Publications by authors named "Jean-Pierre Kahn"

97 Publications

HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders.

Sci Rep 2021 Sep 8;11(1):17823. Epub 2021 Sep 8.

Department of Psychiatry & Center of Sleep Disorders, National Taiwan University Hospital, Taipei, Taiwan.

Bipolar affective disorder (BD) is a severe psychiatric illness, for which lithium (Li) is the gold standard for acute and maintenance therapies. The therapeutic response to Li in BD is heterogeneous and reliable biomarkers allowing patients stratification are still needed. A GWAS performed by the International Consortium on Lithium Genetics (ConLiGen) has recently identified genetic markers associated with treatment responses to Li in the human leukocyte antigens (HLA) region. To better understand the molecular mechanisms underlying this association, we have genetically imputed the classical alleles of the HLA region in the European patients of the ConLiGen cohort. We found our best signal for amino-acid variants belonging to the HLA-DRB1*11:01 classical allele, associated with a better response to Li (p < 1 × 10; FDR < 0.09 in the recessive model). Alanine or Leucine at position 74 of the HLA-DRB1 heavy chain was associated with a good response while Arginine or Glutamic acid with a poor response. As these variants have been implicated in common inflammatory/autoimmune processes, our findings strongly suggest that HLA-mediated low inflammatory background may contribute to the efficient response to Li in BD patients, while an inflammatory status overriding Li anti-inflammatory properties would favor a weak response.
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http://dx.doi.org/10.1038/s41598-021-97140-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426488PMC
September 2021

Excessive and pathological Internet use - Risk-behavior or psychopathology?

Addict Behav 2021 12 9;123:107045. Epub 2021 Jul 9.

National Centre for Suicide Research and Prevention of Mental Ill-Health (NASP), Karolinska Institutet, Stockholm, Sweden.

Pathological Internet use (but only with respect to gaming) is classified as mental disorder in the ICD-11. However, there is a large group of adolescents showing excessive Internet use, which may rather be considered adolescent risk-behavior. The aim was to test whether pathological and excessive Internet use should be considered as "psychopathology" or "risk-behavior". A representative, cross-sectional sample of 11.110 students from 10 European Union countries was analyzed. Structural equation models, including the factors "risk-behavior" and "psychopathology" and the variables excessive and pathological Internet use, were tested against each other. "Risk-behavior" was operationalized by several risk-behaviors (e.g. drug abuse, truancy, etc). "Psychopathology" included measures of several mental disorders (e.g. depression, hyperactivity, etc). Excessive Internet use was assessed as the duration and frequency of Internet use. Pathological Internet use was assessed with the Young Diagnostic Questionnaire (i.e., presence of addiction criteria). Excessive Internet use loaded on "risk-behavior" (λ = 0.484, p < .001) and on "psychopathology" (λ = 0.071, p < .007). Pathological Internet use loaded on "risk-behavior" (λ = 0.333, p < .001) and on "psychopathology" (λ = 0.852, p < .001). Chi-square tests determined that the loadings of excessive Internet use (χ (1) = 81.98, p < .001) were significantly stronger on "risk-behavior" than "psychopathology". Vice versa, pathological Internet use loaded significantly stronger on "psychopathology" (χ (1) = 107.10, p < .001). The results indicate that pathological Internet use should rather be considered as psychopathology. Excessive Internet use on the other hand, should be classified as adolescent risk-behavior.
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http://dx.doi.org/10.1016/j.addbeh.2021.107045DOI Listing
December 2021

Trajectories of functioning in bipolar disorders: A longitudinal study in the FondaMental Advanced Centers of Expertise in Bipolar Disorders cohort.

Aust N Z J Psychiatry 2020 10 11;54(10):985-996. Epub 2020 Aug 11.

Fondation FondaMental, Créteil, France.

Objective: We aimed at identifying distinct trajectories of functioning and at describing their respective clinical characteristics in a cohort of individuals with bipolar disorders.

Methods: We included a sample of 2351 individuals with bipolar disorders who have been followed-up to 3 years as part as the FondaMental Advanced Centers of Expertise in Bipolar Disorders cohort. Global functioning was measured using the Functioning Assessment Short Test. We used latent class mixed models to identify distinct longitudinal trajectories of functioning over 3 years. Multivariable logistic regression models were used to identify the baseline factors that were associated with the membership to each trajectory of functioning.

Results: Three distinct trajectories of functioning were identified: (1) a majority of individuals (72%) had a stable trajectory of mild functional impairment, (2) 20% of individuals had a stable trajectory of severe functional impairment and (3) 8% of individuals had a trajectory of moderate functional impairment that improved over time. The membership to a trajectory of stable severe versus stable mild functional impairment was associated with unemployment, a higher number of previous hospitalizations, childhood maltreatment, a higher level of residual depressive symptoms, higher sleep disturbances, a higher body mass index and a higher number of psychotropic medications being prescribed at baseline. The model that included these seven factors led to an area under the curve of 0.85.

Conclusion: This study enabled to stratify individuals with bipolar disorders according to three distinct trajectories of functioning. The results regarding the potential determinants of the trajectory of severe functional impairment needs to be replicated in independent samples. Nevertheless, these potential determinants may represent possible therapeutic targets to improve the prognosis of those patients at risk of persistent poor functioning.
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http://dx.doi.org/10.1177/0004867420945796DOI Listing
October 2020

Trajectories of functioning in bipolar disorders: A longitudinal study in the FondaMental Advanced Centers of Expertise in Bipolar Disorders cohort.

Aust N Z J Psychiatry 2020 10 11;54(10):985-996. Epub 2020 Aug 11.

Fondation FondaMental, Créteil, France.

Objective: We aimed at identifying distinct trajectories of functioning and at describing their respective clinical characteristics in a cohort of individuals with bipolar disorders.

Methods: We included a sample of 2351 individuals with bipolar disorders who have been followed-up to 3 years as part as the FondaMental Advanced Centers of Expertise in Bipolar Disorders cohort. Global functioning was measured using the Functioning Assessment Short Test. We used latent class mixed models to identify distinct longitudinal trajectories of functioning over 3 years. Multivariable logistic regression models were used to identify the baseline factors that were associated with the membership to each trajectory of functioning.

Results: Three distinct trajectories of functioning were identified: (1) a majority of individuals (72%) had a stable trajectory of mild functional impairment, (2) 20% of individuals had a stable trajectory of severe functional impairment and (3) 8% of individuals had a trajectory of moderate functional impairment that improved over time. The membership to a trajectory of stable severe versus stable mild functional impairment was associated with unemployment, a higher number of previous hospitalizations, childhood maltreatment, a higher level of residual depressive symptoms, higher sleep disturbances, a higher body mass index and a higher number of psychotropic medications being prescribed at baseline. The model that included these seven factors led to an area under the curve of 0.85.

Conclusion: This study enabled to stratify individuals with bipolar disorders according to three distinct trajectories of functioning. The results regarding the potential determinants of the trajectory of severe functional impairment needs to be replicated in independent samples. Nevertheless, these potential determinants may represent possible therapeutic targets to improve the prognosis of those patients at risk of persistent poor functioning.
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http://dx.doi.org/10.1177/0004867420945796DOI Listing
October 2020

Allostatic load, emotional hyper-reactivity, and functioning in individuals with bipolar disorder.

Bipolar Disord 2020 11 16;22(7):711-721. Epub 2020 May 16.

Institut Pasteur, Unité Perception et Mémoire, Paris, France.

Objectives: Diagnosis and management of bipolar disorder (BD) are limited by the absence of available biomarkers. Allostatic load (AL) represents the strain that stress, including the effects of acute phases and inter-episode chronic mood instability, exerts on interconnected biological systems. This study aimed to operationalize an AL index and explore whether it could be relevant to better characterize BD patients with and without emotional hyper-reactivity particularly those at higher risk of immune-cardiometabolic dysregulation and functional impairment.

Methods: Levels of biomarkers of chronic inflammation (hsCRP and albumin), cardiovascular (systolic/diastolic blood pressure) and metabolic functions (fasting glucose, glycosylated hemoglobin, total cholesterol, LDL, HDL, and triglycerides) were measured in 1072 adult BD outpatients. Patients were classified in two groups (with/without emotional hyper-reactivity) assessed by the Multidimensional Assessment of Thymic States scale. An Allostatic Load Index for BD (BALLI), comprising six biomarkers, was constructed using data-driven biomarker selection.

Results: BALLI showed 81.1% accuracy with good sensitivity (81%) and specificity (81.2%) for characterizing BD patients presenting emotional hyper-reactivity, elevated risk of inflammation (increased hsCRP, hypoalbuminemia) and cardiometabolic disturbances (hypertension, hyperglycemia, and hypertriglyceridemia). Patients classified by the BALLI as presenting emotional hyper-reactivity had significantly lower global and cognitive functioning than those without emotional hyper-reactivity (P < .0001).

Conclusions: A multidimensional approach based on a simple AL score (eg, BALLI) and dimensions of behavior (eg, emotional hyper-reactivity) alongside mood is clinically relevant. AL index could be a useful tool to detect multisystemic physiological dysregulations in BD patients with/without emotional hyper-reactivity particularly those at higher risk of immune-cardiometabolic disturbances and functional impairment.
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http://dx.doi.org/10.1111/bdi.12927DOI Listing
November 2020

Contribution of common and rare damaging variants in familial forms of bipolar disorder and phenotypic outcome.

Transl Psychiatry 2020 04 28;10(1):124. Epub 2020 Apr 28.

INSERM U955, Psychiatrie Translationnelle, Créteil, 94000, France.

Genome-wide association studies on bipolar disorders (BD) have revealed an additive polygenic contribution of common single-nucleotide polymorphisms (SNPs). However, these SNPs explain only 25% of the overall genetic variance and suggest a role of rare variants in BD vulnerability. Here, we combined high-throughput genotyping data and whole-exome sequencing in cohorts of individuals with BD as well as in multiplex families with a high density of affected individuals in order to determine the contribution of both common and rare variants to BD genetic vulnerability. Using polygenic risk scores (PRS), we showed a strong contribution of common polymorphisms previously associated with BD and schizophrenia (SZ) and noticed that those specifically associated with SZ contributed more in familial forms of BD than in non-familial ones. The analysis of rare damaging variants shared by affected individuals in multiplex families with BD revealed a single interaction network enriched in neuronal and developmental biological pathways, as well as in the regulation of gene expression. We identified four genes with a higher mutation rate in individuals with BD than in the general population and showed that mutations in two of them were associated with specific clinical manifestations. In addition, we showed a significant negative correlation between PRS and the number of rare damaging variants specifically in unaffected individuals of multiplex families. Altogether, our results suggest that common and rare genetic variants both contribute to the familial aggregation of BD and this genetic architecture may explain the heterogeneity of clinical manifestations in multiplex families.
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http://dx.doi.org/10.1038/s41398-020-0783-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7188882PMC
April 2020

Association of polygenic score for major depression with response to lithium in patients with bipolar disorder.

Mol Psychiatry 2021 06 16;26(6):2457-2470. Epub 2020 Mar 16.

Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada.

Lithium is a first-line medication for bipolar disorder (BD), but only one in three patients respond optimally to the drug. Since evidence shows a strong clinical and genetic overlap between depression and bipolar disorder, we investigated whether a polygenic susceptibility to major depression is associated with response to lithium treatment in patients with BD. Weighted polygenic scores (PGSs) were computed for major depression (MD) at different GWAS p value thresholds using genetic data obtained from 2586 bipolar patients who received lithium treatment and took part in the Consortium on Lithium Genetics (ConLiGen) study. Summary statistics from genome-wide association studies in MD (135,458 cases and 344,901 controls) from the Psychiatric Genomics Consortium (PGC) were used for PGS weighting. Response to lithium treatment was defined by continuous scores and categorical outcome (responders versus non-responders) using measurements on the Alda scale. Associations between PGSs of MD and lithium treatment response were assessed using a linear and binary logistic regression modeling for the continuous and categorical outcomes, respectively. The analysis was performed for the entire cohort, and for European and Asian sub-samples. The PGSs for MD were significantly associated with lithium treatment response in multi-ethnic, European or Asian populations, at various p value thresholds. Bipolar patients with a low polygenic load for MD were more likely to respond well to lithium, compared to those patients with high polygenic load [lowest vs highest PGS quartiles, multi-ethnic sample: OR = 1.54 (95% CI: 1.18-2.01) and European sample: OR = 1.75 (95% CI: 1.30-2.36)]. While our analysis in the Asian sample found equivalent effect size in the same direction: OR = 1.71 (95% CI: 0.61-4.90), this was not statistically significant. Using PGS decile comparison, we found a similar trend of association between a high genetic loading for MD and lower response to lithium. Our findings underscore the genetic contribution to lithium response in BD and support the emerging concept of a lithium-responsive biotype in BD.
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http://dx.doi.org/10.1038/s41380-020-0689-5DOI Listing
June 2021

Association between coffee, tobacco, and alcohol daily consumption and sleep/wake cycle: an actigraphy study in euthymic patients with bipolar disorders.

Chronobiol Int 2020 05 12;37(5):712-722. Epub 2020 Feb 12.

INSERM U1144, Optimisation Thérapeutique en Neuropsychopharmacologie , Paris, France.

Individuals with bipolar disorder (BD) have higher than average rates of coffee, tobacco and alcohol use. These substances may have deleterious effects on sleep quality and quantity, which may destabilize sleep/wake cycles and negatively impact the clinical course and prognosis of BD. The use of these substances may also be perceived as a self-medication attempt, for example, to induce sleep or to increase vigilance during the day. The objective of the current study was to investigate associations between the self-reported daily use of coffee, tobacco, and alcohol, and objective measures of sleep and activity patterns in adult individuals with BD. A sample of 147 euthymic individuals with BD were assessed for daily coffee, tobacco and alcohol consumption and 21 days of actigraphy monitoring. Actigraphic measures of sleep quantity and daytime activity were compared between groups classified as coffee+/coffee-, tobacco+/tobacco- and alcohol+/alcohol-, defined according to their current daily use. Then, we examined potential correlations between sleep/wake cycle parameters and the amount of daily consumption of each substance. Multivariable analyses identified associations between the use of coffee, tobacco, and alcohol and several sleep and activity parameters, such as between coffee, alcohol, and the relative amplitude of activity (respectively, = .003 and = .005), between alcohol and M10 onset (onset time of the 10 most active hours during the 24-h cycle) ( = .003), and between coffee and sleep duration ( = .047). This study supports the hypothesis that there is a relationship, whose direction would be bidirectional, between the daily use of these substances and the sleep/wake cycle in euthymic individuals with BD. These preliminary results require replications in other retrospective and prospective samples. They may have a clinical impact on psycho-education strategies to be proposed to individuals with BD.
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http://dx.doi.org/10.1080/07420528.2020.1725542DOI Listing
May 2020

Association between coffee, tobacco, and alcohol daily consumption and sleep/wake cycle: an actigraphy study in euthymic patients with bipolar disorders.

Chronobiol Int 2020 05 12;37(5):712-722. Epub 2020 Feb 12.

INSERM U1144, Optimisation Thérapeutique en Neuropsychopharmacologie , Paris, France.

Individuals with bipolar disorder (BD) have higher than average rates of coffee, tobacco and alcohol use. These substances may have deleterious effects on sleep quality and quantity, which may destabilize sleep/wake cycles and negatively impact the clinical course and prognosis of BD. The use of these substances may also be perceived as a self-medication attempt, for example, to induce sleep or to increase vigilance during the day. The objective of the current study was to investigate associations between the self-reported daily use of coffee, tobacco, and alcohol, and objective measures of sleep and activity patterns in adult individuals with BD. A sample of 147 euthymic individuals with BD were assessed for daily coffee, tobacco and alcohol consumption and 21 days of actigraphy monitoring. Actigraphic measures of sleep quantity and daytime activity were compared between groups classified as coffee+/coffee-, tobacco+/tobacco- and alcohol+/alcohol-, defined according to their current daily use. Then, we examined potential correlations between sleep/wake cycle parameters and the amount of daily consumption of each substance. Multivariable analyses identified associations between the use of coffee, tobacco, and alcohol and several sleep and activity parameters, such as between coffee, alcohol, and the relative amplitude of activity (respectively, = .003 and = .005), between alcohol and M10 onset (onset time of the 10 most active hours during the 24-h cycle) ( = .003), and between coffee and sleep duration ( = .047). This study supports the hypothesis that there is a relationship, whose direction would be bidirectional, between the daily use of these substances and the sleep/wake cycle in euthymic individuals with BD. These preliminary results require replications in other retrospective and prospective samples. They may have a clinical impact on psycho-education strategies to be proposed to individuals with BD.
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http://dx.doi.org/10.1080/07420528.2020.1725542DOI Listing
May 2020

[French trends in the misuse of Fentanyl: From 2010 to 2015].

Therapie 2020 Sep - Oct;75(5):491-502. Epub 2019 Nov 25.

French Addictovigilance Network (FAN), France.

Objectives: The aim of this study was to evaluate the French use, misuse and abuse/dependence of non-injectable forms of fentanyl (transdermal and transmucosal fentanyl formulations).

Methods: Problematic use of transdermal and transmucosal fentanyl formulations was evaluated using an approach combining multiple sources of information: (1) spontaneous notifications recorded during 6 years (2010-2015) for transdermal fentanyl form and 3 years for transmucosal fentanyl forms and (2) data from annual epidemiological systematic surveys conducted by the French Addictovigilance Network during 6 years (2010-2015).

Results: In all, 147 cases were notified for transdermal fentanyl formulation and 109 cases for transmucosal fentanyl formulations. According to the galenic formulation, analysis of these cases emphasizes different profiles: for transdermal fentanyl formulation, two consumption profiles: 1/mainly for analgesic effects (74 %): women (61 %), 47 years, with addictive and/or psychiatric history (46 %), treated for chronic non-cancer related pain (93 %), 2/seeking positive psychic effects other than analgesia (26 %): men (82 %), 32 years, with addictive and/or psychiatric history (87 %) and having obtained the fentanyl patch illegally (60 %) for non-medical use. For transmucosal fentanyl formulations, only one consumption profile was observed: women (52 %), 48 years, with addictive (24 %) and/or psychiatric history (28 %), off label indication (72 %) (indications for non-cancer pain and/or no or insufficient opioid background treatment). The misuse of transmucosal fentanyl formulations implies a high risk of adverse effects: those already known of opioid-based drugs, sometimes lethal (withdrawal syndrome, respiratory and central nervous system depression…) but also serious reactions at the application site (buccal or nasal). For the transdermal fentanyl formulation, 27 cases (18 %) of involuntary intoxication were observed, of which 25 were serious. Nineteen deaths involving both forms of fentanyl have been reported (2 for the transmucosal formulations and 17 for the transdermal formulation).

Conclusion: Our results report significant and worrying misuse of transmucosal fentanyl formulations with wide off-label use and also primary dependence on fentanyl, regardless of galenic formulation, in patients treated for chronic non cancer pain. Given the significant risks of fentanyl, it is necessary to continue the monitoring of misuse, in particular, thanks to the activities of the French Addictovigilance network allowing a multisource approach and who provides information concerning cases of abuse, misuse and dependence.
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http://dx.doi.org/10.1016/j.therap.2019.11.002DOI Listing
September 2021

Unipolar mania: Identification and characterisation of cases in France and the United Kingdom.

J Affect Disord 2020 02 9;263:228-235. Epub 2019 Nov 9.

Centre for Affective Disorders, Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom; South London and Maudsley NHS Foundation Trust, Bethlem Royal Hospital, Monks Orchard Road, Beckenham, Kent BR3 3BX, United Kingdom.

Background: Unipolar mania is a putative subtype of bipolar disorder (BD) in which individuals experience recurrent manic but not major depressive episodes. Few studies of unipolar mania have been conducted in developed countries and none in the UK. This study aimed to identify and characterise people with unipolar mania in the UK and France.

Methods: People with unipolar mania were ascertained using a South London UK electronic case register and a French BD case series. Each unipolar mania group was compared to a matched group of people with BD who have experienced depressive episodes.

Results: 17 people with unipolar mania were identified in South London and 13 in France. The frequency of unipolar mania as a percentage of the BD clinical population was 1.2% for the South London cohort and 3.3% for the French cohort. In both cohorts, people with unipolar mania experienced more manic episodes than people with BD, and in the French cohort were more likely to experience a psychotic illness onset and more psychiatric admissions. Treatment and self-harm characteristics of people with unipolar mania were similar to people with BD.

Limitations: The relatively small number of people with unipolar mania identified by this study limits its power to detect differences in clinical variables.

Conclusions: People with unipolar mania can be identified in France and the UK, and they may experience a higher frequency of manic episodes but have similar treatment and self-harm characteristics as people with BD.
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http://dx.doi.org/10.1016/j.jad.2019.11.024DOI Listing
February 2020

Life Events Predicting the First Onset of Adolescent Direct Self-Injurious Behavior-A Prospective Multicenter Study.

J Adolesc Health 2020 02 31;66(2):195-201. Epub 2019 Oct 31.

National Centre for Suicide Research and Prevention of Mental Ill-Health (NASP), Karolinska Institute, Stockholm, Sweden.

Purpose: Self-injurious behavior is a frequent phenomenon in adolescence. The present study prospectively examined life events as risk factors for the first onset of direct self-injurious behavior (D-SIB) in the Saving and Empowering Young Lives in Europe school-based multicenter sample.

Methods: Longitudinal assessments with an interval of 1 year were performed within a sample of 1,933 adolescents (51.47% females; mean age 14.84 ± .9 years) from 10 European countries and Israel.

Results: The number of life events during the past 6 months predicted the first onset of D-SIB in the following year. Gender neither predicted the onset of D-SIB nor moderated the association with life events. Moreover, analyses of individual events identified a range of mainly interpersonal events within both family and peer group as proximal risk factors for first episode D-SIB.

Conclusions: The results support the critical role of interpersonal life events in the development of D-SIB for both genders and refine the conceptualization of proximal risk factors in terms of accumulated stressors and interpersonal events.
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http://dx.doi.org/10.1016/j.jadohealth.2019.08.018DOI Listing
February 2020

Childhood maltreatment and polygenic risk in bipolar disorders.

Bipolar Disord 2020 03 13;22(2):174-181. Epub 2019 Nov 13.

Université Paris Diderot, Paris, France.

Background: Childhood maltreatment is a well-known risk factor for developing a more severe and complex form of bipolar disorders (BD). However, knowledge is scarce about the interactions between childhood maltreatment and underlying genetic vulnerability on the clinical expression of BD.

Method: We assigned a BD-polygenic risk score (BD-PRS), calculated from the Psychiatric Genomics Consortium, to each individual in a sample of 402 cases with BD. The lifetime clinical expression of BD was characterized using structured interviews and patients completed the Childhood Trauma Questionnaire (CTQ) to assess the severity of childhood maltreatment.

Results: Cases who reported more severe childhood maltreatment had a lower BD-PRS (rho = -0.12, P = .01), especially when considering emotional abuse (rho = -0.16, P = .001). An interaction between BD-PRS and childhood maltreatment was observed for the risk of rapid cycling (P = .01). No further interactions between BD-PRS and childhood maltreatment were observed for other clinical characteristics (age at onset, suicide attempts, number of mood episodes, mixed features, substance use disorders and psychotic symptoms).

Conclusion: Our study is the first to show that less genetic risk may be needed to develop a more unstable form of BD when exposed to childhood maltreatment. Our study supports childhood trauma as an independent risk factor for BD.
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http://dx.doi.org/10.1111/bdi.12851DOI Listing
March 2020

Childhood maltreatment and polygenic risk in bipolar disorders.

Bipolar Disord 2020 03 13;22(2):174-181. Epub 2019 Nov 13.

Université Paris Diderot, Paris, France.

Background: Childhood maltreatment is a well-known risk factor for developing a more severe and complex form of bipolar disorders (BD). However, knowledge is scarce about the interactions between childhood maltreatment and underlying genetic vulnerability on the clinical expression of BD.

Method: We assigned a BD-polygenic risk score (BD-PRS), calculated from the Psychiatric Genomics Consortium, to each individual in a sample of 402 cases with BD. The lifetime clinical expression of BD was characterized using structured interviews and patients completed the Childhood Trauma Questionnaire (CTQ) to assess the severity of childhood maltreatment.

Results: Cases who reported more severe childhood maltreatment had a lower BD-PRS (rho = -0.12, P = .01), especially when considering emotional abuse (rho = -0.16, P = .001). An interaction between BD-PRS and childhood maltreatment was observed for the risk of rapid cycling (P = .01). No further interactions between BD-PRS and childhood maltreatment were observed for other clinical characteristics (age at onset, suicide attempts, number of mood episodes, mixed features, substance use disorders and psychotic symptoms).

Conclusion: Our study is the first to show that less genetic risk may be needed to develop a more unstable form of BD when exposed to childhood maltreatment. Our study supports childhood trauma as an independent risk factor for BD.
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http://dx.doi.org/10.1111/bdi.12851DOI Listing
March 2020

Longitudinal relationships between cognition and functioning over 2 years in euthymic patients with bipolar disorder: a cross-lagged panel model approach with the FACE-BD cohort.

Br J Psychiatry 2021 02;218(2):80-87

Psychiatrist, Researcher, Department of Adult Psychiatry, Versailles Hospital; HandiRESP Laboratory, EA4047, Department of Health Sciences, University of Versailles Saint-Quentin-En-Yvelines; and Centers of Expertise, Fondamental Foundation, France.

Background: Longitudinal studies of the relationship between cognition and functioning in bipolar disorder are scarce, although cognition is thought to be a key determinant of functioning. The causal structure between cognition and psychosocial functioning in bipolar disorder is unknown.

Aims: We sought to examine the direction of causality between cognitive performance and functional outcome over 2 years in a large cohort of euthymic patients with bipolar disorder.

Method: The sample consisted of 272 adults diagnosed with bipolar disorder who were euthymic at baseline, 12 and 24 months. All participants were recruited via the FondaMental Advanced Centers of Expertise in Bipolar Disorders. We used a battery of tests, assessing six domains of cognition at baseline and 24 months. Residual depressive symptoms and psychosocial functioning were measured at baseline and 12 and 24 months. The possible causal structure between cognition and psychosocial functioning was investigated with cross-lagged panel models with residual depressive symptoms as a covariate.

Results: The analyses support a causal model in which cognition moderately predicts and is causally primary to functional outcome 1 year later, whereas psychosocial functioning does not predict later cognitive performance. Subthreshold depressive symptoms concurrently affected functioning at each time of measure.

Conclusions: Our results are compatible with an upward causal effect of cognition on functional outcome in euthymic patients with bipolar disorder. Neuropsychological assessment may help specify individual prognoses. Further studies are warranted to confirm this causal link and evaluate cognitive remediation, before or simultaneously with functional remediation, as an intervention to improve functional outcome.
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http://dx.doi.org/10.1192/bjp.2019.180DOI Listing
February 2021

Links between traumatic experiences in childhood or early adulthood and lifetime binge eating disorder.

Psychiatry Res 2019 06 6;276:134-141. Epub 2019 May 6.

Unité Multidisciplinaire de Chirurgie de l'Obésité, CHRU de Nancy, Rue du Morvan, 54511 Vandoeuvre les Nancy Cedex, France; Service de Psychiatrie et de Psychologie Clinique, CHRU de Nancy, France.

Objectives: To evaluate the association between childhood or early adulthood traumatic experiences and adulthood binge eating disorder (BED) in 326 male and 1158 female patients. A structured clinical interview for the DSM-IV (SCID-I/P)-adapted to lifetime exploration for the diagnosis of BED and for DSM-IV Childhood Disorders was conducted by the psychiatrist.

Results: Emotional neglect was the most frequent event experienced (77.8% of females vs. 63.5% of males, p < 0.0001), ahead of physical abuse (23.3%), witnessed domestic violence (17.7%) and sexual abuse (11.8% of females vs. 2.8% of males (p < 0.0001)). The prevalence rate for BED in the whole population was 34.9%. The independent predictors for BED were emotional neglect in male obese patients (OR = 3.49; IC95% (1.94-6.29); p < 0.0001) and physical abuse (OR = 1.56; IC95% (1.14-2.12); p = 0.0047), emotional neglect (OR = 1.83; IC95% (1.37-2.44); p < 0.0001), and sexual abuse (OR = 1.80; IC95% (1.22-2.65); p = 0.0029) in female patients. With a cut-off value of 17, the sensitivity of the Binge Eating Scale for BED during lifetime was 50.8% with 74.7% specificity.

Conclusions: This study shows that early psychological events are independent predictors of BED in obese female and male adults. The BES questionnaire is a poor predictor of BED during lifetime and a structured clinical interview should be recommended.
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http://dx.doi.org/10.1016/j.psychres.2019.05.008DOI Listing
June 2019

Reconsideration of the factorial structure of the Barratt Impulsiveness Scale (BIS-11): Assessment of impulsivity in a large population of euthymic bipolar patients.

J Affect Disord 2019 06 9;253:203-209. Epub 2019 Apr 9.

Fondation Fondamental, Créteil, France; AP-HP, Hôpitaux Universitaires Henri Mondor, DHU Pepsy, Pôle de Psychiatrie et d'Addictologie, Créteil 94000, France; Université Paris Est, Faculté de Médecine, Créteil 94000, France.

Background: Impulsivity is commonly assessed using the Barratt Impulsiveness Scale (BIS-11). Some studies challenged the reliability of its three dimensional structure and proposed a bi-dimensional structure.

Methods: The psychometric reliability of the BIS-11 scale was studied in a sample of 580 euthymic bipolar patients. An alternative structure of the scale was conceived, using confirmatory factorial analysis (CFA) in the first half (N = 290) and cross-validated in the second half of our sample. Associations between the newly defined shortened scale and predefined clinical variables were computed.

Results: The original three dimensional structure did not fit in our sample according to statistical criteria in CFA. A 12 items Impulsivity Scale (IS-12) was designed with strong indices of fitting in the first half of our sample and replicated in the second half of our sample. The IS-12 evidences two dimensions: "behavioral impulsivity" and "cognitive impulsivity". Associations between "behavioral impulsivity" and both presence of past suicide attempts and number of suicide attempts were observed. Substance misuse was strongly associated with both subscores of the new scale.

Limitations: The rating of the items assessing the two dimensions of the IS-12 is reversed. The population is restricted to euthymic bipolar patients.

Conclusions: The Impulsivity Scale assesses two distinct dimensions named behavioral and cognitive impulsivity. It was reliable and valid in our sample and associated with the existence of suicidal behavior and with substance misuse (alcohol and cannabis). Further studies are needed to demonstrate its predictive validity.
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http://dx.doi.org/10.1016/j.jad.2019.04.060DOI Listing
June 2019

Psychopathology is associated with reproductive health risk in European adolescents.

Reprod Health 2018 Nov 6;15(1):186. Epub 2018 Nov 6.

National Centre for Suicide Research and Prevention of Mental Ill-Health (NASP), Department of Learning, Informatics, Management and Ethics (LIME), Karolinska Institutet, 171 77, Stockholm, Sweden.

Background: Reproductive and mental health are key domains of adolescent wellbeing but possible interrelationships are poorly understood. This cross-sectional study evaluated the association between psychopathology and reproductive health risk among European adolescents.

Methods: A structured self-report questionnaire was delivered to 12,395 pupils of 179 randomly selected schools in 11 European countries within the EU funded "Saving and Empowering Young Lives in Europe" (SEYLE) project. The questionnaire included items about sexual initiation and reproductive health risk factors, such as number of sexual partners, frequency of condom use, and pregnancy involvement. Psychopathology was evaluated with validated instruments and/or ad-hoc questions.

Results: Of 11,406 respondents (median age 15; interquartile range [IQR] 14-15; 57% females), 18.8% reported sexual initiation. Sixty percent of them also reported at least one reproductive risk factor. Sexual initiation was significantly more common among pupils older than 15 years (38% versus 13.2% younger pupils) and males (21.3% versus 16.9% females). It was also more common among pupils with depression (age/sex-adjusted odds ratio [aOR] 1.871), anxiety (aOR 2.190), severe suicidal ideation (aOR 2.259), self-injurious behaviour (aOR 2.892), and suicide attempts (aOR 3.091). These associations were particularly strong among pupils ≤15 years old and, for overt psychopathology, among pupils with low non-sexual risk behaviour profile and females. Depression (aOR 1.937), anxiety (aOR 2.282), severe suicidal ideation (aOR 2.354), self-injurious behaviour (aOR 3.022), and suicide attempts (aOR 3.284) were associated with higher reproductive health risk, defined by an increasing number of coexisting reproductive risk factors.

Conclusions: These findings suggest an alignment between mental and reproductive health risk and support the value of cross-domain collaboration in adolescent health. The association between psychopathology and reproductive health risk, as well as its variations with age, sex, and associated risk behaviours, should be considered when designing health-promoting or disease-preventing interventions for adolescents.
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http://dx.doi.org/10.1186/s12978-018-0618-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6220505PMC
November 2018

[Identification of abuse/dependence cases by the French addictovigilance network (FAN): A pilot study of the addictovigilance center and the psychotherapeutic center of Nancy (France)].

Therapie 2019 Jun 13;74(3):389-397. Epub 2018 Oct 13.

Centre d'évaluation et d'information sur la pharmacodépendance et addictovigilance (CEIP-A), CHRU de Nancy, hôpital central, 29, avenue du Maréchal de Lattre de Tassigny, 54035 Nancy, France; French Addictovigilance Network (FAN), 54035 Nancy, France; Unité 6, Centre psychothérapique de Nancy, pôle de psychiatrie et psychologie clinique, 54520 Laxou, France; Université de Lorraine, 54035 Nancy, France.

Objectives: France is the only European country with a dedicated addictovigilance network (French addictovigilance network [FAN]). However, the reporting of cases of abuse/dependence is insufficient. In an attempt to overcome this under-reporting, data from the medical information systems program (PMSI) is regularly used to identify cases. Since addictions are frequently associated with psychiatric comorbidities, a pilot study was conducted for the first time in a psychiatric hospital. It aims, through a PMSI request, to identify the sociodemographic characteristics and psychiatric diagnoses of patients consuming psychoactive substances (PAS) and the PAS types consumed.

Methods: This is a retrospective observational study conducted over a nine-month period at the psychotherapeutic center of Nancy (CPN). The codes used for the PMSI request are those of the international classification of diseases, tenth revision (ICD-10), codes F10 to F19 that characterize mental and behavioral disorders associated with the use of PAS. Cases presenting the four criteria necessary for an addictovigilance notification: (1) identified notifier, (2) identified patient, (3) known consumed product (s) and (4) presence of an effect related to the abuse/dependence of PAS; were retained and analyzed.

Results: On an initial number of 252 cases, 82 cases of abuse/dependence were retained. The selected sample is predominantly male (67%). Cannabis (29%) and heroin (15%) are the most common illicit PAS. Regarding drugs, the consumption of benzodiazepines, a predominantly female phenomenon, is observed in 34% of subjects. Sixty-four per cent of the subjects were diagnosed "disorders related to the use of PAS", 14% as neurotic disorders, 9% as schizophrenia and 5% as of the mood disorders.

Conclusion: This study identified a significant number of potentially reportable cases to the French Addictovigilance Network and demonstrated the interest of investigating cases of abuse/dependence in a psychiatric hospital.
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http://dx.doi.org/10.1016/j.therap.2018.10.002DOI Listing
June 2019

[Identification of abuse/dependence cases by the French addictovigilance network (FAN): A pilot study of the addictovigilance center and the psychotherapeutic center of Nancy (France)].

Therapie 2019 Jun 13;74(3):389-397. Epub 2018 Oct 13.

Centre d'évaluation et d'information sur la pharmacodépendance et addictovigilance (CEIP-A), CHRU de Nancy, hôpital central, 29, avenue du Maréchal de Lattre de Tassigny, 54035 Nancy, France; French Addictovigilance Network (FAN), 54035 Nancy, France; Unité 6, Centre psychothérapique de Nancy, pôle de psychiatrie et psychologie clinique, 54520 Laxou, France; Université de Lorraine, 54035 Nancy, France.

Objectives: France is the only European country with a dedicated addictovigilance network (French addictovigilance network [FAN]). However, the reporting of cases of abuse/dependence is insufficient. In an attempt to overcome this under-reporting, data from the medical information systems program (PMSI) is regularly used to identify cases. Since addictions are frequently associated with psychiatric comorbidities, a pilot study was conducted for the first time in a psychiatric hospital. It aims, through a PMSI request, to identify the sociodemographic characteristics and psychiatric diagnoses of patients consuming psychoactive substances (PAS) and the PAS types consumed.

Methods: This is a retrospective observational study conducted over a nine-month period at the psychotherapeutic center of Nancy (CPN). The codes used for the PMSI request are those of the international classification of diseases, tenth revision (ICD-10), codes F10 to F19 that characterize mental and behavioral disorders associated with the use of PAS. Cases presenting the four criteria necessary for an addictovigilance notification: (1) identified notifier, (2) identified patient, (3) known consumed product (s) and (4) presence of an effect related to the abuse/dependence of PAS; were retained and analyzed.

Results: On an initial number of 252 cases, 82 cases of abuse/dependence were retained. The selected sample is predominantly male (67%). Cannabis (29%) and heroin (15%) are the most common illicit PAS. Regarding drugs, the consumption of benzodiazepines, a predominantly female phenomenon, is observed in 34% of subjects. Sixty-four per cent of the subjects were diagnosed "disorders related to the use of PAS", 14% as neurotic disorders, 9% as schizophrenia and 5% as of the mood disorders.

Conclusion: This study identified a significant number of potentially reportable cases to the French Addictovigilance Network and demonstrated the interest of investigating cases of abuse/dependence in a psychiatric hospital.
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http://dx.doi.org/10.1016/j.therap.2018.10.002DOI Listing
June 2019

Comorbidity of Physical and Anxiety Symptoms in Adolescent: Functional Impairment, Self-Rated Health and Subjective Well-Being.

Int J Environ Res Public Health 2018 08 9;15(8). Epub 2018 Aug 9.

National Centre for Suicide Research and Prevention of Mental Ill-Health (NASP), Karolinska Institute, SE-171 77 Stockholm, Sweden.

Physical disorders and anxiety are frequently comorbid. This study investigates the characteristics of physical disorders, self-rated heath, subjective well-being and anxiety in adolescents. Data were drawn from the cohort study. From 11 countries 11,230 adolescents, aged 14⁻16 years were included. Zung Self-Rating Anxiety Scale (SAS), WHO-5 Well-Being Index and five questions prepared for this study to evaluate physical illnesses and self-rated heath were administered. Anxiety levels were significantly higher in adolescents who reported having physical disability ( < 0.001, Cohen's = 0.40), suffering from chronic illnesses ( < 0.001, Cohen's = 0.40), impairments associated to health conditions ( < 0.001, Cohen's = 0.61), or reported poor to very poor self-rated health ( < 0.001, Cohen's = 1.11). Mediational analyses revealed no direct effect of having a chronic illness/physical disability on subjective well-being, but the indirect effects through higher levels of anxiety were significant. Functional impairment related to health conditions was both directly and indirectly (through higher levels of anxiety) associated with lower well-being. The co-occurrence of anxiety and physical disorders may confer a greater level of disability and lower levels of subjective well-being. Clinicians have to screen anxiety, even in a subthreshold level in patients with choric physical illness or with medically unexplained physical symptoms.
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http://dx.doi.org/10.3390/ijerph15081698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6121583PMC
August 2018

Comorbidity of Physical and Anxiety Symptoms in Adolescent: Functional Impairment, Self-Rated Health and Subjective Well-Being.

Int J Environ Res Public Health 2018 08 9;15(8). Epub 2018 Aug 9.

National Centre for Suicide Research and Prevention of Mental Ill-Health (NASP), Karolinska Institute, SE-171 77 Stockholm, Sweden.

Physical disorders and anxiety are frequently comorbid. This study investigates the characteristics of physical disorders, self-rated heath, subjective well-being and anxiety in adolescents. Data were drawn from the cohort study. From 11 countries 11,230 adolescents, aged 14⁻16 years were included. Zung Self-Rating Anxiety Scale (SAS), WHO-5 Well-Being Index and five questions prepared for this study to evaluate physical illnesses and self-rated heath were administered. Anxiety levels were significantly higher in adolescents who reported having physical disability ( < 0.001, Cohen's = 0.40), suffering from chronic illnesses ( < 0.001, Cohen's = 0.40), impairments associated to health conditions ( < 0.001, Cohen's = 0.61), or reported poor to very poor self-rated health ( < 0.001, Cohen's = 1.11). Mediational analyses revealed no direct effect of having a chronic illness/physical disability on subjective well-being, but the indirect effects through higher levels of anxiety were significant. Functional impairment related to health conditions was both directly and indirectly (through higher levels of anxiety) associated with lower well-being. The co-occurrence of anxiety and physical disorders may confer a greater level of disability and lower levels of subjective well-being. Clinicians have to screen anxiety, even in a subthreshold level in patients with choric physical illness or with medically unexplained physical symptoms.
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http://dx.doi.org/10.3390/ijerph15081698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6121583PMC
August 2018

Investigating polygenic burden in age at disease onset in bipolar disorder: Findings from an international multicentric study.

Bipolar Disord 2019 02 28;21(1):68-75. Epub 2018 Jun 28.

Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Munich, Germany.

Objectives: Bipolar disorder (BD) with early disease onset is associated with an unfavorable clinical outcome and constitutes a clinically and biologically homogenous subgroup within the heterogeneous BD spectrum. Previous studies have found an accumulation of early age at onset (AAO) in BD families and have therefore hypothesized that there is a larger genetic contribution to the early-onset cases than to late onset BD. To investigate the genetic background of this subphenotype, we evaluated whether an increased polygenic burden of BD- and schizophrenia (SCZ)-associated risk variants is associated with an earlier AAO in BD patients.

Methods: A total of 1995 BD type 1 patients from the Consortium of Lithium Genetics (ConLiGen), PsyCourse and Bonn-Mannheim samples were genotyped and their BD and SCZ polygenic risk scores (PRSs) were calculated using the summary statistics of the Psychiatric Genomics Consortium as a training data set. AAO was either separated into onset groups of clinical interest (childhood and adolescence [≤18 years] vs adulthood [>18 years]) or considered as a continuous measure. The associations between BD- and SCZ-PRSs and AAO were evaluated with regression models.

Results: BD- and SCZ-PRSs were not significantly associated with age at disease onset. Results remained the same when analyses were stratified by site of recruitment.

Conclusions: The current study is the largest conducted so far to investigate the association between the cumulative BD and SCZ polygenic risk and AAO in BD patients. The reported negative results suggest that such a polygenic influence, if there is any, is not large, and highlight the importance of conducting further, larger scale studies to obtain more information on the genetic architecture of this clinically relevant phenotype.
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http://dx.doi.org/10.1111/bdi.12659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6585855PMC
February 2019

Analysis of the Influence of microRNAs in Lithium Response in Bipolar Disorder.

Front Psychiatry 2018 31;9:207. Epub 2018 May 31.

Mood Disorders Unit, HUG - Geneva University Hospitals, Geneva, Switzerland.

Bipolar disorder (BD) is a common, highly heritable neuropsychiatric disease characterized by recurrent episodes of mania and depression. Lithium is the best-established long-term treatment for BD, even though individual response is highly variable. Evidence suggests that some of this variability has a genetic basis. This is supported by the largest genome-wide association study (GWAS) of lithium response to date conducted by the International Consortium on Lithium Genetics (ConLiGen). Recently, we performed the first genome-wide analysis of the involvement of miRNAs in BD and identified nine BD-associated miRNAs. However, it is unknown whether these miRNAs are also associated with lithium response in BD. In the present study, we therefore tested whether common variants at these nine candidate miRNAs contribute to the variance in lithium response in BD. Furthermore, we systematically analyzed whether any other miRNA in the genome is implicated in the response to lithium. For this purpose, we performed gene-based tests for all known miRNA coding genes in the ConLiGen GWAS dataset ( = 2,563 patients) using a set-based testing approach adapted from the versatile gene-based test for GWAS (VEGAS2). In the candidate approach, showed a nominally significant association with lithium response, providing some evidence for involvement in both development and treatment of BD. In the genome-wide miRNA analysis, 71 miRNAs showed nominally significant associations with the dichotomous phenotype and 106 with the continuous trait for treatment response. A total of 15 miRNAs revealed nominal significance in both phenotypes with showing the strongest association with the continuous trait ( = 9.80E-04) and with the dichotomous phenotype ( = 5.79E-04). No association between miRNAs and treatment response to lithium in BD in either of the tested conditions withstood multiple testing correction. Given the limited power of our study, the investigation of miRNAs in larger GWAS samples of BD and lithium response is warranted.
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http://dx.doi.org/10.3389/fpsyt.2018.00207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5991073PMC
May 2018

Prevalence and determinants of cognitive impairment in the euthymic phase of bipolar disorders: results from the FACE-BD cohort.

Psychol Med 2019 02 8;49(3):519-527. Epub 2018 May 8.

Service Universitaire de Psychiatrie d'Adultes, Centre Hospitalier de Versailles,177 rue de Versailles, 78157 Le Chesnay,France.

Background: Cognitive deficits are a well-established feature of bipolar disorders (BD), even during periods of euthymia, but risk factors associated with cognitive deficits in euthymic BD are still poorly understood. We aimed to validate classification criteria for the identification of clinically significant cognitive impairment, based on psychometric properties, to estimate the prevalence of neuropsychological deficits in euthymic BD, and identify risk factors for cognitive deficits using a multivariate approach.

Methods: We investigated neuropsychological performance in 476 euthymic patients with BD recruited via the French network of BD expert centres. We used a battery of tests, assessing five domains of cognition. Five criteria for the identification of neuropsychological impairment were tested based on their convergent and concurrent validity. Uni- and multivariate logistic regressions between cognitive impairment and several clinical and demographic variables were performed to identify risk factors for neuropsychological impairment in BD.

Results: One cut-off had satisfactory psychometric properties and yielded a prevalence of 12.4% for cognitive deficits in euthymic BD. Antipsychotics use were associated with the presence of a cognitive deficit.

Conclusions: This is the first study to validate a criterion for clinically significant cognitive impairment in BD. We report a lower prevalence of cognitive impairment than previous studies, which may have overestimated its prevalence. Patients with euthymic BD and cognitive impairment may benefit from cognitive remediation.
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http://dx.doi.org/10.1017/S0033291718001186DOI Listing
February 2019

Prevalence and determinants of cognitive impairment in the euthymic phase of bipolar disorders: results from the FACE-BD cohort.

Psychol Med 2019 02 8;49(3):519-527. Epub 2018 May 8.

Service Universitaire de Psychiatrie d'Adultes, Centre Hospitalier de Versailles,177 rue de Versailles, 78157 Le Chesnay,France.

Background: Cognitive deficits are a well-established feature of bipolar disorders (BD), even during periods of euthymia, but risk factors associated with cognitive deficits in euthymic BD are still poorly understood. We aimed to validate classification criteria for the identification of clinically significant cognitive impairment, based on psychometric properties, to estimate the prevalence of neuropsychological deficits in euthymic BD, and identify risk factors for cognitive deficits using a multivariate approach.

Methods: We investigated neuropsychological performance in 476 euthymic patients with BD recruited via the French network of BD expert centres. We used a battery of tests, assessing five domains of cognition. Five criteria for the identification of neuropsychological impairment were tested based on their convergent and concurrent validity. Uni- and multivariate logistic regressions between cognitive impairment and several clinical and demographic variables were performed to identify risk factors for neuropsychological impairment in BD.

Results: One cut-off had satisfactory psychometric properties and yielded a prevalence of 12.4% for cognitive deficits in euthymic BD. Antipsychotics use were associated with the presence of a cognitive deficit.

Conclusions: This is the first study to validate a criterion for clinically significant cognitive impairment in BD. We report a lower prevalence of cognitive impairment than previous studies, which may have overestimated its prevalence. Patients with euthymic BD and cognitive impairment may benefit from cognitive remediation.
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http://dx.doi.org/10.1017/S0033291718001186DOI Listing
February 2019

Correlates of sexual initiation among European adolescents.

PLoS One 2018 8;13(2):e0191451. Epub 2018 Feb 8.

National Centre for Suicide Research and Prevention of Mental Ill-Health (NASP), Department of Learning, Informatics, Management and Ethics (LIME), Karolinska Institutet, Stockholm, Sweden.

Background: Sexuality is a physiological component of adolescent development, though early initiation is associated with reproductive health risk. This study aimed at identifying correlates and predictors of sexual initiation in a large multinational cohort of European adolescents.

Methods: A questionnaire addressing socio-demographics, behaviours, mental health and sexual activity, was delivered to 11,110 adolescents recruited from 168 randomly selected schools in 10 European countries between 2009 and 2011. A follow-up questionnaire was delivered after 12 months. The longitudinal association of baseline risk behaviors, psychological attributes and contextual vulnerabilities, with sexual initiation during follow-up was evaluated through simple and multivariable age/sex stratified logistic regression. Multinomial logistic regression measured the association between predictors and sexual initiation with or without coexisting reproductive risk factors, such as multiple partners or infrequent condom use.

Results: Baseline sexual experience was reported by 19.2% of 10,757 respondents (median age 15; IQR 14-15; females 59.6%). This was significantly more frequent among pupils older than 15 (41%) and males (20.8%). Of 7,111 pupils without previous experience who were available at follow-up (response rate 81.8%), 17% reported sexual initiation, without differences between females and males. Baseline smoking (age/sex adjusted odds ratio [aOR] 3.63), alcohol use (aOR 2.95), illegal drugs use (aOR 2.72), and poor sleep (aOR 1.71) predicted sexual initiation. Stratified analyses showed a particularly strong association in case of younger and female pupils, and, among girls, when initiation was reported together with multiple partners and/or infrequent condom use. Externalizing (i.e. conduct and hyperactivity) symptoms independently predicted sexual initiation. Internalizing difficulties (i.e. emotional and peer problems) were negatively associated with early and risky sexual initiation among boys. Significant predictors included also being bullied, fighting, truancy, and low parental involvement.

Conclusions: Adolescent sexual behaviours are related to non-sexual risk behaviours, psychological difficulties and contextual vulnerabilities. While gateway effects explain some associations, a comprehensive model is needed to understand adolescent sexual behaviours, their physical, mental, and social health outcomes, and their potential positive effects on wellbeing. Tailored interventions may need to consider younger girls as a particularly vulnerable group in view of a strong association between non-sexual and sexual behaviors.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0191451PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5805230PMC
March 2018

Association between CRP genetic diversity and bipolar disorder comorbid complications.

Int J Bipolar Disord 2018 Jan 20;6(1). Epub 2018 Jan 20.

INSERM, U1160, Hôpital Saint Louis, 75010, Paris, France.

Background: Chronic low-grade inflammation is believed to contribute, at least in a subset of patients, to the development of bipolar disorder (BD). In this context, the most investigated biological marker is the acute phase response molecule, C-reactive protein (CRP). While the genetic diversity of CRP was amply studied in various pathological settings, little is known in BD.

Methods: 568 BD patients along with 163 healthy controls (HC) were genotyped for the following single-nucleotide polymorphisms (SNPs) on the CRP gene: intron rs1417938 (+ 29) T/A, 3'-UTR rs1130864 (+ 1444) G/A, and downstream rs1205 (+ 1846) (C/T). The statistical analysis was performed using Chi-square testing and consisted of comparisons of allele/genotype frequencies between patients and controls and within patient sub-groups according to BD clinical phenotypes and the presence of thyroid disorders.

Results: We found that the frequencies of the studied SNPs were similar in BD and HC groups. However, the CRP rs1130864 A allele carrier state was significantly more frequent: (i) in BD patients with thyroid disorders than in those without (pc = 0.046), especially among females (pc = 0.01) and independently of lithium treatment, (ii) in BD patients with rapid cycling than in those without (pc = 0.004).

Conclusions: Overall, our findings suggest the possibility that CRP genetic diversity may contribute to the development of auto-immune comorbid disorders and rapid cycling, both proxy of BD severity. Such findings, if replicated, may allow to predict complex clinical presentations of the disease, a possible step towards precision medicine in psychiatry.
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http://dx.doi.org/10.1186/s40345-017-0109-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6161963PMC
January 2018

Association between CRP genetic diversity and bipolar disorder comorbid complications.

Int J Bipolar Disord 2018 Jan 20;6(1). Epub 2018 Jan 20.

INSERM, U1160, Hôpital Saint Louis, 75010, Paris, France.

Background: Chronic low-grade inflammation is believed to contribute, at least in a subset of patients, to the development of bipolar disorder (BD). In this context, the most investigated biological marker is the acute phase response molecule, C-reactive protein (CRP). While the genetic diversity of CRP was amply studied in various pathological settings, little is known in BD.

Methods: 568 BD patients along with 163 healthy controls (HC) were genotyped for the following single-nucleotide polymorphisms (SNPs) on the CRP gene: intron rs1417938 (+ 29) T/A, 3'-UTR rs1130864 (+ 1444) G/A, and downstream rs1205 (+ 1846) (C/T). The statistical analysis was performed using Chi-square testing and consisted of comparisons of allele/genotype frequencies between patients and controls and within patient sub-groups according to BD clinical phenotypes and the presence of thyroid disorders.

Results: We found that the frequencies of the studied SNPs were similar in BD and HC groups. However, the CRP rs1130864 A allele carrier state was significantly more frequent: (i) in BD patients with thyroid disorders than in those without (pc = 0.046), especially among females (pc = 0.01) and independently of lithium treatment, (ii) in BD patients with rapid cycling than in those without (pc = 0.004).

Conclusions: Overall, our findings suggest the possibility that CRP genetic diversity may contribute to the development of auto-immune comorbid disorders and rapid cycling, both proxy of BD severity. Such findings, if replicated, may allow to predict complex clinical presentations of the disease, a possible step towards precision medicine in psychiatry.
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http://dx.doi.org/10.1186/s40345-017-0109-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6161963PMC
January 2018
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