Publications by authors named "Ana Catalan"

39 Publications

Universal and Selective Interventions to Prevent Poor Mental Health Outcomes in Young People: Systematic Review and Meta-analysis.

Harv Rev Psychiatry 2021 May-Jun 01;29(3):196-215

From the Early Psychosis: Interventions and Clinical-Detection (EPIC) Laboratory, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London (Drs. Salazar de Pablo, De Micheli, Catalan, Verdino, Di Maggio, Radua, Provenzani, Montealegre, Signorini, and Fusar-Poli, and Mr. Oliver); Departments of Child and Adolescent Psychiatry (Dr. Salazar de Pablo) and of Psychosis Studies (Drs. Bonoldi and Baccaredda Boy), Institute of Psychiatry, Psychology & Neuroscience, King's College London; Institute of Psychiatry and Mental Health. Department of Child and Adolescent Psychiatry, Hospital General Universitario Gregorio Marañón School of Medicine, Universidad Complutense, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), CIBERSAM, Madrid (Drs. Salazar de Pablo and Arango); National Institute for Health Research, Maudsley Biomedical Research Centre, South London and Maudsley NHS Foundation Trust, London (Drs. De Micheli and Fusar-Poli); Department of Brain and Behavioral Sciences, University of Pavia (Drs. Di Maggio, Provenzani, Ruzzi, Calorio, Nosari, Di Marco, Famularo, Molteni, Filosi, Mensi, Balottin, Politi, and Fusar-Poli); Neurosciences Department, University of Padova (Dr. Solmi); Mental Health Department, Biocruces Bizkaia Health Research Institute, Basurto University Hospital, Facultad de Medicina y Odontología, Campus de Leioa, University of the Basque Country, UPV/EHU, Barakaldo, Bizkaia, Spain (Dr. Catalan); Department of Molecular and Developmental Medicine, Division of Psychiatry, University of Siena (Dr. Verdino); Imaging of Mood- and Anxiety-Related Disorders (IMARD) group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CIBERSAM, Barcelona (Dr. Radua); Department of Clinical Neuroscience, Centre for Psychiatric Research and Education, Karolinska Institutet, Stockholm (Dr. Radua); Scientific Institute for Research, Hospitalization and Healthcare (IRCCS) Mondino Foundation, Child and Adolescent Neuropsychiatric Unit (Dr. Mensi); Department of Paediatrics, Yonsei University College of Medicine, Seoul (Dr. Shin); Zucker Hillside Hospital, Department of Psychiatry, Northwell Health, Glen Oaks, NY (Dr. Correll); Department of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY (Dr. Correll); Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, NY (Dr. Correll); Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin Berlin (Dr. Correll); OASIS service, South London and Maudsley NHS Foundation Trust, London (Dr. Fusar-Poli).

Background: Much is not known about the efficacy of interventions to prevent poor mental health outcomes in young people by targeting either the general population (universal prevention) or asymptomatic individuals with high risk of developing a mental disorder (selective prevention).

Methods: We conducted a PRISMA/MOOSE-compliant systematic review and meta-analysis of Web of Science to identify studies comparing post-test efficacy (effect size [ES]; Hedges' g) of universal or selective interventions for poor mental health outcomes versus control groups, in samples with mean age <35 years (PROSPERO: CRD42018102143). Measurements included random-effects models, I2 statistics, publication bias, meta-regression, sensitivity analyses, quality assessments, number needed to treat, and population impact number.

Results: 295 articles (447,206 individuals; mean age = 15.4) appraising 17 poor mental health outcomes were included. Compared to control conditions, universal and selective interventions improved (in descending magnitude order) interpersonal violence, general psychological distress, alcohol use, anxiety features, affective symptoms, other emotional and behavioral problems, consequences of alcohol use, posttraumatic stress disorder features, conduct problems, tobacco use, externalizing behaviors, attention-deficit/hyperactivity disorder features, and cannabis use, but not eating-related problems, impaired functioning, internalizing behavior, or sleep-related problems. Psychoeducation had the highest effect size for ADHD features, affective symptoms, and interpersonal violence. Psychotherapy had the highest effect size for anxiety features.

Conclusion: Universal and selective preventive interventions for young individuals are feasible and can improve poor mental health outcomes.
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http://dx.doi.org/10.1097/HRP.0000000000000294DOI Listing
May 2021

Real clinical setting intravenous ketamine use for treatment resistant depression: 12 month follow-up after initial response.

Rev Psiquiatr Salud Ment (Engl Ed) 2021 Jan 27. Epub 2021 Jan 27.

OSI Bilbao-Basurto. Hospital Basurto, Bilbao, Spain; Neuroscience Department, University of the Basque Country, Spain.

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http://dx.doi.org/10.1016/j.rpsm.2021.01.002DOI Listing
January 2021

Early intervention services, patterns of prescription and rates of discontinuation of antipsychotic treatment in first-episode psychosis.

Early Interv Psychiatry 2020 Dec 7. Epub 2020 Dec 7.

Early Intervention Service for Psychosis, Department of Mental Health, Parc Taulí Hospital Universitari, I3PT, Universitat Autònoma de Barcelona (Department of Psychiatry and Forensic Medicine), CIBERSAM, Sabadell, Spain.

Aims: Non-compliance is still an important problem in psychotic patients. Although antipsychotic (AP) treatment leads to a decrease in psychotic relapses, there are no clear recommendations about how long treatment should be maintained after first-episode psychosis (FEP) and no indication of the rates and causes of treatment withdrawal in this group.

Methods: We evaluated a large sample of patients with FEP for 2 years to compare the time to all-cause treatment discontinuation of AP drugs and the time to the first relapse. We collected the sociodemographic and psychopathological characteristics of the sample. The number of relapses was also recorded.

Results: A total of 310 FEP patients were assessed across seven early intervention teams (mean age = 30.2 years; SD = 11.2). The most prevalent diagnosis at baseline was psychotic disorder not otherwise specified (36.1%), and the most commonly used APs were risperidone (26.5%) and olanzapine (18.7%). A lack of efficacy was the most frequent reason for the withdrawal of the first AP prescribed, followed by non-compliance. There were no differences in the relapse rates between different APs. Patients treated with long-acting injectable (LAI) APs presented less disengagement from services than patients treated with oral APs.

Conclusions: Although there were no differences between the different APs in terms of relapse rates, LAIs had higher retention rates than oral APs in early intervention services. Compliance is still an important issue in Psychiatry, so clinicians should use different strategies to encourage it, such as the use of LAI treatments.
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http://dx.doi.org/10.1111/eip.13098DOI Listing
December 2020

Universal and selective interventions to promote good mental health in young people: Systematic review and meta-analysis.

Eur Neuropsychopharmacol 2020 12 6;41:28-39. Epub 2020 Nov 6.

Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.

Promotion of good mental health in young people is important. Our aim was to evaluate the consistency and magnitude of the efficacy of universal/selective interventions to promote good mental health. A systematic PRISMA/RIGHT-compliant meta-analysis (PROSPERO: CRD42018088708) search of Web of Science until 04/31/2019 identified original studies comparing the efficacy of universal/selective interventions for good mental health vs a control group, in samples with a mean age <35 years. Meta-analytical random-effects model, heterogeneity statistics, assessment of publication bias, study quality and sensitivity analyses investigated the efficacy (Hedges' g=effect size, ES) of universal/selective interventions to promote 14 good mental health outcomes defined a-priori. 276 studies were included (total participants: 159,508, 79,142 interventions and 80,366 controls), mean age=15.0 (SD=7.4); female=56.0%. There was a significant overall improvement in 10/13 good mental health outcome categories that could be meta-analysed: compared to controls, interventions significantly improved (in descending order of magnitude) mental health literacy (ES=0.685, p<0.001), emotions (ES=0.541, p<0.001), self-perceptions and values (ES=0.49, p<0.001), quality of life (ES=0.457, p=0.001), cognitive skills (ES=0.428, p<0.001), social skills (ES=0.371, p<0.001), physical health (ES=0.285, p<0.001), sexual health (ES=0.257, p=0.017), academic/occupational performance (ES=0.211, p<0.001) and attitude towards mental disorders (ES=0.177, p=0.006). Psychoeducation was the most effective intervention for promoting mental health literacy (ES=0.774, p<0.001) and cognitive skills (ES=1.153, p=0.03). Physical therapy, exercise and relaxation were more effective than psychoeducation and psychotherapy for promoting physical health (ES=0.498, p<0.001). In conclusion, several universal/selective interventions can be effective to promote good mental health in young people. Future research should consolidate and extend these findings.
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http://dx.doi.org/10.1016/j.euroneuro.2020.10.007DOI Listing
December 2020

Relationship between jumping to conclusions and clinical outcomes in people at clinical high-risk for psychosis.

Psychol Med 2020 Oct 6:1-9. Epub 2020 Oct 6.

Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.

Background: Psychosis is associated with a reasoning bias, which manifests as a tendency to 'jump to conclusions'. We examined this bias in people at clinical high-risk for psychosis (CHR) and investigated its relationship with their clinical outcomes.

Methods: In total, 303 CHR subjects and 57 healthy controls (HC) were included. Both groups were assessed at baseline, and after 1 and 2 years. A 'beads' task was used to assess reasoning bias. Symptoms and level of functioning were assessed using the Comprehensive Assessment of At-Risk Mental States scale (CAARMS) and the Global Assessment of Functioning (GAF), respectively. During follow up, 58 (16.1%) of the CHR group developed psychosis (CHR-T), and 245 did not (CHR-NT). Logistic regressions, multilevel mixed models, and Cox regression were used to analyse the relationship between reasoning bias and transition to psychosis and level of functioning, at each time point.

Results: There was no association between reasoning bias at baseline and the subsequent onset of psychosis. However, when assessed after the transition to psychosis, CHR-T participants showed a greater tendency to jump to conclusions than CHR-NT and HC participants (55, 17, 17%; χ2 = 8.13, p = 0.012). There was a significant association between jumping to conclusions (JTC) at baseline and a reduced level of functioning at 2-year follow-up in the CHR group after adjusting for transition, gender, ethnicity, age, and IQ.

Conclusions: In CHR participants, JTC at baseline was associated with adverse functioning at the follow-up. Interventions designed to improve JTC could be beneficial in the CHR population.
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http://dx.doi.org/10.1017/S0033291720003396DOI Listing
October 2020

Annual Research Review: Prevention of psychosis in adolescents - systematic review and meta-analysis of advances in detection, prognosis and intervention.

J Child Psychol Psychiatry 2021 May 14;62(5):657-673. Epub 2020 Sep 14.

Early Psychosis: Interventions and Clinical-detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.

Background: The clinical high-risk state for psychosis (CHR-P) paradigm has facilitated the implementation of psychosis prevention into clinical practice; however, advancements in adolescent CHR-P populations are less established.

Methods: We performed a PRISMA/MOOSE-compliant systematic review of the Web of Science database, from inception until 7 October 2019, to identify original studies conducted in CHR-P children and adolescents (mean age <18 years). Findings were systematically appraised around core themes: detection, prognosis and intervention. We performed meta-analyses (employing Q statistics and I test) regarding the proportion of CHR-P subgroups, the prevalence of baseline comorbid mental disorders, the risk of psychosis onset and the type of interventions received at baseline. Quality assessment and publication bias were also analysed.

Results: Eighty-seven articles were included (n = 4,667 CHR-P individuals). Quality of studies ranged from 3.5 to 8 (median 5.5) on a modified Newcastle-Ottawa scale. Detection: Individuals were aged 15.6 ± 1.2 years (51.5% males), mostly (83%) presenting with attenuated positive psychotic symptoms. CHR-P psychometric accuracy improved when caregivers served as additional informants. Comorbid mood (46.4%) and anxiety (31.4%) disorders were highly prevalent. Functioning and cognition were impaired. Neurobiological studies were inconclusive.

Prognosis: Risk for psychosis was 10.4% (95%CI: 5.8%-18.1%) at 6 months, 20% (95%CI: 15%-26%) at 12 months, 23% (95%CI: 18%-29%) at 24 months and 23.3% (95%CI: 17.3%-30.7%) at ≥36 months.

Interventions: There was not enough evidence to recommend one specific treatment (including cognitive behavioural therapy) over the others (including control conditions) to prevent the transition to psychosis in this population. Randomised controlled trials suggested that family interventions, cognitive remediation and fish oil supplementation may improve cognition, symptoms and functioning. At baseline, 30% of CHR-P adolescents were prescribed antipsychotics and 60% received psychotherapy.

Conclusions: It is possible to detect and formulate a group-level prognosis in adolescents at risk for psychosis. Future interventional research is required.
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http://dx.doi.org/10.1111/jcpp.13322DOI Listing
May 2021

Implementing Precision Psychiatry: A Systematic Review of Individualized Prediction Models for Clinical Practice.

Schizophr Bull 2021 03;47(2):284-297

Early Psychosis: Interventions and Clinical-detection Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, 16 De Crespigny Park, London, UK.

Background: The impact of precision psychiatry for clinical practice has not been systematically appraised. This study aims to provide a comprehensive review of validated prediction models to estimate the individual risk of being affected with a condition (diagnostic), developing outcomes (prognostic), or responding to treatments (predictive) in mental disorders.

Methods: PRISMA/RIGHT/CHARMS-compliant systematic review of the Web of Science, Cochrane Central Register of Reviews, and Ovid/PsycINFO databases from inception until July 21, 2019 (PROSPERO CRD42019155713) to identify diagnostic/prognostic/predictive prediction studies that reported individualized estimates in psychiatry and that were internally or externally validated or implemented. Random effect meta-regression analyses addressed the impact of several factors on the accuracy of prediction models.

Findings: Literature search identified 584 prediction modeling studies, of which 89 were included. 10.4% of the total studies included prediction models internally validated (n = 61), 4.6% models externally validated (n = 27), and 0.2% (n = 1) models considered for implementation. Across validated prediction modeling studies (n = 88), 18.2% were diagnostic, 68.2% prognostic, and 13.6% predictive. The most frequently investigated condition was psychosis (36.4%), and the most frequently employed predictors clinical (69.5%). Unimodal compared to multimodal models (β = .29, P = .03) and diagnostic compared to prognostic (β = .84, p < .0001) and predictive (β = .87, P = .002) models were associated with increased accuracy.

Interpretation: To date, several validated prediction models are available to support the diagnosis and prognosis of psychiatric conditions, in particular, psychosis, or to predict treatment response. Advancements of knowledge are limited by the lack of implementation research in real-world clinical practice. A new generation of implementation research is required to address this translational gap.
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http://dx.doi.org/10.1093/schbul/sbaa120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7965077PMC
March 2021

Impact of coronavirus syndromes on physical and mental health of health care workers: Systematic review and meta-analysis.

J Affect Disord 2020 10 25;275:48-57. Epub 2020 Jun 25.

Early Psychosis: Interventions and Clinical-detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; Section of Psychiatry, Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy; OASIS service, South London and Maudsley NHS Foundation Trust, London, UK; National Institute for Health Research, Maudsley Biomedical Research Centre, South London and Maudsley NHS Foundation Trust, London, UK.

Background: Health care workers (HCW) are at high risk of developing physical/mental health outcomes related to coronavirus syndromes. Nature and frequency of these outcomes are undetermined.

Methods: PRISMA/MOOSE-compliant (PROSPERO-CRD42020180205) systematic review of Web of Science/grey literature until 15th April 2020, to identify studies reporting physical/mental health outcomes in HCW infected/exposed to Severe Acute Respiratory Syndrome -SARS-, Middle East Respiratory Syndrome -MERS-, Novel coronavirus -COVID-19-. Proportion random effect meta-analyses, I statistic, quality assessment and sensitivity analysis.

Results: 115 articles were included (n=60,458 HCW, age 36.1±7.1, 77.1% female). Physical health outcomes: 75.9% HCW infected by SARS/MERS/COVID-19 reported fever (95%CI=65.9-83.7%, k=12, n=949), 47.9% cough (95%CI=39.2-56.8%, k=14, n=970), 43.6% myalgias (95%CI=31.9-56.0%, k=13, n=898), 42.3% chills (95%CI=20.2-67.9%, k=7, n=716), 41.2% fatigue (95%CI=18.2-68.8%, k=6, n=386), 34.6% headaches (95%CI=23.1-48.2%, k=11, n=893), 31.2% dyspnoea (95%CI=23.2-40.5%, k=12, n=1003), 25.3% sore throat (95%CI=18.8-33.2%, k=8, n=747), 22.2% nausea/vomiting (95%CI=14.9-31.8%, k=6, n=662), 18.8% diarrhoea (95%CI=11.9-28.4%, k=9, n=824). Mental health outcomes: 62.5% HCW exposed to SARS/MERS/COVID-19 reported general health concerns (95%CI=57.0-67,8%, k=2, n=2254), 43.7% fear (95%CI=33.9-54.0%, k=4, n=584), 37.9% insomnia (95%CI=30.9-45.5%, k=6, n=5067), 37.8% psychological distress (95%CI=28.4-48.2%, k=15, n=24,346), 34.4% burnout (95%CI=19.3-53.5%, k=3, n=1337), 29.0% anxiety features (95%CI=14.2-50.3%, k=6, n=9191), 26.3% depressive symptoms (95%CI=12.5-47.1%, k=8, n=9893), 20.7% post-traumatic stress disorder features (95%CI=13.2-31%, k=11, n=3826), 16.1% somatisation (95%CI=0.2-96.0%, k=2, n=2184), 14.0% stigmatisation feelings (95%CI=6.4-28.1%, k=2, n=411).

Limitations: Limited amount of evidence for some outcomes and suboptimal design in several studies included.

Conclusions: SARS/MERS/COVID-19 have a substantial impact on the physical and mental health of HCW, which should become a priority for public health strategies.
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http://dx.doi.org/10.1016/j.jad.2020.06.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314697PMC
October 2020

Discovery and population genomics of structural variation in a songbird genus.

Nat Commun 2020 07 7;11(1):3403. Epub 2020 Jul 7.

Department of Evolutionary Biology and Science for Life Laboratory, Uppsala University, 752 36, Uppsala, Sweden.

Structural variation (SV) constitutes an important type of genetic mutations providing the raw material for evolution. Here, we uncover the genome-wide spectrum of intra- and interspecific SV segregating in natural populations of seven songbird species in the genus Corvus. Combining short-read (N = 127) and long-read re-sequencing (N = 31), as well as optical mapping (N = 16), we apply both assembly- and read mapping approaches to detect SV and characterize a total of 220,452 insertions, deletions and inversions. We exploit sampling across wide phylogenetic timescales to validate SV genotypes and assess the contribution of SV to evolutionary processes in an avian model of incipient speciation. We reveal an evolutionary young (~530,000 years) cis-acting 2.25-kb LTR retrotransposon insertion reducing expression of the NDP gene with consequences for premating isolation. Our results attest to the wealth and evolutionary significance of SV segregating in natural populations and highlight the need for reliable SV genotyping.
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http://dx.doi.org/10.1038/s41467-020-17195-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341801PMC
July 2020

Therapeutic drug monitoring of nivolumab in routine clinical practice. A pilot study.

Farm Hosp 2020 04 17;44(3):81-86. Epub 2020 Apr 17.

Plataforma de Oncología, Hospital Quironsalud Torrevieja, Torrevieja (Alicante). Spain.

Objective: A review of the literature about the anti-programmed death 1 monoclonal antibody nivolumab permits to verify the existence  of several issues still unresolved about their dosing schedule. The aim of the present work was to explore possibilities of nivolumab treatment  personalization through therapeutic drug monitoring, in order to  improve their effectiveness and efficiency.

Method: Observational, prospective study carried out from May 2017  through June 2019 in patients with different tumor diagnoses treated with nivolumab. Blood samples were obtained in the routine  clinical practice, once nivolumab steady state was reached. Serum  nivolumab levels were determined by means of quantitative ELISA. The  standard schedule of 3 mg/kg every two weeks (Q2W) was modified in  some patients due to different circumstances, and resulting serum  concentrations were compared with those from the non-modified  patients and the published data.

Results: Blood samples from 19 patients in treatment with nivolumab were analyzed. A total of 39 samples of nivolumab were  analyzed between 6th and 27th cycles. The standard schedule of 3  mg/kg every two weeks was modified in 12/19 (60%) patients, with  intervals of 3, 4, 5, 6 or 7 weeks, once the steady state was reached.  No statistically significant differences were detected when comparing  every two weeks and every four week intervals. When the intervals  were six or seven weeks, mean plasma concentration showed a  statistically significant difference compared with every two weeks.

Conclusions: Current data contribute to confirm former suspects about the possibilities of exploring new scenarios to improve and  personalize nivolumab dosage. Additional studies to confirm it in bigger  series and correlate it with clinical results, and to better define the role  of therapeutic drug monitoring in the treatment, are warranted, not only by financial concerns but also for improving quality of life of patients  and clinical management aspects.
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http://dx.doi.org/10.7399/fh.11319DOI Listing
April 2020

Glyceryl trinitrate in first-episode psychosis unmedicated with antipsychotics: A randomised controlled pilot study.

J Psychopharmacol 2020 08 21;34(8):839-847. Epub 2020 May 21.

Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, London, UK.

Background: There is a pressing need for new classes of treatment for psychosis. A key therapeutic target for novel compounds is the NMDA receptor, which may be modulated by nitric oxide donors such as sodium nitroprusside (SNP). Recent studies of SNP in patients with psychosis have mixed results, and the drug has to be administered intravenously. Glyceryl trinitrate (GTN) is a well-established cardiovascular medicine that is also a nitric oxide donor, and can be given orally.

Aims: We explored the safety and potential effects of GTN in unmedicated patients with a first episode of psychosis.

Methods: This was a single-centre, randomised, double-blind, placebo-controlled trial from December 2016 to April 2019 (ClinicalTrials.gov identifier: NCT02906553). Patients received 3 × sprays of GTN or placebo for three consecutive days, and were re-assessed on Days 1, 2, 3 and 7. The primary outcome was cognition (Jumping to Conclusions task), secondary outcomes were symptoms (Positive and Negative Syndrome Scale (PANSS)), verbal memory (Hopkins Verbal Learning task), and mood (Bond-Lader Visual Analogue Scales).

Results: Nineteen patients were randomised, and 13 participants were included in the analyses. Compared with placebo, GTN was well tolerated, but was not associated with significant effects on cognition, symptoms, or mood. Bayesian statistics indicate that our results were 2× more likely under the null hypothesis than the alternative hypothesis, providing anecdotal evidence that GTN does not improve psychotic symptoms.

Conclusions: We found no indication of an effect of GTN on symptoms of psychosis or cognition.
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http://dx.doi.org/10.1177/0269881120922967DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376621PMC
August 2020

Emotion Recognition and Adverse Childhood Experiences in Individuals at Clinical High Risk of Psychosis.

Schizophr Bull 2020 07;46(4):823-833

Department of Psychology, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.

Objective: To investigate the association between facial affect recognition (FAR) and type of adverse childhood experiences (ACEs) in a sample of clinical high risk (CHR) individuals and a matched sample of healthy controls (HCs).

Methods: In total, 309 CHR individuals and 51 HC were recruited as part of an European Union-funded multicenter study (EU-GEI) and included in this work. During a 2-year follow-up period, 65 CHR participants made a transition to psychosis (CHR-T) and 279 did not (CHR-NT). FAR ability was measured using a computerized version of the Degraded Facial Affect Recognition (DFAR) task. ACEs were measured using the Childhood Experience of Care and Abuse Questionnaire, the Childhood Trauma Questionnaire, and the Bullying Questionnaire. Generalized regression models were used to investigate the relationship between ACE and FAR. Logistic regressions were used to investigate the relationship between FAR and psychotic transition.

Results: In CHR individuals, having experienced emotional abuse was associated with decreased total and neutral DFAR scores. CHR individuals who had experienced bullying performed better in the total DFAR and in the frightened condition. In HC and CHR, having experienced the death of a parent during childhood was associated with lower DFAR total score and lower neutral DFAR score, respectively. Analyses revealed a modest increase of transition risk with increasing mistakes from happy to angry faces.

Conclusions: Adverse experiences in childhood seem to have a significant impact on emotional processing in adult life. This information could be helpful in a therapeutic setting where both difficulties in social interactions and adverse experiences are often addressed.
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http://dx.doi.org/10.1093/schbul/sbz128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7345818PMC
July 2020

Clinical Validity of DSM-5 Attenuated Psychosis Syndrome: Advances in Diagnosis, Prognosis, and Treatment.

JAMA Psychiatry 2020 03;77(3):311-320

Early Psychosis: Interventions and Clinical-detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.

Importance: Since the release of the DSM-5 diagnosis of attenuated psychosis syndrome (DSM-5-APS) in 2013, several research studies have investigated its clinical validity. Although critical and narrative reviews have reviewed these progresses, no systematic review has comprehensively summarized the available evidence regarding the clinical validity of DSM-5-APS.

Objective: To provide current evidence on the clinical validity of DSM-5-APS, focusing on recent advances in diagnosis, prognosis, and treatment.

Evidence Review: A multistep literature search using the Web of Science database, Cochrane Central Register of Reviews, Ovid/PsychINFO, conference proceedings, and trial registries from database inception to June 16, 2019, was conducted following PRISMA and MOOSE guidelines and PROSPERO protocol. Studies with original data investigating individuals diagnosed using DSM-5-APS or meeting comparable criteria were included. The results of the systematic review were summarized in tables and narratively synthesized against established evidence-based antecedent, concurrent, and prognostic validators. A quantitative meta-analysis was conducted to explore the cumulative risk of psychosis onset at 6, 12, 24, and 36 months in individuals diagnosed using DSM-5-APS criteria.

Findings: The systematic review included 56 articles, which reported on 124 validators, including 15 antecedent, 55 concurrent, and 54 prognostic validators. The epidemiological prevalence of the general non-help-seeking young population meeting DSM-5-APS criteria was 0.3%; the prevalence of individuals meeting DSM-5-APS criteria was variable in clinical samples. The interrater reliability for DSM-5-APS criteria was comparable with that of other DSM-5 mental disorders and can be optimized by the use of specific psychometric instruments. DSM-5-APS criteria were associated with frequent depressive comorbid disorders, distress, suicidality, and functional impairment. The meta-analysis included 23 prospective cohort studies, including 2376 individuals. The meta-analytical risk of psychosis onset was 11% at 6 months, 15% at 12 months, 20% at 24 months, and 23% at 36 months. Research into predisposing and precipitating epidemiological factors, neurobiological correlates, and effective treatments for DSM-5-APS criteria has been limited.

Conclusions And Relevance: Over recent years, DSM-5-APS criteria have received substantial concurrent and prognostic validation, mostly driven by research into the clinical high-risk state for psychosis. Precipitating and predisposing factors, neurobiological correlates, and effective treatments are undetermined to date.
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http://dx.doi.org/10.1001/jamapsychiatry.2019.3561DOI Listing
March 2020

Genetic modulation of facial emotion recognition in borderline personality disorder.

Prog Neuropsychopharmacol Biol Psychiatry 2020 04 15;99:109816. Epub 2019 Nov 15.

BioCruces-Bizkaia Health Research Institute, Barakaldo, Spain; Osakidetza Basque Health Service, Bizkaia Mental Health Network, Neurochemical Research Unit, Barakaldo, Spain.

Facial emotion recognition (FER) has been described to be impaired in borderline personality disorder (BPD), especially for neutral faces. Genetic modulation of FER has been studied in healthy individuals and some psychiatric conditions, but no genetic association studies have been conducted in BPD hitherto. The main objective of our study was to explore the influence of the serotonin-transporter-linked promoter region (5HTTLPR) and catechol-o-methyltransferase (COMT) Val158Met on facial emotion processing among BPD patients. To that end, seventy-six BPD outpatients were asked to complete a computer-based facial affect recognition task, representing four emotions (neutral, happy, fearful or angry). Accuracy of FER and perceptual biases were calculated. The 5HTTLPR and COMT Val158Met polymorphisms were genotyped using saliva samples. Individuals with the high-activity serotonin-transporter genotype and those with the low-activity COMT genotype had significantly more difficulties identifying neutral faces; the former showed stronger bias to perceive neutral faces as happy, and the latter, neutral faces as fearful. Interestingly, the perceptual biases observed in our patients are similar to previous reports in healthy individuals. The authors propose that the ability to accurately recognize neutral faces might be a possible endophenotype of BPD. Sex-genotype interactions were also observed in relation to angry faces and 5HTTLPR, and neutral faces and COMT Val158Met polymorphisms, in line with sex-related differences previously described for both polymorphisms in relation to FER and other cognitive and behavioral outcomes. The impact of inaccurate FER on psychosocial functioning and potential interventions are also discussed.
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http://dx.doi.org/10.1016/j.pnpbp.2019.109816DOI Listing
April 2020

Drift and Directional Selection Are the Evolutionary Forces Driving Gene Expression Divergence in Eye and Brain Tissue of Butterflies.

Genetics 2019 10 29;213(2):581-594. Epub 2019 Aug 29.

Division of Evolutionary Biology, Ludwig-Maximilians-Universität München, Planegg-Martinsried 82152, Germany

Investigating gene expression evolution over micro- and macroevolutionary timescales will expand our understanding of the role of gene expression in adaptation and speciation. In this study, we characterized the evolutionary forces acting on gene expression levels in eye and brain tissue of five butterflies with divergence times of ∼5-12 MYA. We developed and applied Brownian motion (BM) and Ornstein-Uhlenbeck (OU) models to identify genes whose expression levels are evolving through drift, stabilizing selection, or a lineage-specific shift. We found that 81% of the genes evolve under genetic drift. When testing for branch-specific shifts in gene expression, we detected 368 (16%) shift events. Genes showing a shift toward upregulation have significantly lower gene expression variance than those genes showing a shift leading toward downregulation. We hypothesize that directional selection is acting in shifts causing upregulation, since transcription is costly. We further uncovered through simulations that parameter estimation of OU models is biased when using small phylogenies and only becomes reliable with phylogenies having ≥ 50 taxa. Therefore, we developed a new statistical test based on BM to identify highly conserved genes (, evolving under strong stabilizing selection), which comprised 3% of the orthoclusters. In conclusion, we found that drift is the dominant evolutionary force driving gene expression evolution in eye and brain tissue in Nevertheless, the higher proportion of genes evolving under directional than under stabilizing selection might reflect species-specific selective pressures on vision and the brain that are necessary to fulfill species-specific requirements.
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http://dx.doi.org/10.1534/genetics.119.302493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6781903PMC
October 2019

Population Genetic and Functional Analysis of a -Regulatory Polymorphism in the gene.

Genes (Basel) 2019 02 14;10(2). Epub 2019 Feb 14.

Division of Evolutionary Biology, Faculty of Biology, LMU Munich, Grosshaderner Str. 2, 82152 Planegg-Martinsried, Germany.

Although gene expression can vary extensively within and among populations, the genetic basis of this variation and the evolutionary forces that maintain it are largely unknown. In , a 49-bp insertion/deletion (indel) polymorphism in the () gene is associated with variation in expression and oxidative stress tolerance. To better understand the functional and evolutionary significance of this polymorphism, we investigated it in several worldwide populations. In a German population, the deletion was present at a high and stable frequency over multiple seasons and years, and was associated with increased expression. There was, however, no evidence that the polymorphism was maintained by overdominant, seasonally fluctuating, or sexually antagonistic selection. The deletion was rare in a population from the species' ancestral range in sub-Saharan Africa and is likely the result of non-African admixture, suggesting that it spread to high frequency following the species' out-of-Africa expansion. Using data from a North American population, we found that the deletion was associated with expression and tolerance to oxidative stress induced by menadione sodium bisulfite. Our results are consistent with the deletion being selectively favored in temperate populations due to the increased expression and oxidative stress tolerance that it confers.
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http://dx.doi.org/10.3390/genes10020147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6410240PMC
February 2019

GAD1 gene polymorphisms are associated with bipolar I disorder and with blood homovanillic acid levels but not with plasma GABA levels.

Neurochem Int 2019 03 6;124:152-161. Epub 2019 Jan 6.

Departamento de Investigación Neuroquímica, Hospital de Zamudio, Red de Salud Mental de Bizkaia, Zamudio, Spain; BioCruces Health Research Institute, Barakaldo, Spain.

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http://dx.doi.org/10.1016/j.neuint.2019.01.004DOI Listing
March 2019

Can childhood trauma influence facial emotion recognition independently from a diagnosis of severe mental disorder?

Rev Psiquiatr Salud Ment (Engl Ed) 2020 Jul - Sep;13(3):140-149. Epub 2018 Dec 14.

Departamento de Neurociencias, Universidad del País-Vasco-Euskal Herriko Unibertsitatea, Leioa, Vizcaya, España; Departamento de Psiquiatría, Hospital Universitario Basurto, Bilbao, Vizcaya, España; Instituto de Investigación de BioCruces, Barakaldo, Vizcaya, España.

Introduction: Facial emotion recognition (FER) is a fundamental component in social interaction. We know that FER is disturbed in patients with severe mental disorder (SMD), as well as those with a history of childhood trauma.

Material And Methods: We intend to analyze the possible relationship between the existence of trauma in childhood irrespective of a SMD, measured by the CTQ scale and facial expression recognition, in a sample of three types of subjects (n=321): healthy controls (n=179), patients with BPD (n=69) and patients with a first psychotic episode (n=73). Likewise, clinical and socio-demographic data were collected. The relationship was analyzed by a technique of multivariate regression adjusting for sex, age, IQ, current consumption of drugs and group to which the subject belonged.

Results: Sexual and/or physical trauma in childhood related independently to the existence of SMD with a worse total FER ratio, as well as to a worse rate of recognition in expressions of happiness. Furthermore, the subjects with a history of childhood trauma attributed expressions of anger and fear more frequently to neutral and happy faces, irrespective of other variables.

Conclusions: The existence of trauma in childhood seems to influence the ability of subjects to recognize facial expressions, irrespective of SMD. Trauma is a preventable factor with specific treatment; therefore, attention should be paid to the existence of this background in clinical populations.
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http://dx.doi.org/10.1016/j.rpsm.2018.10.003DOI Listing
December 2018

Propionic acid metabolism and poly-3-hydroxybutyrate-co-3-hydroxyvalerate production by a prpC mutant of Herbaspirillum seropedicae Z69.

J Biotechnol 2018 Nov 18;286:36-44. Epub 2018 Sep 18.

Unidad Microbiología Molecular - Depto. BIOGEM, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE), Av. Italia 3318, Montevideo, CP11600, Uruguay.

Polyhydroxyalkanoates (PHAs) are thermoplastic polyesters produced by a wide range of bacteria as carbon and energy reserves. PHA accumulation is typically increased under unbalanced growth conditions and with carbon source in excess. Although polyhydroxybutyrate (PHB) could be used for specific applications, it is brittle and not a useful alternative for plastics like polypropylene. Far more useful polypropylene-like PHAs, are copolymers composed of 3-hydroxybutyrate and 3-hydroxyvalerate, P(3HB-co-3HV). Propionic acid is one of the carbon sources that can be used to generate 3HV. A mutant derived from Herbaspirillum seropedicae Z69, a strain previously described as capable of producing P(3HB-co-3HV) from propionic acid, was constructed to increase 3HV biosynthetic efficiency. The strategy involved elimination of a catabolic route for propionyl-CoA by deficiency marker exchange of a selected gene. The mutant (Z69Prp) was constructed by elimination of the 2-methylcitrate synthase (PrpC) gene of the 2-methylcitrate cycle for propionate catabolism. Strain Z69Prp was unable to grow on sodium propionate, but in cultures with glucose-propionate accumulated 50% of its dry weight as copolymer. Z69Prp had 14.1 mol% 3HV; greater than that of strain Z69 (2.89 mol%). The 3HV yield from propionic acid (Y) was 0.80 g g, and below the maximum theoretical value (1.35 g g).
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http://dx.doi.org/10.1016/j.jbiotec.2018.09.008DOI Listing
November 2018

The relationship between theory of mind deficits and neurocognition in first episode-psychosis.

Psychiatry Res 2018 10 22;268:361-367. Epub 2018 Jul 22.

Department of Neuroscience, University of the Basque Country, Basque Country, Leioa, Spain; Department of Psychiatry, Basurto University Hospital, Bilbao, Spain; Mental Health Group, BioCruces Health Research Institute. Plaza de Cruces 12, Barakaldo, Bizkaia 48903, Spain.

Research suggests that theory of mind (ToM) deficits are related to chronic psychosis and to first-episode psychosis (FEP) independently of other neurocognition domains. The aim of this study was to measure the differences in ToM area in a Spanish population of FEP sample (N = 32) and in a healthy control group (N = 32). A further aim was to describe the relationship between different domains of neurocognition, psychotic symptoms and social functioning with ToM in this sample. ToM was assessed with the MASC task. Estimated IQ with a short version of the WAIS III, Rey-Osterrieth Complex figure, Trail Making Test, Stroop test and Wisconsin Carting Sorting test were used to assess neurocognition. Psychotic symptoms were assessed with Community Assessment of Psychic Experiences (CAPE) in both groups and with PANSS scale in FEP group. GAF and Cannon-Spoor scales were used to measure social functioning before and after onset of psychosis. FEP showed important deficits in ToM domain compared to controls. A worse executive functioning was associated with worse scores in ToM task. However, no relation was found between positive or negative psychotic symptoms and ToM or social functioning and ToM. In our sample neurocognition tests were strongly related to ToM domain independently of other variables.
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http://dx.doi.org/10.1016/j.psychres.2018.06.066DOI Listing
October 2018

Evolution of Sex-Biased Gene Expression and Dosage Compensation in the Eye and Brain of Heliconius Butterflies.

Mol Biol Evol 2018 09;35(9):2120-2134

Department of Ecology and Evolutionary Biology, University of California, Irvine, CA.

Differences in behavior and life history traits between females and males are the basis of divergent selective pressures between sexes. It has been suggested that a way for the two sexes to deal with different life history requirements is through sex-biased gene expression. In this study, we performed a comparative sex-biased gene expression analysis of the combined eye and brain transcriptome from five Heliconius species, H. charithonia, H. sara, H. erato, H. melpomene and H. doris, representing five of the main clades from the Heliconius phylogeny. We found that the degree of sexual dimorphism in gene expression is not conserved across Heliconius. Most of the sex-biased genes identified in each species are not sex-biased in any other, suggesting that sexual selection might have driven sexually dimorphic gene expression. Only three genes shared sex-biased expression across multiple species: ultraviolet opsin UVRh1 and orthologs of Drosophila Krüppel-homolog 1 and CG9492. We also observed that in some species female-biased genes have higher evolutionary rates, but in others, male-biased genes show the fastest rates when compared with unbiased genes, suggesting that selective forces driving sex-biased gene evolution in Heliconius act in a sex- and species-specific manner. Furthermore, we found dosage compensation in all the Heliconius tested, providing additional evidence for the conservation of dosage compensation across Lepidoptera. Finally, sex-biased genes are significantly enriched on the Z, a pattern that could be a result of sexually antagonistic selection.
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http://dx.doi.org/10.1093/molbev/msy111DOI Listing
September 2018

Can an experimental white noise task assess psychosis vulnerability in adult healthy controls?

PLoS One 2018 15;13(2):e0192373. Epub 2018 Feb 15.

Department of Neuroscience, University of the Basque Country, Leioa, Basque Country, Spain.

Background: This is an extension of a paper published earlier. We investigated the association between the tendency to detect speech illusion in random noise and levels of positive schizotypy in a sample of 185 adult healthy controls.

Materials And Methods: Subclinical positive, negative and depressive symptoms were assessed with the Community Assessment of Psychic Experiences (CAPE); positive and negative schizotypy was assessed with the Structured Interview for Schizotypy-Revised (SIS-R).

Results: Speech illusions were associated with positive schizotypy (OR: 4.139, 95% CI: 1.074-15.938; p = 0.039) but not with negative schizotypy (OR: 1.151, 95% CI: 0.183-7.244; p = 0.881). However, the association of positive schizotypy with speech illusions was no longer significant after adjusting for age, sex and WAIS-III (OR: 2.577, 95% CI: 0.620-10.700; p = 0.192). Speech illusions were not associated with self-reported CAPE measures.

Conclusions: The association between schizotypy and the tendency to assign meaning in random noise in healthy controls may be mediated by cognitive ability and not constitute an independent trait.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0192373PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5813930PMC
April 2018

Affectively salient signal to random noise might be used to identify psychosis vulnerability in severe mental disorders.

Eur Psychiatry 2018 03 3;49:37-42. Epub 2018 Feb 3.

Department of Neuroscience, University of the Basque Country, Leioa, Basque Country, Spain; Department of Psychiatry, Basurto University Hospital, Bilbao, Spain; BioCruces Research Institute, Barakaldo, Spain.

Background: Subclinical psychotic symptoms are present in the general population. Furthermore, they are quite common in diagnostic categories beyond psychosis, such as BPD patients.

Methods: We want to assess the differences between 3 groups: BPD (n = 68), FEP (n = 83) and controls (n = 203) in an experimental paradigm measuring the presence of speech illusions in white noise. The Positive and Negative Syndrome Scale was administered in the patient group, the Structured Interview for Schizotypy-Revised, and the Community Assessment of Psychic Experiences in the control and BPD group. The white noise task was also analysed within a signal detection theory (SDT) framework. Logistic regression analyses and the general linear models were used to analyse the adjusted differences between groups.

Results: Differences were more prevalent in signals that were perceived as affectively salient in patients groups (9.6% in FEP vs 5.9% in BPD and 1% in controls; OR: 10.7; 95%CI: 2.2-51.6, p = 0.003 in FEP; OR: 6.3; 95%CI: 1.1-35.0, p = 0.036 in BPD). Besides, we found a worse general performance and more false alarms in the task for FEP group using SDT framework.

Conclusions: Experimental paradigms indexing the tendency to detect affectively salient signals in noise may be used to identify liability to psychosis in people with vulnerability. Its predictable value in other diagnostic categories and general population requires further research.
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http://dx.doi.org/10.1016/j.eurpsy.2017.12.008DOI Listing
March 2018

Relation between psychotic symptoms, parental care and childhood trauma in severe mental disorders.

Psychiatry Res 2017 May 6;251:78-84. Epub 2017 Feb 6.

Department of Neuroscience, University of the Basque Country, Basque Country, Spain; Department of Psychiatry, Basurto University Hospital, Bilbao, Spain.

A relation between different types of parental care, trauma in childhood and psychotic symptoms in adulthood has been proposed. The nature of this association is not clear and if it is more related to psychotic disorders per se or to a cluster of symptoms such as positive psychotic symptoms remains undefined. We have analysed the presence of childhood trauma using the CTQ scale and types of parental care using the PBI scale in three groups of subjects: borderline personality disorder patients (n=36), first psychotic episode patients (n=61) and healthy controls (n=173). Positive psychotic symptomatology was assessed with the CAPE scale. General linear models were used to study the relation between positive psychotic symptomatology and variables of interest. BPD patients had the highest rate of any kind of trauma, followed by FEP patients. We found a positive relationship between psychotic symptomatology and the existence of trauma in childhood in all groups. Moreover, an affectionless control rearing style was directly associated with the existence of trauma. Furthermore, subjects with trauma presented less probability of having an optimal parenting style in childhood. The relation between psychotic symptoms and trauma remained statistically significant after adjusting for other variables including parental rearing style. There seems to be a link between trauma in childhood and psychotic symptomatology across different populations independently of psychiatric diagnosis. Taking into account that there is an association between trauma and psychosis and that trauma is a modifiable factor, clinicians should pay special attention to these facts.
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http://dx.doi.org/10.1016/j.psychres.2017.02.017DOI Listing
May 2017

Differences in Facial Emotion Recognition between First Episode Psychosis, Borderline Personality Disorder and Healthy Controls.

PLoS One 2016 28;11(7):e0160056. Epub 2016 Jul 28.

Department of Neuroscience, University of the Basque Country, Leioa, Basque Country, Spain.

Background: Facial emotion recognition (FER) is essential to guide social functioning and behaviour for interpersonal communication. FER may be altered in severe mental illness such as in psychosis and in borderline personality disorder patients. However, it is unclear if these FER alterations are specifically related to psychosis. Awareness of FER alterations may be useful in clinical settings to improve treatment strategies. The aim of our study was to examine FER in patients with severe mental disorder and their relation with psychotic symptomatology.

Materials And Methods: Socio-demographic and clinical variables were collected. Alterations on emotion recognition were assessed in 3 groups: patients with first episode psychosis (FEP) (n = 64), borderline personality patients (BPD) (n = 37) and healthy controls (n = 137), using the Degraded Facial Affect Recognition Task. The Positive and Negative Syndrome Scale, Structured Interview for Schizotypy Revised and Community Assessment of Psychic Experiences scales were used to assess positive psychotic symptoms. WAIS III subtests were used to assess IQ.

Results: Kruskal-Wallis analysis showed a significant difference between groups on the FER of neutral faces score between FEP, BPD patients and controls and between FEP patients and controls in angry face recognition. No significant differences were found between groups in the fear or happy conditions. There was a significant difference between groups in the attribution of negative emotion to happy faces. BPD and FEP groups had a much higher tendency to recognize happy faces as negatives. There was no association with the different symptom domains in either group.

Conclusions: FEP and BPD patients have problems in recognizing neutral faces more frequently than controls. Moreover, patients tend to over-report negative emotions in recognition of happy faces. Although no relation between psychotic symptoms and FER alterations was found, these deficits could contribute to a patient's misinterpretations in daily life.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0160056PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4965014PMC
August 2017

COMT haplotypes, catecholamine metabolites in plasma and clinical response in schizophrenic and bipolar patients.

Pharmacogenomics 2016 06 7;17(8):837-51. Epub 2016 Jun 7.

Departamento de Psiquiatría y Psicología Médica, Facultad de Medicina, Universidad del País Vasco, Barrio Sarriena s/n, 48940 Leioa, Bizkaia, Spain.

Aim: We examined the association of COMT haplotypes and plasma metabolites of catecholamines in relation to the clinical response to antipsychotics in schizophrenic and bipolar patients.

Patients & Methods: We studied 165 patients before and after four weeks of treatment, and 163 healthy controls. We assessed four COMT haplotypes and the plasma concentrations of HVA, DOPAC and MHPG.

Results: Bipolar patients: haplotypes are associated with age at onset and clinical evolution. In schizophrenic patients, an haplotype previously associated with increased risk, is related to better response of negative symptoms.

Conclusion: Haplotypes would be good indicators of the clinical status and the treatment response in bipolar and schizophrenic patients. Larger studies are required to elucidate the clinical usefulness of these findings.
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http://dx.doi.org/10.2217/pgs-2016-0022DOI Listing
June 2016

An Indel Polymorphism in the MtnA 3' Untranslated Region Is Associated with Gene Expression Variation and Local Adaptation in Drosophila melanogaster.

PLoS Genet 2016 Apr 27;12(4):e1005987. Epub 2016 Apr 27.

Faculty of Biology, Ludwig-Maximilians-Universität München, Planegg, Germany.

Insertions and deletions (indels) are a major source of genetic variation within species and may result in functional changes to coding or regulatory sequences. In this study we report that an indel polymorphism in the 3' untranslated region (UTR) of the metallothionein gene MtnA is associated with gene expression variation in natural populations of Drosophila melanogaster. A derived allele of MtnA with a 49-bp deletion in the 3' UTR segregates at high frequency in populations outside of sub-Saharan Africa. The frequency of the deletion increases with latitude across multiple continents and approaches 100% in northern Europe. Flies with the deletion have more than 4-fold higher MtnA expression than flies with the ancestral sequence. Using reporter gene constructs in transgenic flies, we show that the 3' UTR deletion significantly contributes to the observed expression difference. Population genetic analyses uncovered signatures of a selective sweep in the MtnA region within populations from northern Europe. We also find that the 3' UTR deletion is associated with increased oxidative stress tolerance. These results suggest that the 3' UTR deletion has been a target of selection for its ability to confer increased levels of MtnA expression in northern European populations, likely due to a local adaptive advantage of increased oxidative stress tolerance.
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http://dx.doi.org/10.1371/journal.pgen.1005987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4847869PMC
April 2016

Data Gathering Bias: Trait Vulnerability to Psychotic Symptoms?

PLoS One 2015 6;10(7):e0132442. Epub 2015 Jul 6.

Department of Neuroscience, University of the Basque Country, Basque Country, Spain; Department of Psychiatry, Basurto University Hospital, Bilbao, Spain.

Background: Jumping to conclusions (JTC) is associated with psychotic disorder and psychotic symptoms. If JTC represents a trait, the rate should be (i) increased in people with elevated levels of psychosis proneness such as individuals diagnosed with borderline personality disorder (BPD), and (ii) show a degree of stability over time.

Methods: The JTC rate was examined in 3 groups: patients with first episode psychosis (FEP), BPD patients and controls, using the Beads Task. PANSS, SIS-R and CAPE scales were used to assess positive psychotic symptoms. Four WAIS III subtests were used to assess IQ.

Results: A total of 61 FEP, 26 BPD and 150 controls were evaluated. 29 FEP were revaluated after one year. 44% of FEP (OR = 8.4, 95% CI: 3.9-17.9) displayed a JTC reasoning bias versus 19% of BPD (OR = 2.5, 95% CI: 0.8-7.8) and 9% of controls. JTC was not associated with level of psychotic symptoms or specifically delusionality across the different groups. Differences between FEP and controls were independent of sex, educational level, cannabis use and IQ. After one year, 47.8% of FEP with JTC at baseline again displayed JTC.

Conclusions: JTC in part reflects trait vulnerability to develop disorders with expression of psychotic symptoms.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0132442PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4493127PMC
April 2016