Publications by authors named "Philippe Courtet"

285 Publications

Relationship between childhood physical abuse and clinical severity of treatment-resistant depression in a geriatric population.

PLoS One 2021 20;16(4):e0250148. Epub 2021 Apr 20.

Fondation FondaMental, Creteil, France.

Introduction: We assessed the correlation between childhood maltreatment (CM) and severity of depression in an elderly unipolar Treatment-Resistant Depression (TRD) sample.

Methods: Patients were enrolled from a longitudinal cohort (FACE-DR) of the French Network of Expert TRD Centres.

Results: Our sample included 96 patients (33% of the overall cohort) aged 60 years or above, with a mean age of 67.2 (SD = 5.7). The majority of the patients were female (62.5%). The Montgomery and Asberg Depression Rating Scale (MADRS) and Quick Inventory Depression Scale-Self Report (QIDS-SR) mean scores were high, 28.2 (SD = 7.49) [MADRS score range: 0-60; moderate severity≥20, high severity≥35] and 16.5 (SD = 4.94) [IDS-SR score range: 0-27; moderate severity≥11, high severity≥16], respectively. Mean self-esteem scores were 22.47 (SD = 6.26) [range 0-30]. In an age- and sex-adjusted model, we found a positive correlation between childhood trauma (CTQ scores) and depressive symptom severity [MADRS (β = 0.274; p = 0.07) and QIDS-SR (β = 0.302; p = 0.005) scores]. We detected a statistically significant correlation between physical abuse and depressive symptom severity [MADRS (β = 0.304; p = 0.03) and QIDS-SR (β = 0.362; p = 0.005) scores]. We did not observe any significant correlation between other types of trauma and depressive symptom severity. We showed that self-esteem (Rosenberg scale) mediated the effect of physical abuse (PA) on the intensity of depressive symptoms [MADRS: b = 0.318, 95% BCa C.I. [0.07, 0.62]; QIDS-SR: b = 0.177, 95% BCa C.I. [0.04, 0.37]]. Preacher & Kelly's Kappa Squared values of 19.1% (k2 = 0.191) and 16% (k2 = 0.16), respectively for the two scales, indicate a moderate effect.

Conclusion: To our knowledge, this is the first study conducted in a geriatric TRD population documenting an association between childhood trauma (mainly relating to PA) and the intensity of depressive symptoms.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250148PLOS
April 2021

Relationship between childhood physical abuse and clinical severity of treatment-resistant depression in a geriatric population.

PLoS One 2021 20;16(4):e0250148. Epub 2021 Apr 20.

Fondation FondaMental, Creteil, France.

Introduction: We assessed the correlation between childhood maltreatment (CM) and severity of depression in an elderly unipolar Treatment-Resistant Depression (TRD) sample.

Methods: Patients were enrolled from a longitudinal cohort (FACE-DR) of the French Network of Expert TRD Centres.

Results: Our sample included 96 patients (33% of the overall cohort) aged 60 years or above, with a mean age of 67.2 (SD = 5.7). The majority of the patients were female (62.5%). The Montgomery and Asberg Depression Rating Scale (MADRS) and Quick Inventory Depression Scale-Self Report (QIDS-SR) mean scores were high, 28.2 (SD = 7.49) [MADRS score range: 0-60; moderate severity≥20, high severity≥35] and 16.5 (SD = 4.94) [IDS-SR score range: 0-27; moderate severity≥11, high severity≥16], respectively. Mean self-esteem scores were 22.47 (SD = 6.26) [range 0-30]. In an age- and sex-adjusted model, we found a positive correlation between childhood trauma (CTQ scores) and depressive symptom severity [MADRS (β = 0.274; p = 0.07) and QIDS-SR (β = 0.302; p = 0.005) scores]. We detected a statistically significant correlation between physical abuse and depressive symptom severity [MADRS (β = 0.304; p = 0.03) and QIDS-SR (β = 0.362; p = 0.005) scores]. We did not observe any significant correlation between other types of trauma and depressive symptom severity. We showed that self-esteem (Rosenberg scale) mediated the effect of physical abuse (PA) on the intensity of depressive symptoms [MADRS: b = 0.318, 95% BCa C.I. [0.07, 0.62]; QIDS-SR: b = 0.177, 95% BCa C.I. [0.04, 0.37]]. Preacher & Kelly's Kappa Squared values of 19.1% (k2 = 0.191) and 16% (k2 = 0.16), respectively for the two scales, indicate a moderate effect.

Conclusion: To our knowledge, this is the first study conducted in a geriatric TRD population documenting an association between childhood trauma (mainly relating to PA) and the intensity of depressive symptoms.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250148PLOS
April 2021

Pharmacological treatment profiles in the FACE-BD cohort: Treatment description and complete data for bipolar subtypes.

Data Brief 2021 Jun 25;36:107004. Epub 2021 Mar 25.

Service Universitaire de Psychiatrie, CHU de Grenoble et des Alpes, T. Bougerol, B. Fredembach, A. Suisse, S. Brodeur, A. Pouchon, and M. Polosan,  Grenoble, France.

In the current study, we provide the list of pharmacological interventions applied during the one-year follow-up period of the Pharmacological treatment profiles in the FACE-BD cohort study. These data show the treatments used in the new clusters formed in this previous study and also in usual bipolarity subtypes. The proportion of each treatment used during the follow-up was calculated. Days on each treatment were also included in this dataset. The complete clinical and paraclinical data analyzed for clusters and bipolar subtypes were included in this dataset. Socio-demographic self-administered and clinician-administered scales, clinical evaluation during the follow-up, psychiatric and somatic comorbidities, and blood tests are shown in this material.
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http://dx.doi.org/10.1016/j.dib.2021.107004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027517PMC
June 2021

Late-life cynical hostility is associated with white matter alterations and the risk of Alzheimer's disease.

Psychol Med 2021 Apr 14:1-10. Epub 2021 Apr 14.

IGF, Univ Montpellier, CNRS, INSERM, Montpellier, France.

Background: Cynical hostility (CH), a specific dimension of hostility that consists of a mistrust of others, has been suggested as a high-risk trait for dementia. However, the influence of CH on the incidence of Alzheimer's disease (AD) remains poorly understood. This study investigated whether late-life CH is associated with AD risk and structural neuroimaging markers of AD.

Methods: In community-dwelling older adults from the French ESPRIT cohort (n = 1388), incident dementia rate according to CH level was monitored during an 8-year follow-up and analyzed using Cox proportional hazards regression models. Brain magnetic resonance imaging volumes were measured at baseline (n = 508). Using automated segmentation procedures (Freesurfer 6.0), the authors assessed brain grey and white volumes on all magnetic resonance imaging scans. They also measured white matter hyperintensities volumes using semi-automated procedures. Mean volumes according to the level of CH were compared using ANOVA.

Results: Eighty-four participants developed dementia (32 with AD). After controlling for potential confounders, high CH was predictive of AD (HR 2.74; 95% CI 1.10-6.85; p = 0.030) and all dementia types are taken together (HR 2.30; 95% CI 1.10-4.80; p = 0.027). High CH was associated with white matter alterations, particularly smaller anterior corpus callosum volume (p < 0.01) after False Discovery Rate correction, but not with grey matter volumes.

Conclusions: High CH in late life is associated with cerebral white matter alterations, designated as early markers of dementia, and higher AD risk. Identifying lifestyle and biological determinants related to CH could provide clues on AD physiopathology and avenues for prevention strategies.
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http://dx.doi.org/10.1017/S0033291721000416DOI Listing
April 2021

The course of bipolar disorder as a function of the presence and sequence of onset of comorbid alcohol use disorders in outpatients attending the Fondamental Advanced Centres of Expertise.

J Affect Disord 2021 Mar 19;287:196-203. Epub 2021 Mar 19.

Fondation Fondamental, Créteil, France; Department of Emergency Psychiatry and Acute Care, Lapeyronie Hospital, CHU Montpellier, Montpellier, France; PSNREC, Univ Montpellier, INSERM, CHU Montpellier, Montpellier, France.

Objectives: The comorbidity of alcohol use disorder (AUD) and bipolar disorder (BD) has been repeatedly associated with poorer clinical outcomes than BD without AUD. We aimed to extend these findings by focusing on the characteristics associated with the sequence of onset of BD and AUD.

Methods: 3,027 outpatients from the Fondamental Advanced Centres of Expertise were ascertained for BD-1, BD-2 and AUD diagnoses, including their respective ages at onset (AAOs, N =2,804). We selected the variables associated with both the presence and sequence of onset of comorbid AUD using bivariate analyses corrected for multiple testing to enter a binary regression model with the sequence of onset of BD and AUD as the dependent variable (AUD first - which also included 88 same-year onsets, vs. BD first).

Results: BD patients with comorbid AUD showed more severe clinical profile than those without. Compared to BD-AUD (N =269), AUD-BD (N =276) was independently associated with a higher AAO of BD (OR =1.1, p <0.001), increased prevalence of comorbid cannabis use disorder (OR =2.8, p <0.001) a higher number of (hypo)manic/mixed BD episodes per year of bipolar illness (OR =3, p <0.01).

Limitations: The transversal design prevents from drawing causal conclusions.

Conclusion: Increased severity of BD with AUD compared to BD alone did not differ according to the sequence of onset. A few differences, though, could be used to better monitor the trajectory of patients showing either one of these disorders.
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http://dx.doi.org/10.1016/j.jad.2021.03.041DOI Listing
March 2021

The course of bipolar disorder as a function of the presence and sequence of onset of comorbid alcohol use disorders in outpatients attending the Fondamental Advanced Centres of Expertise.

J Affect Disord 2021 Mar 19;287:196-203. Epub 2021 Mar 19.

Fondation Fondamental, Créteil, France; Department of Emergency Psychiatry and Acute Care, Lapeyronie Hospital, CHU Montpellier, Montpellier, France; PSNREC, Univ Montpellier, INSERM, CHU Montpellier, Montpellier, France.

Objectives: The comorbidity of alcohol use disorder (AUD) and bipolar disorder (BD) has been repeatedly associated with poorer clinical outcomes than BD without AUD. We aimed to extend these findings by focusing on the characteristics associated with the sequence of onset of BD and AUD.

Methods: 3,027 outpatients from the Fondamental Advanced Centres of Expertise were ascertained for BD-1, BD-2 and AUD diagnoses, including their respective ages at onset (AAOs, N =2,804). We selected the variables associated with both the presence and sequence of onset of comorbid AUD using bivariate analyses corrected for multiple testing to enter a binary regression model with the sequence of onset of BD and AUD as the dependent variable (AUD first - which also included 88 same-year onsets, vs. BD first).

Results: BD patients with comorbid AUD showed more severe clinical profile than those without. Compared to BD-AUD (N =269), AUD-BD (N =276) was independently associated with a higher AAO of BD (OR =1.1, p <0.001), increased prevalence of comorbid cannabis use disorder (OR =2.8, p <0.001) a higher number of (hypo)manic/mixed BD episodes per year of bipolar illness (OR =3, p <0.01).

Limitations: The transversal design prevents from drawing causal conclusions.

Conclusion: Increased severity of BD with AUD compared to BD alone did not differ according to the sequence of onset. A few differences, though, could be used to better monitor the trajectory of patients showing either one of these disorders.
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http://dx.doi.org/10.1016/j.jad.2021.03.041DOI Listing
March 2021

The course of bipolar disorder as a function of the presence and sequence of onset of comorbid alcohol use disorders in outpatients attending the Fondamental Advanced Centres of Expertise.

J Affect Disord 2021 Mar 19;287:196-203. Epub 2021 Mar 19.

Fondation Fondamental, Créteil, France; Department of Emergency Psychiatry and Acute Care, Lapeyronie Hospital, CHU Montpellier, Montpellier, France; PSNREC, Univ Montpellier, INSERM, CHU Montpellier, Montpellier, France.

Objectives: The comorbidity of alcohol use disorder (AUD) and bipolar disorder (BD) has been repeatedly associated with poorer clinical outcomes than BD without AUD. We aimed to extend these findings by focusing on the characteristics associated with the sequence of onset of BD and AUD.

Methods: 3,027 outpatients from the Fondamental Advanced Centres of Expertise were ascertained for BD-1, BD-2 and AUD diagnoses, including their respective ages at onset (AAOs, N =2,804). We selected the variables associated with both the presence and sequence of onset of comorbid AUD using bivariate analyses corrected for multiple testing to enter a binary regression model with the sequence of onset of BD and AUD as the dependent variable (AUD first - which also included 88 same-year onsets, vs. BD first).

Results: BD patients with comorbid AUD showed more severe clinical profile than those without. Compared to BD-AUD (N =269), AUD-BD (N =276) was independently associated with a higher AAO of BD (OR =1.1, p <0.001), increased prevalence of comorbid cannabis use disorder (OR =2.8, p <0.001) a higher number of (hypo)manic/mixed BD episodes per year of bipolar illness (OR =3, p <0.01).

Limitations: The transversal design prevents from drawing causal conclusions.

Conclusion: Increased severity of BD with AUD compared to BD alone did not differ according to the sequence of onset. A few differences, though, could be used to better monitor the trajectory of patients showing either one of these disorders.
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http://dx.doi.org/10.1016/j.jad.2021.03.041DOI Listing
March 2021

The course of bipolar disorder as a function of the presence and sequence of onset of comorbid alcohol use disorders in outpatients attending the Fondamental Advanced Centres of Expertise.

J Affect Disord 2021 Mar 19;287:196-203. Epub 2021 Mar 19.

Fondation Fondamental, Créteil, France; Department of Emergency Psychiatry and Acute Care, Lapeyronie Hospital, CHU Montpellier, Montpellier, France; PSNREC, Univ Montpellier, INSERM, CHU Montpellier, Montpellier, France.

Objectives: The comorbidity of alcohol use disorder (AUD) and bipolar disorder (BD) has been repeatedly associated with poorer clinical outcomes than BD without AUD. We aimed to extend these findings by focusing on the characteristics associated with the sequence of onset of BD and AUD.

Methods: 3,027 outpatients from the Fondamental Advanced Centres of Expertise were ascertained for BD-1, BD-2 and AUD diagnoses, including their respective ages at onset (AAOs, N =2,804). We selected the variables associated with both the presence and sequence of onset of comorbid AUD using bivariate analyses corrected for multiple testing to enter a binary regression model with the sequence of onset of BD and AUD as the dependent variable (AUD first - which also included 88 same-year onsets, vs. BD first).

Results: BD patients with comorbid AUD showed more severe clinical profile than those without. Compared to BD-AUD (N =269), AUD-BD (N =276) was independently associated with a higher AAO of BD (OR =1.1, p <0.001), increased prevalence of comorbid cannabis use disorder (OR =2.8, p <0.001) a higher number of (hypo)manic/mixed BD episodes per year of bipolar illness (OR =3, p <0.01).

Limitations: The transversal design prevents from drawing causal conclusions.

Conclusion: Increased severity of BD with AUD compared to BD alone did not differ according to the sequence of onset. A few differences, though, could be used to better monitor the trajectory of patients showing either one of these disorders.
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http://dx.doi.org/10.1016/j.jad.2021.03.041DOI Listing
March 2021

Pharmacological treatment profiles in the FACE-BD cohort: An unsupervised machine learning study, applied to a nationwide bipolar cohort.

J Affect Disord 2021 May 13;286:309-319. Epub 2021 Feb 13.

Service Universitaire de Psychiatrie, CHU de Grenoble et des Alpes, Grenoble , T. Bougerol, B. Fredembach, A. Suisse, S. Brodeur, A. Pouchon, and M. Polosan, France. Electronic address:

Background: Despite thorough and validated clinical guidelines based on bipolar disorders subtypes, large pharmacological treatment heterogeneity remains in these patients. There is limited knowledge about the different treatment combinations used and their influence on patient outcomes. We attempted to determine profiles of patients based on their treatments and to understand the clinical characteristics associated with these treatment profiles.

Methods: This multicentre longitudinal study was performed on a French nationwide bipolar cohort database. We performed hierarchical agglomerative clustering to search for clusters of individuals based on their treatments during the first year following inclusion. We then compared patient clinical characteristics according to these clusters.

Results: Four groups were identified among the 1795 included patients: group 1 ("heterogeneous" n = 1099), group 2 ("lithium" n = 265), group 3 ("valproate" n = 268), and group 4 ("lamotrigine" n = 163). Proportion of bipolar 1 disorder, in groups 1 to 4 were: 48.2%, 57.0%, 48.9% and 32.5%. Groups 1 and 4 had greater functional impact at baseline and a less favorable clinical and functioning evolution at one-year follow-up, especially on GAF and FAST scales.

Limitations: The one-year period used for the analysis of mood stabilizing treatments remains short in the evolution of bipolar disorder.

Conclusions: Treatment profiles are associated with functional evolution of patients and were not clearly determined by bipolar subtypes. These profiles seem to group together common patient phenotypes. These findings do not seem to be influenced by the duration of disease prior to inclusion and neither by the number of treatments used during the follow-up period.
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http://dx.doi.org/10.1016/j.jad.2021.02.036DOI Listing
May 2021

Pharmacological treatment profiles in the FACE-BD cohort: An unsupervised machine learning study, applied to a nationwide bipolar cohort.

J Affect Disord 2021 May 13;286:309-319. Epub 2021 Feb 13.

Service Universitaire de Psychiatrie, CHU de Grenoble et des Alpes, Grenoble , T. Bougerol, B. Fredembach, A. Suisse, S. Brodeur, A. Pouchon, and M. Polosan, France. Electronic address:

Background: Despite thorough and validated clinical guidelines based on bipolar disorders subtypes, large pharmacological treatment heterogeneity remains in these patients. There is limited knowledge about the different treatment combinations used and their influence on patient outcomes. We attempted to determine profiles of patients based on their treatments and to understand the clinical characteristics associated with these treatment profiles.

Methods: This multicentre longitudinal study was performed on a French nationwide bipolar cohort database. We performed hierarchical agglomerative clustering to search for clusters of individuals based on their treatments during the first year following inclusion. We then compared patient clinical characteristics according to these clusters.

Results: Four groups were identified among the 1795 included patients: group 1 ("heterogeneous" n = 1099), group 2 ("lithium" n = 265), group 3 ("valproate" n = 268), and group 4 ("lamotrigine" n = 163). Proportion of bipolar 1 disorder, in groups 1 to 4 were: 48.2%, 57.0%, 48.9% and 32.5%. Groups 1 and 4 had greater functional impact at baseline and a less favorable clinical and functioning evolution at one-year follow-up, especially on GAF and FAST scales.

Limitations: The one-year period used for the analysis of mood stabilizing treatments remains short in the evolution of bipolar disorder.

Conclusions: Treatment profiles are associated with functional evolution of patients and were not clearly determined by bipolar subtypes. These profiles seem to group together common patient phenotypes. These findings do not seem to be influenced by the duration of disease prior to inclusion and neither by the number of treatments used during the follow-up period.
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http://dx.doi.org/10.1016/j.jad.2021.02.036DOI Listing
May 2021

Pharmacological treatment profiles in the FACE-BD cohort: An unsupervised machine learning study, applied to a nationwide bipolar cohort.

J Affect Disord 2021 May 13;286:309-319. Epub 2021 Feb 13.

Service Universitaire de Psychiatrie, CHU de Grenoble et des Alpes, Grenoble , T. Bougerol, B. Fredembach, A. Suisse, S. Brodeur, A. Pouchon, and M. Polosan, France. Electronic address:

Background: Despite thorough and validated clinical guidelines based on bipolar disorders subtypes, large pharmacological treatment heterogeneity remains in these patients. There is limited knowledge about the different treatment combinations used and their influence on patient outcomes. We attempted to determine profiles of patients based on their treatments and to understand the clinical characteristics associated with these treatment profiles.

Methods: This multicentre longitudinal study was performed on a French nationwide bipolar cohort database. We performed hierarchical agglomerative clustering to search for clusters of individuals based on their treatments during the first year following inclusion. We then compared patient clinical characteristics according to these clusters.

Results: Four groups were identified among the 1795 included patients: group 1 ("heterogeneous" n = 1099), group 2 ("lithium" n = 265), group 3 ("valproate" n = 268), and group 4 ("lamotrigine" n = 163). Proportion of bipolar 1 disorder, in groups 1 to 4 were: 48.2%, 57.0%, 48.9% and 32.5%. Groups 1 and 4 had greater functional impact at baseline and a less favorable clinical and functioning evolution at one-year follow-up, especially on GAF and FAST scales.

Limitations: The one-year period used for the analysis of mood stabilizing treatments remains short in the evolution of bipolar disorder.

Conclusions: Treatment profiles are associated with functional evolution of patients and were not clearly determined by bipolar subtypes. These profiles seem to group together common patient phenotypes. These findings do not seem to be influenced by the duration of disease prior to inclusion and neither by the number of treatments used during the follow-up period.
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http://dx.doi.org/10.1016/j.jad.2021.02.036DOI Listing
May 2021

Trajectories of medication adherence in patients with Bipolar Disorder along 2 years-follow-up.

J Affect Disord 2021 Mar 31;282:812-819. Epub 2020 Dec 31.

Pôle de Psychiatrie, Assistance Publique Hôpitaux de Marseille, Marseille, France; Fondation FondaMental, fondation de coopération scientifique, Créteil, France; INT-UMR7289, CNRS, Aix-Marseille Université, Marseille, France. Electronic address:

Background: Bipolar disorder (BD) is a chronic and severe mental illness. It requires a non-discontinued pharmacological treatment to prevent mood recurrences but nonadherence to medication is frequent. To this date, medication adherence in BD has been mostly evaluated in cross-sectional studies and often considered as a stable trait. We aimed to study medication adherence using a prospective person-oriented approach.

Methods: 1627 BD patients were followed on a 2 years period and assessed every 6 months. Medication adherence was evaluated at each visit with the Medication Adherence Rating Scale (MARS). A latent class mixed model (LCMM) was used to identify trajectory classes of adherence over time. Regression analyses and linear mixed model were used to search for predictors and covariables of the trajectories.

Results: Three distinct and robust trajectories of medication adherence have been identified: one that starts poorly and keeps deteriorating (4.8%), one that starts poorly but improves (9%) and one that starts well and keeps improving (86.2%). A good tolerance to psychotropic medications, low depressive symptoms, the absence of comorbid eating disorders and anticonvulsant medication were associated to a better prognosis of adherence. Along the follow-up, the lower were the depressive symptoms, the better was the medication adherence (p < .001) LIMITATIONS: The use of a single measure of medication adherence although it is a validated instrument and a possible positive selection bias that might limit the generalization of our findings.

Conclusions: This study demonstrates that medication adherence in BD patients is a heterogeneous and potentially variable phenomenon.
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http://dx.doi.org/10.1016/j.jad.2020.12.192DOI Listing
March 2021

Trajectories of medication adherence in patients with Bipolar Disorder along 2 years-follow-up.

J Affect Disord 2021 Mar 31;282:812-819. Epub 2020 Dec 31.

Pôle de Psychiatrie, Assistance Publique Hôpitaux de Marseille, Marseille, France; Fondation FondaMental, fondation de coopération scientifique, Créteil, France; INT-UMR7289, CNRS, Aix-Marseille Université, Marseille, France. Electronic address:

Background: Bipolar disorder (BD) is a chronic and severe mental illness. It requires a non-discontinued pharmacological treatment to prevent mood recurrences but nonadherence to medication is frequent. To this date, medication adherence in BD has been mostly evaluated in cross-sectional studies and often considered as a stable trait. We aimed to study medication adherence using a prospective person-oriented approach.

Methods: 1627 BD patients were followed on a 2 years period and assessed every 6 months. Medication adherence was evaluated at each visit with the Medication Adherence Rating Scale (MARS). A latent class mixed model (LCMM) was used to identify trajectory classes of adherence over time. Regression analyses and linear mixed model were used to search for predictors and covariables of the trajectories.

Results: Three distinct and robust trajectories of medication adherence have been identified: one that starts poorly and keeps deteriorating (4.8%), one that starts poorly but improves (9%) and one that starts well and keeps improving (86.2%). A good tolerance to psychotropic medications, low depressive symptoms, the absence of comorbid eating disorders and anticonvulsant medication were associated to a better prognosis of adherence. Along the follow-up, the lower were the depressive symptoms, the better was the medication adherence (p < .001) LIMITATIONS: The use of a single measure of medication adherence although it is a validated instrument and a possible positive selection bias that might limit the generalization of our findings.

Conclusions: This study demonstrates that medication adherence in BD patients is a heterogeneous and potentially variable phenomenon.
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http://dx.doi.org/10.1016/j.jad.2020.12.192DOI Listing
March 2021

Psychiatric patients are more vulnerable to the Spanish euthanasia law?

Rev Psiquiatr Salud Ment 2021 Jan 23. Epub 2021 Jan 23.

PSNREC, Univ Montpellier, INSERM, CHU de Montpellier, Montpellier, Francia; Department of Emergency Psychiatry and Acute Care, Lapeyronie Hospital, CHU Montpellier, Montpellier, Francia.

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http://dx.doi.org/10.1016/j.rpsm.2021.01.003DOI Listing
January 2021

Psychiatric patients are more vulnerable to the Spanish euthanasia law?

Rev Psiquiatr Salud Ment 2021 Jan 23. Epub 2021 Jan 23.

PSNREC, Univ Montpellier, INSERM, CHU de Montpellier, Montpellier, Francia; Department of Emergency Psychiatry and Acute Care, Lapeyronie Hospital, CHU Montpellier, Montpellier, Francia.

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http://dx.doi.org/10.1016/j.rpsm.2021.01.003DOI Listing
January 2021

Psychiatric Profiles of eHealth Users Evaluated Using Data Mining Techniques: Cohort Study.

JMIR Ment Health 2021 Jan 20;8(1):e17116. Epub 2021 Jan 20.

Department of Psychiatry, Nimes University Hospital, Nimes, France.

Background: New technologies are changing access to medical records and the relationship between physicians and patients. Professionals can now use e-mental health tools to provide prompt and personalized responses to patients with mental illness. However, there is a lack of knowledge about the digital phenotypes of patients who use e-mental health apps.

Objective: This study aimed to reveal the profiles of users of a mental health app through machine learning techniques.

Methods: We applied a nonparametric model, the Sparse Poisson Factorization Model, to discover latent features in the response patterns of 2254 psychiatric outpatients to a short self-assessment on general health. The assessment was completed through a mental health app after the first login.

Results: The results showed the following four different profiles of patients: (1) all patients had feelings of worthlessness, aggressiveness, and suicidal ideas; (2) one in four reported low energy and difficulties to cope with problems; (3) less than a quarter described depressive symptoms with extremely high scores in suicidal thoughts and aggressiveness; and (4) a small number, possibly with the most severe conditions, reported a combination of all these features.

Conclusions: User profiles did not overlap with clinician-made diagnoses. Since each profile seems to be associated with a different level of severity, the profiles could be useful for the prediction of behavioral risks among users of e-mental health apps.
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http://dx.doi.org/10.2196/17116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857940PMC
January 2021

Sociocultural Attitudes Towards Appearance Questionnaire-4: Psychometric properties among a French clinical eating disorder sample and normative comparisons.

Eat Behav 2021 Jan 5;40:101466. Epub 2021 Jan 5.

Department of Psychiatric Emergency & Acute Care, Lapeyronie Hospital, CHRU, Montpellier, France.

Although the Sociocultural Attitudes Towards Appearance Questionnaire-4 (SATAQ-4) has been shown to be a reliable and valid tool for assessing appearance pressures and appearance ideal internalization among French college students, to date its psychometric properties among French clinical populations have not been examined. The aim of this study was to evaluate the factor structure, reliability, and validity of the SATAQ-4 among a French female clinical eating disorder sample, and to compare the mean SATAQ-4 scores from this clinical sample to previously published means observed among French female college women. The current sample included 192 French women consecutively recruited from an outpatient eating disorders unit in France. Participants completed the SATAQ-4, as well as validated measures of body image and eating pathology. Confirmatory factor analysis revealed that the original 22-item five-factor solution provided less than adequate fit to the data. In contrast, the reduced 20-item five-factor solution identified among French college students provided a good fit to the data. The SATAQ-4 subscales generally exhibited moderate positive associations with convergent measures of body image and eating disturbance, consistent with expectations. Differences in SATAQ-4 subscale means across diagnostic groups were observed. In addition, the clinical group reported higher scores on the Internalization: Thin/Low Body Fat and Internalization: Muscular/Athletic subscales compared to a non-clinical French sample. Findings support the SATAQ-4 as a valuable tool for assessing sociocultural influences on body image and eating concerns among French women with eating disorders.
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http://dx.doi.org/10.1016/j.eatbeh.2020.101466DOI Listing
January 2021

The quantitative ultrasound method for assessing low bone mass in women with anorexia nervosa.

Arch Osteoporos 2021 01 14;16(1):13. Epub 2021 Jan 14.

Département de Médecine Nucléaire, Hôpital Lapeyronie, Centre Hospitalier Régional Universitaire (CHRU) Montpellier, 34295, Montpellier, France.

This study investigated the potential role of quantitative ultrasound (QUS) to assess low bone mass in anorexia nervosa patients (AN). Bone parameters from QUS and DXA were positively correlated and significantly reduced in AN compared with controls, suggesting that QUS is a pertinent technique to assess low bone mass in these patients.

Purpose: The aim of this study was to investigate the potential role of an alternative technique, quantitative ultrasound (QUS), to assess low bone mass in patients with anorexia nervosa (AN).

Methods: Two hundred seven young women (134 patients with AN and 73 healthy controls) with ages ranging from 14.4 to 38.4 years participated in this observational cross-sectional study. Bone mass was concomitantly evaluated by DXA to determine areal bone mineral density (aBMD; g/cm) at hip, lumbar spine, and radius and by QUS to determine broadband ultrasound attenuation (BUA; dB/MHz) at the heel.

Results: BUA (66.5 ± 4.6 dB/MHz vs 61.0 ± 5.0 dB/MHz) and aBMD at the hip (0.916 ± 0.013 g/cm vs 0.806 ± 0.010 g/cm), lumbar spine (0.966 ± 0.012 g/cm vs 0.886 ± 0.010 g/cm), and radius (0.545 ± 0.005 g/cm vs 0.526 ± 0.04 g/cm) were significantly decreased (p < 0.01) in patients with AN compared with controls. When patient and control data were pooled, BUA was significantly correlated with aBMD at the hip (r = 0.60, p < 0.001), lumbar spine (r = 0.48, p < 0.001), and radius (r = 0.40, p<0.001). In patients with AN, BUA and aBMD were mainly and positively correlated with weight, lean tissue mass, body mass index (BMI), and minimal BMI life and negatively with the duration of both disease and amenorrhea. Better concordance between the two techniques was obtained when absolute BUA and aBMD values were used according to the WHO T score classification.

Conclusion: BUA measurement at the heel by QUS appears to be a pertinent nonionizing technique to assess low bone mass in patients with AN.
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January 2021

The quantitative ultrasound method for assessing low bone mass in women with anorexia nervosa.

Arch Osteoporos 2021 01 14;16(1):13. Epub 2021 Jan 14.

Département de Médecine Nucléaire, Hôpital Lapeyronie, Centre Hospitalier Régional Universitaire (CHRU) Montpellier, 34295, Montpellier, France.

This study investigated the potential role of quantitative ultrasound (QUS) to assess low bone mass in anorexia nervosa patients (AN). Bone parameters from QUS and DXA were positively correlated and significantly reduced in AN compared with controls, suggesting that QUS is a pertinent technique to assess low bone mass in these patients.

Purpose: The aim of this study was to investigate the potential role of an alternative technique, quantitative ultrasound (QUS), to assess low bone mass in patients with anorexia nervosa (AN).

Methods: Two hundred seven young women (134 patients with AN and 73 healthy controls) with ages ranging from 14.4 to 38.4 years participated in this observational cross-sectional study. Bone mass was concomitantly evaluated by DXA to determine areal bone mineral density (aBMD; g/cm) at hip, lumbar spine, and radius and by QUS to determine broadband ultrasound attenuation (BUA; dB/MHz) at the heel.

Results: BUA (66.5 ± 4.6 dB/MHz vs 61.0 ± 5.0 dB/MHz) and aBMD at the hip (0.916 ± 0.013 g/cm vs 0.806 ± 0.010 g/cm), lumbar spine (0.966 ± 0.012 g/cm vs 0.886 ± 0.010 g/cm), and radius (0.545 ± 0.005 g/cm vs 0.526 ± 0.04 g/cm) were significantly decreased (p < 0.01) in patients with AN compared with controls. When patient and control data were pooled, BUA was significantly correlated with aBMD at the hip (r = 0.60, p < 0.001), lumbar spine (r = 0.48, p < 0.001), and radius (r = 0.40, p<0.001). In patients with AN, BUA and aBMD were mainly and positively correlated with weight, lean tissue mass, body mass index (BMI), and minimal BMI life and negatively with the duration of both disease and amenorrhea. Better concordance between the two techniques was obtained when absolute BUA and aBMD values were used according to the WHO T score classification.

Conclusion: BUA measurement at the heel by QUS appears to be a pertinent nonionizing technique to assess low bone mass in patients with AN.
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http://dx.doi.org/10.1007/s11657-020-00870-wDOI Listing
January 2021

Clinical characteristics of bipolar disorders with postpartum depressive onset.

Prog Neuropsychopharmacol Biol Psychiatry 2021 Apr 19;107:110225. Epub 2020 Dec 19.

AP-HP, Groupe Hospitalo-Universitaire AP-HP Nord, DMU ESPRIT, service de Psychiatrie et Addictologie, Hopital Louis Mourier, Colombes, Inserm U1266, Faculté de médecine, Université de Paris, France; Fondation Fondamental, Creteil 94000, France.

Background: Postpartum period is associated with an increased risk of bipolar disorder diagnosis and relapse, mainly major depressive episode. Onset during this period might be associated with specific characteristics.

Aim: To compare the socio-demographic and clinical characteristics of parous women presenting with bipolar disorder and an index depressive episode occurring during or outside the postpartum period.

Methods: Using the multicenter cohort FACE-BD (FondaMental Academic Centers of Expertise for Bipolar Disorders), we considered all women who started their BD with a major depressive episode and have at least one child. We compared two groups depending on the onset: in or outside the postpartum period.

Results: Among the 759 women who started BD with a major depressive episode, 93 (12.2%) had a postpartum onset, and 666 (87.8%) had not. Women who started BD in the postpartum period with a major depressive episode have a more stable family life, more children, an older age at onset, more Bipolar 2 disorder, less history of suicide attempts, less depressive episodes and more mood stabilizer treatments as compared to those who started with a major depressive episode outside the postpartum period. The multivariable logistic regression showed that women with an onset in the postpartum period had significantly more children, less lifetime depressive episodes and a lower rate of history of suicide attempts as compared to women with an onset outside the postpartum period.

Discussion: Our results suggest that women starting their BD with postpartum depression have a more favorable course of BD, especially less history of suicide attempt and less lifetime depressive episodes.
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http://dx.doi.org/10.1016/j.pnpbp.2020.110225DOI Listing
April 2021

Commentary: Psychedelic Psychiatry's Brave New World.

Front Psychiatry 2020 26;11:594077. Epub 2020 Nov 26.

Department of Emergency Psychiatry and Acute Care, Lapeyronie Hospital, CHU Montpellier, Montpellier, France.

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http://dx.doi.org/10.3389/fpsyt.2020.594077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725759PMC
November 2020

Treatment-Resistant Depression in a Real-World Setting: First Interim Analysis of Characteristics, Healthcare Resource Use, and Utility Values of the FondaMental Cohort.

Brain Sci 2020 Dec 10;10(12). Epub 2020 Dec 10.

Fondation FondaMental, 94000 Créteil, France.

Background: Major depressive disorder (MDD) is among the most common psychiatric disorders. One-third of patients are usually unresponsive to several lines of treatment. This study aimed to describe the FondaMental French cohort of patients with treatment-resistant depression (TRD) and to estimate utility and healthcare resource use outcomes.

Methods: Patients with TRD were evaluated prospectively over four years (baseline, 6, 12, 18, 24, 36 and 48 months) in a real-world clinical setting. Interim analyses focused on the first two consecutive years. Four MDD-related states (major depressive episode (MDE), response, remission, recovery) were defined based on the MADRS (Montgomery-Åsberg depression rating scale) and other clinical events. Health status was assessed with the EuroQol 5 Dimensions 5 Level (EQ-5D-5L) questionnaire. Utility values were estimated as preference measures that the patients assigned to their overall health status.

Results: This study was based on 252 patients with TRD. The mean utility value by health state was 0.41, 0.63, 0.80, and 0.90, for MDE, response, remission, and recovery, respectively. At baseline, 59% of patients had an MADRS score of at least 28. Their baseline average utility value was lower compared to the other patients (0.43 versus 0.58, < 0.001). This significant difference persisted at the following visits. The rate of patients in MDEs having at least one hospitalisation for depression or other reasons than depression was generally higher than that in the other health states.

Conclusion: This study documented patterns in healthcare resource consumption, quality of life, and other characteristics in patients with TRD, both globally and by health state and depression severity.
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http://dx.doi.org/10.3390/brainsci10120962DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764571PMC
December 2020

Treatment-Resistant Depression in a Real-World Setting: First Interim Analysis of Characteristics, Healthcare Resource Use, and Utility Values of the FondaMental Cohort.

Brain Sci 2020 Dec 10;10(12). Epub 2020 Dec 10.

Fondation FondaMental, 94000 Créteil, France.

Background: Major depressive disorder (MDD) is among the most common psychiatric disorders. One-third of patients are usually unresponsive to several lines of treatment. This study aimed to describe the FondaMental French cohort of patients with treatment-resistant depression (TRD) and to estimate utility and healthcare resource use outcomes.

Methods: Patients with TRD were evaluated prospectively over four years (baseline, 6, 12, 18, 24, 36 and 48 months) in a real-world clinical setting. Interim analyses focused on the first two consecutive years. Four MDD-related states (major depressive episode (MDE), response, remission, recovery) were defined based on the MADRS (Montgomery-Åsberg depression rating scale) and other clinical events. Health status was assessed with the EuroQol 5 Dimensions 5 Level (EQ-5D-5L) questionnaire. Utility values were estimated as preference measures that the patients assigned to their overall health status.

Results: This study was based on 252 patients with TRD. The mean utility value by health state was 0.41, 0.63, 0.80, and 0.90, for MDE, response, remission, and recovery, respectively. At baseline, 59% of patients had an MADRS score of at least 28. Their baseline average utility value was lower compared to the other patients (0.43 versus 0.58, < 0.001). This significant difference persisted at the following visits. The rate of patients in MDEs having at least one hospitalisation for depression or other reasons than depression was generally higher than that in the other health states.

Conclusion: This study documented patterns in healthcare resource consumption, quality of life, and other characteristics in patients with TRD, both globally and by health state and depression severity.
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http://dx.doi.org/10.3390/brainsci10120962DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764571PMC
December 2020

Psychological pain and depression: it's hard to speak when it hurts.

Int J Psychiatry Clin Pract 2020 Dec 4:1-7. Epub 2020 Dec 4.

Psychiatric Emergency and Post Emergency Department, Hospital Lapeyronie, CHU Montpellier, Montpellier, France.

Objective: To investigate the neuropsychological features of depressed patients reporting high level of psychological pain.

Methods: Sixty-two inpatients were included and divided into two groups according to the level of psychological pain assessed by a Likert scale. Cognitive abilities were assessed using the Trail Making Test, the Stroop test, and Verbal Fluency Test (semantic and phonemic verbal fluency). Univariate and multivariate analyses were performed to determine neuropsychological factors associated with a high level of psychological pain.

Results: The median level of psychological pain was 8/10. High level of psychological pain was associated with poor phonemic verbal fluency performance in men ( = 0.009), but not in women, even after controlling for confounding factors (age, level of depression, anxiety). Groups did not differ on the Trail Making Test, the Stroop test, or the semantic verbal fluency measure.

Conclusion: Psychological pain is a specific clinical entity that should be considered to be more significant than just a symptom of depression. High level of psychological pain appears to be associated with a deficit of phonemic verbal fluency in depressed men. This finding could help to target psychotherapeutic treatments and improve screening. Key points Patients with high psychological pain do not differ on the Trail Making Test, the Stroop Test or the Sematic Verbal Fluency Measure to patients with low psychological pain High psychological pain is associated with a deficit in phonemic verbal fluency in depressed men Future research should aim to clarify gender differences in psychological pain in participants with and without major depressive disorder, as well as explore the complex relationship between cognition and the different forms of pain (psychological, physical and psychosomatic).
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http://dx.doi.org/10.1080/13651501.2020.1836225DOI Listing
December 2020

Psychological pain and depression: it's hard to speak when it hurts.

Int J Psychiatry Clin Pract 2020 Dec 4:1-7. Epub 2020 Dec 4.

Psychiatric Emergency and Post Emergency Department, Hospital Lapeyronie, CHU Montpellier, Montpellier, France.

Objective: To investigate the neuropsychological features of depressed patients reporting high level of psychological pain.

Methods: Sixty-two inpatients were included and divided into two groups according to the level of psychological pain assessed by a Likert scale. Cognitive abilities were assessed using the Trail Making Test, the Stroop test, and Verbal Fluency Test (semantic and phonemic verbal fluency). Univariate and multivariate analyses were performed to determine neuropsychological factors associated with a high level of psychological pain.

Results: The median level of psychological pain was 8/10. High level of psychological pain was associated with poor phonemic verbal fluency performance in men ( = 0.009), but not in women, even after controlling for confounding factors (age, level of depression, anxiety). Groups did not differ on the Trail Making Test, the Stroop test, or the semantic verbal fluency measure.

Conclusion: Psychological pain is a specific clinical entity that should be considered to be more significant than just a symptom of depression. High level of psychological pain appears to be associated with a deficit of phonemic verbal fluency in depressed men. This finding could help to target psychotherapeutic treatments and improve screening. Key points Patients with high psychological pain do not differ on the Trail Making Test, the Stroop Test or the Sematic Verbal Fluency Measure to patients with low psychological pain High psychological pain is associated with a deficit in phonemic verbal fluency in depressed men Future research should aim to clarify gender differences in psychological pain in participants with and without major depressive disorder, as well as explore the complex relationship between cognition and the different forms of pain (psychological, physical and psychosomatic).
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http://dx.doi.org/10.1080/13651501.2020.1836225DOI Listing
December 2020

Corticotropin releasing hormone receptor CRHR1 gene is associated with tianeptine antidepressant response in a large sample of outpatients from real-life settings.

Transl Psychiatry 2020 11 5;10(1):378. Epub 2020 Nov 5.

Université de Paris, Institute of Psychiatry and Neuroscience of Paris (IPNP), INSERM U1266, Team Vulnerability of Psychiatric and Addictive Disorders, 75014, Paris, France.

Polymorphisms of genes involved in the hypothalamic-pituitary-adrenocortical (HPA) axis have been associated with response to several antidepressant treatments in patients suffering of depression. These pharmacogenetics findings have been reported from independent cohorts of patients mostly treated with selective serotonin reuptake inhibitors, tricyclic antidepressant, and mirtazapine. Tianeptine, an atypical antidepressant, recently identified as a mu opioid receptor agonist, which prevents and reverses the stress induced by glucocorticoids, has been investigated in this present pharmacogenetics study. More than 3200 Caucasian outpatients with a major depressive episode (MDE) from real-life settings were herein analyzed for clinical response to tianeptine, a treatment initiated from 79.5% of the subjects, during 6-8 weeks follow-up, assessing polymorphisms targeting four genes involved in the HPA axis (NR3C1, FKPB5, CRHR1, and AVPR1B). We found a significant association (p < 0.001) between CRHR1 gene variants rs878886 and rs16940665, or haplotype rs878886*C-rs16940665*T, and tianeptine antidepressant response and remission according to the hospital anxiety and depression scale. Analyses, including a structural equation model with simple mediation, suggest a moderate effect of sociodemographic characteristics and depressive disorder features on treatment response in individuals carrying the antidepressant responder allele rs8788861 (allele C). These findings suggest direct pharmacological consequences of CRHR1 polymorphisms in the antidepressant tianeptine response and remission, in MDE patients. This study replicates the association of the CRHR1 gene, involved in the HPA axis, with (1) a specificity attributed to treatment response, (2) a lower risk of chance finding, and in (3) an ecological situation.
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http://dx.doi.org/10.1038/s41398-020-01067-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644692PMC
November 2020

Corticotropin releasing hormone receptor CRHR1 gene is associated with tianeptine antidepressant response in a large sample of outpatients from real-life settings.

Transl Psychiatry 2020 11 5;10(1):378. Epub 2020 Nov 5.

Université de Paris, Institute of Psychiatry and Neuroscience of Paris (IPNP), INSERM U1266, Team Vulnerability of Psychiatric and Addictive Disorders, 75014, Paris, France.

Polymorphisms of genes involved in the hypothalamic-pituitary-adrenocortical (HPA) axis have been associated with response to several antidepressant treatments in patients suffering of depression. These pharmacogenetics findings have been reported from independent cohorts of patients mostly treated with selective serotonin reuptake inhibitors, tricyclic antidepressant, and mirtazapine. Tianeptine, an atypical antidepressant, recently identified as a mu opioid receptor agonist, which prevents and reverses the stress induced by glucocorticoids, has been investigated in this present pharmacogenetics study. More than 3200 Caucasian outpatients with a major depressive episode (MDE) from real-life settings were herein analyzed for clinical response to tianeptine, a treatment initiated from 79.5% of the subjects, during 6-8 weeks follow-up, assessing polymorphisms targeting four genes involved in the HPA axis (NR3C1, FKPB5, CRHR1, and AVPR1B). We found a significant association (p < 0.001) between CRHR1 gene variants rs878886 and rs16940665, or haplotype rs878886*C-rs16940665*T, and tianeptine antidepressant response and remission according to the hospital anxiety and depression scale. Analyses, including a structural equation model with simple mediation, suggest a moderate effect of sociodemographic characteristics and depressive disorder features on treatment response in individuals carrying the antidepressant responder allele rs8788861 (allele C). These findings suggest direct pharmacological consequences of CRHR1 polymorphisms in the antidepressant tianeptine response and remission, in MDE patients. This study replicates the association of the CRHR1 gene, involved in the HPA axis, with (1) a specificity attributed to treatment response, (2) a lower risk of chance finding, and in (3) an ecological situation.
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http://dx.doi.org/10.1038/s41398-020-01067-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644692PMC
November 2020

Corticotropin releasing hormone receptor CRHR1 gene is associated with tianeptine antidepressant response in a large sample of outpatients from real-life settings.

Transl Psychiatry 2020 11 5;10(1):378. Epub 2020 Nov 5.

Université de Paris, Institute of Psychiatry and Neuroscience of Paris (IPNP), INSERM U1266, Team Vulnerability of Psychiatric and Addictive Disorders, 75014, Paris, France.

Polymorphisms of genes involved in the hypothalamic-pituitary-adrenocortical (HPA) axis have been associated with response to several antidepressant treatments in patients suffering of depression. These pharmacogenetics findings have been reported from independent cohorts of patients mostly treated with selective serotonin reuptake inhibitors, tricyclic antidepressant, and mirtazapine. Tianeptine, an atypical antidepressant, recently identified as a mu opioid receptor agonist, which prevents and reverses the stress induced by glucocorticoids, has been investigated in this present pharmacogenetics study. More than 3200 Caucasian outpatients with a major depressive episode (MDE) from real-life settings were herein analyzed for clinical response to tianeptine, a treatment initiated from 79.5% of the subjects, during 6-8 weeks follow-up, assessing polymorphisms targeting four genes involved in the HPA axis (NR3C1, FKPB5, CRHR1, and AVPR1B). We found a significant association (p < 0.001) between CRHR1 gene variants rs878886 and rs16940665, or haplotype rs878886*C-rs16940665*T, and tianeptine antidepressant response and remission according to the hospital anxiety and depression scale. Analyses, including a structural equation model with simple mediation, suggest a moderate effect of sociodemographic characteristics and depressive disorder features on treatment response in individuals carrying the antidepressant responder allele rs8788861 (allele C). These findings suggest direct pharmacological consequences of CRHR1 polymorphisms in the antidepressant tianeptine response and remission, in MDE patients. This study replicates the association of the CRHR1 gene, involved in the HPA axis, with (1) a specificity attributed to treatment response, (2) a lower risk of chance finding, and in (3) an ecological situation.
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http://dx.doi.org/10.1038/s41398-020-01067-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644692PMC
November 2020

Corticotropin releasing hormone receptor CRHR1 gene is associated with tianeptine antidepressant response in a large sample of outpatients from real-life settings.

Transl Psychiatry 2020 11 5;10(1):378. Epub 2020 Nov 5.

Université de Paris, Institute of Psychiatry and Neuroscience of Paris (IPNP), INSERM U1266, Team Vulnerability of Psychiatric and Addictive Disorders, 75014, Paris, France.

Polymorphisms of genes involved in the hypothalamic-pituitary-adrenocortical (HPA) axis have been associated with response to several antidepressant treatments in patients suffering of depression. These pharmacogenetics findings have been reported from independent cohorts of patients mostly treated with selective serotonin reuptake inhibitors, tricyclic antidepressant, and mirtazapine. Tianeptine, an atypical antidepressant, recently identified as a mu opioid receptor agonist, which prevents and reverses the stress induced by glucocorticoids, has been investigated in this present pharmacogenetics study. More than 3200 Caucasian outpatients with a major depressive episode (MDE) from real-life settings were herein analyzed for clinical response to tianeptine, a treatment initiated from 79.5% of the subjects, during 6-8 weeks follow-up, assessing polymorphisms targeting four genes involved in the HPA axis (NR3C1, FKPB5, CRHR1, and AVPR1B). We found a significant association (p < 0.001) between CRHR1 gene variants rs878886 and rs16940665, or haplotype rs878886*C-rs16940665*T, and tianeptine antidepressant response and remission according to the hospital anxiety and depression scale. Analyses, including a structural equation model with simple mediation, suggest a moderate effect of sociodemographic characteristics and depressive disorder features on treatment response in individuals carrying the antidepressant responder allele rs8788861 (allele C). These findings suggest direct pharmacological consequences of CRHR1 polymorphisms in the antidepressant tianeptine response and remission, in MDE patients. This study replicates the association of the CRHR1 gene, involved in the HPA axis, with (1) a specificity attributed to treatment response, (2) a lower risk of chance finding, and in (3) an ecological situation.
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http://dx.doi.org/10.1038/s41398-020-01067-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644692PMC
November 2020