psychiatry aims to integrate biological and environmental information to personalise treatments and complement clinical judgementPharmacogenetic biomarkers in cytochrome genes were included in prescribing guidelines and represented an important step towards precision psychiatryTherapeutic drug monitoring is an important and cost-effective tool which should be integrated with genetic testing and clinical evaluation in order to optimise pharmacotherapyOther individual factors relevant to pharmacotherapy response (e.g., individual's symptom profile, concomitant diseases) can be integrated with genetic information through artificial intelligence to provide treatment recommendationsThe creation of pharmacogenetic services within healthcare systems is a challenging and multi-step process, education of health professionals, promotion by institutions and regulatory bodies, economic and ethical barriers are the main issues.

Personality traits and escitalopram treatment outcome in major depression.

BACKGROUND: Selective serotonin re-uptake inhibitors (SSRI) have proven to be effective in treatment of depression. Still, treatment efficacy varies significantly from patient to patient and about 40% of patients do not respond to initial treatment. Personality traits have been considered one source of variability in treatment outcome. AIM: Current study aimed at identifying specific personality traits that could be predictive of treatment response and/or the dynamics of symptom change in depressive patients. METHOD: In a sample of 132 outpatients with major depressive disorder (MDD) treated with an SSRI-group antidepressant escitalopram, the Swedish universities Scales of Personality (SSP) were used in order to find predictive personality traits. For the assessment of the severity of depressive symptoms and the improvement rates, the Hamilton Depression Scale (HAM-D) and Montgomery-Åsberg Depression Rating Scale (MADRS) were used. RESULTS: Escitalopram-treated MDD patients with higher social desirability achieved more rapid decrease in symptom severity. None of the studied traits predicted the end result of the treatment. CONCLUSION: The findings suggest that specific personality traits may predict the trajectory of symptom change rather than the overall improvement rate.

Association between personality traits and Escitalopram treatment efficacy in panic disorder.

BACKGROUND: There is strong evidence to suggest that personality factors may interact with the development and clinical expression of panic disorder (PD). A greater understanding of these relationships may have important implications for clinical practice and implications for searching reliable predictors of treatment outcome. AIMS: The study aimed to examine the effect of escitalopram treatment on personality traits in PD patients, and to identify whether the treatment outcome could be predicted by any personality trait. METHOD: A study sample consisting of 110 outpatients with PD treated with 10-20 mg/day of escitalopram for 12 weeks. The personality traits were evaluated before and after 12 weeks of medication by using the Swedish universities Scales of Personality (SSP). RESULTS: Although almost all personality traits on the SSP measurement were improved after 12 weeks of medication in comparison with the baseline scores, none of these changes reached a statistically significant level. Only higher impulsivity at baseline SSP predicted non-remission to 12-weeks treatment with escitalopram; however, this association did not withstand the Bonferroni correction in multiple comparisons. LIMITATIONS: All patients were treated in a naturalistic way using an open-label drug, so placebo responses cannot be excluded. The sample size can still be considered not large enough to reveal statistically significant findings. CONCLUSIONS: Maladaptive personality disposition in patients with PD seems to have a trait character and shows little trend toward normalization after 12-weeks treatment with the antidepressant, while the association between impulsivity and treatment response needs further investigation.

Unedited in vivo detection and quantification of γ-aminobutyric acid in the occipital cortex using short-TE MRS at 3 T.

Short-TE MRS has been proposed recently as a method for the in vivo detection and quantification of γ-aminobutyric acid (GABA) in the human brain at 3 T. In this study, we investigated the accuracy and reproducibility of short-TE MRS measurements of GABA at 3 T using both simulations and experiments. LCModel analysis was performed on a large number of simulated spectra with known metabolite input concentrations. Simulated spectra were generated using a range of spectral linewidths and signal-to-noise ratios to investigate the effect of varying experimental conditions, and analyses were performed using two different baseline models to investigate the effect of an inaccurate baseline model on GABA quantification. The results of these analyses indicated that, under experimental conditions corresponding to those typically observed in the occipital cortex, GABA concentration estimates are reproducible (mean reproducibility error, <20%), even when an incorrect baseline model is used. However, simulations indicate that the accuracy of GABA concentration estimates depends strongly on the experimental conditions (linewidth and signal-to-noise ratio). In addition to simulations, in vivo GABA measurements were performed using both spectral editing and short-TE MRS in the occipital cortex of 14 healthy volunteers. Short-TE MRS measurements of GABA exhibited a significant positive correlation with edited GABA measurements (R = 0.58, p < 0.05), suggesting that short-TE measurements of GABA correspond well with measurements made using spectral editing techniques. Finally, within-session reproducibility was assessed in the same 14 subjects using four consecutive short-TE GABA measurements in the occipital cortex. Across all subjects, the average coefficient of variation of these four GABA measurements was 8.7 ± 4.9%. This study demonstrates that, under some experimental conditions, short-TE MRS can be employed for the reproducible detection of GABA at 3 T, but that the technique should be used with caution, as the results are dependent on the experimental conditions.

Subjective Well-Being Under Neuroleptics Scale short form (SWN-K): reliability and validity in an Estonian speaking sample.

BACKGROUND: The Subjective Well-Being Under Neuroleptic Treatment Scale short form (SWN-K) is a self-rating scale developed to measure mentally ill patients' well-being under the antipsychotic drug treatment. This paper reports on adaptation and psychometric properties of the instrument in an Estonian psychiatric sample. METHODS: In a naturalistic study design, 124 inpatients or outpatients suffering from the first psychotic episode or chronic psychotic illness completed the translated SWN-K instrument. Item content analysis, internal consistency analysis, exploratory principal components analysis, and confirmatory factor analysis were used to construct the Estonian version of the SWN-K (SWN-K-E). Additionally, socio-demographic and clinical data, observer-rated psychopathology, medication side effects, daily antipsychotic drug dosages, and general functioning were assessed at two time points, at baseline and after a 29-week period; the associations of the SWN-K-E scores with these variables were explored. RESULTS: After having selected 20 items for the Estonian adaptation, the internal consistency of the total SWN-K-E was 0.93 and the subscale consistencies ranged from 0.70 to 0.80. Good test-retest reliabilities were observed for the adapted scale scores, with the correlation of the total score over about 6 months being r = 0.70. Confirmatory factor analysis replicated the presence of a higher-order factor (general well-being) and five first-order factors (mental functioning, physical functioning, social integration, emotional regulation, and self-control); the model fitted the data well. The results indicated a moderate-high correlations r = 0.54 between the SWN-K-E total score and the evaluation how satisfied patients were with their lives in generally. No significant correlations were found between the overall subjective well-being score and age, severity of the psychopathology, drug adverse effects, or prescribed drug dosage. CONCLUSION: Taken together, the results demonstrated that the Estonian version of the SWN-K is a reliable and valid instrument with psychometric properties similar to the original English version. The potential uses of the scale in both research and clinical settings are considered.

Multi-omics data integration methods and their applications in psychiatric disorders.

To study mental illness and health, in the past researchers have often broken down their complexity into individual subsystems (e.g., genomics, transcriptomics, proteomics, clinical data) and explored the components independently. Technological advancements and decreasing costs of high throughput sequencing has led to an unprecedented increase in data generation. Furthermore, over the years it has become increasingly clear that these subsystems do not act in isolation but instead interact with each other to drive mental illness and health. Consequently, individual subsystems are now analysed jointly to promote a holistic understanding of the underlying biological complexity of health and disease. Complementing the increasing data availability, current research is geared towards developing novel methods that can efficiently combine the information rich multi-omics data to discover biologically meaningful biomarkers for diagnosis, treatment, and prognosis. However, clinical translation of the research is still challenging. In this review, we summarise conventional and state-of-the-art statistical and machine learning approaches for discovery of biomarker, diagnosis, as well as outcome and treatment response prediction through integrating multi-omics and clinical data. In addition, we describe the role of biological model systems and in silico multi-omics model designs in clinical translation of psychiatric research from bench to bedside. Finally, we discuss the current challenges and explore the application of multi-omics integration in future psychiatric research. The review provides a structured overview and latest updates in the field of multi-omics in psychiatry.

Digital tools for the assessment of pharmacological treatment for depressive disorder: State of the art.

Depression is an invalidating disorder, marked by phenotypic heterogeneity. Clinical assessments for treatment adjustments and data-collection for pharmacological research often rely on subjective representations of functioning. Better phenotyping through digital applications may add unseen information and facilitate disentangling the clinical characteristics and impact of depression and its pharmacological treatment in everyday life. Researchers, physicians, and patients benefit from well-understood digital phenotyping approaches to assess the treatment efficacy and side-effects. This review discusses the current possibilities and pitfalls of wearables and technology for the assessment of the pharmacological treatment of depression. Their applications in the whole spectrum of treatment for depression, including diagnosis, treatment of an episode, and monitoring of relapse risk and prevention are discussed. Multiple aspects are to be considered, including concerns that come with collecting sensitive data and health recordings. Also, privacy and trust are addressed. Available applications range from questionnaire-like apps to objective assessment of behavioural patterns and promises in handling suicidality. Nonetheless, interpretation and integration of this high-resolution information with other phenotyping levels, remains challenging. This review provides a state-of-the-art description of wearables and technology in digital phenotyping for monitoring pharmacological treatment in depression, focusing on the challenges and opportunities of its application in clinical trials and research.

Transcriptional biomarkers of response to pharmacological treatments in severe mental disorders: A systematic review.

Variation in the expression level and activity of genes involved in drug disposition and action in tissues of pharmacological importance have been increasingly investigated in patients treated with psychotropic drugs. Findings are promising, but reliable predictive biomarkers of response have yet to be identified. Here we conducted a PRISMA-compliant systematic search of PubMed, Scopus and PsycInfo up to 12 September 2020 for studies investigating RNA expression levels in cells or biofluids from patients with major depressive disorder, schizophrenia or bipolar disorder characterized for response to psychotropic drugs (antidepressants, antipsychotics or mood stabilizers) or adverse effects. Among 5497 retrieved studies, 123 (63 on antidepressants, 33 on antipsychotics and 27 on mood stabilizers) met inclusion criteria. Studies were either focused on mRNAs (n = 96), microRNAs (n = 19) or long non-coding RNAs (n = 1), with only a minority investigating both mRNAs and microRNAs levels (n = 7). The most replicated results include genes playing a role in inflammation (antidepressants), neurotransmission (antidepressants and antipsychotics) or mitochondrial function (mood stabilizers). Compared to those investigating response to antidepressants, studies focused on antipsychotics or mood stabilizers more often showed lower sample size and lacked replication. Strengths and limitations of available studies are presented and discussed in light of the specific designs, methodology and clinical characterization of included patients for transcriptomic compared to DNA-based studies. Finally, future directions of transcriptomics of psychopharmacological interventions in psychiatric disorders are discussed.

A meta-analysis of polygenic risk scores for mood disorders, neuroticism, and schizophrenia in antidepressant response.

About two-thirds of patients with major depressive disorder (MDD) fail to achieve symptom remission after the initial antidepressant treatment. Despite a role of genetic factors was proven, the specific underpinnings are not fully understood yet. Polygenic risk scores (PRSs), which summarise the additive effect of multiple risk variants across the genome, might provide insights into the underlying genetics. This study aims to investigate the possible association of PRSs for bipolar disorder, MDD, neuroticism, and schizophrenia (SCZ) with antidepressant non-response or non-remission in patients with MDD. PRSs were calculated at eight genome-wide P-thresholds based on publicly available summary statistics of the largest genome-wide association studies. Logistic regressions were performed between PRSs and non-response or non-remission in six European clinical samples, adjusting for age, sex, baseline symptom severity, recruitment sites, and population stratification. Results were meta-analysed across samples, including up to 3,637 individuals. Bonferroni correction was applied. In the meta-analysis, no result was significant after Bonferroni correction. The top result was found for MDD-PRS and non-remission (p = 0.004), with patients in the highest vs. lowest PRS quintile being more likely not to achieve remission (OR=1.5, 95% CI=1.11-1.98, p = 0.007). Nominal associations were also found between MDD-PRS and non-response (p = 0.013), as well as between SCZ-PRS and non-remission (p = 0.035). Although PRSs are still not able to predict non-response or non-remission, our results are in line with previous works; methodological improvements in PRSs calculation may improve their predictive performance and have a meaningful role in precision psychiatry.

Diagnostic stability over 2 years in patients with acute and transient psychotic disorders.

OBJECTIVE: The nosological entity of acute and transient psychotic disorders (ATPD) as an independent diagnostic category has become a subject of controversial opinions. The present study aimed to follow-up the diagnostic stability of index episode of ATPD and to examine the influence of clinical and socio-demographic factors on the ATPD prognosis. METHOD: A sample of 153 (60.1% females; mean age 27.8 ± 8.2) first-admitted patients with ATPD was followed over 2 years. The clinical manifestations, global functioning and quality of life were regularly evaluated during follow-up period. RESULTS: At the end of follow-up, the overall stability rate of ATPD, excluding the cases not readmitted until last assessment, reached 34%. The diagnostic transition was observed in 35.9% of the patients, mostly to schizophrenia and schizoaffective disorders. There was a significant deterioration in several clinical and social indicators among the patients who developed schizophrenia, compared with those with stable ATPD, whereas no reliable predictors were found for diagnostic transition to schizophrenia, except younger age, unmarried status and period of the first hospitalization. CONCLUSION: A sizeable proportion of the patients with initial diagnosis of ATPD is likely to represent early manifestations of schizophrenia-related disorders. In agreement with some previous observations, our study indicates a lack of strong rationale for separating ATPD from other psychotic disorders within the ICD-10 F2 category.

Associations between personality traits and CCK-4-induced panic attacks in healthy volunteers.

In this study we examined how personality disposition may affect the response to cholecystokinin tetrapeptide (CCK-4; 50 microg) challenge in healthy volunteers (n=105). Personality traits were assessed with the Swedish universities Scales of Personality (SSP). Statistical methods employed were correlation analysis and logistic regression. The results showed that the occurrence of CCK-4-induced panic attacks was best predicted by baseline diastolic blood pressure, preceding anxiety and SSP-defined traits of lack of assertiveness, detachment, embitterment and verbal aggression. Significant interactions were noted between the above mentioned variables, modifying their individual effects. For different subsets of CCK-4-induced symptoms, the traits of physical aggression, irritability, somatic anxiety and stress susceptibility also appeared related to panic manifestations. These findings suggest that some personality traits and their interactions may influence vulnerability to CCK-4-induced panic attacks in healthy volunteers.

Thyroid autoimmunity and treatment response to escitalopram in major depression.

BACKGROUND: There is evidence that immune alterations play an important part in the pathogenesis of major depression. Thyroid autoimmunity has been found in association with major depression in several studies. AIM: 1) to examine whether the prevalence of anti-thyroid peroxidase autoantibodies (anti-TPO) in depressive patients differs from that in healthy controls; 2) to investigate the possible relationship between thyroid autoimmunity, total T3, free T3, free T4, thyroid-stimulating hormone (TSH), clinical status and treatment outcome in depression. METHOD: The study group consisted of 129 outpatients (69.8% female; mean age 31.7+/-12.0 years) with major depressive disorder with a Montgomery-Azsberg Depression Rating Scale total score of 22 or higher and 72 healthy controls (62.5% female; mean age 31.7+/-13.1 years). The patients were treated with escitalopram 10-20 mg/day for 12 weeks using open-label placebo non-controlled design. Anti-TPO, total T3, free T3, free T4 and TSH were measured before the treatment. RESULTS: The anti-TPO was found in eight (8.9%) depressive and two (4.8%) healthy females without statistical difference between these groups. Since anti-TPO was not seen in males, all further statistical analyses were carried out in females. At the end of week 12 of the treatment, 60 female patients (66.7%) were defined as responders and 30 depressive females (33.3%) showed insufficient response to treatment. Although there were no significant differences in the measurements between responders and non-responders, the last group showed a trend for a higher prevalence of anti-TPO compared with responders. CONCLUSION: Thyroid autoimmunity might be a factor predicting treatment response to antidepressants in depressive patients.

Peripheral gene expression profiling of CCK-4-induced panic in healthy subjects.

Progress in understanding the genetic basis of panic attacks may extend current knowledge on susceptibility to panic and pathogenesis of panic disorder. In the present study we applied the microarray Illumina platform for whole genome expression profiling in healthy subjects participating in the CCK-4-induced panic test. The study sample consisted of 31 male and female healthy volunteers, who were categorized according to predefined criteria as "panickers" or "non-panickers" to a CCK-4 challenge. The gene expression profiles were measured on peripheral blood cells at baseline and at 120 min post-CCK-4 injection using Illumina Human-6 v2 BeadChips. The fold change was used to demonstrate rate of changes in average gene expressions between studied groups. Statistical analyses were performed using the false discovery rate (FDR). Gene expression profiling 2 hr post-CCK-4 challenge showed changes in transcriptional levels of 226 genes. A total of 61 genes were differentially expressed between panickers and non-panickers with most of them related to immune, enzymatic or stress regulation systems. Other distinctive mRNA transcripts were from the genes known to be related to phenotypes associated with increased occurrence of panic attacks, such as asthma, diabetes, or myocardial ischemia. Our findings provide preliminary evidence for genetic substrates of panic attacks on the transcriptional level and indicate potential biological proximity between acute panicogenesis and several somatic conditions.

Variation in tryptophan hydroxylase-2 gene is not associated to male completed suicide in Estonian population.

Dysfunction of the central serotonergic system has been related to a spectrum of psychiatric disorders, including suicidal behavior. Tryptophan hydroxylase isoform 2 (TPH2) is the rate-limiting enzyme in the biosynthetic pathway of serotonin, being expressed in serotonergic neurons of raphe nuclei. We investigated genetic variation in TPH2 gene in two samples of male subjects: 288 suicide completers and 327 volunteers, in order to reveal any associations between 14 single nucleotide polymorphisms and completed suicide. No associations were revealed neither on allelic nor haplotype level. Our finding does not support the hypothesis of TPH2 being a susceptibility factor for completed suicide in males of Estonian origin.

Personality traits measured by the Swedish universities Scales of Personality: factor structure and position within the five-factor model in an Estonian sample.

The study aims to test the reliability and validity of the Estonian version of the Swedish universities Scales of Personality (SSP), and to characterize the position of the SSP-measured traits within the basic personality dimensions of the five-factor model. A total of 529 participants completed the Estonian version of the SSP. A subsample of 197 persons completed the SSP together with the Revised NEO Personality Inventory (NEO-PI-R). The internal consistency of the SSP scales was satisfactory. Principal component analysis yielded three factors representing neuroticism, aggression and disinhibition. The factor solution obtained in the Estonian sample was similar to the original SSP study in the Swedish normative sample. NEO-PI-R Neuroticism had highest correlations with SSP neuroticism factor scales. Extraversion had strongest relationship with adventure seeking and low detachment. Agreeableness correlated positively with SSP social desirability and negatively to aggression-irritability scales. Conscientiousness facet Deliberation correlated with Impulsiveness. The Estonian SSP showed acceptable reliability and validity, which confirms that SSP is applicable in different social and cultural background. The SSP measures traits that correspond to the major personality models. The SSP characterizes three broad dimensions of personality, namely neuroticism, disinhibition and aggression, which are useful in assessment of personality correlates of mental disorders.

Soluble interleukin-2 receptor and tumor necrosis factor levels in depressed patients in Estonia.

Several studies have reported immune system alterations in depressed patients. Furthermore, correlations between some interleukins and specific depressive symptoms have been found, but results are ambiguous. It might be caused by heterogeneous patient population and concomitant administration of antidepressants. The aim of our study was to look at differences in the levels of soluble interleukin-2 receptor (sIL-2R) and tumor necrosis factor-alpha (TNFalpha) between currently depressed patients with first or recurrent episode of depression, patients in full remission and healthy controls. Secondly, we looked for correlations between sIL-2R and TNFalpha and different depressive symptoms. A total of 75 medication-free currently depressed patients (76% of females), 17 patients in the full remission phase of major depression (58.8% of females), and 55 healthy controls (58.2% of females) participated in this study. The results showed that the level of sIL-2R was significantly lower in depressed patients in remission phase compared to the healthy controls and subjects with recurrent depression. Drug-nalve patients with major depressive disorder with recurrent episode had higher levels of sIL-2R than previously treated or patients with the first episode. TNFalpha levels were higher in drug-nalve patients with major depressive disorder with recurrent episode compared with previously treated patients. Further analysis of patients revealed that sIL-2R was positively correlated with decreased activity and agitation. TNFalpha was associated with decreased activity and suicidality.

Polymorphisms in the interleukin-10 gene cluster are possibly involved in the increased risk for major depressive disorder.

BACKGROUND: Innate immune inflammatory response is suggested to have a role in the pathogenesis of major depressive disorder (MDD). Interleukin (IL)-10 family cytokines IL-10, IL-19, IL-20, and IL-24 are all implicated in the inflammatory processes and polymorphisms in respective genes have been associated with various immunopathological conditions. This study was carried out to investigate whether single-nucleotide polymorphisms (SNPs) in these genes are also associated with MDD. METHODS: Case-control association study was performed with seven SNPs from the IL10 gene cluster. 153 patients with MDD and 277 healthy control individuals were recruited. RESULTS: None of the selected SNPs were individually associated with MDD. The linkage disequilibrium (LD) analysis indicated the existence of two recombination sites in the IL10 gene cluster, thus confirming the formerly established LD pattern of this genomic region. This also created two haplotype blocks, both consisting of three SNPs. Additionally, the haplotype analysis detected a significantly higher frequency of block 2 (IL20 and IL24 genes) haplotype TGC in the patients group compared to healthy control individuals (P = 0.0097). CONCLUSION: Our study established increased risk for MDD related to the IL20 and IL24 haplotype and suggests that cytokines may contribute to the pathogenesis of MDD. Since none of the block 2 SNPs were individually associated with MDD, it is possible that other polymorphisms linked to them contribute to the disease susceptibility. Future studies are needed to confirm the results and to find the possible functional explanation.

Association of limbic system-associated membrane protein (LSAMP) to male completed suicide.

BACKGROUND: Neuroimaging studies have demonstrated volumetric abnormalities in limbic structures of suicide victims. The morphological changes might be caused by some inherited neurodevelopmental defect, such as failure to form proper axonal connections due to genetically determined dysfunction of neurite guidance molecules. Limbic system-associated membrane protein (LSAMP) is a neuronal adhesive molecule, preferentially expressed in developing limbic system neuronal dendrites and somata. Some evidence for the association between LSAMP gene and behavior has come from both animal as well as human studies but further investigation is required. In current study, polymorphic loci in human LSAMP gene were examined in order to reveal any associations between genetic variation in LSAMP and suicidal behaviour. METHODS: DNA was obtained from 288 male suicide victims and 327 healthy male volunteers. Thirty SNPs from LSAMP gene and adjacent region were selected by Tagger algorithm implemented in Haploview 3.32. Genotyping was performed using the SNPlex (Applied Biosystems) platform. Data was analyzed by Genemapper 3.7, Haploview 3.32 and SPSS 13.0. RESULTS: Chi square test revealed four allelic variants (rs2918215, rs2918213, rs9874470 and rs4821129) located in the intronic region of the gene to be associated with suicide, major alleles being overrepresented in suicide group. However, the associations did not survive multiple correction test. Defining the haplotype blocks using confidence interval algorithm implemented in Haploview 3.32, we failed to detect any associated haplotypes. CONCLUSION: Despite a considerable amount of investigation on the nature of suicidal behaviour, its aetiology and pathogenesis remain unknown. This study examined the variability in LSAMP gene in relation to completed suicide. Our results indicate that LSAMP might play a role in pathoaetiology of suicidal behaviour but further studies are needed to understand its exact contribution.