Abstract The use of apps is increasing in the field of mental health due to their ease of use and accessibility, although there is not enough evidence on their effectiveness and safety. EvalDepApps aims to develop an evaluation tool for depression management apps. A systematic review with meta-analysis (SRMA) was performed to evaluate the efficacy and safety of apps for depression, and to identify the evaluation criteria used. PRISMA methodology was followed. The MEDLINE, PsycINFO, and Embase databases were consulted. The risk of bias was assessed with the RoB2 scale. An online 2 rounds Delphi was carried out to prioritize the most relevant criteria identified. 44 people (26 professionals, 18 patients) were invited. They were asked to rate the importance of each criterion on a Likert scale (1 - 6). Those that obtained a high consensus were selected; those with a medium were submitted to the 2nd round. Empathization (6) and co-design (6) sessions were held with patients (23) and professionals (33) in Catalonia, the Canary Islands and Andalusia to identify what relevant aspects the tool should have. Twenty-nine studies were included in the SRMA (67% unclear bias), finding a significant effect of mHealth interventions in reducing depressive symptoms compared to non-active control (Hedges g = −0.62, 95% CI: −0.87 to − 0.37, I2 = 87%). In Round 1 of the Delphi (59% participation) 24 criteria obtained a high consensus, 20 a medium and 7 a low. In Round 2 (52% participation), 4 criteria reached high consensus. The empathy sessions showed that the actions most requested by patients were reduce anxiety, and information about their condition; for professionals, suicide prevention. Regarding co-design, it was proposed that the tool provide ranking of the apps, recommendation systems and a very visual format. The RSMA and Delphi guarantee that the tool will be based on scientific evidence and expert judgment, while empathization and co-design that it will fit with the needs of end users. Key messages • It is relevant to evaluate the quality of health apps, especially those addressed to vulnerable populations such as people with depression. • It is crucial that the development of evaluation tools for digital health interventions will be developed based on evidence-based but also includes end users.

Sexual assault is one of the most traumatic events a person can experience. Despite this, information regarding the risk factors associated with the development of Acute Stress Disorder (ASD) in sexual assault victims is scarce. A follow-up prospective cohort study was designed to examine the prevalence and risk factors of ASD in women exposed to a recent sexual assault. A total of 156 women were treated at the Emergency Department of a university general hospital shortly after sexual assault. Sociodemographic, clinical and sexual assault-related variables were collected. The Acute Stress Disorder Interview was used to estimate the prevalence of ASD at three weeks post-SA. From the 156 victims, 66.6% (N = 104) met ASD diagnosis using DSM-5 criteria, whereas 59.6% (N = 93) met ASD diagnosis using DSM-IV criteria. The risk factors associated with the development of ASD were nationality, psychiatric history, peritraumatic dissociation and type of assault. In conclusion, the prevalence of ASD in female victims of recent sexual assault was high, affecting approximately two thirds of them. The recognition of the risk factors associated with ASD development, like peritraumatic dissociation or type of assault, may aid in the prompt detection of vulnerable women that require early and specific interventions shortly after trauma.

Suicidability has been associated with neuroticism and psychoticism, but its role during perinatal period has not been analyzed. We explore the association between personality dimensions, depressive symptoms, and other psychosocial variables in postpartum suicidal ideation. A cohort of 1795 healthy Spanish women from the general population was assessed for suicidal ideation (EPDS-Item10) in early postpartum, 8 and 32 weeks postpartum. Sociodemographic, obstetric, and reproductive variables, psychiatric history, social support, stressful life-events during pregnancy, depressive symptoms (EPDS), and the Eysenck’s personality dimensions (EPQ-RS) were also assessed at baseline. A major depressive episode (DSM-IV) was confirmed in women with EPDS>10 at follow-up assessments. Descriptive, bivariate, and multivariate analyses were conducted. Adjusted logistic regression analysis was reported as odds ratio (ORs) with 95% confidence intervals (CIs). Seven percent of mothers reported suicidal ideation during the first 8 months postpartum. Sixty-two percent of women with suicidal ideation had a major depressive episode at 8 weeks, and 70% at 32 weeks postpartum. Neuroticism and psychoticism predicted suicidal ideation throughout the first 2 weeks after delivery (OR, 1.03; 95%CI 1.01–1.06; and OR, 1.03; 95%CI 1.01–1.05 respectively). Early postpartum depressive symptoms (OR 1.2; 95%CI 1.11–1.26), personal psychiatric history (OR 2.1; 95%CI 1.33–3.27), and stressful life events during pregnancy (OR 1.88; 95%CI 1.12–3.16) also emerged as predictors of postpartum suicidal ideation. Analysis of women for postpartum suicidal ideation should include not only psychiatric symptoms but also psychosocial assessment (i.e., covering psychiatric history, stressful events, or long-standing personality vulnerabilities) in order to identify those in need of early psychosocial or psychiatric care.

The limited efficacy of available treatments for hepatocellular carcinoma (HCC) requires the development of novel therapeutic approaches. We synthesized a novel cationic polymer based on α,β-poly-(N-2-hydroxyethyl)-d,L-aspartamide (PHEA) for drug delivery to HCC cells. The copolymer was synthesized by subsequent derivatization of PHEA with diethylene triamine (DETA) and with a polyethylene glycol (PEG) derivative bearing galactose (GAL) molecules, obtaining the cationic derivative PHEA-DETA-PEG-GAL. PHEA-DETA-PEG-GAL has suitable chemical-physical characteristics for a potential systemic use and can effectively deliver a siRNA (siE2F1) targeted against the transcription factor E2F1, a gene product involved in HCC. The presence of GAL residues in the polyplexes allows the targeting of HCC cells that express the asialo-glycoprotein receptor (ASGP-R). In these cells, but not in ASGP-R non-expressing cells, PHEA-DETA-PEG-GAL/siE2F1 polyplexes induce the reduction of the mRNA and protein levels of E2F1 and of E2F1-regulated genes, all involved in the promotion of the G1/S phase transition. This results in a decrease of cell proliferation with a G1/G0 phase cells accumulation. Notably, removal of GAL residue almost completely abrogates the targeting capacity of the developed polyplexes.In conclusion, the generated polyplexes demonstrate the potential to effectively contributing to the development of novel anti-HCC therapeutic approaches via a siRNA-targeted delivery.

The assessment of quality of life (HRQoL) is a significant outcome indicator for patients with chronic diseases and treatments. Chronic hepatitis C is one of world's most important chronic diseases. To carry out a systematic review of HRQoL during antiviral treatment with interferon and the new direct-acting antiviral agents (DAA), its baseline risk factors such a psychiatric history and HIV comorbidity, and its relationship with treatment efficacy. A protocol based on the PRISMA&CONSORT guides was used. A comprehensive, computerized search (2004-2014) was conducted. Of 314 observational and RCT studies, 24 studies met the inclusion criteria. HRQoL tools used were SF-36 and EQ-5D. Studies showed a moderate to good quality. HRQoL changes from baseline and predictive variables were abstracted, and weighted means (SD) of HRQoL score changes in treatment groups throughout treatment from baseline were analyzed. HRQoL decreased during any interferon treatment, especially the physical component. The DAA sofosbuvir showed no significant decline in HRQoL. HIV co-infection and a psychiatric history were risk factor for impairment during treatment with interferon. Previous non-responders did not recover in HRQoL to baseline scores at 24 weeks of follow-up. Cohort studies showed impairment 3 times greater than RCTs. Any antiviral treatment impairs HRQoL. Interferon seems to have more impact than new treatments. Future studies using DAAs should assess HRQoL and its risk factors in depth. Clinicians should attempt a full evaluation of patients before starting treatment, in order to identify risk factors and take preventive measures. Grant:Instituto Carlos III:FIS:P110/01827,and SGR2014/1135.

Purpose To study qualitatively different subgroups of Social Anxiety Disorder (SAD) based on harm-avoidance (HA) and novelty-seeking (NS) dimensions. Method One-hundred and forty-two university students with SAD (SCID-DSM-IV) were included in the study. The temperament dimensions HA and NS from the Cloninger's Temperament and Character Inventory were subjected to cluster analysis to identify meaningful subgroups. The identified subgroups were compared for sociodemographics, SAD severity, substance use, history of suicide and self-harm attempts, early life events, and two serotonin-transporter-gene-polymorphisms (5-HTTLPR and STin2.VNTR). Results Two subgroups of SAD were identified by cluster-analysis: a larger (61% of the sample) inhibited subgroup of subjects with ‘high-HA/low-NS’, and a smaller (39%) atypical impulsive subgroup with high-moderate HA and NS. The two groups did not differ in social anxiety severity, but did differ in history of lifetime impulsive-related-problems. History of suicide attempts and self-harm were as twice as frequent in the impulsive subgroup. Significant differences were observed in the pattern of substance misuse. Whereas subjects in the inhibited subgroup showed a greater use of alcohol (p=0.002), subjects in the impulsive subgroup showed a greater use of substances with a high-sensation-seeking-profile (p<0.001). The STin2.VNTR genotype frequency showed an inverse distribution between subgroups (p=0.005). Conclusions Our study provides further evidence for the presence of qualitatively different SAD subgroups and the propensity of a subset of people with SAD to exhibit impulsive, high-risk behaviors.

Introduction Huntington’s disease (HD) is a neurodegenerative disorder that induces striatal and cortical neuronal dysfunction and loss which main symptom is motor impairment. Goals to study whether this motor impairment is accompanied by changes in brain activity and functional connectivity. Methods Fifteen early stage HD patients with a UHDRS motor score > 5 (9 men, mean age = 48 ± 8.9, mean TFC = 11.7 ± 1.17) and 15 controls (9 men, mean age = 46.6 ± 8.1) matched in age, gender and educational background underwent 3T structural and functional MRI scanning while they performed a sequential tapping task with their right or left hand in alternated blocks. Results Compared to rest blocks, active tapping activated the contralateral primary motor, premotor and supplementary motor areas, thalamus and cerebellum in both patients and controls. However, in the right hand condition, patients deactivated the right putamen to a greater extent than controls, which suggests that patients need a greater inhibition of the ipsilateral putamen in order to suppress the movement of the opposite hand. Furthermore, HD patients showed less activation in the right putamen during the left hand condition compared to controls. These effects could be ascribed to the general imbalance in the Go and No-Go cortico-striatal pathways that is believed to occur in HD. The left precentral gyrus, was selected as a seed region for a whole brain functional connectivity analysis. Compared with controls, right precentral gyrus, right SMA and right putamen were more connected (negatively) to the left precentral gyrus in patients. This indicates that not only the right putamen, but all the right motor circuit undergoes a greater deactivation in HD patients when they move their left hand. In addition, the negative functional connectivity between the left precentral gyrus and the right putamen showed a positive correlation with the motor-UHDRS score and the TFC score. Conclusions These results indicate that HD patients need to inhibit the contralateral motor circuit of the moving hand to compensate for the hyperactivation of the dopaminergic system that underlies their motor symptoms. This effect is specific to the right hemisphere, showing an asymmetry of the motor circuit dysfunction.

Patients with Huntington Disease (HD) show poor self-awareness of a variety of symptoms. Previous research in HD has primarily examined awareness of motor symptoms, whereas less attention has been given to unawareness of cognitive function and behavioural disorders. This study aim to assess self-awareness of executive deficits in HD and to explore the association between impaired awareness, cognition (executive function and memory) and evolution of the disease. Self-awareness was tested in 17 patients with HD (8 male, age=50.5 ± 9.8 years) at early stage of the disease (mean TFC 11.7) by comparing patient and family ratings using the Dysexecutive Questionnaire (DEX) with five-factor factorial structure (Inhibition, Intentionality, executive memory, negative and positive affect). Executive and memory functions were assessed by different standardised neuropsychological tests included in cognitive protocol Registry 3. Finally, we extracted the volume of the different striatal substructures (left and right caudate, putamen and nucleus accumbens) as a neuroanatomical signature of disease progression in HD. Statistical analysis revealed a significant discrepancy between the DEX-Family and DEX-Patient specifically in the second factor of DEX (intentionality). This factor contains items about disinhibition, aggression, euphoria, lack of insight and social conscience. We also found that poor insight in this area measured by DEX is significantly and specifically related with the atrophy of the left caudate. None of the cognitive tests that were administrated showed significant correlation with unawareness. Our results are consistent with previous literature, indicating that patients with HD generally overestimate their abilities. This study shows that the awareness of dysexecutive function in HD is not a general and uniform process, but is specific to certain symptoms (predominantly behaviours related with intentionality and disinhibition) and suggests the involvement of specific neuroanatomical substrates for unawareness in HD.

Background: Social Anxiety Disorder (SAD) and Williams-Beuren Syndrome (WS) are two conditions which seem to be at opposite ends in the continuum of social fear but show compromised abilities in some overlapping areas, including some social interactions, gaze contact and processing of facial emotional cues. The increase in the number of neuroimaging studies has greatly expanded our knowledge of the neural bases of facial emotion processing in both conditions. However, to date, SAD and WS have not been compared.Methods: We conducted a systematic review of functional magnetic resonance imaging (fMRI) studies comparing SAD and WS cases to healthy control participants (HC) using facial emotion processing paradigms. Two researchers conducted comprehensive PubMed/Medline searches to identify all fMRI studies of facial emotion processing in SAD and WS. The following search key-words were used: "emotion processing"; "facial emotion"; "social anxiety"; "social phobia"; "Williams syndrome"; "neuroimaging"; "functional magnetic resonance"; "fMR1" and their combinations, as well as terms specifying individual facial emotions. We extracted spatial coordinates from each study and conducted two separate voxel-wise activation likelihood estimation meta-analyses, one for SAD and one for WS.Results: Twenty-two studies met the inclusion criteria: 17 studies of SAD and five of WS. We found evidence for both common and distinct patterns of neural activation. Limbic engagement was common to SAD and WS during facial emotion processing, although we observed opposite patterns of activation for each disorder. Compared to HC, SAD cases showed hyperactivation of the amygdala, the parahippocampal gyrus and the globus pallidus. Compared to controls, participants with WS showed hypoactivation of these regions. Differential activation in a number of regions specific to either condition was also identified: SAD cases exhibited greater activation of the insula, putamen, the superior temporal gyrus, medial frontal regions and the cuneus, while WS subjects showed decreased activation in the inferior region of the parietal lobule.Conclusions: The identification of limbic structures as a shared correlate and the patterns of activation observed for each condition may reflect the aberrant patterns of facial emotion processing that the two conditions share, and may contribute to explaining part of the underlying neural substrate of exaggerated/diminished fear responses to social cues that characterize SAD and WS respectively. We believe that insights from WS and the inclusion of this syndrome as a control group in future experimental studies may improve our understanding of the neural correlates of social fear in general, and of SAD in particular. (C) 2014 Elsevier Ltd. All rights reserved.

Huntington’s disease (HD) is a neurodegenerative disease that affects different capacities and general well-being. Therefore, it requires a comprehensive and coordinated treatment. Duran i Reynals Day Hospital (HDDR) provide Neurorehabilitation to both young people and adults with brain damage or dysfunction. HDDR has developed a specific therapeutic program aimed at people who suffer HD and their families, offering continuous attention ranging from presymptomatic to later stages of the disease. The aim of this poster is to raise awareness of the support program offered to sufferers and their families. It describes the circuit of admission and follow-up of the case, as well as the available programs of specialised treatments (neuropsychology, genetic counselling, physiotherapy, speech therapy, social work, psychiatry). It shows the rise in the number of cases treated since the HDDR’s programme commenced, reflecting the increase of patients and families treated. The Socio-demographic trends are presented of the patients currently being treated (23 patients). Finally, it is of importance to note the views of patients and their families regarding the benefits of this treatment. The HDDR is a specialised facility and a reference point for HD in Catalonia and the centre of expertise in this field. Specific resources dedicated to HD should be strengthened, ensuring a continuous and specialised treatment while patients and families are dealing with this disease.

IntroductionPanic disorder is an anxiety disorder characterized by unexpected and repeated episodes of intense fear accompanied by physical symptoms. The diagnosis frequently is associated to other comorbid axis-I psychiatric disorders, especially depressive disorders. Moreover panic disorder can also be comorbid with axis-II diagnosis of Personality Disorder1(PDs).ObjectiveThe aim of this study was to evaluate the existing comorbidity between current DSM-IV axis I panic disorder with and without co-occurring depression and current DSM-IV axis II PDs.MethodsWe review all database from 1987 until January 2012 of all relevant cross-sectional and case-control studies which evaluate the comorbidity between panic disorders and PDs.ResultsWe found 97 possible papers, 20 entered in the review. Among patients with a current DSM-IV panic disorder 44.3% [34.6, 54.2] had any PDs; 6.3% [3.1, 10.4] had any cluster A-PDs; 17.9% [12.2, 24.2] any cluster B-PDs, and 34.9% [25.6, 44.7] had any cluster C-PDs. Among patients with a current DSM-IV panic disorder and co-occurring depression 61.8% [44.6, 77.7] had any personality disorder 7.2% [4.4, 10.5] had any cluster A-PDs; 24.0% [17.6, 30.9] any cluster B-PDs, and 38.6% [25.7, 52.2] had any cluster C-PDs.ConclusionsThe comorbidity between Panic disorder and Personality disorders is common. Cluster C-PDs was the most frequent PDs subtype related to panic disorder. Personality disorders were more prevalent among individuals with panic disorder and co-occurring depression. Further evaluations including dimensional and characterial dimensions are needed.Goodwin RD, Brook JS, Cohen P. Panic attacks and the risk of personality disorder. Psychol Med. 2005;35:227-35.

BackgroundThere is increasing data supporting the role of endocannabinoid system (eCB) in the control of emotional homeostasis, mainly acting through CB1R activation (Menchoulam&Parker, 2012). eCB seems important to maintain baseline anxiety levels and to recovery/adapt to stressful and aversive situations (Moreira&Luz, 2008). A misbalance in eCB system might contribute to the etiology of anxiety related disorders (Crippa et al., 2009; Marco et al., 2012). The cannabinoid receptor 1 (CNR1) gene has been associated to “high neuroticism” and “low agreeableness” phenotype (Juhasz et al., 2009).AimsStudy the association between personality traits and genetic polymorphisms located in genes related to eCB (CNR1, CNR2, FAAH and MGKLL) in patients with anxiety disorders.MethodsIn a case-control study, we analyzed 48 polymophisms tagSNPs in sample of 507 Caucasians subjects of both genders. All were assessed using the Semi-Structural Interview of DSM-IV criteria and the Temperament and Character Inventory of Cloninger. Multiple regression analysis was used to determine whether the different personality traits were associated with each variant in CNr1, CNr2, FAAH, and MGKLL, using age and gender as confounder variables.ResultsA significant association was found between “high Harm-avoidance” trait and rs1049353 in the CNR1 gene (p< 0.005) and rs1157694 in the FAAH gene (p< 0.001). “Low novelty-seeking” trait was associated with rs324490 in the FAAH gene (p< 0.005).ConclusionsThese findings suggest that genetic variations in the CNR1 and FAAH genes may modulate the expression of some clinical aspects of anxiety traits and probably anxiety disorders. Grants: ICIII G03/184; SGR2009/1435.

Objective: To identify the factors associated with discontinuation of selective serotonin reuptake inhibitors (SSRIs) in pregnant women and to determine the rates of SSRI reintroduction during pregnancy.Method: A prospective study was conducted in the Perinatal Psychiatry Service of the Hospital Clinic in Barcelona. The total sample comprised 132 consecutive pregnant women with depressive or anxiety disorder (DSM-IV criteria), seen between January 2005 and December 2008 and who were receiving SSRIs at the time of conception. Clinical, psychometric and socio-demographic variables were collected at the first visit. All women were assessed during treatment with the Edinburgh Perinatal Depression Scale (EPDS) and the Spielberger State-Trait Anxiety Inventory (STAI). Dose and type of antidepressant were recorded at each visit during pregnancy.Results: Seventy women (53%) discontinued SSRI treatment upon confirmation of pregnancy. Sociodemographic, obstetric and psychiatric variables did not differ significantly between women who maintained and women who discontinued treatment. Only unplanned pregnancy was associated with a greater risk of discontinuation (OR=2.7, 95% CI=1.34-5.52). Women who discontinued treatment also had higher EPDS and STAI scores in the first visit and prenatal visit (34-36 weeks) (p<.05). Of the 70 women who discontinued treatment, 57.1% (N=40) reintroduced treatment, almost half of these in the first trimester of pregnancy.Conclusions: Unplanned pregnancy was a risk factor for abrupt discontinuation of SSRIs upon confirmation of pregnancy in women with depressive or anxiety disorder. More than half the pregnant women who discontinued SSRIs reintroduced antidepressant therapy during pregnancy. (C) 2013 Elsevier B.V. All rights reserved.

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Objectives The aim of the study was to assess the effect of exposure to selective serotonin reuptake inhibitors (SSRI) in utero on child IQ and psychopathological syndromes. Methods A two cohorts study was designed. A cohort of 40 mother-child pairs with depressive or anxiety disorders (DSM-IV criteria) attended at a Perinatal Psychiatry Program between 2004 and 2006 and exposed in utero to SSRI was compared with a healthy cohort of 40 mother-child pairs, paired by gender and gestational age. The two groups were compared in terms of children's IQ between ages 60 and 72 months, assessed blindly through Kaufman Assessment Battery for Children (K-ABC). The Early Childhood Inventory teachers’ and parents’ versions (ECI-4) were used to assess psychopathological syndromes. Statistical analysis were done with paired t-test, Chi square test, and Fisher's exact test. Results There were no differences among the groups in maternal IQ, socioeconomic status and obstetric variables. There were no differences among the groups (exposed vs. non-exposed) in the Mental Processing Composite (101.20 vs. 106.95; p = 0.07), the Sequential Processing Scale (97.78 vs. 103.00; p = 0.11), the Simultaneous Processing Scale (103.90 vs. 109.23; p = 0.13) and the Achievement Scale (98.80 vs. 103.13; p = 0.13). The ECI-4 psychopathological syndromes rates of exposed children were slightly higher than non-exposed children, but these differences were only significant on Adjustment Disorder in parents’ reports (30% vs. 10%; p = 0.04). Conclusions Exposure to SSRI during pregnancy does not appear to adversely affect cognitive functioning. Exposed children showed slightly higher rates of psychopathology, especially Adjustment Disorder.

Social anxiety disorder (SAD) is a common anxiety disorder with a life-time prevalence around 7–10%. Perfectionism is a personality construct defined as the setting of high standards paired with overly critical self-evaluation in pursuit of those standards. Although perfectionism has generally been associated with several forms of psychopathology, research in social anxiety has received less attention. To explore the relationship between perfectionism and SAD. A cross-sectional survey of 571 university students was designed. We analysed the association between perfectionism components (concern over mistakes, personal standards, parental expectations, parental criticism, doubt about actions and organisation) and SAD with the Frost Multidimensional Perfectionism Scale (FMPS) and the Liebowitz Social Anxiety Scale (LSAS). SAD diagnostic was confirmed using the Structured Clinical Interview for DSM-IV-Axis-I. Twelve percent of the sample had SAD, with no gender differences. For both sex, the prevalence of high-perfectionism (FMPS total) was higher in SAD than in control group (p < 0.001). Specifically, high-concern over mistakes and high-doubt about actions was associated to SAD in both gender whereas high-parental criticism was associated to SAD only in women. After controlling for age and personal psychiatric history, only high-concern over mistakes was associated with an increased risk of SAD (OR = 3.41;95%CI = 1.56–7.46) in women. This study supports the association between SAD and perfectionism specifically with the high-concern over mistakes component in women.