Physical and mental health status of former smokers and non-smokers patients with bipolar disorder.

OBJECTIVES: Up to 70% individuals with bipolar disorder (BD) are lifetime tobacco smokers, a major modifiable risk factor for morbidity. However, quitting smoking is rarely proposed to individuals with BD, mainly because of fear of unfavorable metabolic or psychiatric changes. Evaluating the physical and mental impact of tobacco cessation is primordial. The aim of this study was to characterize the psychiatric and nonpsychiatric correlates of tobacco smoking status (never- vs. current vs. former smokers) in individuals with BD. METHODS: 3860 individuals with ascertained BD recruited in the network of Fondamental expert centers for BD between 2009 and 2020 were categorized into current, former, and never tobacco smokers. We compared the sociodemographic and clinical characteristics assessed by standard instruments (e.g., BD type, current symptoms load, and non-psychiatric morbidity-including anthropometric and biological data) of the three groups using multinomial regression logistic models. Corrections for multiple testing were applied. RESULTS: Current smokers had higher depression, anxiety, and impulsivity levels than former and never-smokers, and also higher risk of comorbid substance use disorders with a gradient from never to former to current smokers-suggesting shared liability. Current smokers were at higher risk to have a metabolic syndrome than never-smokers, although this was only evidenced in cases, who were not using antipsychotics. CONCLUSIONS: Tobacco smoking was associated with high morbidity level. Strikingly, as in the general population, quitting smoking seemed associated with their return to the never-smokers' levels. Our findings strongly highlight the need to spread strategies to treat tobacco addiction in the BD population.

Factors associated with lamotrigine concentration/dose ratio in individuals with bipolar disorders.

Monitoring of lamotrigine levels is recommended in epilepsy. However, in bipolar disorders (BD), no study has described the therapeutic range in daily practice and factors being associated to it. We used retrospective data of individuals with BD, treated with lamotrigine, and included in the FondaMental Advanced Centers of Expertise for Bipolar Disorders cohort. We extracted clinical and biological data and explored associations between these variables and lamotrigine concentration/dose (C/D) ratio. The database included 675 individuals who received lamotrigine at inclusion, whose main characteristics were female sex (68.3%) and BD type 2 (52.1%). Data about lamotrigine C/D ratio were available for 205 individuals. Lamotrigine C/D ratio was significantly associated with: Body Mass Index (BMI) (r=-0.159), estimated GFR (glomerular filtration rate) (r=-0.228), total bilirubin (r = 0.241) and at a trend level, antidepressant co-prescription (U = 3169). The model obtained was: lamotrigine C/D ratio = 1.736 - 0.013*BMI + 0.095*total bilirubin (UI/L) - 0.007*eGFR (ml/min) + 0.210*AST/ALT - 0.004*GGT (UI/L) + 0.014*age (year) + 0.303*currently smoking (yes or no) - 0.588*antidepressant co-prescription (yes or no) - 0.357*gender (F = 1.899, p = 0.057, adjusted R2 = 0.11) Information about plasma lamotrigine C/D ratio were available for only 205 out of the 675 individuals in the database and has been obtained from different laboratories. The representativeness of the included sample may be questionable. This is the first study providing information on a large sample of individuals with BD regarding factors associated with lamotrigine C/D ratio. This study allows to propose a model of lamotrigine C/D ratio that would deserve further replication.

A one-year follow-up study of treatment-compliant suicide attempt survivors: relationship of CYP2D6-CYP2C19 and polypharmacy with suicide reattempts.

This study of a cohort of 1-year treatment-compliant survivors of a suicide attempt examined for the first time whether a high CYP2D6-CYP2C19 metabolic capacity (pharmacogenes related to psychopathology, suicide, and attempt severity) and/or polypharmacy treatments predicted repeat suicide attempts, adjusting for sociodemographic and clinical factors as confounders. Of the 461 (63% women) consecutively hospitalized patients who attempted suicide and were evaluated and treated after an index attempt, 191 (67.5% women) attended their 6- and 12-month follow-up sessions. Clinicians were blinded to the activity scores (AS) of their genotypes, which were calculated as the sum of the values assigned to each allele (CYP2C19 *2, *17; CYP2D6 *3, *4, *4xN, *5, *6, *10, wtxN). No differences were found in polypharmacy prescription patterns and the variability of CYP2D6 and CYP2C19 genotypes between adherents and dropouts, but the formers were older, with a higher frequency of anxiety and bipolar disorders and fewer alcohol and substance use disorders. The risk of reattempts was higher for CYP2D6 ultrarapid (AS > 2) metabolizers (ß = 0.561, p = 0.005) and violent suicide survivors (ß = -0.219, p = 0.042) if the attempt occurred during the first 6-month period, individuals with an increased number of MINI DSM-IV Axis I mental disorders (ß = 0.092, p = 0.032) during the second 6-month period and individuals with a combined high CYP2D6-CYP2C19 metabolic capacity (AS > 4) (ß = 0.345, p = 0.024) and an increased use of drugs other than antidepressants, anxiolytics-depressants and antipsychotics-lithium (ß = 0.088, p = 0.005) in multiple repeaters during both periods. CYP2D6 and CYP2C19 rapid metabolism and polypharmacy treatment for somatic comorbidities must be considered to prevent the severe side effects of short-term multiple suicide reattempts after a previous attempt.

A Complex Relationship Between Suicide, Dementia, and Amyloid: A Narrative Review.

Background: Suicide rates are high among older adults and many conditions have been related to suicide in this population: chronic illnesses, physical disabilities, cancer, social isolation, mental disorders and neurocognitive disorders. Objectives: Among neurocognitive disorders, analysis of the relationships between dementia and suicidal behaviors led to conflicting results and some questions are still without answer. Particularly, it is not known whether (i) Alzheimer's disease (AD) increases the risk of suicidal ideation and suicide attempts (SA) or the frequency of death by suicide; (ii) the presence of suicidal ideation or SA in people older than 65 years of age is an early dementia sign; and (iii) amyloid load in frontal areas facilitates SA by modifying the decision-making pathway. Methods: Therefore, in this narrative review, we searched the PubMed database using the medical subject heading (MeSH) terms ("Suicide" AND "Depression") OR ("Amyloid" OR "Dementia") to identify recent (from 2000 to 2017) original studies on the links between suicidal behavior, dementia and brain amyloid load. We also explored the clinical and pathophysiological role of depression in these relationships. Results and Discussion: The findings from these studies suggest that late stage dementia could protect against suicidal ideation and SA. Conversely, the risk of complete suicide is increased during the early phase of cognitive decline. Conclusions: Serious cognitive impairment and decline of executive functions could protect against negative thoughts related to cognitive disability awareness and against suicide planning.Several factors, including brain amyloid load, could be involved in the increased suicide rate early after the diagnosis of dementia.

Impact of axis-I comorbidity and suicidal behavior disorders on sensitivity and specificity of the Mood Disorder Questionnaire in complex depressed inpatients.

OBJECTIVE: This study assessed the psychometric performance of the Mood Disorder Questionnaire (MDQ) and its modified MDQ7 version, to screen for bipolar disorders (BD) in depressive inpatients according to depression severity, number of current axis I psychiatric comorbidities and suicidal behavior disorders. METHODS: Depressed adult inpatients (n=195) were consecutively enrolled. Psychiatric diagnoses were made using the standardized DSM-IV-TR structured interview MINI 5.0.0 and medical case notes. Depression severity was assessed with the Beck Depression Inventory and the Hamilton Depression Scale. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of each MDQ version were evaluated in the whole sample and according to depression severity, current axis I psychiatric comorbidities and suicidal behavior. RESULTS: The occurrence and the number of axis I disorders affected performance of both versions. Among depressed patients with two or more comorbidities, PPV and NPV of the MDQ were 65% and 80%, respectively, and they were respectively 56.2% and 87.9% with MDQ7. Current suicidal behavior disorders also dramatically reduced the PPV of MDQ (from 81.2% to 63.3%) and MDQ7 (from 72.2% to 52.6%) but the NPV remained above 80%. The performance of both versions of the MDQ tended to improve with the severity of depression. CONCLUSION: The MDQ is not a suitable screening instrument to diagnose BD in subjects with a complex major depressive episode and/or a current history of suicidal behavior. Nevertheless MDQ particularly in its modified version may be useful for ruling out the presence of BD among these complex patients.

Higher psychological pain during a major depressive episode may be a factor of vulnerability to suicidal ideation and act.

BACKGROUND: It has been suggested that psychological pain ("psychache") is a key factor in the suicidal process. In addition, suicidal acts may be best understood within a stress-vulnerability model. We hypothesized that more intense psychache during a major depressive episode would be a factor of vulnerability to suicidal behavior. METHODS: Patients hospitalized for a major depressive episode, including 87 individuals with a recent history of suicidal acts, 61 individuals with a past history of suicidal acts, and 62 individuals without any suicidal history, were assessed at admission using several Visual Analog scales to measure levels of psychache, physical pain and suicidal ideation. RESULTS: Patients with a recent or past history of suicide attempts expressed significantly higher levels of current psychological pain, and a higher intensity and frequency of current suicidal ideation than patients without any history of suicidal acts. The level of current psychache was significantly and positively associated with intensity and frequency of suicidal ideation. There were no between-group differences for physical pain. LIMITATIONS: Medication status was not controlled. A lack of statistical power may have masked an association between physical pain and suicidal ideation. CONCLUSIONS: Higher psychological pain during a major depressive episode may be a factor of vulnerability to suicidal behavior, by increasing the propensity to suicidal ideation. Measuring and taking care of psychache during a depressive episode should be a major therapeutic target during crisis intervention.