Vickybot, a Chatbot for Anxiety-Depressive Symptoms and Work-Related Burnout in Primary Care and Health Care Professionals: Development, Feasibility, and Potential Effectiveness Studies.

BACKGROUND: Many people attending primary care (PC) have anxiety-depressive symptoms and work-related burnout compounded by a lack of resources to meet their needs. The COVID-19 pandemic has exacerbated this problem, and digital tools have been proposed as a solution. OBJECTIVE: We aimed to present the development, feasibility, and potential effectiveness of Vickybot, a chatbot aimed at screening, monitoring, and reducing anxiety-depressive symptoms and work-related burnout, and detecting suicide risk in patients from PC and health care workers. METHODS: Healthy controls (HCs) tested Vickybot for reliability. For the simulation study, HCs used Vickybot for 2 weeks to simulate different clinical situations. For feasibility and effectiveness study, people consulting PC or health care workers with mental health problems used Vickybot for 1 month. Self-assessments for anxiety (Generalized Anxiety Disorder 7-item) and depression (Patient Health Questionnaire-9) symptoms and work-related burnout (based on the Maslach Burnout Inventory) were administered at baseline and every 2 weeks. Feasibility was determined from both subjective and objective user-engagement indicators (UEIs). Potential effectiveness was measured using paired 2-tailed t tests or Wilcoxon signed-rank test for changes in self-assessment scores. RESULTS: Overall, 40 HCs tested Vickybot simultaneously, and the data were reliably transmitted and registered. For simulation, 17 HCs (n=13, 76% female; mean age 36.5, SD 9.7 years) received 98.8% of the expected modules. Suicidal alerts were received correctly. For the feasibility and potential effectiveness study, 34 patients (15 from PC and 19 health care workers; 76% [26/34] female; mean age 35.3, SD 10.1 years) completed the first self-assessments, with 100% (34/34) presenting anxiety symptoms, 94% (32/34) depressive symptoms, and 65% (22/34) work-related burnout. In addition, 27% (9/34) of patients completed the second self-assessment after 2 weeks of use. No significant differences were found between the first and second self-assessments for anxiety (t8=1.000; P=.34) or depressive (t8=0.40; P=.70) symptoms. However, work-related burnout scores were moderately reduced (z=-2.07, P=.04, r=0.32). There was a nonsignificant trend toward a greater reduction in anxiety-depressive symptoms and work-related burnout with greater use of the chatbot. Furthermore, 9% (3/34) of patients activated the suicide alert, and the research team promptly intervened with successful outcomes. Vickybot showed high subjective UEI (acceptability, usability, and satisfaction), but low objective UEI (completion, adherence, compliance, and engagement). Vickybot was moderately feasible. CONCLUSIONS: The chatbot was useful in screening for the presence and severity of anxiety and depressive symptoms, and for detecting suicidal risk. Potential effectiveness was shown to reduce work-related burnout but not anxiety or depressive symptoms. Subjective perceptions of use contrasted with low objective-use metrics. Our results are promising but suggest the need to adapt and enhance the smartphone-based solution to improve engagement. A consensus on how to report UEIs and validate digital solutions, particularly for chatbots, is required.

High S100B Levels Predict Antidepressant Response in Patients With Major Depression Even When Considering Inflammatory and Metabolic Markers.

BACKGROUND: The relationship between antidepressant response and glial, inflammatory, and metabolic markers is poorly understood in depression. This study assessed the ability of biological markers to predict antidepressant response in major depressive disorder (MDD). METHODS: We included 31 MDD outpatients treated with escitalopram or sertraline for 8 consecutive weeks. The Montgomery-Åsberg Depression Rating Scale (MADRS) was administered at baseline and at week 4 and 8 of treatment. Concomitantly, blood samples were collected for the determination of serum S100B, C-reactive protein (CRP), and high-density lipoprotein cholesterol (HDL)-C levels. Treatment response was defined as ≥50% improvement in the MADRS score from baseline to either week 4 or 8. Variables associated with treatment response were included in a linear regression model as predictors of treatment response. RESULTS: Twenty-seven patients (87%) completed 8 weeks of treatment; 74% and 63% were responders at week 4 and 8, respectively. High S100B and low HDL-C levels at baseline were associated with better treatment response at both time points. Low CRP levels were correlated with better response at week 4. Multivariate analysis showed that high baseline S100B levels and low baseline HDL-C levels were good predictors of treatment response at week 4 (R2 = 0.457, P = .001), while S100B was at week 8 (R2 = 0.239, P = .011). Importantly, baseline S100B and HDL-C levels were not associated with depression severity and did not change over time with clinical improvement. CONCLUSIONS: Serum S100B levels appear to be a useful biomarker of antidepressant response in MDD even when considering inflammatory and metabolic markers.

Improvement of sexuality after hepatitis C cure with direct acting antivirals.

Despite rarely assessed, sexuality is a relevant domain in Quality of Life. We prospectively evaluated the impact of direct-acting antiviral therapy on sexuality in a cohort of 186 patients with chronic hepatitis C (HCV). Sexual dysfunction was assessed by validated scales CSFQ-14/CSFQ-VAS at baseline and one year after treatment finalization. Median age was 55 years and 87% had mild liver disease. Basal prevalence of sexual dysfunction (62%) and fear of HCV transmission (25%) were high. After HCV cure, both sexual dysfunction prevalence and CSFQ-VAS improved (P = .058 and P < .01, respectively), and fear of HCV transmission dropped to 16% (P = .02). These changes were especially relevant in young men (<55), where sexual dysfunction decreased from 48.6% to 29.7% (P = .04) and among non-depressed patients in whom sexual dysfunction decreased from 54.6% to 47% (P < .01). Age and major depression remained as independent factors of sexual dysfunction persistence after HCV cure. Our data suggest that HCV eradication is associated with an improvement in sexuality, in those patients without depression.

Interaction between the functional SNP rs2070951 in NR3C2 gene and high levels of plasma corticotropin-releasing hormone associates to postpartum depression.

Postpartum depression (PPD) is a common mood disorder that occurs after delivery with a prevalence of approximately 10%. Recent reports have related placental corticotropin-releasing hormone (pCRH) to postpartum depressive symptoms. The aim of this study was to determine whether pCRH, ACTH, and cortisol (measured 48 h after delivery) and glucocorticoid and mineralocorticoid receptor genotypes (NR3C1 and NR3C2) and their interaction are associated with PPD. A longitudinal 32-week prospective study of five hundred twenty-five Caucasian depression-free women that were recruited from obstetric units at two Spanish general hospitals immediately after delivery. Of the women included in the sample, forty-two (8%) developed PPD. A strong association between PPD and the interaction between the pCRH and NR3C2 rs2070951 genotype was observed. The mean level of pCRH in rs2070951GG carriers with PPD was 56% higher than the mean in the CG and CC genotype groups (P < 0.00005). Carriers of the rs2070951GG genotype with high levels of pCRH had a higher risk of developing PPD (OR = 1.020, 95% CI 1.007-1.034, P = 0.002). This association remained even after controlling for variables such as neuroticism, obstetric complications and the number of stressful life events during pregnancy. There is an important interaction between pCRH 48 h postpartum and the NR3C2 rs2070951GG genotype. This interaction moderately associates with the presence of PPD. These results may open a new line of research and, if confirmed in other settings, will help to identify better risk predictors and the treatment for PPD.

Substance use during pregnancy and personality dimensions. / Consumo de substancias durante el embarazo y dimensiones de personalidad.

Our aim was to assess personality traits associated with substance use during pregnancy in a population-based, multicentre study of 1804 pregnant women. On day 2-3 postpartum, participants completed a semi-structured interview, including self-reported drug use (alcohol, tobacco, caffeine, cannabis, cocaine, opioids) during pregnancy, and socio-demographic, reproductive and obstetric variables, personal and family psychiatric history, social support, and the Eysenck personality questionnaire, short version (EPQ-RS). Logistic regression models were conducted. Fifty per cent of women reported substance use during pregnancy: 40% caffeine, 21% tobacco, 3.5% alcohol, and 0.3 % cannabis. Mean T-scores (SD) for personality dimensions were 51.1 (9.6) for extraversion, 48 (8.9) for psychoticism, and 43.6 (8.5) for neuroticism. Extroversion (p = .029) and psychoticism (p = .009) were identified as risk factors after adjustment by age, level of education, employment status during pregnancy, low social support, and previous psychiatric history. For each increment of 10 units in their scores, the odds of substance use increased by 12% and 16% respectively. Low education, being on leave during pregnancy, and previous psychiatric history were independent factors (p < .05) associated with substance use during pregnancy. Primiparity was a protective factor (p = .001). The final models showed a good fit (p = .26). The screening of substance use during pregnancy should include personality dimensions apart from psychosocial variables and history of psychiatric disorders. It is important to identify the associated risk factors for substance use during pregnancy to prevent and improve foetal/neonatal and maternal health during perinatal period.

Este estudio evalúa los patrones de consumo de substancias durante el embarazo y las dimensiones de personalidad asociadas, en una muestra multicéntrica de 1804 mujeres de población general. En el 2-3 día posparto, completaron una entrevista auto-administrada sobre el consumo de alcohol, tabaco, cafeína, cannabis, cocaína, opiáceos, drogas de diseño, además de variables socio-demográficas, obstétricas/reproductivas, historia psiquiátrica previa, apoyo social durante el embarazo y el cuestionario de personalidad de Eysenck (EPQ-RS). Se generaron modelos de regresión logística múltiple. La prevalencia del consumo fue del 50% (N=909): 40% cafeína, 21% tabaco, 3,5% alcohol, y 0,3 cannabis. Las puntuaciones T medias (DE) de personalidad fueron: extraversión 51,1 (9,6), psicoticismo 48 (8,9) y neuroticismo 43,6 (8,5). Las dimensiones de extraversión (p=0,029) y psicoticismo (p=0,009), fueron identificadas como factores de riesgo tras ajustar por edad, nivel educación, estatus laboral durante el embarazo, bajo apoyo social, e historia psiquiátrica previa. Para cada incremento de 10 unidades en sus puntuaciones, el odds de consumo de substancias durante el embarazo se incrementó un 12% y un 16% respectivamente. Menor educación, estar de baja, y antecedentes psiquiátricos fueron también factores independientes (p<0,05) asociados al consumo. Ser primípara fue factor protector (p=0,001). El modelo final mostró un ajuste satisfactorio (p=0,26). El cribaje de las mujeres con riesgo de consumo de substancias durante el embarazo debería incluir la personalidad además de variables psicosociales y antecedentes psiquiátricos. Identificar los factores de riesgo asociados es importante para prevenir y mejorar la salud materna y fetal/neonatal durante el embarazo y posparto.

Association of chronic inflammation and perceived stress with abnormal functional connectivity in brain areas involved with interoception in hepatitis C patients.

BACKGROUND: Sickness behavioral changes elicited by inflammation may become prolonged and dysfunctional in patients with chronic disease, such as chronic hepatitis C (CHC). Neuroimaging studies show that the basal ganglia and insula are sensitive to systemic inflammation. AIM: To elucidate the clinical and neurobiological aspects of prolonged illnesses in patients with CHC. METHODS: Thirty-five CHC patients not treated with interferon-α or other antiviral therapy, and 30 control subjects matched for age and sex, were evaluated for perceived stress (perceived stress scale; PSS), depression (PHQ-9), fatigue and irritability through a visual analog scale (VAS), as well as serum levels of interleukin-6 (IL-6), prostaglandin E2 (PGE2) and oxidative stress markers. Functional MRI was performed, measuring resting-state functional connectivity using a region-of-interest (seed)-based approach focusing on the bilateral insula, subgenual anterior cingulate cortex and bilateral putamen. Between-group differences in functional connectivity patterns were assessed with two-sample t-tests, while the associations between symptoms, inflammatory markers and functional connectivity patterns were analyzed with multiple regression analyses. RESULTS: CHC patients had higher PSS, PHQ-9 and VAS scores for fatigue and irritability, as well as increased IL-6 levels, PGE2 concentrations and antioxidant system activation compared to controls. PSS scores positively correlated with functional connectivity between the right anterior insula and right putamen, whereas PHQ-9 scores correlated with functional connectivity between most of the seeds and the right anterior insula. PGE2 (positively) and IL-6 (negatively) correlated with functional connectivity between the right anterior insula and right caudate nucleus and between the right ventral putamen and right putamen/globus pallidus. PGE2 and PSS scores accounted for 46% of the variance in functional connectivity between the anterior insula and putamen. CONCLUSIONS: CHC patients exhibited increased perceived stress and depressive symptoms, which were associated with changes in inflammatory marker levels and in functional connectivity between the insula and putamen, areas involved in interoceptive integration, emotional awareness, and orientation of motivational state.

Factor Structure of the Spanish Version of the Edinburgh Postnatal Depression Scale.

INTRODUCTION: The Edinburgh Postnatal Depression Scale (EPDS) is considered the gold standard in screening for postpartum depression. Although the Spanish version has been widely used, its factorial structure has not yet been studied . METHODS: A total of 1,204 women completed the EPDS 32 weeks after delivery. To avoid multiple testing, we split the sample into two halves, randomly drawing two subsamples of 602 participants each. We conducted exploratory factor analysis (EFA), followed by an oblimin rotation with the first sub-sample. Confirmatory factor analysis (CFA) was conducted using a Weighted Least Squares Means and Variance (WLSMV) estimation of the data. We explored different solutions between two and four factors. We compared the factors between two groups with depression and non-depression (evaluated with the Diagnostic Interview for Genetic Studies (DIGS) for the DSM-IV). RESULTS: The EFA indicated a three-factor model consisting of anxiety, depression and anhedonia. The results of the CFA confirmed the three-factor model (χ2=99.203, p<0.001; RMSEA=0.06, 90% CI=0.04/0.07, CFI=0.87 and TLI=0.82). Women with depression in the first 32 weeks obtained higher scores for anxiety, depression and anhedonia dimensions (p<0.001). CONCLUSIONS: This is the first study of confirmatory analysis with the Spanish version of EPDS in a large sample of women without psychiatric care during pregnancy. A three-factor model consisting of anxiety, depression and anhedonia was used. Women with depression had a higher score in the three dimensions of the EPDS.

Facial emotion processing in patients with social anxiety disorder and Williams-Beuren syndrome: an fMRI study.

BACKGROUND: Social anxiety disorder (SAD) and Williams-Beuren syndrome (WBS) are 2 conditions with major differences in terms of genetics, development and cognitive profiles. Both conditions are associated with compromised abilities in overlapping areas, including social approach, processing of social emotional cues and gaze behaviour, and to some extent they are associated with opposite behaviours in these domains. We examined common and distinct patterns of brain activation during a facial emotion processing paradigm in patients with SAD and WBS. METHODS: We examined patients with SAD and WBS and healthy controls matched by age and laterality using functional MRI during the processing of happy, fearful and angry faces. RESULTS: We included 20 patients with SAD and 20 with WBS as well as 20 matched controls in our study. Patients with SAD and WBS did not differ in the pattern of limbic activation. We observed differences in early visual areas of the face processing network in patients with WBS and differences in the cortical prefrontal regions involved in the top-down regulation of anxiety and in the fusiform gyrus for patients with SAD. Compared with those in the SAD and control groups, participants in the WBS group did not activate the right lateral inferior occipital cortex. In addition, compared with controls, patients with WBS hypoactivated the posterior primary visual cortex and showed significantly less deactivation in the right temporal operculum. Participants in the SAD group showed decreased prefrontal activation compared with those in the WBS and control groups. In addition, compared with controls, participants with SAD showed decreased fusiform activation. Participants with SAD and WBS also differed in the pattern of activation in the superior temporal gyrus, a region that has been linked to gaze processing. LIMITATIONS: The results observed in the WBS group are limited by the IQ of the WBS sample; however, the specificity of findings suggests that the pattern of brain activation observed for WBS is more likely to reflect a neurobiological substrate rather than intellectual impairment per se. CONCLUSION: Patients with SAD and WBS showed common and specific patterns of brain activation. Our results highlight the role of cortical regions during facial emotion processing in individuals with SAD and WBS.

Coping strategies for postpartum depression: a multi-centric study of 1626 women.

The transition to motherhood is stressful as it requires several important changes in family dynamics, finances, and working life, along with physical and psychological adjustments. This study aimed at determining whether some forms of coping might predict postpartum depressive symptomatology. A total of 1626 pregnant women participated in a multi-centric longitudinal study. Different evaluations were performed 8 and 32 weeks after delivery. Depression was assessed using the Edinburgh Postnatal Depression Scale (EPDS) and the structured Diagnostic Interview for Genetic Studies (DIGS). The brief Coping Orientation for Problem Experiences (COPE) scale was used to measure coping strategies 2-3 days postpartum. Some coping strategies differentiate between women with and without postpartum depression. A logistic regression analysis was used to explore the relationships between the predictors of coping strategies and major depression (according to DSM-IV criteria). In this model, the predictor variables during the first 32 weeks were self-distraction (OR 1.18, 95 % CI 1.04-1.33), substance use (OR 0.58, 95 % CI 0.35-0.97), and self-blame (OR 1.18, 95 % CI 1.04-1.34). In healthy women with no psychiatric history, some passive coping strategies, both cognitive and behavioral, are predictors of depressive symptoms and postpartum depression and help differentiate between patients with and without depression.

A multidisciplinary support programme increases the efficiency of pegylated interferon alfa-2a and ribavirin in hepatitis C.

BACKGROUND & AIMS: Adherence to antiviral treatment is important to achieve sustained virological response (SVR) in chronic hepatitis C (CHC). We evaluated the efficiency of a multidisciplinary support programme (MSP), based on published HIV treatment experience, to increase patient adherence and the efficacy of pegylated interferon alfa-2a and ribavirin in CHC. METHODS: 447 patients receiving antiviral treatment were distributed into 3 groups: control group (2003-2004, n=147), MSP group (2005-2006, n=131), and MSP-validation group (2007-2009, n=169). The MSP group included two hepatologists, two nurses, one pharmacist, one psychologist, one administrative assistant, and one psychiatrist. Cost-effectiveness analysis was performed using a Markov model. RESULTS: Adherence and SVR rates were higher in the MSP (94.6% and 77.1%) and MSP-validation (91.7% and 74.6%) groups compared to controls (78.9% and 61.9%) (p<0.05 in all cases). SVR was higher in genotypes 1 or 4 followed by the MSP group vs. controls (67.7% vs. 48.9%, p=0.02) compared with genotypes 2 or 3 (87.7% vs. 81.4%, p=n.s.). The MSP was the main predictive factor of SVR in patients with genotype 1. The rate of adherence in patients with psychiatric disorders was higher in the MSP groups (n=95, 90.5%) compared to controls (n=28, 75.7%) (p=0.02). The cost per patient was € 13,319 in the MSP group and € 16,184 in the control group. The MSP group achieved more quality-adjusted life years (QALYs) (16.317 QALYs) than controls (15.814 QALYs) and was dominant in all genotypes. CONCLUSIONS: MSP improves patient compliance and increases the efficiency of antiviral treatment in CHC, being cost-effective.

Burnout in residents during the first wave of the COVID-19 pandemic: a systematic review and meta-analysis.

Introduction: The high prevalence of burnout in resident physicians is expected to have increased as a result of the expansion of the pandemic. We conducted a systematic review with a meta-analysis of studies conducted during the first wave of the COVID-19 pandemic on burnout in residents and potential associated risk factors. Methods: The search was done in the Web of Science, MEDLINE, Scopus, and Lillac databases (April 2020-October 2021) using a priori protocol based on the PRISMA guidelines. The Newcastle Ottawa Scale was used to assess the risk of bias in the included studies. We estimated the pooled prevalence (95% CI) of burnout and the prevalence ratio (95% CI) of each risk factor associated. Results: We included 23 studies from 451 potential initial articles and those written in the English language; all of the collected studies were cross-sectional with anonymous online surveys, involving 4,998 responders (34%), of which 53.2% were female responders, 51% were R1-2, and 71% were in direct contact with COVID-19 patients. Eighty-seven percent presented a low-to-moderate risk of bias. Publication bias was not shown. The estimated pooled prevalence of burnout was 40% (95% CI = 0.26 - 0.57). Burnout was associated with psychiatry history (PR = 4.60, 95% CI = 1.06 - 20.06). There were no differences by gender, civil status, children in-charge, year of residency, or time exposure to COVID-19. Discussion: The overall prevalence of burnout in residents during the first wave of the pandemic was in line with the results described in this collective before the pandemic. The presence of a psychiatry history was a potential burnout risk factor, suggesting a high vulnerability during the peak of the stress period and the need to implement mental health surveillance for this subgroup.

Patients Undergoing Bariatric Surgery: a Special Risk Group for Lifestyle, Emotional and Behavioral Adaptations During the COVID-19 Lockdown. Lessons from the First Wave.

OBJECTIVES: To determine how the COVID-19 lockdown influenced the lifestyle, eating behavior, use of substances, mental health, and weight in patients who had undergone bariatric surgery (BS) and explore the self-perception of one's own health and fears related to COVID-19. METHODS: We performed a cross-sectional exploratory study in obesity patients who had undergone BS surgery > 1 year previously in a university hospital. Assessment was performed 40 days after initiating lockdown and included 2 periods: from April 24 until May 8 and during the initial de-escalation period: from May 9 until 22, 2020. A structured telephone interview and an online survey were administered. RESULTS: One hundred eighty-eight patients were interviewed; 156 also responded to the online survey (77% females, mean age 53.46 ± 10.48 years, mean follow-up 5.71 ± 4.30 years). Dietary habits were affected in 72% of the participants, with 15% reporting better diet planning; 83.5% reported having more sedentary behaviors; 27% and 36% showed depression and anxiety, respectively; and 45% of participants reported bad sleep quality. In relation to changes in the use of any substance, the use increased in the majority of patients who were previously users. Self-perception of one's own health and fears related to COVID-19 were only moderate. Finally, emotional eating and time since BS were statistically significant risk factors for predicting weight gain. CONCLUSIONS: Lockdown during COVID-19 pandemic negatively influenced the lifestyle, mental health, substance use, and weight in BS patients. These alterations were somewhat similar to those observed in the general population but more severe and with important clinical implications.

Depersonalization and personality in panic disorder.

BACKGROUND: Prevalence and clinical correlates of depersonalization symptoms have been associated with panic disorder. Personality traits might increase the likelihood of experiencing depersonalization symptoms or depersonalization disorder in panic patients. AIMS: The objectives of this study are to establish the prevalence of depersonalization symptoms during the panic attack and in depersonalization disorder and to examine the personality factors associated with the presence of depersonalization in patients with panic disorder. METHODS: The sample comprised 104 consecutive adult outpatients with panic disorder, diagnosed according to the Semistructured Clinical Interview for DSM-IV (Axis I/II disorders). Participants were assessed with the Cambridge Depersonalization Scales, the Temperament and Character Inventory, and the Panic and Agoraphobia Scale. RESULTS: Forty-eight percent of the sample had depersonalization symptoms during the panic attack, whereas 20% of patients had a depersonalization disorder. Women presented more depersonalization disorders than did men (P = .036). Patients with panic disorder with depersonalization disorder had a more severe panic disorder (P = .002). Logistic regression analysis showed that self-transcendence trait (odds ratio, 1.089; 95% confidence interval, 1.021-1.162; P = .010) and severity of panic (odds ratio, 1.056; 95% confidence interval, 1.005-1.110; P = .032) were independently associated with depersonalization disorder. CONCLUSIONS: A high prevalence of depersonalization symptoms and depersonalization disorder was confirmed in patients with panic disorder, supporting a dosage effect model for understanding depersonalization pathology. Self-transcendence trait and severity of panic disorder were reported as risk factors for depersonalization disorder.

Incidence of depression in patients with hepatitis C treated with direct-acting antivirals.

OBJECTIVE: Depression has been associated with hepatitis C, as well as with its treatment with proinflammatory cytokines (i.e., interferon). The new direct-acting antiviral agents (DAAs) have minimal adverse effects and high potency, with a direct inhibitory effect on non-structural viral proteins. We studied the incidence and associated factors of depression in a real-life prospective cohort of chronic hepatitis C patients treated with the new DAAs. METHODS: The sample was recruited from a cohort of 91 patients with hepatitis C, of both sexes, with advanced level of fibrosis and no HIV coinfection, consecutively enrolled during a 6-month period for DAA treatment; those euthymic at baseline (n=54) were selected. All were evaluated through the depression module of the Patient Health Questionnaire (PHQ-9-DSM-IV), at three time points: baseline, 4 weeks, and end-of-treatment. RESULTS: The cumulative incidence (95%CI) of major depression and any depressive disorder during DAA treatment was 13% (6.4-24.4) and 46.3% (33.7-59.4), respectively. No differences were observed between those patients with and without cirrhosis or ribavirin treatment (p > 0.05). Risk factors for incident major depression during DAA treatment included family depression (relative risk 9.1 [1.62-51.1]), substance use disorder (11.0 [1.7-73.5]), and baseline PHQ-9 score (2.1 [1.1-3.1]). CONCLUSIONS: The findings of this study highlight the importance of screening for new depression among patients receiving new DAAs, and identify potential associated risk factors.

Allele variants in functional MicroRNA target sites of the neurotrophin-3 receptor gene (NTRK3) as susceptibility factors for anxiety disorders.

Genetic and functional data indicate that variation in the expression of the neurotrophin-3 receptor gene (NTRK3) may have an impact on neuronal plasticity, suggesting a role for NTRK3 in the pathophysiology of anxiety disorders. MicroRNA (miRNA) posttranscriptional gene regulators act by base-pairing to specific sequence sites, usually at the 3'UTR of the target mRNA. Variants at these sites might result in gene expression changes contributing to disease susceptibility. We investigated genetic variation in two different isoforms of NTRK3 as candidate susceptibility factors for anxiety by resequencing their 3'UTRs in patients with panic disorder (PD), obsessive-compulsive disorder (OCD), and in controls. We have found the C allele of rs28521337, located in a functional target site for miR-485-3p in the truncated isoform of NTRK3, to be significantly associated with the hoarding phenotype of OCD. We have also identified two new rare variants in the 3'UTR of NTRK3, ss102661458 and ss102661460, each present only in one chromosome of a patient with PD. The ss102661458 variant is located in a functional target site for miR-765, and the ss102661460 in functional target sites for two miRNAs, miR-509 and miR-128, the latter being a brain-enriched miRNA involved in neuronal differentiation and synaptic processing. Interestingly, these two variants significantly alter the miRNA-mediated regulation of NTRK3, resulting in recovery of gene expression. These data implicate miRNAs as key posttranscriptional regulators of NTRK3 and provide a framework for allele-specific miRNA regulation of NTRK3 in anxiety disorders.

Depression in hospitalized patients with malignant melanoma treated with interferon-alpha-2b: primary to induced disorders.

Our objective was to study the clinical and management differences between primary and interferon (IFN)-induced depressive disorders in malignant melanoma patients visited by the consultation-liaison team during a two year period. This was a prospective study of 31 patients with malignant melanoma treated with IFN-alpha in a general teaching hospital. Clinical, psychiatric variables and DSM-IV-TR diagnosis were analyzed. The Clinical Global Impression Severity (CGI-S) and Improvement (CGI-I) of illness scales were administered at the time of consultation and at the end of hospitalization. The main diagnoses were depressive adjustment disorders in 14 patients (45.16%) followed by interferon-induced depressive disorders in 6 (19.36%). In patients with adjustment disorders, melanoma stage was significantly more advanced than in those with interferon-induced depressive disorder (p = 0.019). The latter scored higher in the CGI-S scale (p = 0.044) and in the CGI-I scale (p = 0.029). The interferon-induced depressive disorders, except one who required a reduction of IFN-alpha-2b dose, were successfully treated with antidepressant drugs. Clinical management and antidepressant treatment allowed the continuation of interferon therapy in malignant melanoma patients. Interferon-induced depression occurred in a few patients, which in turn were the most severe. Adjustment depressive disorder was the most common psychiatric diagnosis.

Interaction between serotonin 5-HT1A receptors and beta-endorphins modulates antidepressant response.

UNLABELLED: Interactions between serotonergic and the endogenous opioid systems have been suggested to be involved in the etiopathogenesis of depression and in the mechanism of action of antidepressants. Activation of serotonin 5-HT1A receptors has been shown to increase plasma beta-endorphin (beta-END) levels in animal studies and in healthy humans. OBJECTIVES: To assess interaction abnormalities between 5-HT1A receptors and the endogenous opioid system in patients with major depression and the possible modulating effect of citalopram. METHODS: The beta-END response to the 5-HT1A receptor agonist, buspirone (30 mg), was measured in 30 patients with major depression and in 30 age- and sex-matched healthy controls before and after an 8-week treatment with citalopram. Pre-treatment score of the Hamilton Rating Scale for Depression (HRSD) was >or=17. Antidepressant response was defined by a 50% decrease in the HRSD. Pre- and post-treatment maximum peak response (Deltamax) and the area under the curve (AUC) of beta-END response were compared. Three time points were measured (60, 90 and 120 min). We also examined the correlations between the beta-END response and the antidepressant response. Buspirone plasma levels were not measured. RESULTS: At baseline, beta-END response was similar in patients and controls. After 8 weeks of citalopram treatment depressed patients showed a significant decrease in the beta-END response (Deltamax: p<.001; AUC: p<.001). A significant correlation between the beta-END reduction in the response and the reduction in the HRSD score (r=.656; p<.001) was observed. CONCLUSIONS: Changes in interaction between 5-HT1A receptor system and the endogenous opioid system may play a role both in the mechanism of action and response to antidepressant drugs.

Utilization of psychiatric emergency services by homeless persons in Spain.

OBJECTIVE: Studies examining the relationship between homeless persons and the use of psychiatric emergency services (PES) in a country with universal access to health care are lacking. This study aimed to determine the prevalence of homelessness in adults visiting a PES in Spain, identify the differences between homeless and non-homeless patients in the use of PES and analyze the factors associated with homelessness and the decision to hospitalize. METHOD: The study included a total of 11 578 consecutive admissions to a PES in a tertiary hospital in Barcelona, Spain, over a 4-year period. Data collected included socio-demographic and clinical information, and score on the Severity of Psychiatric Illness (SPI) scale. Multivariate logistic regression analyses were used to calculate odds ratios for the factors associated with homelessness and the decision to hospitalize. RESULTS: Five hundred sixty (4.8%) admissions were considered homeless. Homeless patients had more psychotic and drug abuse disorders, greater severity of symptoms, more risk of being a danger to others and more frequent hospitalization needs than non-homeless patients. Factors related to homelessness were male gender, substance abuse and immigrant status from North Africa, Sub-Sahara Africa and Western countries. The decision to hospitalize homeless patients was associated with psychosis diagnosis, suicide risk, danger to others, symptom severity, medical problems and noncompliance with treatment. CONCLUSIONS: In an attempt to decrease the use of emergency resources and prevent the risk of homelessness, mental health planners in a universal healthcare system should improve outpatient access for populations with risk factors such as substance abuse and immigration.

What do all personality disorders have in common? Ineffectiveness and uncooperativeness.

We still lack operative and theoretically founded definitions of what a personality disorder (PD) is, as well as empirically validated and feasible instruments to measure the disorder construct. The Temperament and Character Inventory (TCI) is the only personality instrument that explicitly distinguishes personality style and disordered functioning. Here, we seek to (1) confirm in a clinical sample that the character dimensions of the TCI capture a general construct of PD across all specific PD subtypes, (2) determine whether such core features can be used to detect the presence of PD, and (3) analyze whether such detection is affected by the presence and severity of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) Axis I symptoms. Two hundred five anxious/depressed outpatients were evaluated with the Structural Clinical Interview for DSM-IV Axis I and II Disorders. Assessment also included the TCI, the Hamilton rating scales for depression and anxiety, and the Panic and Agoraphobia Scale. Sixty-one patients (29.8%) were diagnosed as having a DSM-IV PD. Self-directedness and Cooperativeness, but no other TCI dimensions, predicted the presence of PD (Nagelkerke R(2) = 0.35-0.45) and had a moderate diagnostic utility (kappa = 0.47-0.58) when Axis I symptoms were absent or mild. However, accuracy decreased in anxious or depressed patients. Our study supports the hypothesis of a disorder construct that is not related to the intensity of any specific PD subtype but which is common to all PDs. This construct relies largely on internal representations of the self revealing ineffectiveness and uncooperativeness.

Effects of citalopram treatment on hypothermic and hormonal responses to the 5-HT1A receptor agonist buspirone in patients with major depression and therapeutic response.

Serotonin (5-HT) 5-HT1A receptor seems to play an important role in the pathophysiology of major depression and in the mechanism of action of antidepressants. In vivo function of 5-HT1A receptors can be monitored using specific pharmacological challenge tests. The present study aimed at exploring the adaptative 5-HT1A receptor changes in depressed patients before and after 8 week treatment with citalopram. The study population consisted of 30 consecutive outpatients of both sexes aged 18-45 years with major depressive disorders (DSM-IV). Basal score in the Hamilton Rating Scale for Depression (HRSD) was higher than 17. Therapeutic response was defined as a 50% decrease in the HRSD score. The hypothermic and endocrine responses (ACTH, cortisol, and prolactin) induced by the 5-HT1A receptor agonist, buspirone (30 mg p.o.) were measured. After 8 weeks on citalopram, the delta max of hypothermic response elicited by buspirone was markedly decreased (p<0.001). Patients showed a decrease in responses to ACTH (delta max p=0.005; AUC p=0.028) and cortisol (delta max p=0.05). However, the prolactin response increased (delta max p=0.02; AUC p=0.005). There was a significant correlation between the therapeutic effect and reductions of ACTH (r=0.883; p<0.001) and cortisol (r=0.610; p=0.001) responses. Changes induced by citalopram support an alteration of 5-HT1A receptors in major depression. A decrease in the overactivity of the HPA axis may be one factor associated with the response to citalopram.