Publications by authors named "Eduard Vieta"

753 Publications

Study Protocol-Coping With the Pandemics: What Works Best to Reduce Anxiety and Depressive Symptoms.

Front Psychiatry 2021 2;12:642763. Epub 2021 Jul 2.

Imaging of Mood- and Anxiety-Related Disorders (IMARD) Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.

The coronavirus disease 2019 (COVID-19) pandemic and lockdown might increase anxiety and depressive symptoms in most individuals. Health bodies recommend several coping behaviors to protect against such symptoms, but evidence on the relationship between these behaviors and symptoms mostly comes from cross-sectional studies in convenience samples. We will conduct a prospective longitudinal study of the associations between coping behaviors and subsequent anxiety and depressive symptoms during the COVID-19 pandemic in a representative sample of the Spanish general adult population. We will recruit 1,000 adult participants from all autonomous communities of Spain and with sex, age, and urbanicity distributions similar to those of their populations and assess anxiety and depressive symptoms and coping behaviors using fortnightly questionnaires and real-time methods (ecological momentary assessments) for 1 year. The fortnightly questionnaires will inquire about anxiety and depressive symptoms [General Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9)] and the frequency of 10 potential coping behaviors (e.g., follow a routine) during the past 2 weeks. In addition, we will collect several variables that could confound or moderate these associations. These will include subjective well-being [International Positive and Negative Affect Schedule Short Form (I-PANAS-SF) and Satisfaction with Life Scale (SWLS)], obsessive-compulsive symptoms [Obsessive Compulsive Inventory-Revised (OCI-R)], personality and emotional intelligence [International Personality Item Pool (IPIP) and Trait Emotional Intelligence Questionnaire Short Form (TEIQue-SF)], sociodemographic factors (e.g., work status, housing-built environment), and COVID-19 pandemic-related variables (e.g., hospitalizations or limitations in social gatherings). Finally, to analyze the primary relationship between coping behaviors and subsequent anxiety and depressive symptoms, we will use autoregressive moving average (ARMA) models. Based on the study results, we will develop evidence-based, clear, and specific recommendations on coping behaviors during the COVID-19 pandemic and lockdown. Such suggestions might eventually help health bodies or individuals to manage current or future pandemics.
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http://dx.doi.org/10.3389/fpsyt.2021.642763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282901PMC
July 2021

Bipolar disorder and Susac syndrome: a case report.

Int Clin Psychopharmacol 2021 Jul 15. Epub 2021 Jul 15.

Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM Autoimmune Diseases Department, Institut d'Investigacions August Pi i Sunyer, Universitat de Barcelona, Hospital Clinic, Barcelona, Catalonia, Spain.

Susac-syndrome is a rare autoimmune disease that manifests with mood alterations in up to 15% of cases and is usually treated with corticosteroids. We present the case of a 41-year-old woman with a first manic episode and history of Susac-syndrome, secondary Cushing's syndrome after receiving high doses of corticosteroids and a previous depressive episode. Differentiating between primary and secondary mania is difficult, as people with bipolar disorder are prone to multiple psychiatric and nonpsychiatric comorbidities, in this case, the differential diagnosis included secondary mania, corticoid-induced manic episode and primary bipolar disorder. Upon admission, corticosteroid treatment was suspended, and the patient was started on lithium and risperidone. Secondary causes of mania were discarded and, assessing temporal and dosage criteria, it was deemed unlikely that the present episode was corticosteroid-induced. One-year outpatient follow-up pointed towards a primary bipolar type I disorder, as a separate entity from her Susac-syndrome. Corticosteroid use or abrupt withdrawal pose an underestimated risk of inducing depressive or manic symptoms, which may unmask affective disorders in susceptible individuals. Many medical conditions share CNS involvement and/or high-dose/prolonged corticosteroid treatment. In such cases, psychiatric manifestations such as mania or depression should be regarded as secondary and studied to determine the existence of medical complications before considering primary psychiatric conditions.
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http://dx.doi.org/10.1097/YIC.0000000000000375DOI Listing
July 2021

Lithium therapy and weight change in people with Bipolar Disorder: a systematic review and meta-analysis.

Neurosci Biobehav Rev 2021 Jul 12. Epub 2021 Jul 12.

Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, 170 Villarroel st, 12-0, 08036, Barcelona, Spain.

Lithium remains the gold standard maintenance treatment for Bipolar Disorder (BD). However, weight gain is a side effect of increasing relevance due to its metabolic implications. We conducted a systematic review and meta-analysis aimed at summarizing evidence on the use of lithium and weight change in BD. We followed the PRISMA methodology, searching Pubmed, Scopus and Web of Science. From 1003 screened references, 20 studies were included in the systematic review and 9 included in the meta-analysis. In line with the studies included in the systematic review, the meta-analysis revealed that weight gain with lithium was not significant, noting a weight increase of 0.462 Kg (p = 0,158). A shorter duration of treatment was significantly associated with more weight gain. Compared to placebo, there were no significant differences in weight gain. Weight gain was significantly lower with lithium than with active comparators. This work reveals a low impact of lithium on weight change, especially compared to some of the most widely used active comparators. Our results could impact clinical decisions.
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http://dx.doi.org/10.1016/j.neubiorev.2021.07.011DOI Listing
July 2021

Structural Brain Correlates in Major Depression, Anxiety Disorders and Post-traumatic Stress Disorder: A Voxel-Based Morphometry Meta-analysis.

Neurosci Biobehav Rev 2021 Jul 10. Epub 2021 Jul 10.

Mental Health Department, Hospital Universitari Parc Taulí, Institut d'Investigació i Innovació Parc Taulí (I3PT), Spain; Department of Psychiatry and Legal Medicine, Universitat Autònoma de Barcelona, Spain; Carlos III Health Institute, Mental Health Networking Biomedical Research Centre (CIBERSAM), Spain. Electronic address:

The high comorbidity of Major Depressive Disorder (MDD), Anxiety Disorders (ANX), and Posttraumatic Stress Disorder (PTSD) has hindered the study of their structural neural correlates. The authors analyzed specific and common grey matter volume (GMV) characteristics by comparing them with healthy controls (HC). The meta-analysis of voxel-based morphometry (VBM) studies showed unique GMV diminutions for each disorder (p < 0.05, corrected) and less robust smaller GMV across diagnostics (p < 0.01, uncorrected). Pairwise comparison between the disorders showed GMV differences in MDD versus ANX and in ANX versus PTSD. These results endorse the hypothesis that unique clinical features characterizing MDD, ANX, and PTSD are also reflected by disorder specific GMV correlates.
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http://dx.doi.org/10.1016/j.neubiorev.2021.07.002DOI Listing
July 2021

Age- and gender-related differences in brain tissue microstructure revealed by multi-component T relaxometry.

Neurobiol Aging 2021 Jun 10;106:68-79. Epub 2021 Jun 10.

FIDMAG Germanes Hospitalàries Research Foundation, Sant Boi de Llobregat, Barcelona, Spain; Mental Health Research Networking Center (CIBERSAM), Madrid, Spain.

In spite of extensive work, inconsistent findings and lack of specificity in most neuroimaging techniques used to examine age- and gender-related patterns in brain tissue microstructure indicate the need for additional research. Here, we performed the largest Multi-component T relaxometry cross-sectional study to date in healthy adults (N = 145, 18-60 years). Five quantitative microstructure parameters derived from various segments of the estimated T spectra were evaluated, allowing a more specific interpretation of results in terms of tissue microstructure. We found similar age-related myelin water fraction (MWF) patterns in men and women but we also observed differential male related results including increased MWF content in a few white matter tracts, a faster decline with age of the intra- and extra-cellular water fraction and its T relaxation time (i.e. steeper age related negative slopes) and a faster increase in the free and quasi-free water fraction, spanning the whole grey matter. Such results point to a sexual dimorphism in brain tissue microstructure and suggest a lesser vulnerability to age-related changes in women.
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http://dx.doi.org/10.1016/j.neurobiolaging.2021.06.002DOI Listing
June 2021

Group and sex differences in social cognition in bipolar disorder, schizophrenia/schizoaffective disorder and healthy people.

Compr Psychiatry 2021 Jul 5;109:152258. Epub 2021 Jul 5.

Department of Mental Health, Hospital Universitari Parc Taulí, Institut d'Investigació i Innovació Parc Taulí I3PT, Universitat Autònoma de Barcelona, Sabadell, Catalonia, Spain; Department of Psychiatry and Forensic Medicine, Universitat Autònoma de Barcelona, International Excellence Campus, Bellaterra, Cerdanyola del Vallès, Catalonia, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain. Electronic address:

Background: Impairment of social cognition is documented in bipolar disorder (BD) and schizophrenia/schizoaffective disorder (SCH). In healthy individuals, women perform better than men in some of its sub-domains. However, in BD and SCH the results are mixed. Our aim was to compare emotion recognition, affective Theory of Mind (ToM) and first- and second-order cognitive ToM in BD, SCH and healthy subjects, and to investigate sex-related differences.

Methods: 120 patients (BD = 60, SCH = 60) and 40 healthy subjects were recruited. Emotion recognition was assessed by the Pictures of Facial Affect (POFA) test, affective ToM by the Reading the Mind in the Eyes Test (RMET) and cognitive ToM by several false-belief stories. Group and sex differences were analyzed using parametric (POFA, RMET) and non-parametric (false-belief stories) tests. The impact of age, intelligence quotient (IQ) and clinical variables on patient performance was examined using a series of linear/logistic regressions.

Results: Both groups of patients performed worse than healthy subjects on POFA, RMET and second-order false-belief (p < 0.001), but no differences were found between them. Instead, their deficits were related to older age and/or lower IQ (p < 0.01). Subthreshold depression was associated with a 6-fold increased risk of first-order false-belief failure (p < 0.001). Sex differences were only found in healthy subjects, with women outperforming men on POFA and RMET (p ≤ 0.012), but not on first/second-order false-belief.

Limitations: The cross-sectional design does not allow for causal inferences.

Conclusion: BD and SCH patients had deficits in emotion recognition, affective ToM, and second-order cognitive ToM, but their performance was comparable to each other, highlighting that the differences between them may be subtler than previously thought. First-order cognitive ToM remained intact, but subthreshold depression altered their normal functioning. Our results suggest that the advantage of healthy women in the emotional and affective aspects of social cognition would not be maintained in BD and SCH.
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http://dx.doi.org/10.1016/j.comppsych.2021.152258DOI Listing
July 2021

In Memory of Hagop Akiskal.

Clin Pract Epidemiol Ment Health 2021 31;17:48-51. Epub 2021 May 31.

Department of Psychiatry and Clinical Psychology, Faculty of Medicine, Balamand University, Beirut, Lebanon.

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http://dx.doi.org/10.2174/1745017902117010048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227446PMC
May 2021

Searching for factors associated with the "Revolving Door phenomenon" in the psychiatric inpatient unit: A 5-year retrospective cohort study.

Psychiatry Res 2021 Jun 30;303:114080. Epub 2021 Jun 30.

Department of Psychiatry, University of Perugia, Edificio Ellisse, 8 Piano, Sant'Andrea delle Fratte, 06132, Perugia, Italy. Electronic address:

The revolving door (RD) phenomenon refers to subjects who undergo frequent rehospitalizations in psychiatric units. The main aim of this study was to analyze clinical factors associated with RD in acute inpatient psychiatric ward. In a 5-year cohort study, subjects hospitalized three or more times in 12 months (revolving door subjects-RDS) were identified. A total of 1,324 subjects were hospitalized. RDS represented 6.3% (n = 84) of the entire sample with a total of 337 RD hospitalizations (revolving door hospitalizations-RDH) (16.7% of all admissions). RDS were younger, unmarried, with comorbid substance related disorders, with mood or psychotic disorders and affected by comorbid medical conditions. After controlling for age, sex and marital status, the most strongly associated variable with RDH was the comorbidity between mood and substance use disorders. Other associated factors were the presence of a comorbid medical condition and a longer length of stay. The commitment to community residential facilities and the treatment with a first generation long-acting antipsychotic were also associated with RDH. On the contrary, admissions to the psychiatric unit for manic/hypomanic episode or for self-directed harmful behavior were inversely associated with RDH. Attention should be given to these clinical variables in order to reduce RD.
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http://dx.doi.org/10.1016/j.psychres.2021.114080DOI Listing
June 2021

Lithium concentration and recurrence risk during maintenance treatment of bipolar disorder: Multicenter cohort and meta-analysis.

Acta Psychiatr Scand 2021 Jul 6. Epub 2021 Jul 6.

Department of Computer Science and Information Engineering, National Cheng Kung University, Tainan, Taiwan.

Objective: To compare differences in efficacy during maintenance treatment for bipolar disorder (BD) according to lithium serum levels. A multicenter retrospective cohort study and a dose-response meta-analysis were conducted.

Methods: The cohort study was conducted in Taiwan from 2001 to 2019 to identify patients with euthymic BD according to different serum levels (<0.4, 0.4-0.8, and 0.8-1.2 mmol/L). We adopted adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) for time to the recurrence of mood episodes having the <0.4 mmol/L group as the reference group. Moreover, we systematically searched for related articles in major databases before January 31, 2021 (PROSPERO: CRD42021235812). We used random-effects modeling to estimate the dose-response relationships between lithium serum levels and recurrence of mood episodes, which were depicted as odds ratios (ORs) with 95% CIs.

Results: A total of 1406 participants (cohort: 466; meta-analysis: 940) were included. In the cohort study, the 0.4-0.8 mmol/L group was associated with a significantly lower risk of recurrences (aHR: 0.75), while the 0.8-1.2 mmol/L group had a lower risk without statistical significance (aHR: 0.77). The dose-response meta-analysis showed that with the increase in lithium serum levels, the risk decreased (linear model OR: 0.85, for every 0.1 mmol/L increase; non-linear model OR: 1.00 at 0.0 mmol/L, 0.42 at 0.4 mmol/L, and 0.27 at 0.8 mmol/L).

Conclusion: Although confounding by indication cannot be excluded, the combined results suggest a significant preventative effect on the recurrence of major affective episodes among those with serum levels of 0.4-0.8 mmol/L.
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http://dx.doi.org/10.1111/acps.13346DOI Listing
July 2021

The Role of Premorbid IQ and Age of Onset as Useful Predictors of Clinical, Functional Outcomes, and Recovery of Individuals with a First Episode of Psychosis.

J Clin Med 2021 Jun 2;10(11). Epub 2021 Jun 2.

Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Gregorio Marañón Health Research Institute (IiSGM), Hospital General Universitario Gregorio Marañón, Research Networking Center for Mental Health Network (CIBERSAM), School of Medicine, Complutense University of Madrid (UCM), 28007 Madrid, Spain.

Background: premorbid IQ (pIQ) and age of onset are predictors of clinical severity and long-term functioning after a first episode of psychosis. However, the additive influence of these variables on clinical, functional, and recovery rates outcomes is largely unknown.

Methods: we characterized 255 individuals who have experienced a first episode of psychosis in four a priori defined subgroups based on pIQ (low pIQ < 85; average pIQ ≥ 85) and age of onset (early onset < 18 years; adult onset ≥ 18 years). We conducted clinical and functional assessments at baseline and at two-year follow-up. We calculated symptom remission and recovery rates using the Positive and Negative Symptoms of Schizophrenia Schedule (PANSS) and the Global Assessment Functioning (GAF or Children-GAF). We examined clinical and functional changes with pair-wise comparisons and two-way mixed ANOVA. We built hierarchical lineal and logistic regression models to estimate the predictive value of the independent variables over functioning or recovery rates.

Results: early-onset patients had more severe positive symptoms and poorer functioning than adult-onset patients. At two-year follow-up, only early-onset with low pIQ and adult-onset with average pIQ subgroups differed consistently, with the former having more negative symptoms ( = 0.59), poorer functioning ( = 0.82), lower remission (61% vs. 81.1%), and clinical recovery (34.1% vs. 62.2%).

Conclusions: early-onset individuals with low pIQ may present persistent negative symptoms, lower functioning, and less recovery likelihood at two-year follow-up. Intensive cognitive and functional programs for these individuals merit testing to improve long-term recovery rates in this subgroup.
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http://dx.doi.org/10.3390/jcm10112474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199787PMC
June 2021

Functioning assessment short test (FAST): validity and reliability in adults with Autism Spectrum Disorder.

BMC Psychiatry 2021 Jun 29;21(1):321. Epub 2021 Jun 29.

Department of Psychiatry, Universitari Vall d'Hebron Hospital, Barcelona, Catalonia, Spain.

Background: The assessment of functional impairment is crucial both for the diagnosis and the therapeutic approach to autism spectrum disorder (ASD). The purpose of the present study was to evaluate whether the FAST is a reliable and valid tool to assess functional impairment in adults with Level 1 ASD and to study the differences in psychosocial functioning between younger and older adults with ASD.

Methods: A case-control study was carried out in a sample of 150 participants, 71 adults with Level 1 ASD, and 79 adults without psychiatric history records.

Results: Results showed good psychometric properties in terms of validity and reliability. Cronbach's alpha for the total scale was .91 and the area under the curve was .98. The study also showed that adults with ASD present different profiles of functional impairment depending on their age: while younger patients present greater impairment in autonomy, older patients show more difficulties in interpersonal relationships.

Conclusions: Our results support the use of the FAST in the evaluation of adaptive functioning in adults with Level 1 ASD.
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http://dx.doi.org/10.1186/s12888-021-03330-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243726PMC
June 2021

Consensus on nomenclature for clinical staging models in bipolar disorder: A narrative review from the International Society for Bipolar Disorders (ISBD) Staging Task Force.

Bipolar Disord 2021 Jun 26. Epub 2021 Jun 26.

St. Joseph's Healthcare Hamilton McMaster University, Hamilton, ON, Canada.

Objectives: Clinical staging is widely used in medicine to map disease progression, inform prognosis, and guide treatment decisions; in psychiatry, however, staging remains a hypothetical construct. To facilitate future research in bipolar disorders (BD), a well-defined nomenclature is needed, especially since diagnosis is often imprecise with blurred boundaries, and a full understanding of pathophysiology is lacking.

Methods: Under the auspices of the International Society of Bipolar Disorders, a Task Force of international experts was convened to review, discuss, and integrate findings from the scientific literature relevant to the development of a consensus staging model and standardize a terminology that could be used to advance future research including staging of BD and related disorders.

Results: Consensus opinion and areas of uncertainty or difference were identified in regard to terms referring to staging as it may apply to BD, to at-risk status and subthreshold stages, and to various clinical stages of BD as it is currently diagnosed.

Conclusion: The use of a standardized nomenclature about the clinical stages of BD will facilitate communication about research on clinical and pathological components of this heterogeneous group of disorders. The concepts presented are based on current evidence, but the template provided allows for further refinements as etiological advances come to light.
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http://dx.doi.org/10.1111/bdi.13105DOI Listing
June 2021

Mental health impact of the first wave of COVID-19 pandemic on Spanish healthcare workers: A large cross-sectional survey.

Rev Psiquiatr Salud Ment (Engl Ed) 2021 Apr-Jun;14(2):90-105

Center for Public Health Psychiatry, Universitair Psychiatrisch Centrum, KU Leuven, Leuven, Belgium.

Introduction: Healthcare workers are vulnerable to adverse mental health impacts of the COVID-19 pandemic. We assessed prevalence of mental disorders and associated factors during the first wave of the pandemic among healthcare professionals in Spain.

Methods: All workers in 18 healthcare institutions (6 AACC) in Spain were invited to web-based surveys assessing individual characteristics, COVID-19 infection status and exposure, and mental health status (May 5 - September 7, 2020). We report: probable current mental disorders (Major Depressive Disorder-MDD- [PHQ-8≥10], Generalized Anxiety Disorder-GAD- [GAD-7≥10], Panic attacks, Posttraumatic Stress Disorder -PTSD- [PCL-5≥7]; and Substance Use Disorder -SUD-[CAGE-AID≥2]. Severe disability assessed by the Sheehan Disability Scale was used to identify probable "disabling" current mental disorders.

Results: 9,138 healthcare workers participated. Prevalence of screen-positive disorder: 28.1% MDD; 22.5% GAD, 24.0% Panic; 22.2% PTSD; and 6.2% SUD. Overall 45.7% presented any current and 14.5% any disabling current mental disorder. Workers with pre-pandemic lifetime mental disorders had almost twice the prevalence than those without. Adjusting for all other variables, odds of any disabling mental disorder were: prior lifetime disorders (TUS: OR=5.74; 95%CI 2.53-13.03; Mood: OR=3.23; 95%CI:2.27-4.60; Anxiety: OR=3.03; 95%CI:2.53-3.62); age category 18-29 years (OR=1.36; 95%CI:1.02-1.82), caring "all of the time" for COVID-19 patients (OR=5.19; 95%CI: 3.61-7.46), female gender (OR=1.58; 95%CI: 1.27-1.96) and having being in quarantine or isolated (OR= 1.60; 95CI:1.31-1.95).

Conclusions: One in seven Spanish healthcare workers screened positive for a disabling mental disorder during the first wave of the COVID-19 pandemic. Workers reporting pre-pandemic lifetime mental disorders, those frequently exposed to COVID-19 patients, infected or quarantined/isolated, female workers, and auxiliary nurses should be considered groups in need of mental health monitoring and support.
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http://dx.doi.org/10.1016/j.rpsmen.2021.05.003DOI Listing
June 2021

Effects of Cariprazine on Cognition in Patients With Bipolar Mania or Mixed States: Post Hoc Analysis From 3 Randomized, Controlled Phase III Studies.

CNS Spectr 2021 04;26(2):182

AbbVie, Madison, NJ, USA.

Introduction: Cariprazine, a dopamine D3-preferring D3/D2 and serotonin 5-HT1A receptor partial agonist, is approved for the treatment of schizophrenia and for depressive, manic, or mixed episodes associated with bipolar I disorder. Previous post hoc analyses have demonstrated that cariprazine was effective versus placebo for improving cognitive symptoms in patients with schizophrenia or bipolar depression. This post hoc analysis evaluated the effects of cariprazine on cognitive symptoms in patients with acute manic or mixed bipolar episodes.

Methods: Data from 3 phase II/III, randomized, double-blind, placebo-controlled studies in patients with manic or mixed episodes associated with bipolar I disorder (NCT00488618, NCT01058096, NCT01058668) were pooled and analyzed. Patients were randomized to placebo or flexibly dosed cariprazine (3-12 mg/d, 3-6 mg/d, or 6-12 mg/d [1 study only]) for 3 weeks of double-blind treatment; all dose groups were combined for the pooled analysis. Cognitive symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) Cognitive subscale (sum of PANSS items P2, N5, N7, G10, G11); a score of 15 or greater at baseline indicated the presence of cognitive symptoms. Mean changes from baseline to week 3 in PANSS cognitive subscale/item scores and Young Mania Rating Scale (YMRS) total score were evaluated in the overall intent-to-treat (ITT) population and in the subgroup of patients with baseline cognitive symptoms. A mixed-effects model for repeated measures (MMRM) was used to impute missing values.

Results: Of the 1012 patients in the ITT population, 174 (placebo=71; cariprazine=103) had a PANSS Cognitive subscale score of 15 or greater at baseline. At week 3, the cariprazine group demonstrated significantly greater mean improvement than the placebo group on PANSS cognitive subscale scores in both the ITT population (-2.2 vs -1.3; P<.0001) and the subgroup with baseline cognitive symptoms (-4.0 vs -1.9; P=.0002). In patients with baseline cognitive symptoms, improvement was significantly greater for cariprazine- versus placebo-treated patients on YMRS total score (-16.7 vs -8.2; P<.0001) and the individual PANSS cognitive subscale items of conceptual disorganization (-1.1 vs -0.5; P=.0004), difficulty in abstract thinking (-0.8 vs -0.3; P=.0044), stereotyped thinking (-0.3 vs -0.1; P=.0350), and poor attention (-1.1 vs -0.6; P=.0043).

Conclusion: In patients with manic or mixed episodes associated with bipolar I disorder, cariprazine versus placebo was effective in improving cognitive symptoms in the overall patient population as well as in patients with baseline cognitive symptoms. In addition, cariprazine versus placebo also demonstrated efficacy in improving manic symptoms in patients with baseline cognitive symptoms. These results suggest that cariprazine may provide benefits for the treatment of cognitive symptoms in patients with bipolar I mania.

Funding: AbbVie Inc.
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http://dx.doi.org/10.1017/S1092852921000213DOI Listing
April 2021

Effects of Cariprazine on Cognition in Patients With Bipolar Mania or Mixed States: Post Hoc Analysis From 3 Randomized, Controlled Phase III Studies.

CNS Spectr 2021 04;26(2):182

AbbVie, Madison, NJ, USA.

Introduction: Cariprazine, a dopamine D3-preferring D3/D2 and serotonin 5-HT1A receptor partial agonist, is approved for the treatment of schizophrenia and for depressive, manic, or mixed episodes associated with bipolar I disorder. Previous post hoc analyses have demonstrated that cariprazine was effective versus placebo for improving cognitive symptoms in patients with schizophrenia or bipolar depression. This post hoc analysis evaluated the effects of cariprazine on cognitive symptoms in patients with acute manic or mixed bipolar episodes.

Methods: Data from 3 phase II/III, randomized, double-blind, placebo-controlled studies in patients with manic or mixed episodes associated with bipolar I disorder (NCT00488618, NCT01058096, NCT01058668) were pooled and analyzed. Patients were randomized to placebo or flexibly dosed cariprazine (3-12 mg/d, 3-6 mg/d, or 6-12 mg/d [1 study only]) for 3 weeks of double-blind treatment; all dose groups were combined for the pooled analysis. Cognitive symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) Cognitive subscale (sum of PANSS items P2, N5, N7, G10, G11); a score of 15 or greater at baseline indicated the presence of cognitive symptoms. Mean changes from baseline to week 3 in PANSS cognitive subscale/item scores and Young Mania Rating Scale (YMRS) total score were evaluated in the overall intent-to-treat (ITT) population and in the subgroup of patients with baseline cognitive symptoms. A mixed-effects model for repeated measures (MMRM) was used to impute missing values.

Results: Of the 1012 patients in the ITT population, 174 (placebo=71; cariprazine=103) had a PANSS Cognitive subscale score of 15 or greater at baseline. At week 3, the cariprazine group demonstrated significantly greater mean improvement than the placebo group on PANSS cognitive subscale scores in both the ITT population (-2.2 vs -1.3; P<.0001) and the subgroup with baseline cognitive symptoms (-4.0 vs -1.9; P=.0002). In patients with baseline cognitive symptoms, improvement was significantly greater for cariprazine- versus placebo-treated patients on YMRS total score (-16.7 vs -8.2; P<.0001) and the individual PANSS cognitive subscale items of conceptual disorganization (-1.1 vs -0.5; P=.0004), difficulty in abstract thinking (-0.8 vs -0.3; P=.0044), stereotyped thinking (-0.3 vs -0.1; P=.0350), and poor attention (-1.1 vs -0.6; P=.0043).

Conclusion: In patients with manic or mixed episodes associated with bipolar I disorder, cariprazine versus placebo was effective in improving cognitive symptoms in the overall patient population as well as in patients with baseline cognitive symptoms. In addition, cariprazine versus placebo also demonstrated efficacy in improving manic symptoms in patients with baseline cognitive symptoms. These results suggest that cariprazine may provide benefits for the treatment of cognitive symptoms in patients with bipolar I mania.

Funding: AbbVie Inc.
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http://dx.doi.org/10.1017/S1092852921000213DOI Listing
April 2021

Feasibility of mHealth interventions for depressive symptoms in Latin America: a systematic review.

Int Rev Psychiatry 2021 May 9;33(3):300-311. Epub 2021 Jun 9.

Bipolar and Depressive Disorders Unit, Hospital Clinic de Barcelona, Institute of Neuroscience, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain.

Depression is a prevalent disorder and leading cause of disability in Latin America, where the mental health treatment gap is still above 50%. We sought to synthesise and assess the quality of the evidence on the feasibility of mHealth-based interventions for depression in Latin America. We conducted a literature search of studies published in 2007 and after using four electronic databases. We included peer-reviewed articles, in English, Spanish or Portuguese, that evaluated interventions for depressive symptoms. Two authors independently extracted data using forms developed a priori. We assessed appropriateness of reporting utilising the CONSORT checklist for feasibility trials. Eight manuscripts were included for full data extraction. Appropriate reporting varied greatly. Most ( = 6, 75%) of studies were conducted in primary care settings and sought to deliver psychoeducation or behaviour change interventions for depressive symptoms. We found great heterogeneity in the assessment of feasibility. Two studies used comparator conditions. mHealth research for depression in Latin America is scarce. Included studies showed some feasibility despite methodological inconsistencies. Given the dire need for evidence-based mental health interventions in this region, governments and stakeholders must continue promoting and funding research tailored to cultural and population characteristics with subsequent pragmatic clinical trials.
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http://dx.doi.org/10.1080/09540261.2021.1887822DOI Listing
May 2021

Emotional cognition subgroups in mood disorders: Associations with familial risk.

Eur Neuropsychopharmacol 2021 Jun 4;51:71-83. Epub 2021 Jun 4.

Mental Health Services, Capital Region of Denmark, Copenhagen Affective Disorder research Centre (CADIC), Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; Department of Psychology, University of Copenhagen, Copenhagen, Denmark. Electronic address:

Patients with mood disorders show heterogeneity in non-emotional cognition. However, it is unclear whether emotional cognition (EC) is characterised by similar heterogeneity. We aimed to investigate the heterogeneity in EC among remitted patients with mood disorders and explore its association with familial risk. Data from 269 partially or fully remitted patients with mood disorders, 87 of their unaffected relatives (UR) and 203 healthy controls (HC) were pooled from two cohort studies. Hierarchical cluster analysis was conducted using the EC data from patients. UR were categorised into groups consistent with their affected relatives' cluster assignment. Clusters were compared to HC on EC, non-emotional cognition, clinical characteristics and functioning.  We identified three clusters: an 'emotionally preserved' (57%), an 'emotionally blunted' (26%) and an 'emotionally volatile' cluster (17%). 'Emotionally blunted' and 'emotionally volatile' patients also presented more deficits in non-emotional cognition (global cognition read z=-0.3 and -0.5 respectively). Relatives of 'emotionally preserved' patients were more successful at dampening negative emotions (p=.01, d=0.39, 95% CI [-0.76,-0.09]), whereas UR of 'emotionally impaired' patients underperformed in verbal fluency (p=.03, d=0.46, 95% CI [.03, 0.68]) compared to HC. The existence of impaired EC groups in remitted mood disorder highlights a need to screen for and treat EC in mood disorders. Improved ability to dampen emotions in UR of 'emotionally preserved' patients may reflect a resilience marker while impaired verbal fluency in UR of 'emotionally impaired' patients may reflect distinct genetic risk profiles in these EC subgroups.
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http://dx.doi.org/10.1016/j.euroneuro.2021.05.003DOI Listing
June 2021

Biased accuracy in multisite machine-learning studies due to incomplete removal of the effects of the site.

Psychiatry Res Neuroimaging 2021 Aug 29;314:111313. Epub 2021 May 29.

Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Biomedical Network Research Centre on Mental Health (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain; Department of Psychosis Studies, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, United Kingdom; Centre for Psychiatric Research and Education, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. Electronic address:

Brain MRI researchers conducting multisite studies, such as within the ENIGMA Consortium, are very aware of the importance of controlling the effects of the site (EoS) in the statistical analysis. Conversely, authors of the novel machine-learning MRI studies may remove the EoS when training the machine-learning models but not control them when estimating the models' accuracy, potentially leading to severely biased estimates. We show examples from a toy simulation study and real MRI data in which we remove the EoS from both the "training set" and the "test set" during the training and application of the model. However, the accuracy is still inflated (or occasionally shrunk) unless we further control the EoS during the estimation of the accuracy. We also provide several methods for controlling the EoS during the estimation of the accuracy, and a simple R package ("multisite.accuracy") that smoothly does this task for several accuracy estimates (e.g., sensitivity/specificity, area under the curve, correlation, hazard ratio, etc.).
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http://dx.doi.org/10.1016/j.pscychresns.2021.111313DOI Listing
August 2021

Patients' adherence to smartphone apps in the management of bipolar disorder: a systematic review.

Int J Bipolar Disord 2021 Jun 3;9(1):19. Epub 2021 Jun 3.

Department of Psychiatry, CHU Clermont-Ferrand, University of Clermont Auvergne, CNRS, Clermont Auvergne INP, Institut Pascal, Clermont-Ferrand, France.

Background: Despite an increasing number of available mental health apps in the bipolar disorder field, these tools remain scarcely implemented in everyday practice and are quickly discontinued by patients after downloading. The aim of this study is to explore adherence characteristics of bipolar disorder patients to dedicated smartphone interventions in research studies.

Methods: A systematic review following PRISMA guidelines was conducted. Three databases (EMBASE, PsychInfo and MEDLINE) were searched using the following keywords: "bipolar disorder" or "mood disorder" or "bipolar" combined with "digital" or "mobile" or "phone" or "smartphone" or "mHealth" or "ehealth" or "mobile health" or "app" or "mobile-health".

Results: Thirteen articles remained in the review after exclusion criteria were applied. Of the 118 eligible studies, 39 did not provide adherence characteristics. Among the selected papers, study length, sample size and definition of measures of adherence were strongly heterogeneous. Activity rates ranged from 58 to 91.6%.

Conclusion: The adherence of bipolar patients to apps is understudied. Standardised measures of adherence should be defined and systematically evaluated in future studies dedicated to these tools.
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http://dx.doi.org/10.1186/s40345-021-00224-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175501PMC
June 2021

Reliability and Concurrent and Construct Validity of a Food Frequency Questionnaire for Pregnant Women at High Risk to Develop Fetal Growth Restriction.

Nutrients 2021 May 12;13(5). Epub 2021 May 12.

Institut de Recerca Sant Joan de Déu, Endocrinology Department, Esplugues de Llobregat, 08950 Barcelona, Spain.

Accuracy of dietary assessment instruments such as food frequency questionnaire (FFQ) is crucial in the evaluation of diet-disease relationships. Test-retest reliability and concurrent and construct validity of a FFQ were evaluated in 150 pregnant women at high risk to develop fetal growth restriction randomly selected from those included in the improving mothers for better prenatal care trial Barcelona (IMPACT BCN). The FFQ and dietary records were performed at baseline and 34-36 weeks of gestation. Test-retest reliability of the FFQ for 12 food groups and 17 nutrients was moderate (ICC = 0.55) and good (ICC = 0.60), respectively. Concurrent validity between food, nutrients and a composite Mediterranean diet score (MedDiet score) and food records was fair for foods and nutrients (ρ average = 0.38 and 0.32, respectively) and moderate (r = 0.46) for the MedDiet score. Validation with biological markers ranged from poor (r = 0.07) for olives to moderate (r = 0.41) for nuts. A fair concordance between methods were found for nutrients (weighted κ = 0.22) and foods (weighted κ = 0.27). The FFQ-derived MedDiet score correlated in anticipated directions with intakes of nutrients and foods derived by food records. The FFQ showed a moderate test-retest reliability and reasonable validity to rank women according to their food and nutrient consumption and adherence to the Mediterranean diet.
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http://dx.doi.org/10.3390/nu13051629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150790PMC
May 2021

Epidemiology and costs of depressive disorder in Spain: the EPICO study.

Eur Neuropsychopharmacol 2021 May 28;50:93-103. Epub 2021 May 28.

Mental Health and Psychiatric Care Research Group, Biodonostia Health Research Institute Osakidetza, San Sebastian, Spain.

Depressive Disorders are the most common psychiatric diagnoses in the general population. To estimate the frequency, costs associated with Depressive Disorders in usual clinical practice, and in the whole Spanish population, a longitudinal, retrospective, observational study was carried out using data from the BIG-PAC database®. Study population: all patients aged ≥ 18 years with a diagnosis of a Depressive Disorder in 2015-2017. Prevalence was computed as the proportion of Depressive Disorder cases in the adult general population, and the incidence rate, as the number of new Depressive Disorder cases diagnosed per 1,000 person-years in the population using health services, during 2015-2017. We collected demographic variables, comorbidity, direct health costs, and indirect costs (temporary and permanent disability). Health costs related to Depressive Disorders were estimated according to the annual resource use rate (resource/patient/year). Indirect costs were calculated according to the human capital method. Using the study data and information from the Spanish National Institute of Statistics, we estimated the cost of Depressive Disorders corresponding to the Spanish adult population, including premature mortality. 69,217 Depressive Disorder patients aged ≥ 18 years who met the inclusion/exclusion criteria were studied (mean age: 56.8 years; female: 71.4%). Prevalence of Depressive Disorders in the general population was 4.73% (95% CI: 4.70-4.76%). Annual incidence rates (2015-2017) were 7.12, 7.35 and 8.02 per 1,000 person-years, respectively. Total costs observed in our Depressive Disorder patients were € 223.9 million (corresponding to a mean of € 3,235.3; mean/patient/year), of which, 18.4% were direct health care costs and 81.6%, non-health indirect costs (18% temporary occupational disability, 63.6% permanent disability). Considering also the cost of premature death, the mean cost per patient/year was € 3,402 and the estimated societal costs of Depressive Disorders in Spain were € 6,145 million. The prevalence and incidence of Depressive Disorders are consistent with other series reviewed. Resource use and total costs (especially non-health costs) were high.
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http://dx.doi.org/10.1016/j.euroneuro.2021.04.022DOI Listing
May 2021

Misunderstanding precision psychiatry.

Psychol Med 2021 Jul 28;51(9):1418-1419. Epub 2021 May 28.

Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, 08036, Barcelona, Catalonia, Spain.

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http://dx.doi.org/10.1017/S0033291721001173DOI Listing
July 2021

The efficacy of cariprazine on function in patients with bipolar depression: a  analysis of a randomized controlled trial.

Curr Med Res Opin 2021 Jun 7:1-9. Epub 2021 Jun 7.

AbbVie, Madison, NJ, USA.

Introduction: Individuals with bipolar depression often experience functional impairment that interferes with recovery. These analyses examined the effects of cariprazine on functional outcomes in patients with bipolar I disorder.

Methods: Prespecified analyses of data from a randomized, double-blind, placebo-controlled pivotal trial of cariprazine in bipolar I depression (NCT01396447) evaluated mean changes from baseline to week 8 in Functional Assessment Short Test (FAST) total score. analyses with no adjustment for multiplicity evaluated FAST subscale scores, functional recovery and remission (FAST total score ≤11 and ≤20, respectively), and 30% or 50% improvement from baseline.

Results: There were 393 patients with bipolar I disorder (placebo = 132; cariprazine: 1.5 mg/d = 135, 3 mg/d = 126) in the FAST analysis population. Statistically significant differences were noted for cariprazine 1.5 mg/d versus placebo in mean change from baseline in FAST total score (<.01) and on 5 of 6 subscale scores (<.05); cariprazine 3 mg/d was significantly different than placebo on the Interpersonal Relationship subscale (<.05). Rates of functional remission and recovery, and ≥30% or ≥50% improvement were significantly greater for cariprazine 1.5 mg/d versus placebo (<.05 all); the percentage of patients with ≥30% improvement was significantly different for cariprazine 3 mg/d versus placebo (<.05).

Conclusion: At week 8, statistically significant improvements in FAST outcomes were observed for cariprazine versus placebo in patients with bipolar I depression; more consistent results were noted for 1.5 mg/d than 3 mg/d. In addition to improving bipolar depression symptoms, these results suggest that cariprazine may improve functional outcomes.
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http://dx.doi.org/10.1080/03007995.2021.1932446DOI Listing
June 2021

Mediterranean diet, Mindfulness-Based Stress Reduction and usual care during pregnancy for reducing fetal growth restriction and adverse perinatal outcomes: IMPACT BCN (Improving Mothers for a better PrenAtal Care Trial BarCeloNa): a study protocol for a randomized controlled trial.

Trials 2021 May 24;22(1):362. Epub 2021 May 24.

BCNatal | Fetal Medicine Research Center (Hospital Clínic and Hospital Sant Joan de Déu), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.

Background: Fetal growth restriction (FGR) affects 7-10% of all pregnancies resulting in a higher risk of perinatal morbidity and mortality, long-term disabilities, and cognitive impairment. Due to its multifactorial etiology, changes in maternal lifestyle, including suboptimal maternal diet and stress, have increasingly been associated with its prevalence. We present a protocol for the Improving Mothers for a better PrenAtal Care Trial Barcelona (IMPACT BCN), which evaluates two different maternal lifestyle strategies (improved nutrition by promoting Mediterranean diet and stress reduction program based on mindfulness techniques) on perinatal outcomes. The primary objective is to reduce the prevalence of FGR. Secondary aims are to reduce adverse perinatal outcomes and to improve neurodevelopment and cardiovascular profile in children at 2 years of age.

Methods: A randomized parallel, open-blind, single-center trial following a 1:1:1 ratio will select and randomize high-risk singleton pregnancies for FGR (N=1218), according to the criteria of the Royal College of Obstetricians and Gynaecologists (19.0-23.6 weeks' gestation), into three arms: Mediterranean diet, mindfulness-based stress reduction program, and usual care without any intervention. Compliance to the interventions will be randomly tested in 30% of participants with specific biomarkers. Maternal socio-demographic, clinical data, biological samples, and lifestyle questionnaires will be collected at enrollment and at the end of the interventions (34.0-36.6 weeks' gestation), together with a fetoplacental ultrasound and magnetic resonance. Fetoplacental biological samples and perinatal outcomes will be recorded at delivery. Postnatal follow-up is planned up to 2 years of corrected age including neurodevelopmental tests and cardiovascular assessment. Intention-to-treat and population per-protocol analysis will be performed.

Discussion: This is the first randomized study evaluating the impact of maternal lifestyle interventions during pregnancy on perinatal outcomes. The maternal lifestyle interventions (Mediterranean diet and mindfulness-based stress reduction program) are supported by scientific evidence, and their compliance will be evaluated with several biomarkers.

Trial Registration: ClinicalTrials.gov NCT03166332 . Registered on April 19, 2017.
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http://dx.doi.org/10.1186/s13063-021-05309-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147060PMC
May 2021

Cortical gray matter reduction precedes transition to psychosis in individuals at clinical high-risk for psychosis: A voxel-based meta-analysis.

Schizophr Res 2021 06 22;232:98-106. Epub 2021 May 22.

Department of Child and Adolescent Psychiatry and Psychology, 2017SGR881, Institute of Neuroscience, Hospital Clínic, Villarroel 170, 08036 Barcelona, Spain; Fundació Clínic per a la Recerca Biomèdica (FCRB), Esther Koplowitz Centre, Rosselló 153, 08036 Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Rosselló 149, 08036 Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain. Electronic address:

Gray matter and cortical thickness reductions have been documented in individuals at clinical high-risk for psychosis and may be more pronounced in those who transition to psychosis. However, these findings rely on small samples and are inconsistent across studies. In this review and meta-analysis we aimed to investigate neuroanatomical correlates of clinical high-risk for psychosis and potential predictors of transition, using a novel meta-analytic method (Seed-based d Mapping with Permutation of Subject Images) and cortical mask, combining data from surface-based and voxel-based morphometry studies. Individuals at clinical high-risk for psychosis who later transitioned to psychosis were compared to those who did not and to controls, and included three statistical maps. Overall, individuals at clinical high-risk for psychosis did not differ from controls, however, within the clinical high-risk for psychosis group, transition to psychosis was associated with less cortical gray matter in the right temporal lobe (Hedges' g = -0.377), anterior cingulate and paracingulate (Hedges' g = -0.391). These findings have the potential to help refine prognostic and etiopathological research in early psychosis.
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http://dx.doi.org/10.1016/j.schres.2021.05.008DOI Listing
June 2021

Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology.

Nat Genet 2021 06 17;53(6):817-829. Epub 2021 May 17.

Department of Neuroscience, Istituto Di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.

Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies.
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http://dx.doi.org/10.1038/s41588-021-00857-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192451PMC
June 2021

Mind long COVID: Psychiatric sequelae of SARS-CoV-2 infection.

Eur Neuropsychopharmacol 2021 May 5;49:119-121. Epub 2021 May 5.

Department of Psychiatry and Psychology, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, C/Villarroel 170, 08036 Barcelona, Catalonia, Spain. Electronic address:

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http://dx.doi.org/10.1016/j.euroneuro.2021.04.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8098059PMC
May 2021

Neuronal underpinnings of cognitive impairment in bipolar disorder: A large data-driven functional magnetic resonance imaging study.

Bipolar Disord 2021 May 6. Epub 2021 May 6.

Copenhagen Affective Disorder Research Centre (CADIC), Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.

Objectives: Cognitive impairment occurs in approximately 50% of remitted patients with bipolar disorder (BD). However, there exists no treatment with replicated and robust efficacy on cognition in BD. This is partially due to limited insight into the neuronal underpinnings of cognitive impairment in these patients. This is the first study to investigate neuronal underpinnings of cognitive impairment in a large functional magnetic resonance imaging (fMRI) dataset comparing neural activity patterns between distinct neurocognitive subgroups of partially or fully remitted patients with BD.

Methods: Patients (n = 153) and healthy controls (HC) (n = 52) underwent neuropsychological assessment and fMRI, during which they performed a verbal N-back working memory (WM) task. Based on hierarchical cluster analysis of neuropsychological test performance, patients were grouped into one of two neurocognitive subgroups (cognitively impaired, n = 91; cognitively normal compared to HC, n = 62) that were compared on WM-related neural activity.

Results: Cognitively impaired patients displayed WM-related hypo-activity in left dorsolateral prefrontal cortex and frontal and parietal regions within a cognitive control network (CCN) as well as hyper-activity in the default mode network (DMN) compared to cognitively normal patients. In contrast, cognitively normal patients only exhibited hypo-activity within a small cluster in the superior frontal gyrus relative to HC.

Conclusions: Cognitive impairment in BD seems to originate from a failure to recruit key regions in the CCN and to suppress task-irrelevant DMN activity during cognitive performance. These results highlight modulation of aberrant dorsal prefrontal and DMN activity as a putative target for pro-cognitive treatment in BD.
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http://dx.doi.org/10.1111/bdi.13100DOI Listing
May 2021

Higher order theory of mind in patients with bipolar disorder and schizophrenia/schizoaffective disorder.

Eur Arch Psychiatry Clin Neurosci 2021 May 4. Epub 2021 May 4.

Department of Mental Health, Hospital Universitari Parc Taulí, Institut d'Investigació i Innovació Parc Taulí I3PT, Universitat Autònoma de Barcelona, Sabadell, Catalonia, Spain.

Some evidence suggests that patients with bipolar disorder (BD) have better Theory of Mind (ToM) skills than patients with schizophrenia/schizoaffective disorder (SCH). However, this difference is not consistently reported across studies, so rather than being global, it may be restricted to specific aspects of ToM. Our primary objective was to compare higher order ToM performance between BD and SCH patients using the Hinting Task (HT). Ninety-four remitted patients were recruited (BD = 47, SCH = 47). Intelligence quotient (IQ), attention, memory, executive functions, and processing speed were also assessed. Patients with BD performed better on the HT than patients with SCH, even when the analysis was adjusted for IQ and neurocognition (p < 0.001, [Formula: see text] = 0.144). Regression analysis in the total sample showed that a diagnosis of SCH and lower IQ were associated with lower HT scores (R = 0.316, p < 0.001). In the BD group, verbal memory and processing speed were the main predictors of HT performance (R = 0.344, p < 0.001). In the SCH group, no variable was significant in explaining HT performance. In the context of previous studies that found no significant differences in the most basic aspects of ToM (e.g., understand other people's thoughts/beliefs), our results suggest that differences between the two disorders might be limited to the more challenging aspects (e.g., understand the intended meaning of indirect requests). No causal inferences can be made in this cross-sectional study. However, regression analyses show that whereas in BD patients, ToM functioning would be partially modulated by neurocognitive performance, in SCH patients, it could be largely independent of the well-known neurocognitive impairment.
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http://dx.doi.org/10.1007/s00406-021-01265-9DOI Listing
May 2021