Nuestros investigadores

Patricio Molero Santos

Publicaciones científicas más recientes (desde 2010)

Autores: Daly, E. J., (Autor de correspondencia); Trivedi, M. H.; Janik, A. ; et al.
Revista: JAMA PSYCHIATRY
ISSN 2168-622X  Vol. 76  Nº 9  2019  págs. 893 - 903
IMPORTANCE Controlled studies have shown short-term efficacy of esketamine for treatment-resistant depression (TRD), but long-term effects remain to be established. OBJECTIVE To assess the efficacy of esketamine nasal spray plus an oral antidepressant compared with an oral antidepressant plus placebo nasal spray in delaying relapse of depressive symptoms in patients with TRD in stable remission after an induction and optimization course of esketamine nasal spray plus an oral antidepressant. DESIGN, SETTING, AND PARTICIPANTS In this phase 3, multicenter, double-blind, randomized withdrawal study conducted from October 6, 2015, to February 15, 2018, at outpatient referral centers, 705 adults with prospectively confirmed TRD were enrolled; 455 entered the optimization phase and were treated with esketamine nasal spray (56 or 84 mg) plus an oral antidepressant. After 16 weeks of esketamine treatment, 297 who achieved stable remission or stable response entered the randomized withdrawal phase. INTERVENTIONS Patients who achieved stable remission and those who achieved stable response (without remission) were randomized 1:1 to continue esketamine nasal spray or discontinue esketamine treatment and switch to placebo nasal spray, with oral antidepressant treatment continued in each group. MAIN OUTCOMES AND MEASURES Time to relapse was examined in patients who achieved stable remission, as assessed using a weighted combination log-rank test. RESULTS Among the 297 adults (mean age [SD], 46.3 [11.13] years; 197 [66.3%] female) who entered the randomized maintenance phase, 176 achieved stable remission; 24 (26.7%) in the esketamine and antidepressant group and 39 (45.3%) in the antidepressant and placebo group experienced relapse (log-rank P=.003, number needed to treat [NNT], 6). Among the 121 who achieved stable response, 16 (25.8%) in the esketamine and antidepressant group and 34 (57.6%) in the antidepressant and placebo group experienced relapse (log-rank P<.001, NNT, 4). Esketamine and antidepressant treatment decreased the risk of relapse by 51% (hazard ratio [HR], 0.49; 95% CI, 0.29-0.84) among patients who achieved stable remission and 70% (HR, 0.30; 95% CI, 0.16-0.55) among those who achieved stable response compared with antidepressant and placebo treatment. The most common adverse events reported for esketamine-treated patients after randomization were transient dysgeusia, vertigo, dissociation, somnolence, and dizziness (incidence, 20.4%-27.0%), each reported in fewer patients (<7%) treated with an antidepressant and placebo. CONCLUSIONS AND RELEVANCE For patients with TRD who experienced remission or response after esketamine treatment, continuation of esketamine nasal spray in addition to oral antidepressant treatment resulted in clinically meaningful superiority in delaying relapse compared with antidepressant plus placebo.
Autores: Popova, V., (Autor de correspondencia); Daly, E. J.; Trivedi, M. ; et al.
Revista: AMERICAN JOURNAL OF PSYCHIATRY
ISSN 0002-953X  Vol. 176  Nº 6  2019  págs. 428 - 438
Objective: About one-third of patients with depression fail to achieve remission despite treatment with multiple antidepressants. This study compared the efficacy and safety of switching patients with treatment-resistant depression from an ineffective antidepressant to flexibly dosed esketamine nasal spray plus a newly initiated antidepressant or to a newly initiated antidepressant (active comparator) plus placebo nasal spray. Methods: Thiswas a phase 3, double-blind, active-controlled, multicenter study conducted at 39 outpatient referral centers. The study enrolled adults with moderate to severe nonpsychotic depression and a history of nonresponse to at least two antidepressants in the current episode, with one antidepressant assessed prospectively. Confirmed nonresponders were randomly assigned to treatment with esketamine nasal spray (56 or 84 mg twice weekly) and an antidepressant or antidepressant and placebo nasal spray. The primary efficacy endpoint, change from baseline to day 28 in MontgomeryAsberg Depression Rating Scale (MADRS) score, was assessed by a mixed-effects model using repeated measures. Results: Of 435 patients screened, 227 underwent randomization and 197 completed the 28-day double-blind treatment phase. Change in MADRS score with esketamine plus antidepressant was significantly greater than with antidepressant plus placebo at day 28 (difference of least square means=24.0, SE=1.69, 95% CI=27.31, 20.64); likewise, clinically meaningful improvement was observed in the esketamine plus antidepressant arm at earlier time points. The five most common adverse events (dissociation, nausea, vertigo, dysgeusia, and dizziness) all were observed more frequently in the esketamine plus antidepressant arm than in the antidepressant plus placebo arm; 7% and 0.9% of patients in the respective treatment groups discontinued study drug because of an adverse event. Adverse events in the esketamine plus antidepressant arm generally appeared shortly after dosing and resolved by 1.5 hours after dosing. Conclusions: Current treatment options for treatmentresistant depression have considerable limitations in terms of efficacy and patient acceptability. Esketamine is expected to address an unmet medical need in this population through its novel mechanism of action and rapid onset of antidepressant efficacy. The study supports the efficacy and safety of esketamine nasal spray as a rapidly acting antidepressant for patients with treatment-resistant depression.
Autores: Molero, Patricio, (Autor de correspondencia); Lahortiga F, (Autor de correspondencia); et al.
Revista: JOURNAL OF AFFECTIVE DISORDERS
ISSN 0165-0327  Vol. 247  2019  págs. 161 - 167
Background: The potential effect of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) to prevent depression remains largely unknown, in spite of the implication of inflammation in depression. This study aimed to investigate whether the habitual intake of aspirin and other NSAIDs was prospectively associated with a reduction in the observed incidence of depression. Methods: A dynamic cohort including 22,564 Spanish university graduates (mean age: 37 years) initially free of depression was followed during an average of 8.7 years. Exposure to NSAIDs was assessed with specific repeated questionnaires throughout follow-up, starting in the 2-year follow-up questionnaire. Incident cases of depression were defined as either a new validated medical diagnosis of depression or reporting the initiation of habitual use of antidepressants. Results: We identified 772 incident cases of depression. Regular intake of aspirin and other NSAIDs was not associated with depression risk. Only in secondary sensitivity analyses using a definition of the outcome with higher specificity (a validated medical diagnosis of depression), an inverse association of aspirin with depression was found [HR (95%CI): 0.20 (0.04-0.87)]. However, these results were non-significant after adjustment for multiple testing. Limitations: A possible underestimation of incident depression and a limited ability to detect all possible residual confounding. Conclusions: Regular use of NSAIDs was not associated with the incidence of depression. Further longitudinal controlled studies are necessary to clarify a potential role of aspirin use in depression risk.
Autores: Daly, E. J.; Trivedi, M.; Janik, A.; et al.
Revista: EUROPEAN NEUROPSYCHOPHARMACOLOGY
ISSN 0924-977X  Vol. 29  Nº Supl. 1  2019  págs. S92 - S92
Autores: Molendijk, M.; Molero, Patricio; Ortuño, Felipe; et al.
Revista: JOURNAL OF AFFECTIVE DISORDERS
ISSN 0165-0327  Vol. 226  2018  págs. 346 - 354
Background: It has been claimed that the quality of a diet is associated with the incidence of depressive disorders. We sought to investigate the evidence for this claim. Methods: Systematic searches were performed up to March 6th, 2017 in order to identify prospective cohort studies that reported on exposure to dietary patterns or food groups and the incidence of depression/depressive symptoms. Data from 24 independent cohorts (totalling 1,959,217 person-years) were pooled in random-effects meta-analyses. Results: Adherence to a high-quality diet, regardless of type (i.e., healthy/prudent or Mediterranean), was associated with a lower risk of depressive symptoms over time (odds ratios ranged 0.64-0.78 in a linear dose-response fashion [P< 0.01]). A relatively low dietary inflammatory index was also associated with a somewhat lower incidence of depressive symptom (odds ratio = 0.81), although not in a dose-response fashion. Similar associations were found for the consumption of fish and vegetables (odds ratios 0.86 and 0.82 respectively) but not for other high quality food groups (e.g., fruit). Studies that controlled for depression severity at baseline or that used a formal diagnosis as outcome did not yield statistically significant findings. Adherence to low quality diets and food groups was not associated with higher depression incidence. Limitations: Our ability to detect confounders was only limited. Conclusion: There is evidence that a higher quality of a diet is associated with a lower risk for the onset of depressive symptoms, but not all available results are consistent with the hypothesis that diet influences depression risk. Prospective studies that control for relevant confounders such as obesity incidence and randomized controlled prevention trials are needed to increase the validity of findings in this field.
Autores: Leone, A, (Autor de correspondencia); Martínez, Miguel Ángel; Lahortiga F; et al.
Revista: NUTRITION
ISSN 0899-9007  Vol. 54  2018  págs. 19 - 25
Objective To our knowledge, no study has yet assessed the association between dietary patterns and incidence of eating disorders. This study aimed to assess the association between adherence to the Mediterranean dietary pattern (MDP) and incident risk of anorexia (AN) and bulimia nervosa (BN). Methods We conducted a prospective cohort study of 11 800 women from the Seguimiento Universidad de Navarra follow-up project. Participants were classified as having incident AN or BN if they were free of AN or BN at baseline and reported a physician-made diagnosis of AN or BN during the follow-up period. Nutritional status, lifestyle, and behavioral variables were investigated and used as covariates. A validated 136-item food frequency questionnaire and the Trichopoulou score were used to assess adherence to the MDP. Results After a median follow-up time of 9.4 y, 100 new cases of AN and BN were identified. The multivariate hazard ratio of AN and BN for the two upper categories of adherence to the MDP were 0.39 (95% CI: 0.20¿0.75) and 0.32 (95% CI: 0.14¿0.70; Ptrend¿=¿0.021). Inverse dose-response relationships were found for the consumption of cereals and olive oil and marginally for polyunsaturated fatty acid intake. To address reverse causation, multivariable linear regressions were run using a cross-sectional approach between adherence to the MDP and risk of AN and BN at baseline. No difference in adherence was found between participants with and without eating disorders. Conclusions Our results suggest a potential inverse association between the MDP and the risk of AN and BN. Additional longitudinal studies and trials are needed.
Autores: Lahortiga F; Unzueta, C.; Zazpe I; et al.
Revista: BMC PSYCHIATRY
ISSN 1471-244X  Vol. 18  Nº 1  2018  págs. 241
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.
Autores: Leone, A., (Autor de correspondencia); Martínez, Miguel Ángel; Lahortiga F; et al.
Revista: NUTRITION
ISSN 0899-9007  Vol. 54  2018  págs. 19 - 25
Objective: To our knowledge, no study has yet assessed the association between dietary patterns and incidence of eating disorders. This study aimed to assess the association between adherence to the Mediterranean dietary pattern (MDP) and incident risk of anorexia (AN) and bulimia nervosa (BN). Methods: We conducted a prospective cohort study of 11 800 women from the Seguimiento Universidad de Navarra follow-up project. Participants were classified as having incident AN or BN if they were free of AN or BN at baseline and reported a physician-made diagnosis of AN or BN during the follow-up period. Nutritional status, lifestyle, and behavioral variables were investigated and used as covariates. A validated 136-item food frequency questionnaire and the Trichopoulou score were used to assess adherence to the MDP. Results: After a median follow-up time of 9.4 y, 100 new cases of AN and BN were identified. The multivariate hazard ratio of AN and BN for the two upper categories of adherence to the MDP were 0.39 (95% Cl: 0.20-0.75) and 0.32 (95% Cl: 0.14-0.70; P-trend = 0.021). Inverse dose-response relationships were found for the consumption of cereals and olive oil and marginally for polyunsaturated fatty acid intake. To address reverse causation, multivariable linear regressions were run using a cross-sectional approach between adherence to the MDP and risk of AN and BN at baseline. No difference in adherence was found between participants with and without eating disorders. Conclusions: Our results suggest a potential inverse association between the MDP and the risk of AN and BN. Additional longitudinal studies and trials are needed. (C) 2018 Elsevier Inc. All rights reserved.
Autores: Alustiza, Irene Lucila, (Autor de correspondencia); Garces, M. S.; Solanes, A.; et al.
Revista: HELIYON
ISSN 2405-8440  Vol. 4  Nº 12  2018  págs. e01004
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.
Autores: Unzueta, C. R.; Lahortiga F; Santiago, Susana; et al.
Revista: PUBLIC HEALTH
ISSN 0033-3506  Vol. 157  2018  págs. 32 - 42
OBJECTIVE: The objective of this study is to assess the differences in lifestyles according to levels of self-perceived competitiveness, psychological tension, and dependency in a Mediterranean cohort of university graduates. STUDY DESIGN: Levels of personality traits, food consumption, nutrient intake, eating attitudes, physical activity, sedentary lifestyle, and alcohol and tobacco consumption were assessed through a questionnaire administered at baseline. This was a cross-sectional study in the context of the Seguimiento Universidad de Navarra cohort. Participants are 15,346 Spanish adults. RESULTS: Participants with a high level of self-perceived competitiveness consumed more vegetables and fish but less refined grains; they had higher protein intake and healthier eating attitudes. They were more physically active and less likely to be smokers. Participants with a high level of tension or dependency were less physically active, and participants more dependent also had poorer adherence to the Mediterranean diet. CONCLUSIONS: Self-perceived personality traits, especially the trait of competitiveness, are likely to be associated with healthier dietary patterns, better nutrient profile, better eating attitudes, physical activity, and less exposure to smoking. The use of short questions about self-perceived levels of competitiveness, psychological tension, and dependency can contribute to add additional information when assessing lifestyles and diet in adults.
Autores: Popova, V.; Daly, E.; Trivedi, M.; et al.
Revista: BIOLOGICAL PSYCHIATRY
ISSN 0006-3223  Vol. 83  Nº 9, Supl 1  2018  págs. S390
Autores: Martínez, Miguel Ángel; Zazpe I; et al.
Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
ISSN 0014-2972  Vol. 48  Nº Supl 1  2018  págs. 174 - 175
Autores: Alustiza, Irene Lucila; Garces, M. S.; Ortuno, M.; et al.
Revista: SCHIZOPHRENIA BULLETIN
ISSN 0586-7614  Vol. 44  Nº Supl.1.  2018  págs. S352
Autores: Alegre, Manuel; Molero, Patricio; Valencia, Miguel; et al.
Revista: PSYCHIATRY RESEARCH
ISSN 0165-1781  Vol. 247  2017  págs. 214 - 221
The symptoms of schizophrenia might be mediated by a cortical network disconnection which may disrupt the cortical oscillatory activity. Steady-state responses are an easy and consistent way to explore cortical oscillatory activity. A chirp-modulated tone (increasing the frequency of the modulation in a linear manner) allows a fast measure of the steady-state response to different modulation rates. With this approach, we studied the auditory steady-state responses in two groups of patients with schizophrenia (drug-naive and treated with atypical antipsychotic drugs), in order to assess the differences in their responses with respect to healthy subjects, and study any potential effect of medication. Drug-naive patients had reduced amplitude and inter-trial phase coherence of the response in the 30-50Hz range, and reduced amplitude of the response in the 90-100Hz range, when compared to controls. In the treated patients group, the response in the 30-50Hz range was normalized to values similar to the control group, but the reduction in amplitude in the 90-100Hz range remained as in the drug-naive group. These results suggest that gamma activity impairment in schizophrenia is a complex phenomenon that affects a wide band of frequencies and may be influenced by antipsychotic treatment.
Autores: Molero, Patricio; Martínez, Miguel Ángel; Ruiz-Canela, Miguel; et al.
Revista: WORLD PSYCHIATRY
ISSN 1723-8617  Vol. 16  Nº 1  2017  págs. 110 - 111
Autores: Álvarez de Mon, Miguel Ángel; Arrieta, María; Molero, Patricio; et al.
Revista: EUROPEAN PSYCHIATRY
ISSN 0924-9338  Vol. 41  Nº Supl  2017  págs. S178 - S179
Autores: Huang, E.; Zai, C. C.; Lisoway, A.; et al.
Revista: INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
ISSN 1461-1457  Vol. 19  Nº 5  2016  págs. 132
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.
Autores: Bes-Rastrollo, Maira; et al.
Revista: JOURNAL OF NUTRITION
ISSN 0022-3166  Vol. 146  Nº 9  2016  págs. 1731 - 1739
Background: Yogurt and prebiotic consumption has been linked to better health. However, to our knowledge, no longitudinal study has assessed the association of yogurt and prebiotic consumption with depression risk. Objective: We longitudinally evaluated the association of yogurt and prebiotic consumption with depression risk in a Mediterranean cohort. Methods: The SUN (Seguimiento Universidad de Navarra) Project is a dynamic, prospective cohort of Spanish university graduates. A total of 14,539 men and women (mean age: 37 y) initially free of depression were assessed during a median follow-up period of 9.3 y. Validated food-frequency questionnaires at baseline and after a 10-y follow-up were used to assess prebiotic (fructans and galacto-oligosaccharide) intake and yogurt consumption (<0.5, ¿0.5 to <3, ¿3 to <7, and ¿7 servings/wk). Participants were classified as incident cases of depression when they reported a new clinical diagnosis of depression by a physician (previously validated). Multivariable Cox proportional hazards models were used to calculate HRs and 95% CIs. Results: We identified 727 incident cases of depression during follow-up. Whole-fat yogurt intake was associated with reduced depression risk: HR for the highest [¿7 servings/wk (1 serving = 125 g)] compared with the lowest (<0.5 servings/wk) consumption: 0.78 (95% CI: 0.63, 0.98; P-trend = 0.020). When stratified by sex, this association was significant only in women (HR: 0.66; 95% CI: 0.50, 0.87; P-trend = 0.004). Low-fat yogurt consumption was associated with a higher incidence of depression (HR: 1.32; 95% CI: 1.06, 1.65; P-trend = 0.001), although this association lost significance after the exclusion of early incident cases, suggesting possible reverse causation bias. Prebiotic consumption was not significantly associated with depression risk. Conclusions: Our study suggests that high consumption of whole-fat yogurt was related to a lower risk of depression in women of the SUN cohort. No association was observed for prebiotics. Further studies are needed to clarify why the yogurt-depression association may differ by fat content of the yogurt.
Autores: Cristobal-Huerta, A.; et al.
Revista: PROGRESS IN NEURO-PSYCHOPHARMACOLOGY AND BIOLOGICAL PSYCHIATRY
ISSN 0278-5846  Vol. 71   Nº 3  2016  págs. 176 - 182
Context processing deficits have been shown to be present in chronic and first episode schizophrenia patients and in their relatives. This cognitive process is linked to frontal functioning and is highly dependent on dopamine levels in the prefrontal cortex (PFC). The catechol-O-methyltransferase (COMT) enzyme plays a prominent role in regulating dopamine levels in PFC. Genotypic variations in the functional polymorphism Val158Met COMT appear to have an impact in dopamine signaling in the PFC of healthy subjects and schizophrenia patients. We aimed to explore the effect of the Val158Met COMT polymorphism on brain activation during the performance of a context processing task in healthy subjects, schizophrenia spectrum patients and their healthy relatives. Methods: 56 participants performed the Dot Probe Expectancy task (DPX) during the fMRI session. Subjects were genotyped and only the Val and Met homozygotes participated in the study. Results: Schizophrenia spectrum patients and their relatives showed worse performance on context processing measures than healthy control subjects. The Val allele was associated with more context processing errors in healthy controls and in relatives compared to patients. There was a greater recruitment of frontal areas (supplementary motor area/cingulate gyrus) during context processing in patients relative to healthy controls. Met homozygotes subjects activated more frontal areas than Val homozygotes subjects. Conclusions: The Val158Met COMT polymorphism influences context processing and on its underlying brain activation, showing less recruitment of frontal areas in the subjects with the genotype associated to lower dopamine availability in PFC.
Autores: Bes-Rastrollo, Maira; et al.
Revista: PUBLIC HEALTH NUTRITION
ISSN 1368-9800  Vol. 20  Nº 13  2016  págs. 2383 - 2392
Objective: Our aim was to evaluate the relationship between adherence to different Dietary Approaches to Stop Hypertension (DASH) diet indices and the risk of depression. Design: In a prospective study we assessed 14051 participants of a dynamic (permanently ongoing recruitment) prospective cohort (the Seguimiento Universidad de Navarra (SUN) Project), initially free of depression. At baseline, a validated FFQ was used to assess adherence to four previously proposed DASH indices (Dixon, Mellen, Fung and Günther). To define the outcome we applied two definitions of depression: a less conservative definition including only self-reported physician-diagnosed depression (410 incident cases) and a more conservative definition that required both clinical diagnosis of depression and use of antidepressants (113 incident cases). Cox regression and restricted cubic splines analyses were performed. Results: After a median follow-up period of 8 years, the multiple-adjusted model showed an inverse association with the Fung DASH score (hazard ratio (HR)=0·76; 95 % CI 0·61, 0·94) when we used the less conservative definition of depression, and also under the more conservative definition (HR=0·63; 95 % CI 0·41, 0·95). We observed a weak inverse association with the Mellen DASH score, but no statistically significant association was found for the other definitions. The restricted cubic splines analyses suggested that these associations were non-linear (U-shaped). Conclusions: Moderate adherence to the DASH diet as operationalized by Fung and Mellen was related to lower depression risk. Since these associations were non-linear, additional prospective studies are required before the results can be generalized and clinical recommendations can be given.
Autores: Alustiza, Irene Lucila; Pujol, Nuria; Molero, Patricio; et al.
Revista: SCHIZOPHRENIA RESEARCH
ISSN 0920-9964  Vol. 2   Nº 4  2015  págs. 185 - 188
We review the main contributions of the cognitive neuroscience literature in the field of time processing in schizophrenia. First, we summarize the theoretical concepts and terminology related to time and time estimation and the characterization of this deficit in the illness. Second, we thoroughly review the neuroanatomical basis of this deficit and its interactions with other cognitive processes and clinical symptoms. Third, we specifically highlight the main findings of studies that have analyzed temporal discrimination using cognitive tasks performed during functional neuroimaging. Summary This review aims to summarize the main findings of the neuroscientific and cognitive literature on temporality in schizophrenia. First, we will provide a brief introduction regarding the theoretical and conceptual issues and then will delve into the importance of their disturbance in this disorder, particularly underlying brain structures and the interactions they have with other cognitive dysfunctions and psychopathological symptoms. This review includes different studies that describe both behavioral and neuroscientific approaches, although it focuses especially on tasks of temporal discrimination on the milliseconds scale and on the studies that use functional neuroimaging techniques.
Autores: Lorea I; Molero, Patricio;
Revista: ACTAS ESPAÑOLAS DE PSIQUIATRIA
ISSN 1139-9287  Vol. 43  Nº 2  2015  págs. 42-50
Epigenetics deals with the genic expression processes that do not involve modifications of the DNA sequence, that is, focuses on the different trajectories of a given genotype throughout the organism&#8217;s lifespan. These processes are involved in basic biological functions such as the cellular differentiation or sexual selection, in the development of complex diseases such as Rett&#8217;s syndrome and in psychiatric disorders such as schizophrenia and depression among others. Epigenetic studies are yielding evidence that environmental events and psychosocial factors can modify the epigenome. This work reviews studies analyzing the influence of environmental factors involved in the pathogenesis of behavioral features and phenotypic expression of personality disorder&#8217;s symptomatic domains, such as late onset affective symptoms related with early adverse events in childhood and dysfunction of stress modulation mechanisms. In addition, the knowledge of these epigenetic mechanisms may contribute to the identification of novel both psychotherapeutic and pharmacological therapeutic targets for the treatment of personality disorders.
Autores: Henríquez-Sánchez; Ruiz-Canela, Miguel; et al.
Revista: BMC MEDICINE
ISSN 1741-7015  Vol. 13  Nº 1  2015  págs. 197
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 10years of follow-up with a validated semi-quantitative food-frequency 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 8.5years. 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.
Autores: Alustiza, Irene Lucila; Pujol, Nuria; Molero, Patricio; et al.
Revista: SCHIZOPHRENIA RESEARCH: COGNITION
ISSN 2215-0013  Vol. 2  Nº 15  2015  págs. 210-213
Autores: Marín-Méndez, Juan Jesús; Molero, Patricio; et al.
Revista: PSYCHIATRY RESEARCH
ISSN 0165-1781  Vol. 220  Nº 3  2014  págs. 737 - 744
Timing is an essential function for the survival of many living organisms. Despite its significance, it is relatively under-researched, particularly in schizophrenia. We examined neurophysiological, neuropathological, imaging and genetic studies of both healthy subjects and subjects suffering from schizophrenia in relation to time perception as measured by interval timing. We found that the data from studies in healthy populations indicate that time perception may be inter-linked with numerous other cognitive functions and share common brain networks. The same networks are implicated in the pathophysiology of schizophrenia. There is also evidence that several neurotransmitter systems, particularly the dopaminergic D2 system, are involved in interval timing. Patients with schizophrenia have been shown to suffer from a distorted sense of time, which has an impact on their cognitive function and results in both positive and negative symptoms. Therefore, genes involved in interval timing can be considered candidate genes for distorted cognition in schizophrenia. We discuss the hypothesis that time perception dysfunction is a primary cognitive dysfunction in schizophrenia.
Autores: Molero, Patricio; Pla-Vidal, Jorge; et al.
Revista: THE OPEN NEUROIMAGING JOURNAL
ISSN 1874-4400  Vol. 8  2014  págs. 1 - 4
We describe a case of delusional psychosis that was terminated by neurosurgical removal of a large arachnoid cyst. The patient was suffering his first psychotic episode and had symptoms typical of schizophrenia. The case underscores the importance of considering that an arachnoid cyst can induce psychopathological symptoms, even those of schizophrenia. Indeed, such symptoms may be the cyst's only clinical manifestation. In addition, the case highlights the importance of doing a structural imaging test when confronted with a first episode of psychosis, especially if the episode is relatively late in appearance. Such imaging may lead to a diagnosis that in turn can enable a definitive neurosurgical resolution of the psychosis.
Autores: Molero, Patricio; Grunebaum M; Galfalvy HC; et al.
Revista: ARCH SUICIDE RES
ISSN 1381-1118  Vol. 18  Nº 1  2014  págs. 50-57
The objective of this study was to compare structured clinical assessment versus research measurement of suicidal risk among inpatients with major depression. Fifty depressed inpatients underwent a structured clinical and an independent research assessment of suicidal risk. Agreement between both assessments and its impact upon time to first readmission was tested. A false negative rate of 25% in the clinical screening of past suicide attempts was associated with older age, concealment, and reported lower frequency of suicidal thoughts. Mean times to first readmission (2.5 years follow-up) were 74 weeks (discordant responders) and 118 weeks (concordant responders). A failure to detect 25% of patients with past suicide attempt history in the clinical assessment was associated with older age and concealment of suicidal thoughts.
Autores: Molero, Patricio; et al.
Revista: PSYCHIATRY RESEARCH
ISSN 0165-1781  Vol. 208  Nº 2  2013  págs. 118 - 124
Cognitive impairment in schizophrenia is a core feature and seems to be related mainly to dopaminergic dysfunction in the prefrontal cortex (PFC). The functional polymorphism Val158Met of the COMT (catechol-. O-methyltransferase) gene could mediate the relationship between cognition and dopamine activity in PFC. The present study tested the influence of this polymorphism on the cognitive performance of schizophrenia spectrum patients and their relatives, using some subtests of the neuropsychological battery, the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery, and evaluated the impact of this polymorphism on a specific prefrontal cognitive function using a cognitive neuroscience paradigm. A Group of 74 schizophrenia spectrum disorder patients, 48 relatives and 67 controls performed some subtests of the MATRICS Consensus Cognitive Battery. In addition, 40 schizophrenia spectrum disorder patients, 26 relatives and 63 controls performed the Dot Pattern Expectancy Task (DPX) to study context processing. For the neuropsychological battery, no differences in any of the cognitive domains were found according to genotype. The DPX task was sensitive to genotype effects in patients as well as in relatives. Context processing deficits in schizophrenia patients and their relatives may be mediated by COMT genotype. The influence of the COMT genotype on cognition is more relevant in specific cognitive tasks related to prefrontal function. These results should be replicated in larger samples.
Autores: Martinez-Ortega JM; Jurado D; Gutierrez-Rojas L; et al.
Revista: PSYCHIATRY RESEARCH
ISSN 0165-1781  Vol. 198  Nº 1  2012  págs. 161-163
We examined sex differences in the distribution of psychiatric diagnoses among hospitalized patients, controlling for socio-demographic variables. The sample included 1865 psychiatric inpatients consecutively admitted during a 9-year period. The finding of a higher proportion of men among patients hospitalized for schizophrenia or substance use disorder and a higher proportion of women among those admitted for affective disorders, including bipolar disorder, was stable over time. A better understanding of these differences may help to establish more effective treatment strategies.
Autores: de Castro, María Pilar; Molero, Patricio;
Libro:  Lecciones de Psiquiatría
2010  págs. 543-557
Autores: de Castro, María Pilar; Molero, Patricio;
Libro:  Lecciones de Psiquiatría
2010  págs. 519-542

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