Unhealthy lifestyle impacts on biological systems involved in stress response: hypothalamic-pituitary-adrenal axis, inflammation and autonomous nervous system.

An unhealthy lifestyle has a critical role in the pathogenesis and course of several chronic disorders. It has been hypothesized that lifestyle may also impact biological systems involved in stress response. A global index of unhealthy lifestyle was calculated based on the cumulative presence of five self-reported lifestyle habits (smoking, excessive alcohol use, drug use, low physical activity and short sleep) in 2783 participants (18-65 years) from the Netherlands Study of Depression and Anxiety. The functioning of biological stress systems was based on multiple physiological measures of cortisol, inflammatory cytokines and autonomic cardiac activity. The unhealthy lifestyle index was associated with hyperactivity of hypothalamus-pituitary-adrenal axis and increased inflammation, indicating that with increasing unhealthy habits, the level of biological stress increases. No association with the autonomic nervous system activity was observed; however, the use of drugs increased parasympathetic cardiac activity and significantly impacted on ANS. Results were not impacted by a recent episode of depression or anxiety disorder. An unhealthy lifestyle may unfavorably impact on biological systems involved in stress response, which may underlie progression of several psychiatric as well as somatic chronic disorders.

Sex-related effects in major depressive disorder: Results of the European Group for the Study of Resistant Depression.

BACKGROUND: Sex-related effects on the evolution and phenotype of major depressive disorder (MDD) were reported previously. METHODS: This European multicenter cross-sectional study compared sociodemographic, clinical, and treatment patterns between males and females in a real-world sample of 1410 in- and outpatients with current MDD. RESULTS: Male MDD patients (33.1%) were rather inpatients, suffered from moderate to high suicidality levels, received noradrenergic and specific serotonergic antidepressants (ADs) as first-line AD treatment, generally higher mean AD daily doses, and showed a trend towards a more frequent administration of add-on treatments. Female MDD patients (66.9%) were rather outpatients, experienced lower suicidality levels, comorbid thyroid dysfunction, migraine, asthma, and a trend towards earlier disease onset. CONCLUSIONS: The identified divergencies may contribute to the concept of male and female depressive syndromes and serve as predictors of disease severity and course, as they reflect phenomena that were repeatedly related to treatment-resistant depression (TRD). Especially the greater necessity of inpatient treatment and more complex psychopharmacotherapy in men may reflect increased therapeutic efforts undertaken to treat suicidality and to avoid TRD. Hence, considering sex may guide the diagnostic and treatment processes towards targeting challenging clinical manifestations including comorbidities and suicidality, and prevention of TRD and chronicity.

The Role of Relationship Status in Major Depressive Disorder - Results of the European Group for the Study of Resistant Depression.

BACKGROUND: While the association between relationship status and the development of depressive symptoms in the general population were reported previously, its relation to the severity and the course of major depressive disorder (MDD) as well as the treatment patterns and response rates needs to be elucidated. METHODS: The present international multicenter cross-sectional study performed by the European Group for the Study of Resistant Depression (GSRD) investigated socio-demographic and clinical patterns of relationship status in a real-world sample of 1410 adult in- and outpatients with MDD as primary diagnosis. RESULTS: While 49.9% of all MDD patients were partnered, 25.4% were separated, and 24.8% were single. Single relationship status was linked to younger mean age, earlier mean age of onset, and current suicidal risk. Being separated was related to older mean age, unemployment, greater symptom severity, current suicidal risk, and add-on treatment strategies. Partnered relationship status was associated with less frequent current suicidal risk. LIMITATIONS: The retrospective assessment of treatment response that was exclusively based on psychopharmacotherapeutic strategies should be critically considered and weighed while interpreting the present results providing novel insights into the complex interaction of relationship status with the clinical phenotype of MDD. CONCLUSIONS: Although MDD patients living in relationships do not seem to be omitted from the evolution of MDD, they may be spared from chronicity and suicidality. Hence, being aware of the current relationship status might support clinicians in the diagnostic and therapeutic process towards optimized management of such challenging clinical phenomena and their negative consequences.

Possible Modulatory Role of ARC Gene Variants in Mood Disorders.

OBJECTIVE: The genetic background of mood disorders is gradually emerging through the use of large multicenter samples but a detailed phenotyping is complementary in elucidating the role of modulating variants. METHODS: In the present paper we focused on the possible modulatory effects of ARC gene variants on two independent mood disorder samples of European (n = 246 bipolar disorder) and Korean (n = 132 bipolar disorder; n = 242 major depressive disorder [MDD]) ancestry. RESULTS: No result survived Bonferroni correction, however we evidenced promising trend toward possible association between ARC gene variants and mood disorder phenotypes. In particular, we evidenced weak correlations of ARC single nucleotide polymorphisms with depressive symptoms severity (evaluated through Hamilton depression rating scale scores) in the MDD Korean (rs7465272) and European (rs11167152) samples. Additionally rs10110456 was found to be related to Family History, while rs7465272 was related to suicide risk in the Korean sample. Finally, rs7465272 was associated with body mass index in the European sample. CONCLUSION: Overall, ARC gene variants may have a partial role in modulatory effect on treatment efficacy or phenotypes of mood disorders. Further studies, on larger samples may provide a better understanding on the role of ARC gene variants in the symptom severity and treatment outcomes in patients with mood disorders.

Rates of comorbid obsessive-compulsive disorder in eating disorders: A meta-analysis of the literature.

BACKGROUND: The high comorbidity between Eating Disorders (EDs) and Obsessive-Compulsive disorder (OCD) is well known, as well as its implications in terms of worse outcome and need to adapt treatment. Estimates of OCD comorbidities in EDs are variable in different studies and poorly informative for clinical purposes. In this study, we sought to derive more consistent estimates, taking into account potential methodological and sampling confounding factors. METHODS: We searched published studies reporting lifetime and current rates of comorbid OCD in ED samples based on recent diagnostic criteria. Comorbidity rates were meta-analyzed using a binary random effects model. Heterogeneity among the studies and publication bias were systematically checked. Potential confounding factors were tested by meta-regression analysis and adjusted by sensitivity analysis. RESULTS: Globally, respectively 18% and 15% of all patients with an ED had a lifetime and current comorbidity with OCD. Rates were slightly higher in anorexia (19% and 14%) than in bulimia nervosa (13% and 9%), although only the current comorbid OCD was significantly higher in anorexia than in bulimia. Prospective follow-up studies provided considerably higher lifetime estimates (EDs 38%, anorexia 44%, bulimia 19%). LIMITATIONS: Temporal/causal relationship between ED and OCD could not be defined. CONCLUSIONS: OCD comorbidity in EDs is a relevant phenomenon, affecting almost one fifth of the patients in cross-sectional observations and up to nearly 40% in prospective follow-up studies. These data indicate the need for focused attention to non-food or body-shape related OCD symptoms, for better diagnostic and prognostic accuracy, and targeted treatment.

ZNF804A Gene Variants Have a Cross-diagnostic Influence on Psychosis and Treatment Improvement in Mood Disorders.

OBJECTIVE: Genetic variations in the gene encoding zinc finger protein 804A gene (ZNF804A) have been associated with major depression and bipolar disorder. In this work we focused on the potential influence of ZNF804A variations on the risk of developing specific sub-phenotypes as well as the individual response to available treatments. METHODS: We used two samples of different ethnic origin: a Korean sample, composed by 242 patients diagnosed with major depression and 132 patients diagnosed with bipolar disorder and 326 healthy controls; an Italian sample composed 151 major depression subjects, 189 bipolar disorder subjects and 38 outpatients diagnosed for a primary anxiety disorder. RESULTS: Our analyses reported an association of rs1344706 with psychotic phenotype in the cross-diagnostic pooled sample (geno p = 4.15 × 10-4, allelic p = 1.06 × 10-4). In the cross-diagnosis Italian sample but not in the Korean one, rs7597593 was involved with depressive symptoms improvement after treatment (geno p = 0.025, allelic p = 0.007). CONCLUSION: The present study evidenced the role of ZNF804A alterations in symptoms improvement after treatment. Both manic and depressive symptoms seem to be modulated by ZNF804A, though the latter was observed in the bipolar pooled sample only. The role of this factor is likely related to synaptic development and maintenance; however, further analyses will be needed to better understand the molecular mechanics involved with ZNF804A.

Correction to: Psychiatric disorders and SLC6A4 gene variants: possible effects on alcohol dependence and alzheimer's disease.

The following authors have double affiliations: Stefania Boccia, Marco Di Nicola and they should read.

Genetic variants associated with psychotic symptoms across psychiatric disorders.

BACKGROUND: Recent evidence suggests that psychiatric symptoms share a common genetic liability across diagnostic categories. The present study investigated the effects of variants within previously identified relevant genes on specific symptom clusters, independently from the diagnosis. METHODS: 1550 subjects affected by Schizophrenia (SCZ), Major Depressive Disorder or Bipolar Disorder were included. Symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Hamilton Depression Rating Scale (HDRS). Principal component analysis and a further clinical refinement were used to define symptom clusters. Clusters scores were tested for association with 46 genetic variants within nine genes previously linked to one or more major psychiatric disorders by large genome wide association studies (ANK3, CACNA1C, CACNB2, FKBP5, FZD3, GRM7, ITIH3, SYNE1, TCF4). Exploratory analyses were performed in each disorder separately to further elucidate the SNPs effects. RESULTS: five PANSS clusters (Negative; Impulsiveness; Cognitive; Psychotic; Depressive) and four HDRS clusters (Core Depressive; Somatic; Psychotic-like; Insomnia) were identified. CACNA1C rs11615998 was associated with HDRS Psychotic cluster in the whole sample. In the SCZ sample, CACNA1C rs11062296 was associated with PANSS Impulsiveness cluster and CACNA1C rs2238062 was associated with PANSS negative cluster. DISCUSSION: CACNA1C rs11615998 was associated with psychotic symptoms (C-allele carriers have decreased psychotic-risk) independently from the diagnosis, in line with the evidence of a cross disorder effect of many risk variants. This gene was previously associated with SCZ and cross-disorder liability to psychiatric disorders. Our findings confirmed that deep phenotyping is pivotal to clarify the role of genetic variants on symptoms patterns.

Psychiatric disorders and SLC6A4 gene variants: possible effects on alcohol dependence and alzheimer's disease.

Serotoninergic system is one of the most important neurotransmission systems investigated in the field of psychiatry. Extensive evidence reveals how alterations of this system, and especially of the SLC6A4 gene, may be associated with psychiatric disorders. In this study we aimed to evaluate the pleiotropic nature of SLC6A4 alterations and their association with the overall risk of brain diseases rather than disorder-specific. SLC6A4 variants, namely 5HTTLPR, STin2, rs2066713, rs25531, rs4251417, rs6354 and rs7224199 were investigated in 4 independent cohorts of subjects with specific psychiatric disorders, including Alcohol dependence disorder (ALC), Alzheimer disease (ALZ), Schizophrenia (SCZ) and Bipolar disorder (BPD). Other variables (biochemical parameters and Psychiatric scales scores) were also tested for association. SLC6A4 polymorphisms are not associated with the risk of developing major psychiatric disorders (SCZ and BPD); however some signals were detected in ALC (HTTLPR pd = 9.25 × 10-03, pr = 7.24 × 10-03; rs2066713 pd = 6.35 × 10-08; rs25531 pd = 2.95 × 10-02; rs4251417 pd = 2.46 × 10-03), and ALZ (rs6354 pr = 1.22 × 10-02; rs7224199 pd = 1.00 × 10-08, pr = 2.65 × 10-02) cohorts. Some associations were also observed on exploratory analyses. Our findings did not reveal any major influence on SCZ and BPD development; On the other hand, some alteration of the SLC6A4 sequence were associated with an increased risk of ALC and ALZ disorders, suggesting common pathways. The results of this study should be carefully interpreted since it suffers of some inherent limitations (e.g. cohort size, slight ethnic heterogeneity). Further analyses may provide better detail on the molecular processes behind SLC6A4 alterations.

Genes Involved in Neurodevelopment, Neuroplasticity and Major Depression: No Association for CACNA1C, CHRNA7 and MAPK1.

OBJECTIVE: Genetics factors are likely to play a role in the risk, clinical presentation and treatment outcome in major depressive disorder (MDD). In this study, we investigated the role of three candidate genes for MDD; calcium voltage- gated channel subunit alpha1 C ( CACNA1C ), cholinergic receptor nicotinic alpha 7 subunit ( CHRNA7 ), and mitogen- activated protein kinase 1 ( MAPK1 ). METHODS: Two-hundred forty-two MDD patients and 326 healthy controls of Korean ancestry served as samples for the analyses. Thirty-nine single nucleotide polymorphisms (SNPs) within CACNA1C , CHRNA7 , and MAPK1 genes were genotyped and subsequently tested for association with MDD (primary analysis) and other clinical features (symptoms' severity, age of onset, history of suicide attempt, treatment outcome) (secondary analyses). Single SNPs, haplotypes and epistatic analyses were performed. RESULTS: Single SNPs were not associated with disease risk and clinical features. However, a combination of alleles (haplotype) within MAPK1 was found associated with MDD-status. Secondary analyses detected a possible involvement of CACNA1C haplotype in resistance to antidepressant treatment. CONCLUSION: These data suggest a role for MAPK1 and CACNA1C in MDD risk and treatment resistance, respectively. However, since many limitations characterize the analysis, the results must be considered with great caution and verified.

Metabolic Syndrome, Mild Cognitive Impairment, and Dementia: A Meta-Analysis of Longitudinal Studies.

OBJECTIVE: A systematic review and a meta-analysis of both clinical and population-based studies was undertaken according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement to clarify whether Metabolic Syndrome (MetS) is a risk or a protective factor for incident dementia, Alzheimer disease (AD), and vascular dementia (VaD), and whether it's involved in progression to dementia in patients affected by mild cognitive impairment (MCI). METHODS: Search terms included ("metabolic syndrome" OR "syndrome x" OR "plurimetabolic syndrome") AND ("dementia" OR "Alzheimer disease" OR "vascular dementia" OR "mild cognitive impairment" OR "MCI"). Research was restricted to articles published in English between January 1, 2000 and August 31, 2018. No age limit was set. RESULTS: At the end of the selection procedure, nine longitudinal studies were selected for the meta-analysis: six studies enrolled cognitively well-functioning participants and three studies involved MCI patients. A total of 18,313 participants aged older than 40 years with mean MetS prevalence of 22.7% were followed on average for 9.41years. A fixed model was used to estimate pooled hazard ratios and 95% confidence intervals. CONCLUSION: No statistically significant pooled association emerged between MetS and incident dementia and AD. MetS increased the incidence of pure VaD. MetS increased the risk of progression from MCI to dementia. Follow-up length might be a key factor in investigating these associations further. Because MetS is constituted by a set of potentially modifiable factors, further studies with longer follow-up and repeated assessment of both MetS and cognitive status are desirable to draw definite conclusions.

High occupational level is associated with poor response to the treatment of depression: A replication study.

Major depressive disorder (MDD) is a leading cause of disability and inability to work. There is evidence that occupational factors may precipitate a MDD episode and interfere with the recovery process. In a previous investigation, we found that those employed in high occupational levels had a worse outcome after treatment for depression (Mandelli et al., 2016). The aim of the present study was to further investigate response to treatments for depression according to occupational status on an independent sample of MDD patients. Six hundred and forty-seven (647) subjects with a stable working occupation were taken from a larger independent sample of MDD patients evaluated for response and resistance to treatment for depression, after at least one adequate treatment trial. Three broad occupational categories were considered: 'manager', 'white-collar', 'blue-collar' and 'self-employed'. Managers had the highest rate of non-response and resistance to treatments. White-collar workers also had high non-response and resistance rates. At the opposite, Blue-collar workers had significantly lower rates of non-response and resistance. Self-employed were in between White- and Blue-collar workers and did not significantly differ from the other occupational categories. The findings of this replication study substantially support our previous observations. MDD patients employed in high-middle occupations may have a less favorable outcome after standard treatments of depression. Working stressful condition and other psychosocial factors at work should be investigated more closely in relation to treatment outcomes in MDD.

Suicide attempts in eating disorder subtypes: a meta-analysis of the literature employing DSM-IV, DSM-5, or ICD-10 diagnostic criteria.

BACKGROUND: Quantification of suicidal risk in specific populations is important for the adoption of targeted prevention and harm reduction measures. Though there remains little systematic evidence, risk of suicide attempts for bulimia nervosa (BN) and binge-purging anorexia nervosa (AN-bp) appears higher than restrictive AN (AN-r); risk in binge eating disorder (BED) is still unclear. The aim of this meta-analysis was to compare proportions of suicide attempts in eating disorder (ED) subgroups. METHODS: A literature search using combinations of key-words for ED and suicide attempts was performed. Studies reporting proportions of suicide attempters in at least two ED groups, diagnosed according to DSM-IV or -5 and ICD-10 diagnostic criteria were considered. ED subgroups were analyzed in pairs using a binary random effect model for proportions. Publication bias, meta-regression, and sensitivity analyses were performed. RESULTS: In BN, attempted suicide was more frequent (21%) than in AN (12.5%), but the difference was statistically significant only when BN was compared with AN-r (9-10%). In BED, the proportion of suicide attempts was as high as in AN (10-12%). CONCLUSIONS: Though limited by heterogeneity across the studies in terms of methodology and aims, inability to control for relevant confounding variables, exclusion of ED not otherwise specified, this study supports suicide attempts as a major issue in EDs, especially in binge-purging subtypes, i.e. BN and AN-bp. Similar suicidal proportions were observed in AN and BED. The reasons for a greater proportion of attempted suicide in binge/purging subtypes need to be explored in future studies.

Opinion paper: poor response to treatment of depression in people in high occupational levels.

The working environment may have a significant effect on response to treatment of depression and this issue has not yet been sufficiently addressed in the scientific literature. There is evidence showing that being engaged in high-level positions can be an obstacle to the success of treatment. This article discusses the few evidence in the literature and some of the possible mechanisms involved. Specific personality attributes and difficulties in adapting to depression may delay access to care and may also reduce treatment compliance. The presence of stress in jobs that require high cognitive function and lack of social support may be elements that hinder the recovery process. Residual symptoms that impact on cognitive functions may undermine adherence to treatment and adversely affect the response. The implications of these issues are potentially relevant for clinical practice in the treatment of depression and for future research.

A Pharmacogenomic-based Antidepressant Treatment for Patients with Major Depressive Disorder: Results from an 8-week, Randomized, Single-blinded Clinical Trial.

Objective: Pharmacogenomic-based antidepressant treatment (PGATx) may result in more precise pharmacotherapy of major depressive disorder (MDD) with better drug therapy guidance. Methods: An 8-week, randomized, single-blind clinical trial was conducted to evaluate the effectiveness and tolerability of PGATx in 100 patients with MDD. All recruited patients were randomly allocated either to PGATx (n=52) or treatment as usual (TAU, n=48) groups. The primary endpoint was a change of total score of the Hamilton Depression Rating Scale-17 (HAMD-17) from baseline to end of treatment. Response rate (at least 50% reduction in HAMD-17 score from baseline), remission rate (HAMD-17 score ≤7 at the end of treatment) as well as the change of total score of Frequency, Intensity, and Burden of Side Effects Ratings (FIBSER) from baseline to end of treatment were also investigated. Results: The mean change of HAMD-17 score was significantly different between two groups favoring PGATx by -4.1 point of difference (p=0.010) at the end of treatment. The mean change in the FIBSER score from baseline was significantly different between two treatment groups favoring PGATx by -2.5 point of difference (p=0.028). The response rate (71.7 % vs. 43.6%, p=0.014) were also significantly higher in PGATx than in TAU at the end of treatment, while the remission rate was numerically higher in PGATx than in TAU groups without statistical difference (45.5% vs. 25.6%, p=0.071). The reason for early drop-out associated with adverse events was also numerically higher in TAU (n=9, 50.0%) than in PGATx (n=4, 30.8%). Conclusion: The present study clearly demonstrate that PGATx may be a better treatment option in the treatment of MDD in terms of effectiveness and tolerability; however, study shortcomings may limit a generalization. Adequately-powered, well-designed, subsequent studies should be mandatory to prove its practicability and clinical utility for routine practice.

Neuroplasticity, Neurotransmission and Brain-Related Genes in Major Depression and Bipolar Disorder: Focus on Treatment Outcomes in an Asiatic Sample.

INTRODUCTION: Mood disorders are common and disabling disorders. Despite the availability of over 100 psychotropic compounds, only one-third of patients benefit from first-line treatments. Over the past 20 years, many studies have focused on the biological factors modulating disease risk and response to treatments, but with still inconclusive data. In order to improve our current knowledge, in this study, we investigated the role of a set of genes involved in different pathways (neurotransmission, neuroplasticity, circadian rhythms, transcription factors, signal transduction and cellular metabolism) in the treatment outcome of major depressive disorder (MDD) and bipolar disorder (BD) after naturalistic pharmacological treatment. METHODS: Totals of 242 MDD, 132 BD patients and 326 healthy controls of Asian ethnicity (Koreans) were genotyped for polymorphisms within 19 genes. Response and remission after 6-8 weeks of treatment with antidepressants and mood stabilizers were evaluated. In secondary analyses, genetic associations with disease risk and some disease-associated features (age of onset, suicide attempt and psychotic BD) were also tested. RESULTS: None of the variants within the investigated genes was significantly associated with treatment outcomes. Some marginal association (uncorrected p < 0.01) was observed for HTR2A, BDNF, CHL1, RORA and HOMER1 SNPs. In secondary analyses, HTR2A (rs643627, p = 0.002) and CHL1 (rs4003413, p = 0.002) were found associated with risk for BD, HOMER1 (rs6872497, p = 0.002) with lifetime history of suicide attempt in patients, and RORA with early onset and presence of psychotic features in BD. Marginal results were also observed for ST8SIA2 and COMT. DISCUSSION: Despite limitations linked to multiple testing on small samples, methodological shortcomings and small significance of the findings, this study may support the involvement of some candidate genes in the outcomes of treatments for mood disorders, as well as in BD risk and other disease features.

Psychopathological Features of Bipolar Depression: Italian Validation of the Bipolar Depression Rating Scale (I-BDRS).

Background: Aim of the study was the validation of the Bipolar Disorder Rating Scale (BDRS) in an Italian population. Secondary aim was the evaluation of differences between unipolar and bipolar depression and between bipolar I and II depressed patients. Method: 125 Bipolar Disorder and 60 Major Depressive Disorder patients were administered an Italian translation of the BDRS (I-BDRS), Hamilton Depression Rating Scale (HDRS), Montgomery-Asberg Depression Rating Scale (MADRS), Young Mania Rating Scale (YMRS) and Temperament and Character Inventory-Revised (TCI-R). Results: I-BDRS showed considerable validity and reliability. Factor analysis found 3 subscales, two linked to depressive symptoms and one to mixed symptoms. Measures concerning depression (MADRS and HAM-D) were positively related to the I-BDRS's subscales, but mostly to the two subscales measuring depression. In mixed symptoms, the mean of the bipolar group was significantly higher than the unipolar group suggesting that the BDRS was able to distinguish between unipolar and bipolar depressed patients. Conclusion: I-BDRS is a valid scale for the measurement of depression in BD patients, with a notable internal consistency (Cronbach's α 0.82), a significant consistency between items/total (Cronbach's α from 0.80 to 0.82) and positive correlation with other scales (MADRS r = 0.67, p < 0.001; HDRS r = 0.81, p < 0.001; YMRS r = 0.46 p < 0.0001). The mixed state sub-scale shows usefulness in differentiating bipolar from unipolar patients. I-BDRS could be a sensitive tool, both in pure depression and in mixed states, and could be used in the everyday screening and treatment of Bipolar Disorder.

The association between electrodermal activity (EDA), depression and suicidal behaviour: A systematic review and narrative synthesis.

BACKGROUND: Electrodermal activity (EDA) and other peripheral autonomic electrical parameters have been used as indicators of emotional states, including depressive states and suicidal state. We aimed to review EDA research systematically, focusing on EDA's usefulness as a biomarker for depression and suicidal behaviour. METHODS: We searched MEDLINE, Scopus, Cochrane Library, and Web of Science databases, following PRISMA guidelines. The initial screening of articles was based on titles and abstracts; then the full text was reviewed. A preliminary synthesis of findings was developed using tables, thematic analysis and quality ratings. RESULTS: 1287 articles were screened and 77 relevant studies were identified and included in the systematic review. The studies were fairly consistent in maintaining that hypoactive electrodermal response is an established feature of patients affected by depression. There is also preliminary evidence that monitoring EDA may help to differentiate the phases of mood disorders. A few studies provided evidence that EDA can be used to differentiate acutely suicidal subjects from depressed patients who are not severely suicidal. Although EDA has been shown to be a valid, sensitive marker of suicidal ideation, suicide attempts and violent suicidal behaviour, it also seems to be influenced to some extent by antidepressant treatment. CONCLUSIONS: Most of the studies summarised in this review are quite outdated and employed a variety of designs and methods to evaluate EDA. This limits the generalisability of the results and makes it difficult to draw clear conclusions about the role of EDA in real-world settings. Electrodermal hypoactivity seems to be a reliable feature of depression and a valid marker of suicidal risk. Nevertheless, the potential utility of EDA in diagnosis, prevention, and treatment planning for depression and suicidal behaviour, should be thoroughly studied.

The Impact of a Single Nucleotide Polymorphism in SIGMAR1 on Depressive Symptoms in Major Depressive Disorder and Bipolar Disorder.

INTRODUCTION: Ample evidence suggested a role of sigma-1 receptor in affective disorders since the interaction of numerous antidepressants with sigma receptors was discovered. A recent study on Japanese subjects found a genetic variant within the encoding gene SIGMAR1 (rs1800866A>C) associated with major depressive disorder (MDD). We aimed to evaluate the same polymorphism in both MDD and bipolar disorder (BD) as well as its relationship to response to treatment with antidepressants and mood stabilizers. METHODS: A total of 238 MDD patients treated for an acute episode of depression, 132 BD patients in treatment with mood stabilizers for a manic or mixed episode, and 324 controls were genotyped for rs1800866. At discharge, response to treatments was evaluated in MDD and BD patients by the Hamilton Rating Scale for Depression (HRSD) and the Young Mania Rating Score (YMRS), respectively. RESULTS: In our Korean sample, allele frequencies were different from those reported in other Asian and non-Asian populations. The CC genotype was associated with BD and, as a trend, with MDD. No significant effect was observed on response to antidepressants in MDD or mood stabilizers in BD, although the CC genotype was more frequent among BD patients experiencing a mixed episode. CONCLUSION: The present findings are the first to propose the putative role of genetic variants within SIGMAR1 and sigma-1 receptor in BD. Sigma-1 receptor can modulate a number of central neurotransmitter systems as well as some other signaling pathways (e.g., neurotrophin and growth factor signaling) which are seemingly involved in BD and other mood disorders.