Molero, P. (Patricio)
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- Aberrant timing and oddball detection in schizophrenia: findings from a signed differential mapping meta-analysis(Elsevier, 2018) Radua, J. (Joaquim); Solanes, A. (Aleix); Ortuño-Sanchez-Pedreño, F. (Felipe); Ortuño, M. (Marta); Garcés, M.S. (María Sol); Alustiza-Quintana, I. (Irene); Goena, J. (Javier); Molero, P. (Patricio)Schizophrenia (SZ) is associated with deficits in both temporal and salience processing. The underlying neurological dysfunctions in both processes, which are interrelated and share neuroanatomical bases, remain poorly understood. The principal objective of this study was to elucidate whether there are any brain regions that show abnormal response during timing and oddball tasks in patients with SZ. To this end, we conducted a signed differential mapping (SDM) meta-analysis of functional magnetic resonance imaging (fMRI) studies assessing abnormal responses elicited by tasks based on the oddball paradigm in patients with SZ. We conducted a similar SDM meta-analysis of neuroimaging studies of timing tasks in SZ. Finally, we undertook a multimodal meta-analysis to detect the common findings of the two previous meta-analyses. We found that SZ patients showed hypoactivation in cortical and subcortical areas related to timing. The dysfunction observed during timing tasks partially coincided with deficiencies in change-detection functions (particularly in the case of preattentional processing in the mismatch negativity response). We hypothesize that a dysfunctional timing/change detection network underlies the cognitive impairment observed in SZ.
- Cigarette smoking and risk of suicide in bipolar disorder: a systematic review(2023) Gutierrez-Rojas, L. (L.); Girela-Serrano, B. (Braulio); Gómez-Sierra, F.J. (Francisco José); Martínez-Hortelano, A. (Alicia); García-Jiménez, J. (Jesús); Moreno-Merino, P. (Paula); Molero, P. (Patricio)ObjectiveBipolar disorder (BD) is a highly prevalent, chronic and recurrent mental illness. The smoking rates in patients with BD are much higher than those of the general population, and BD is associated with an increased risk of suicide. An association between smoking and suicidal behavior has been found in the general population, this systematic review examines whether there is evidence of an association between smoking and suicide behavior in patients with BD. MethodA database search was carried out in Medline, Embase, The Cochrane Library, Scopus, and Web of Science, updated until December 31st, 2021, according to the 2020 PRISMA guidelines. We identified prospective and retrospective studies that included patients diagnosed with BD types I, II, and not otherwise specified, and in which smoking and suicidal behavior were correlated. Articles that focused exclusively on other mental disorders were excluded. The Ottawa-Newcastle scale was used to assess the methodological quality of the included articles. ResultsFifteen articles (n = 7,395) met all the inclusion criteria. In nine of these articles, the authors found an association between smoking and suicidal behavior in BD, while in the remaining six articles, this association was not found. A great deal of variability was observed between articles, particularly in the measurement of suicidal behavior and tobacco consumption. The risk of bias, as assessed by the NOS, was high for most of the included articles, except for two papers, whose risk was low. ConclusionIt was not possible to establish a clear relationship between tobacco use and the risk of suicide in BD patients due to the heterogeneity of the articles included in this systematic review, which had different sample sizes and methodological issues. However, both conditions are highly prevalent and have a negative impact on the prognosis of BD. Therefore, a systematic approach is needed, based on accurate measurement of a patient's smoking habits and their risk of suicidal behavior, in order to establish an appropriate therapeutic plan. Additional informationThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors and was registered on PROSPERO with the CRD42022301570 on January 21th 2022.
- The impact of the Val158Met COMT polymorphism on context processing in patients on the schizophrenia spectrum and their relatives(Elsevier, 2015) Lopez-Garcia, P. (Pilar); Ortuño-Sanchez-Pedreño, F. (Felipe); Young, L. (Leslie); Marin, J. (Juan); Molero, P. (Patricio)Introduction: The level of dopamine in the prefrontal cortex (PFC) appears to play a fundamental role in cognitive alterations in schizophrenia. The Val158Met polymorphism of the catechol-O-methyltransferase (COMT) enzyme impacts dopamine availability in the prefrontal cortex and can thus influence cognitive functioning. Among the different cognitive deficits found in schizophrenia patients, context processing deficits have been noted as a specific characteristic of schizophrenia, for which the cerebral substrate appears to be located in the dorsolateral PFC. In this study, we examine the impact of the Val158Met COMT polymorphism on context processing in a sample of patients on the schizophrenia spectrum, their relatives, and healthy control subjects evaluated using the Dot Probe Expectancy Task (DPX). Methods: Forty patients on the schizophrenia spectrum, 26 relatives, and 63 healthy control subjects were genotyped and performed the DPX test. Results: Both patients and their relatives demonstrated deficits in context processing influenced by the Val158Met COMT polymorphism. Compared with the other subjects, the Val/Val subjects showed poorer performance on context processing tasks. Conclusions: Deficits in context processing in schizophrenic patients and their families are influenced by the Val158Met COMT functional polymorphism, likely as a consequence of reduced dopamine availability in the PFC.
- Effects of esketamine on patient-reported outcomes in major depressive disorder with active suicidal ideation and intent: a pooled analysis of two randomized phase 3 trials (ASPIRE I and ASPIRE II)(2023) Jamieson, C. (Carol); Lane, R. (Rosanne); Qiu, X. (Xin); Rozjabek, H. (Heather); Ionescu, D.F. (Dawn F.); Fu, D.J. (Dong-Jing); Canuso, C.M. (Carla M.); Molero, P. (Patricio)Purpose: To assess the effect of esketamine nasal spray on patient-reported outcomes (PROs) in patients with major depressive disorder having active suicidal ideation with intent (MDSI). Methods: Patient-level data from two phase 3 studies (ASPIRE I; ASPIRE II) of esketamine + standard of care (SOC) in patients (aged 18-64 years) with MDSI, were pooled. PROs were evaluated from baseline through end of the double-blind treatment phase (day 25). Outcome assessments included: Beck Hopelessness Scale (BHS), Quality of Life (QoL) in Depression Scale (QLDS), European QoL Group-5-Dimension-5-Level (EQ-5D-5L), and 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9). Changes in BHS and QLDS scores (baseline to day 25) were analyzed using a mixed-effects model for repeated measures (MMRM). Results: Pooled data for esketamine + SOC (n = 226; mean age: 40.5 years, 59.3% females) and placebo + SOC (n = 225; mean age: 39.6 years, 62.2% females) were analyzed. Mean ± SD change from baseline to day 25, esketamine + SOC vs placebo + SOC (least-square mean difference [95% CI] based on MMRM): BHS total score, - 7.4 ± 6.7 vs - 6.8 ± 6.5 [- 1.0 (- 2.23, 0.21)]; QLDS score, - 14.4 ± 11.5 vs - 12.2 ± 10.8 [- 3.1 (- 5.21, - 1.02)]. Relative risk (95% CI) of reporting perceived problems (slight to extreme) in EQ-5D-5L dimensions (day 25) in esketamine + SOC vs placebo + SOC: mobility [0.78 (0.50, 1.20)], self-care [0.83 (0.55, 1.27)], usual activities [0.87 (0.72, 1.05)], pain/discomfort [0.85 (0.69, 1.04)], and anxiety/depression [0.90 (0.80, 1.00)]. Mean ± SD changes from baseline in esketamine + SOC vs placebo + SOC for health status index: 0.23 ± 0.21 vs 0.19 ± 0.22; and for EQ-Visual Analogue Scale: 24.0 ± 27.2 vs 19.3 ± 24.4. At day 25, mean ± SD in domains of TSQM-9 scores in esketamine + SOC vs placebo + SOC were: effectiveness, 67.2 ± 25.3 vs 56.2 ± 26.8; global satisfaction, 69.9 ± 25.2 vs 56.3 ± 27.8; and convenience, 74.0 ± 19.4 vs 75.4 ± 18.7. Conclusion: These PRO data support the patient perspective of the effect associated with esketamine + SOC in improving health-related QoL in patients with MDSI. Trial registration: ClinicalTrials.gov Identifier: ASPIRE I, NCT03039192 (Registration date: February 1, 2017); ASPIRE II, NCT03097133 (Registration date: March 31, 2017).
- Preventing the recurrence of depression with a Mediterranean diet supplemented with extra-virgin olive oil. The PREDI-DEP trial: study protocol(Springer Science and Business Media LLC, 2019) Hernández-Fleta, J. L. (J. L.); Pla-Vidal, J. (Jorge); Ortuño-Sanchez-Pedreño, F. (Felipe); Florido-Rodríguez, M. (M.); Navarro, S. (Silvia); Lahortiga, F. (Francisca); Chiclana-Actis, C. (Carlos); Cabrera, C. (Carmen); Calviño-Cabada, M. J. (M. J.); Gonzalez-Pinto, A. (Ana); Almeida, Y. (Y.); Sanchez-Villegas, A. (Almudena); Cabrera-Suárez, B. (B.); Vega-Pérez, R. (R.); Molero, P. (Patricio)Background: The role of dietary patterns in the prevention of unipolar depression has been analyzed in several epidemiological studies. The primary aims of this study are to determine the effectiveness of an extra-olive oil enriched Mediterranean diet in reducing the recurrence of depression and improving the symptoms of this condition. Methods: Multicenter, two-arm, parallel-group clinical trial. Arm 1, extra-virgin olive oil Mediterranean diet; Arm 2, control group without nutritional intervention. Dieticians are in charge of the nutritional intervention and regular contact with the participants. Contacts are made through our web platform (https://predidep.es/participantes/) or by phone. Recurrence of depression is assessed by psychiatrists and clinical psychologists through clinical evaluations (semi-structured clinical interviews: Spanish SCID-I). Depressive symptoms are assessed with the Beck Depression Inventory. Information on quality of life, level of physical activity, dietary habits, and blood, urine and stool samples are collected after the subject has agreed to participate in the study and once a year. Discussion: To the best of our knowledge, the PREDI-DEP trial is the first ongoing randomized clinical trial designed to assess the role of the Mediterranean diet in the prevention of recurrent depression. It could be a cost-effective approach to avoid recurrence and improve the quality of life of these patients.
- Catechol-O-Methyltransferase Val158Met Polymorphism and Clinical Response to Antipsychotic Treatment in Schizophrenia and Schizo-Affective Disorder Patients: a Meta-Analysis(Oxford University Press, 2016) Potkin, S.G. (Steven G.); Kennedy, J.L. (James L.); Kaur, H. (Harpreet); Meltzer, H.Y. (Herbert Y.); Lieberman, J.A. (Jeffrey A.); Ortuño-Sanchez-Pedreño, F. (Felipe); Gao, S. (Shugui); Samochowiec, J. (Jerzy); Lisoway, A. (Amanda); Pelayo-Teran, J.M. (Jose Maria); Ikeda, M. (Masashi); Kukreti, R. (Ritushree); Müller, D.J. (Daniel J.); Bishop, J.R. (Jeffrey R.); Felsky, D. (Daniel); Huang, E. (Eric); Mierzejewski, P. (Pawel); Tiwari, A.K. (Arun K.); Porcelli, S. (Stefano); Zai, C.C. (Clement C.); Crespo-Facorro, B. (Benedicto); Molero, P. (Patricio); Maciukiewicz, M. (Malgorzata)Abstract Background: The catechol-O-methyltransferase (COMT) enzyme plays a crucial role in dopamine degradation, and the COMT Val158Met polymorphism (rs4680) is associated with significant differences in enzymatic activity and consequently dopamine concentrations in the prefrontal cortex. Multiple studies have analyzed the COMT Val158Met variant in relation to antipsychotic response. Here, we conducted a meta-analysis examining the relationship between COMT Val158Met and antipsychotic response. Methods: Searches using PubMed, Web of Science, and PsycInfo databases (03/01/2015) yielded 23 studies investigating COMT Val158Met variation and antipsychotic response in schizophrenia and schizo-affective disorder. Responders/nonresponders were defined using each study’s original criteria. If no binary response definition was used, authors were asked to define response according to at least 30% Positive and Negative Syndrome Scale score reduction (or equivalent in other scales). Analysis was conducted under a fixed-effects model. Results: Ten studies met inclusion criteria for the meta-analysis. Five additional antipsychotic-treated samples were analyzed for Val158Met and response and included in the meta-analysis (ntotal = 1416). Met/Met individuals were significantly more likely to respond than Val-carriers (P = .039, ORMet/Met = 1.37, 95% CI: 1.02–1.85). Met/Met patients also experienced significantly greater improvement in positive symptoms relative to Val-carriers (P = .030, SMD = 0.24, 95% CI: 0.024–0.46). Posthoc analyses on patients treated with atypical antipsychotics (n = 1207) showed that Met/Met patients were significantly more likely to respond relative to Val-carriers (P = .0098, ORMet/Met = 1.54, 95% CI: 1.11–2.14), while no difference was observed for typical-antipsychotic-treated patients (n = 155) (P = .65). Conclusions: Our findings suggest that the COMT Val158Met polymorphism is associated with response to antipsychotics in schizophrenia and schizo-affective disorder patients. This effect may be more pronounced for atypical antipsychotics.
- A longitudinal analysis of diet quality scores and the risk of incident depression in the SUN project(BioMed Central, 2015) Martinez-Gonzalez, M.A. (Miguel Ángel); Toledo, E. (Estefanía); Lahortiga, F. (Francisca); Ruiz-Canela, M. (Miguel); Henriquez-Sanchez, P. (Patricia); Sanchez-Villegas, A. (Almudena); Molero, P. (Patricio)Background: Some studies have pointed out that several dietary patterns could be associated with a reduced risk of depression among adults. This association seems to be consistent across countries, cultures and populations. The objective of the study was to compare and to establish the type of relationship between three diet quality scores and depression in the SUN (Seguimiento Universidad de Navarra) Cohort study. Methods: We performed a dynamic cohort study based on Spanish university graduates free of depression at baseline. Dietary intake was repeatedly assessed at baseline and after 10 years of follow-up with a validated semi-quantitative foodfrequency questionnaire. Three previously described diet quality scores: Mediterranean Diet Score (MDS), Pro-vegetarian Dietary Pattern (PDP) and Alternative Healthy Eating Index-2010 (AHEI-2010) were built. Participants were classified as having depression if they reported a new clinical diagnosis of depression by a physician or initiated the use of an antidepressant drug during follow-up. Time-dependent Cox regression models with cumulative averages of diet and restricted cubic splines were used to estimate hazard ratios of depression according to quintiles of adherence to the MDS, PDP and AHEI-2010. Results: One thousand and fifty one incident cases of depression were observed among 15,093 participants from the SUN Cohort after a median follow-up of 8.5 years. Inverse and significant associations were observed between the three diet quality scores and depression risk. The hazard ratios and 95 % confidence intervals for extreme quintiles (fifth versus first) of updated adherence to MDS, PDP and AHEI-2010 were 0.84 (0.69–1.02), 0.74 (0.61–0.89) and 0.60 (0.49–0.72), respectively. The dose–response analyses showed non-linear associations, suggesting that suboptimal adherence to these dietary patterns may partially be responsible for increased depression risk. Conclusions: Better adherence to the MDS, PDP and AHEI-2010 was associated with a reduced risk of depression among Spanish adults. However, our data suggested a threshold effect so that although the risk of depression was reduced when comparing moderate versus lower adherence, there was not much extra benefit for the comparison between moderate and high or very high adherence.
- Self-perceived level of competitiveness, tension and dependency and depression risk in the SUN cohort(BMC, 2018) Martinez-Gonzalez, M.A. (Miguel Ángel); Raquel; Zazpe, I. (Itziar); Santiago, S. (Susana); Lahortiga, F. (Francisca); Sanchez-Villegas, A. (Almudena); Molero, P. (Patricio)Background: Emerging evidence suggests a possible etiologic role of certain personality traits (not necessary dysfunctional) in the risk of depression, but the longitudinal long-term available evidence is currently scarce. We longitudinally assessed whether 3 common personality traits (competitiveness, tension and dependency) were associated with the risk of depression after a maximum follow-up of 15 years. Methods: We assessed 15,604 university graduates free of depression at baseline through a self-administered questionnaire including personality traits. Simple, Likert-type, questions with 11 possible answers ranging from 0 to 10 were used at baseline to assess the 3 personality traits. We compared participants with high scores (7–10) versus those with low scores (0–4). New medical diagnoses of depression during follow-up were used as the outcome. Results: During a median follow-up of 10.1 y, we prospectively identified 902 new medical diagnoses of depression. The multivariable-adjusted hazard ratios (95% confidence intervals) for depression were 1.85 (1.52–2.24) for participants with higher baseline tension (7–10 versus 0 to 4), P-trend < 0.001; and 1.23 (1.06–1.44) for high versus low baseline dependence levels, P-trend = 0.004. Higher levels of competitiveness were marginally associated with lower risk of depression, with hazard ratio = 0.78 (0.61–1.01), P-trend = 0.105. Conclusion: A simple scoring system of personality traits shows an independent association with the future occurrence of depression. This finding underscores, with now prospective evidence, the importance of personality traits in the aetiology of depression and can provide a clinically useful tool for gathering valid information about depression-related personality traits.
- Takotsubo cardiomyopathy secondary to electroconvulsive therapy in a young adult with Down syndrome regression disorder(2024) Ortuño-Sanchez-Pedreño, F. (Felipe); Real-de-Asua, D. (Diego); Bullard, J.P. (José Pablo); Unceta, M.M. (María del Mar); Ortega, M.C. (Maria del Carmen); Molero, P. (Patricio)We report the case of an 18-year-old woman with Down syndrome (DS) who developed Takotsubo cardiomyopathy (TSC) immediately after the administration of electroconvulsive therapy (ECT), a treatment prescribed for Down syndrome regression disorder resistant to oral psychotropic drugs. TSC is a nonischemic cardiomyopathy related to psychological or physical stress, which has been described as a rare complication of ECT (Kinoshita et al., 2023, Journal of Electroconvulsive Therapy, 39, 185-192). The clinical description of the case is accompanied by a discussion of the peculiarities of the autonomic nervous system in DS.
- Time discrimination and change detection could share a common brain network: findings of a task-based fMRI study(2023) Sol-Garcés, M. (María); Ortuño-Sanchez-Pedreño, F. (Felipe); Garcia-Eulate, R. (Reyes); Fernández-Seara, M.A. (María A.); Alustiza-Quintana, I. (Irene); Goena, J. (Javier); Vidal-Adroher, C. (Cristina); Fernandez-Sanmamed, M. (Miguel); Molero, P. (Patricio)IntroductionOver the past few years, several studies have described the brain activation pattern related to both time discrimination (TD) and change detection processes. We hypothesize that both processes share a common brain network which may play a significant role in more complex cognitive processes. The main goal of this proof-of-concept study is to describe the pattern of brain activity involved in TD and oddball detection (OD) paradigms, and in processes requiring higher cognitive effort. MethodsWe designed an experimental task, including an auditory test tool to assess TD and OD paradigms, which was conducted under functional magnetic resonance imaging (fMRI) in 14 healthy participants. We added a cognitive control component into both paradigms in our test tool. We used the general linear model (GLM) to analyze the individual fMRI data images and the random effects model for group inference. ResultsWe defined the areas of brain activation related to TD and OD paradigms. We performed a conjunction analysis of contrast TD (task > control) and OD (task > control) patterns, finding both similarities and significant differences between them. DiscussionWe conclude that change detection and other cognitive processes requiring an increase in cognitive effort require participation of overlapping functional and neuroanatomical components, suggesting the presence of a common time and change detection network. This is of particular relevance for future research on normal cognitive functioning in the healthy population, as well as for the study of cognitive impairment and clinical manifestations associated with various neuropsychiatric conditions such as schizophrenia.