Baseline circulating biomarkers, their changes, and subsequent suicidal ideation and depression severity at 6 months: A prospective analysis in patients with mood disorders.

BACKGROUND: Identifying circulating biomarkers associated with prospective suicidal ideation (SI) and depression could help better understand the dynamics of these phenomena and identify people in need of intense care. In this study, we investigated the associations between baseline peripheral biomarkers implicated in neuroplasticity, vascular homeostasis and inflammation, and prospective SI and depression severity during 6 months of follow-up in patients with mood disorders. METHODS: 149 patients underwent a psychiatric evaluation and gave blood to measure 32 plasma soluble proteins. At follow-up, SI incidence over six months was measured with the Columbia Suicide Severity Rating Scale, and depressive symptoms were assessed with the Inventory for Depressive Symptomatology. Ninety-six patients provided repeated blood samples. Statistical analyses included Spearman partial correlation and Elastic Net regression, followed by the covariate-adjusted regression models. RESULTS: 51.4 % (N = 71) of patients reported SI during follow-up. After adjustment for covariates, higher baseline levels of interferon-γ were associated with SI occurrence during follow-up. Higher baseline interferon-γ and lower orexin-A were associated with increased depression severity, and atypical and anxious, but not melancholic, symptoms. There was also a tendency for associations of elevated baseline levels of interferon-γ, interleukin-1ß, and lower plasma serotonin levels with SI at the six-month follow-up time point. Meanwhile, reduction in transforming growth factor- ß1 (TGF-ß1) plasma concentration correlated with atypical symptoms reduction. CONCLUSION: We identified interferon-γ and orexin-A as potential predictive biomarkers of SI and depression, whereas TGF-ß1 was identified as a possible target of atypical symptoms.

Higher levels of plasma Adrenocorticotropic hormone (ACTH) are associated with lower suicidal ideation in depressed patients compared to controls and suicide attempters, independently from depression severity.

Introduction: Suicidal ideation, an important risk factor for suicide attempts, has an unclear neurobiological basis and is potentially linked to the dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and immune-inflammatory systems. While inflammatory markers have been associated with suicide attempts and, to a lower extent suicidal ideation, the data on the role of a stress-response system is less robust, with most studies carried out with cortisol showing inconsistent results. The present study extends on the previous studies implicating stress-response and immune-inflammatory systems in suicidal thoughts and behaviours, focusing on the associations of several stress-response (adrenocorticotropic hormone (ACTH), cortisol, and dehydroepiandrosterone (DHEA)) and immune-inflammatory (C-reactive protein (CRP),interle ukin-6 (IL-6), and tumour necrosis factor-alpha (TNF-alpha)) with suicidal ideation severity in recent suicide attempters, patients with major depressive disorder, and non-psychiatric controls. Methods: This observational study included 156 adults from three Vilnius hospitals, recruited into one of the three groups in equal parts: recent suicide attempters, patients with major depressive disorder in current depressive episode, and non-psychiatric controls. Measures included the Hamilton Depression Rating Scale (HDRS-17) and the Beck Scale for Suicide Ideation/Suicide Severity Index (BSS/SSI), alongside sociodemographic data, alcohol, tobacco use, and morning blood samples, measuring plasma ACTH, cortisol, DHEA, CRP, and IL-6. Data were analysed with non-parametric tests, Kendall's tau correlation, and multivariate linear regression adjusted for confounders. Results: We found a negative correlation between the plasma ACTH levels and suicidal ideation severity (tau = -0.130, p = 0.033), which was driven by the patients with major depressive disorder (tau = -0.237, p = 0.031). Suicidal ideation severity was also negatively correlated with TNF-alpha (tau = -0.231; p < 0.001), positively correlated with IL-6 (tau = 0.154, p = 0.015), and CRP levels (tau = 0.153, p = 0.015), but no differences were observed in group-stratified analyses. The association between plasma ACTH levels and suicidal ideation severity in patients with major depressive disorder remained robust to adjustment for major confounders (adjusted for age, sex, education years, body mass index, smoking status, plasma CRP and PEth concentration (measuring chronic alcohol exposure), and antidepressant use) in the linear regression model (t = -2.71, p = 0.011), as well as additionally adjusting for depression severity (t = -2.99, p = 0.006). Discussion: The present study shows an association between plasma ACTH levels and suicidal ideation severity in patients with major depressive disorder, robust to adjustment for antidepressant use and depression severity. This finding highlights the potential role of ACTH, in elucidating the effects of stress and mental health disorders. Our findings underscore the importance of the HPA axis in the diagnosis and treatment of suicidal ideation in major depressive disorder and invite further research on interventions targeting this pathway.

Clinical features in co-occuring obsessive-compulsive disorder and bipolar disorder: A systematic review and meta-analysis.

Obsessive-compulsive disorder (OCD) frequently co-occurs with various psychiatric conditions and may impact as many as one-fifth of individuals diagnosed with bipolar disorder (BD). Despite the expanding body of literature on the coexistence of OCD and BD, there is a notable lack of comprehensive data pertaining to the distinct features of obsessive-compulsive symptoms that define this comorbidity. To bridge this knowledge gap, we conducted a systematic search of PubMed/MEDLINE, Scopus, EMBASE, and PsycINFO until August 7th, 2023. We performed random-effects meta-analyses to compare individuals with both OCD and BD to those with OCD in terms of OCD symptomatology as well as the specific categories of obsessions and compulsions. Out of the 10,393 records initially screened, 17 studies were ultimately incorporated into the qualitative assessment, with 15 of them being included in the quantitative analysis. Individuals with OCD and BD experienced fewer lifetime contamination obsessions (OR=0.71; 95 %CI=0.53, 0.95; p = 0.021) and more sexual obsessions (OR=1.77; 95 %CI=1.03, 3.04; p = 0.04) compared to individuals with OCD without BD. No significant difference was observed for other types of obsessions or compulsions or for the severity of OCD symptoms, although BD type may play a role according to meta-regression analyses. The detection of the presence of sexual or contamination obsessions through a detailed interview may be the focus of clinical attention when assessing OCD in the context of comorbid BD. Sub-phenotyping complex clinical presentation of comorbid psychiatric disorders can aid in making more informed decisions when choosing an appropriate treatment approach.

Attitudes of psychiatrists towards people with mental illness: a cross-sectional, multicentre study of stigma in 32 European countries.

Background: Mental health-related stigma occurs among the public and professionals alike. The lived experience of mental illness has been linked to less stigmatising attitudes. However, data on psychiatrists and the relationship between stigmatising attitudes and psychotherapeutic activity or case discussion groups remains scarce. Methods: A cross-sectional multicentre study was performed in 32 European countries to investigate the lived experiences and attitudes of psychiatrists toward patients with mental illness as well as the relationship between stigma, psychosocial and professional factors. The self-reported, anonymous, internet-based Opening Minds Stigma Scale for Health Care Providers was used to measure the stigmatising attitudes. The survey was translated into the local language of each participating country. All participants were practising specialists and trainees in general adult or child and adolescent psychiatry. The study took place between 2nd October, 2019 and 9th July, 2021 and was preregistered at ClinicalTrial.gov (NCT04644978). Findings: A total of 4245 psychiatrists completed the survey. The majority, 2797 (66%), had completed training in psychiatry, and 3320 (78%) worked in adult psychiatry. The final regression model showed that across European countries more favourable attitudes toward people with mental illness were statistically significantly associated with the lived experience of participants (including seeking help for their own mental health conditions (d = -0.92, 95% confidence interval (CI) = -1.68 to -0.15, p = 0.019), receiving medical treatment for a mental illness (d = -0.88, 95% CI = -1.71 to -0.04, p = 0.040), as well as having a friend or a family member similarly affected (d = -0.68, 95% CI = -1.14 to -0.22, p = 0.004)), being surrounded by colleagues who are less stigmatising (d = -0.98, 95% CI = -1.26 to -0.70, p < 0.001), providing psychotherapy to patients (d = -1.14, 95% CI = -1.63 to -0.65 p < 0.001), and being open to (d = -1.69, 95% CI = -2.53 to -0.85, p < 0.001) and actively participating in (d = -0.94, 95% CI = -1.45 to -0.42, p < 0.001) case discussion, supervision, or Balint groups. Interpretation: Our study highlights the importance of psychotherapy training, supervision, case discussions and Balint groups in reducing the stigmatising attitudes of psychiatrists toward patients. As the findings represent cross-national predictors, Europe-wide policy interventions, national psychiatric education systems and the management of psychiatric institutions should take these findings into consideration. Funding: National Youth Talent Award (Ministry of Human Resources, Hungary, (NTP-NFTÖ-20-B-0134). All authors received no funding for their contribution.

Associations of potential plasma biomarkers with suicide attempt history, current suicidal ideation and subsequent suicidal events in patients with depression: A discovery study.

A growing body of evidences suggests that suicidal ideation (SI) and suicidal behaviors have biological bases. However, no biological marker is currently available to evaluate the suicide risk in individuals with SI or suicide attempt (SA). Moreover, the current risk assessment techniques poorly predict future suicidal events. The aim of this study was to examine the association of 39 new and already described peripheral cells and proteins (implicated in the immune system, oxidative stress and plasticity) with lifetime SA, past month SA, current SI, and future suicidal events (visit to the Emergency Department for SI or SA) in 266 treatment-seeking individuals with mood disorders. Equal parts of patients with and without past history of SA were recruited. All individuals at inclusion gave blood, were evaluated for SA recency, current SI, and were followed for two years afterwards. The 39 peripheral blood cellular and protein markers were entered separately for each outcome in Elastic Net models with 10-fold cross-validation, followed by single-analyte covariate-adjusted regression analyses for pre-selected analytes. Past month SA was associated with increased plasma levels of thrombospondin-2 and C-reactive protein, whereas current SI was associated with lower plasma serotonin levels. These associations were robust to adjustments for key covariates and corrections for multiple testing. The Cox proportional hazards regression showed that higher levels of thrombospondin-1 and of platelet-derived growth factor-AB predicted a future suicidal event. These two associations remained after adjustment for sex, age, and SA history, and outperformed the predictive value of past SA. Thrombospondins and platelet-derived growth factors have never been investigated in the context of suicide. Altogether, our results highlight the involvement in the suicidal process of platelet biological response and plasticity modifiers and also of inflammatory factors. They also suggest that SI and SA may have different biological correlates and that biomarkers associated with past SA or current SI do not automatically also predict future events.

Psychometric properties of the Opening Minds Stigma Scale for Health Care Providers in 32 European countries - A bifactor ESEM representation.

Aims: To measure the stigma of healthcare providers toward people suffering from mental illness, the Opening Minds Stigma Scale for Health Care Providers (OMS-HC) is a commonly applied instrument. However, this scale has not been thoroughly validated in many European countries, its psychometric properties are still unknown and data on practicing psychiatrists is lacking. Therefore, this multicenter study aimed to assess the psychometric characteristics of the 15-item OMS-HC in trainees and specialists in adult and child psychiatry in 32 countries across Europe. Materials and methods: The OMS-HC was conducted as an anonymous online survey and sent via Email to European adult and child psychiatrists. Parallel analysis was used to estimate the number of OMS-HC dimensions. Separate for each country, the bifactor ESEM, a bifactor exploratory structural equation modeling approach, was applied to investigate the factor structure of the scale. Cross-cultural validation was done based on multigroup confirmatory factor analyses and reliability measures. Results: A total of 4,245 practitioners were included, 2,826 (67%) female, 1,389 (33%) male. The majority (66%) of participants were specialists, with 78% working in adult psychiatry. When country data were analyzed separately, the bifactor model (higher-order factor solution with a general factor and three specific factors) showed the best model fit (for the total sample χ2/df = 9.760, RMSEA = 0.045 (0.042-0.049), CFI = 0.981; TLI = 0.960, WRMR = 1.200). The average proportion of variance explained by the general factor was high (ECV = 0.682). This suggests that the aspects of 'attitude,' 'disclosure and help-seeking,' and 'social distance' could be treated as a single dimension of stigma. Among the specific factors, the 'disclosure and help-seeking' factor explained a considerable unique proportion of variance in the observed scores. Conclusion: This international study has led to cross-cultural analysis of the OMS-HC on a large sample of practicing psychiatrists. The bifactor structure displayed the best overall model fit in each country. Rather than using the subscales, we recommend the total score to quantify the overall stigmatizing attitudes. Further studies are required to strengthen our findings in countries where the proposed model was found to be weak.

Significantly elevated phosphatidylethanol levels in recent suicide attempters, but not in depressed controls and healthy volunteers.

INTRODUCTION: Suicide is a complex transdiagnostic phenomenon. It is strongly associated with, but not exclusive to major depressive disorder (MDD). Hazardous alcohol drinking has also been linked to an increased risk of suicidal behaviours, however, it is often underreported. The study aimed to evaluate whether an objective measure of chronic alcohol use, phosphatidylethanol (PEth) could be useful as a biomarker in clinical practice. METHOD: ology. The present case-control multi-centric study recruited 156 participants into three study groups: 52 patients treated for major depressive disorder (MDD), 51 individuals immediately following a suicide attempt (SA), and 53 volunteers. Sociodemographic data, medical history, and laboratory data, including PEth concentrations and C-reactive protein levels, were collected from study participants. RESULTS: PEth concentrations were the highest in suicide attempters (232,54 ± 394,01 ng/ml), followed by patients with MDD (58,39 ± 135,82 ng/ml), and the control group (24,45 ± 70,83 ng/ml) (Kruskall Wallis χ2 = 12.23, df = 2, p = .002). In a multinomial logistic regression model with adjustments, PEth concentration was able to predict belonging to suicide attempters' group, but not to depression group (p = .01). Suicide attempters were also more likely to underreport their recent alcohol consumption. LIMITATIONS: We did not analyze SA methods, psychiatric comorbidity and several other factors that might be associated with PEth levels, such as body mass index, race, and haemoglobin levels. Sample recruited in hospital settings may not be representative of the whole population. The results of this adult-only study cannot be generalized to adolescents. CONCLUSIONS: PEth levels in recent suicide attempters significantly exceeded those of patients with MDD and controls. Suicide attempters also were more likely to underreport their alcohol consumption when questioned about their consuption. PEth might be an interesting biomarker to evaluate individuals at risk of SA.

Associations of white blood cell and platelet counts with specific depressive symptom dimensions in patients with bipolar disorder: Analysis of data from the FACE-BD cohort.

Evidences suggest that inflammation is increased in a subgroup of patients with depression. Moreover, increased peripheral inflammatory markers (cells and proteins) are associated with some, but not all depressive symptoms. On the other hand, similar studies on bipolar disorders mainly focused on blood cytokines. Here, we analysed data from a large (N = 3440), well-characterized cohort of individuals with bipolar disorder using Kendall partial rank correlation, multivariate linear regression, and network analyses to determine whether peripheral blood cell counts are associated with depression severity, its symptoms, and dimensions. Based on the self-reported 16-Item Quick Inventory of Depressive Symptomatology questionnaire scores, we preselected symptom dimensions based on literature and data-driven principal component analysis. We found that the counts of all blood cell types were only marginally associated with depression severity. Conversely, white blood cell count was significantly associated with the sickness dimension and its four components (anhedonia, slowing down, fatigue, and appetite loss). Platelet count was associated with the insomnia/restlessness dimension and its components (initial, middle, late insomnia and restlessness). Principal component analyses corroborated these results. Platelet count was also associated with suicidal ideation. In analyses stratified by sex, the white blood cell count-sickness dimension association remained significant only in men, and the platelet count-insomnia/restlessness dimension association only in women. Without implying causation, these results suggest that peripheral blood cell counts might be associated with different depressive symptoms in individuals with bipolar disorder, and that white blood cells might be implicated in sickness symptoms and platelets in insomnia/agitation and suicidal ideation.

Escitalopram should be investigated in anorexia nervosa: Rationale and review of mechanisms.

One of the biggest ambitions in the field of anorexia nervosa (AN) research is to find a reliable and effective pharmacological treatment. The fact that currently no pharmacological treatment is safe and effective in this disease is worrying and also challenging. On the basis of the progress in our understanding of AN neurobiology, we propose that escitalopram, a widely available drug, might be a safe and effective option that needs to be investigated. Escitalopram is the only selective serotonin reuptake inhibitor, without any catecholaminergic effect. As studies have shown decreased serotonergic and increased dopaminergic transmission in AN, we hypothesized that an ideal drug for AN management should boost serotonin levels to increase serotonergic and decrease dopaminergic transmission, the two main features of escitalopram action. Here, we present a short overview of pharmacological research in AN and discuss the theoretical rationale for escitalopram use in AN. We also call for double-blind, randomized, placebo-controlled trials to test whether this theoretical framework translates into clinical efficacy.

Combined effects of nitric oxide synthase 3 genetic variant and childhood emotional abuse on earlier onset of suicidal behaviours.

Marked heterogeneity in suicide attempters has been observed, with earlier onset being linked to stronger heritability, more childhood maltreatment. Nitric oxide signalling system might be implicated in this relationship through its role in the stress response/adaptation. This study examined how NOS genetic variants and childhood maltreatment were associated with age at first suicide attempt (SA). Adult patients with SA history (N = 414) filled in the Childhood Trauma Questionnaire, and six functionally relevant NOS2 and NOS3 polymorphisms were genotyped. Analyses included χ2, Mann-Whitney U tests, Kendall's regression, multivariate linear and Cox survival regressions, and a moderation analysis. The NOS3 promotor 27-bp variable number tandem repeat (VNTR) bb homozygous state and childhood emotional abuse were independently associated with earlier age at first SA, which was robust after controlling for confounders [regression coefficient - 3.975, 95% CI -6.980 - (-0.970), p = 0.010, and - 1.088, 95% CI -2.172 - (-0.004), p = 0.049]. No interaction was observed. In the Cox proportional hazards model for age at first SA, the hazard ratio for patients with childhood emotional abuse and NOS3 27-bp VNTR bb was 0.533 (95% CI 0.394-0.720, p < 0.001) compared to patients without. Intermediate scores were observed with either only the risk genotype or only childhood emotional abuse. A graded relationship was also observed for repeated SA, family history of SA, and severe SA history. These results are preliminary due to a low statistical power and call for replication and further characterization of the role of nitric oxide system in the susceptibility to early-onset SB.

Selenium deficiency is associated with disease severity, disrupted reward processing, and increased suicide risk in patients with Anorexia Nervosa.

BACKGROUND & AIMS: Patients with Anorexia Nervosa (AN) present many nutritional deficiencies (macro- and often also micro-nutrients), possibly explained by their inadequate food intake. Previous studies reported that selenium (Se) deficiency is common in the general population. As Se can be easily added as a supplement, the goal of this study was to evaluate the clinical impact of Se deficiency in patients with AN. METHODS: This cross-sectional study concerned 153 patients with AN (92.9% women) followed at the Eating Disorder Unit of Lapeyronie Academic Hospital, Montpellier, France. Patients underwent an extensive neuropsychological assessment, and completed validated questionnaires. Blood samples were collected for Se quantification. Results were compared with the t-test, Mann-Whitney U, and Chi square tests, and univariate linear and multivariate logistic regression models. RESULTS: Se plasma levels were below the cut-off of 80 µg/L in 53.6% (N = 82) of patients. AN onset was earlier in patients with Se deficiency, (p = .005), whereas disease duration was comparable between groups (p = .77). General eating disorder symptomatology in the past 28 days (Eating Disorder Examination Questionnaire) was more severe in patients with Se deficiency (p = .010). The suicide risk (MINI International Neuropsychiatric Evaluation) tended to be higher (p = .037), and suicide attempt history was more frequent (28.39% vs 9.85%, p = .004) in patients with low Se levels. Se plasma concentration was negatively correlated with the performance in the temporal delayed discounting task (p = .006). CONCLUSIONS: Our findings suggest that in patients with AN, Se plasma concentration might be implicated in disease severity and suicide risk. The finding that Se deficiency in patients with AN was associated only with reward-related processes, but not with other psychological functions suggests the selective involvement of dopamine-related pathways. Our results suggest that it might be useful to monitor the plasma micronutrient profile in patients with AN. Future studies should determine whether Se supplementation in AN might improve clinical outcomes.

Ketamine and esketamine for crisis management in patients with depression: Why, whom, and how?

Currently, only a limited number of interventions can rapidly relieve depressive symptomatology in patients with major depressive disorder or bipolar disorder experiencing extreme distress. Such crises, especially when suicide attempt or ideation is involved, are a major risk factor of suicide. Ketamine, a N-methyl-d-aspartate glutamate receptor antagonist, and its enantiomer esketamine rapidly reduce depressive symptoms in depressed patients with current suicidal ideation. Recently, esketamine has been approved for use in patients with depression at risk of suicide and for psychiatric emergency by major medical agencies in the United States and Europe, whereas ketamine is increasingly used off-label. However, there is currently limited guidance on why, when, and how to use these drugs in patients with depression to treat a crisis. In this review article, we provide a succinct overview of the cellular and molecular mechanisms of action of ketamine and esketamine, and of the functional brain changes following their administration. We also summarize the major clinical studies on ketamine and esketamine efficacy in patients experiencing a crisis (generally, suicidal ideation), and propose a profile of patients who can benefit most from such drugs, on the basis of neurobiological and clinical observations. Finally, we describe the administration mode, the efficacy and tolerability profiles, the side effect management, possible concomitant treatments and the issue of deprescribing.

A specific association between laxative misuse and suicidal behaviours in patients with anorexia nervosa and bulimia nervosa.

OBJECTIVE: Eating disorders (ED) are associated with an in increased risk of suicidal behaviours. Laxative abuse might alter the gut-brain axis signaling, that might be implicated in the pathophysiology of suicide. This study aims to determine the association between laxative misuse and suicide attempt (SA) and suicidal ideation (SI) in patients with ED. METHODS: 277 patients with ED were recruited from an Eating Disorder Unit of Lapeyronie Academic Hospital, Montpellier, France. Sociodemographic and clinical data were collected. Chi-square and t test were used, with Bonferroni corrections where required. Multiple regression models assessed the relationships between laxative misuse, SA, and SI. RESULTS: 62 (22.4%) patients reported lifetime laxative misuse. They were more likely to have a history of SA than non-misusers [43.83 vs 19.9%, p < 0.001, odds ratio (OR) 3.68]. In the multivariate model, adjusted for other confounders, lifetime laxative misuse remained associated with SA (adjusted OR 3.79, p = 0.041). In past 28 days, patients with SA history reported misusing laxatives for more days than patients without SA history (6 vs 1.5 days, p = 0.01, adjusted for vomiting and ED severity). Laxative use days during past 28 days was associated with current SI, adjusted for vomiting in the same period (p = 0.017). CONCLUSIONS: Current and lifetime laxative misuse were associated with SA history and current SI in patients with ED, at least in part independently of other suicide-related factors. LEVEL OF EVIDENCE: Level III cohort, cross-sectional study.

Psilocybin, a Naturally Occurring Indoleamine Compound, Could Be Useful to Prevent Suicidal Behaviors.

The available interventions for people who are at risk of suicide have limited efficacy. Recently, research on new mental health treatments has started to consider psychedelic compounds, particularly psilocybin, a molecule with a few thousand years of history of use in human societies. The possible effects of psilocybin on suicidal ideation and behaviors have not been specifically studied yet; however, the current knowledge on the suicidal process and the available data on es/ketamine suggest that psylocibin could be used to modulate the thoughts and behavioral patterns in individuals who are at risk of suicidal behaviors. Here, we summarize the available evidence on the possible mechanisms underlying psilocybin positive effects on suicide risk. Major pathways related to suicidal behaviors that might be modulated by psylocibin include serotonin receptors. Specifically, psylocibin directly stimulates the serotonin 2A receptor (5HT2A), targeting the inflammatory and oxidative stress pathways and leading to a rapid increase in brain plasticity and inflammation suppression and increases in cognitive flexibility, spirituality, and empathy. We also present preliminary epidemiological data and provide a rationale for studying psilocybin in individuals with suicidal ideation or who are at risk of suicidal behaviors. This review presents a framework to understand the basis for psilocybin use in individuals who are at risk of suicidal behaviors and calls for clinical studies.

Depressive Symptoms, Help-Seeking, and Barriers to Mental Healthcare Among Healthcare Professionals in Lithuania.

SUMMARY BACKGROUND: Previous research suggests that healthcare professionals (HCPs) experience high levels of work-related psychological distress, including depressive symptoms. Due to the stigma of mental health problems and other barriers, HCPs are likely to be hesitant to seek appropriate mental healthcare. We aimed to explore these phenomena among HCPs in Lithuania. METHODS: A web survey inquiring about depressive symptoms, help-seeking, and barriers to mental health-care was conducted. Depressive symptoms were measured using the Patient Health Questionnaire-9 (PHQ-9). 601 complete questionnaires were included in the analyses. The barriers to help-seeking were identified using the inductive content analysis approach. Descriptive, non-parametric, and robust statistical analysis was performed using SPSS software. RESULTS: Most of the respondents have reported depression-like symptoms over the lifetime, although only about a third of them sought professional help. Of those, roughly half preferred a private specialist. The stigma and neglect of mental health problems were the most common barriers to help-seeking. Around half of the HCPs believed that seeking mental healthcare can imperil their occupational license. About a quarter of the HCPs screened positive for clinically relevant depressive symptoms. Statistically significant differences in the PHQ-9 score were found between categories of healthcare specialty, marital status, religious beliefs, workplace, and years of work as a HCP. Fewer years of work and younger age were associated with the higher PHQ-9 score. CONCLUSIONS: Our findings suggest that HCPs in Lithuania may be inclined not to seek appropriate mental healthcare and experience poor mental health, although stronger evidence is needed to verify these findings.

Significant Association Between Huntingtin Gene Mutation and Prevalence of Hopelessness, Depression and Anxiety Symptoms.

SUMMARY BACKGROUND: In Huntington's disease psychiatric symptoms may manifest prior to motor dysfunction. Such symptoms negatively impact people's quality of life and can worsen the course of the primary disease. The aim of the present study was to assess and compare depression, anxiety and hopelessness rates in individuals with and without an abnormal expansion of CAG repeats in the huntingtin (HTT) gene and healthy controls. MATERIALS AND METHODS: Study involved 31 individuals referred for genetic testing for Huntington's disease and a control group of 41. Depressive and anxiety symptoms were assessed using Beck Hopelessness Scale (BHS) and Hospital Anxiety and Depression Scale (HADS). Results between groups were compared using the Mann-Whitney U test. Two-sided Bonferroni corrected p-value was set at ≤0.017. RESULTS: Individuals with HTT gene mutation ("gene mutation positive", GMP) (N=20) scored higher on the HADS depression subscale (5.90 ± 4.52 vs 1.36 ± 1.91; p ≤ 0.017) than those without HTT gene mutation ("gene mutation negative", GMN) (N=11). GMP and control groups scored higher than the GMN group on the BHS (5.65 ± 3.91 vs 2.09 ± 1.64 and 5.27 ± 4.11 vs 2.09 ± 1.64, respectively; p ≤ 0.017). No differences in anxiety levels were found. CONCLUSIONS: Depressive symptoms and hopelessness were more prevalent in individuals with HTT gene mutation than in individuals who were tested but had no said mutation. Such results emphasise the importance of timely diagnosis and treatment of psychiatric comorbidities in individuals affected by Huntington's disease.

CYP2C19 polymorphisms are associated with severity of depression at initial evaluation and after the treatment independently of the prescribed medications: 4 weeks prospective study.

BACKGROUND: The cytochrome P-450 2C19 (CYP2C19) enzyme is involved in the metabolism of numerous antidepressants. It also metabolises some endogenous substrates, which could also confer to vulnerability. We aimed to establish whether the severity of depression and treatment response are associated with the genetically predicted CYP2C19 phenotype. METHODS: We assessed the CYP2C19 genotype-predicted metabolic phenotypes (normal, intermediate or ultrarapid, there were no poor metabolisers) in patients with moderate or severe depression. We used the self-rated Beck Depression Inventory-II (BDI-II) scale and the clinician-rated Montgomery-Åsberg Depression Rating Scale (MADRS) at baseline, after 2 and 4 weeks of an empirical treatment trial. Patients and clinicians were blind to the genetic testing results. RESULTS: Seventy-six patients participated in the present study. At baseline, impaired CYP2C19 metabolisers, compared to normal metabolisers, had higher BDI-II (P = 0.046; ηp2 = 0.08) but not MADRS score. Intermediate metabolisers more often had a diagnosis of severe depression than normal metabolisers (P = 0.003). After 4 weeks of empirical treatment, intermediate metabolisers had significantly higher MADRS and BDI-II scores than normal metabolisers (P = 0.006; ηp2 = 0.131 and P = 0.030; ηp2 = 0.091). These differences were independent of the use of CYP2C19-metabolised medications in the treatment trial, as well as the treatment discrepancy status. CONCLUSIONS: Intermediate CYP2C19 polymorphism-predicted activity was associated with more severe depression after an empirical treatment trial. The lack of association between the prescription of CYP2C19-metabolised drugs and treatment response calls for a further look into the role of endogenous substrates of CYP2C19.

'An Apple a Day'?: Psychiatrists, Psychologists and Psychotherapists Report Poor Literacy for Nutritional Medicine: International Survey Spanning 52 Countries.

Nutritional interventions have beneficial effects on certain psychiatric disorder symptomatology and common physical health comorbidities. However, studies evaluating nutritional literacy in mental health professionals (MHP) are scarce. This study aimed to assess the across 52 countries. Surveys were distributed via colleagues and professional societies. Data were collected regarding self-reported general nutrition knowledge, nutrition education, learning opportunities, and the tendency to recommend food supplements or prescribe specific diets in clinical practice. In total, 1056 subjects participated in the study: 354 psychiatrists, 511 psychologists, 44 psychotherapists, and 147 MHPs in-training. All participants believed the diet quality of individuals with mental disorders was poorer compared to the general population (p < 0.001). The majority of the psychiatrists (74.2%) and psychologists (66.3%) reported having no training in nutrition. Nevertheless, many of them used nutrition approaches, with 58.6% recommending supplements and 43.8% recommending specific diet strategies to their patients. Only 0.8% of participants rated their education regarding nutrition as 'very good.' Almost all (92.9%) stated they would like to expand their knowledge regarding 'Nutritional Psychiatry.' There is an urgent need to integrate nutrition education into MHP training, ideally in collaboration with nutrition experts to achieve best practice care.

Immediate and short-term efficacy of suicide-targeted interventions in suicidal individuals: A systematic review.

OBJECTIVES: To address the extreme suicide risk period following a suicidal crisis, we aimed to assess the current evidence for specific healthcare system-based interventions on suicide-related outcomes within one-week or one-month in individuals with current suicidal ideation (SI) or a recent suicide attempt (SA). METHODS: We performed a database (Medline, Academic Search Complete, PsycARTICLES, the Cochrane library, PubMed) and manual reference search for randomised controlled trials, published between March 2000 and March 2020. Antisuicidal efficacy was defined as SI, SA, or a closely related concept. Quality was assessed with the Cochrane Risk of Bias 2 tool for randomised trials. RESULTS: Out of 34 trials, five reported ketamine or esketamine superiority over placebo in reducing SI in depressed subjects within one week, while five studies had negative findings. Single trials reported positive results for one-month antisuicidal efficacy of buprenorphine, paroxetine, a crisis response plan, and assertive case management. Most trials were underpowered and had moderate-to-high risk of bias. CONCLUSIONS: Preliminary mixed evidence suggests the possible utility of several pharmacological (ketamine, esketamine paroxetine, and buprenorphine) and non-pharmacological (a crisis response plan, and assertive case management) interventions. Only the immediate efficacy of ketamine was supported by multiple studies, and replication is needed.