Marie-Pierre Françoise Strippoli

This study assessed the prevalence, clinical correlates and polysomnographic features of insomnia symptoms in a population‐based cohort (HypnoLaus, Lausanne, Switzerland). Data were obtained from 3947 participants (mean age 57.5 ± 10.5 years; range 40–82; 52.0% female). Insomnia symptoms were defined as difficulty initiating or maintaining sleep ≥ 3 nights/week during the past month or regular hypnotic use. Independent correlates of insomnia symptoms were examined using logistic regression. In the subset of 1718 participants who underwent polysomnography (performed 1.1 ± 0.9 years after insomnia symptom assessment), associations between insomnia symptoms and sleep variables were examined using linear regression models adjusted for age, sex, depression, anxiety and psychotropic use. Insomnia symptoms affected 32.0% of participants, and 4.2% of the total sample reported regular hypnotic use. Independent correlates included older age, female sex, lower education, dyslipidaemia, lower likelihood of current smoking, excessive alcohol consumption, depression, anxiety, psychotropic use and daytime sleepiness. Compared with those without symptoms, participants with insomnia showed shorter total sleep time, longer sleep onset latency, longer wake after sleep onset and lower sleep efficiency (all small effect sizes). Sleep microstructure analysis showed higher odds ratio product (ORP) values (in wake, NREM, and N2, and ORP‐9), higher normalised EEG power, higher beta power and higher gamma power (all small effect sizes). Insomnia symptoms are highly prevalent in this population‐based cohort and are linked to multiple sociodemographic and clinical factors. Polysomnographic findings indicate modest sleep macrostructural differences, whereas microstructural alterations, although subtle in magnitude, appeared more consistently associated with insomnia symptoms.

Objectives: Adverse parenting styles during childhood have been shown to contribute to influencing later pain characteristics in clinical populations with chronic pain (CP). However, few studies have addressed this question in the general population. We assessed the associations of perceived parenting styles with incident, persistent, and remitted CP during a 5-year follow-up in middle-aged community-dwellers as well as the potentially moderating effect of sex on these associations. Methods: Data stemmed from the 2 first follow-up (FU1, FU2) evaluations of CoLaus|PsyCoLaus, a prospective cohort study conducted in the general population of Lausanne, Switzerland. Parental bonding was assessed using the Parental Bonding Instrument (PBI). The 1,739 participants of this analysis were divided into 4 groups according to their CP status at follow-up: (1) incident CP, (2) persistent CP, (3) remitted CP, and (4) CP free (reference group). The associations between PBI categories (high vs low) and subsequent CP status were assessed using multinomial logistic regressions, controlling for confounding factors including lifetime major depressive disorder, neuroticism, and psychotropic drug use. Results: Sex and PBI categories did not interact regarding CP status during follow-up. The only significant main effect was between high levels of denial of autonomy by the father and a higher risk of reporting persistent CP at follow-up (odds ratio: 1.42 [1.05; 1.91] P = 0.02). Conclusion: Our results suggest that earlier perceived high psychological denial of autonomy by the father is associated with the subsequent risk of CP in mid-life. Prospective studies following adolescents into adulthood should determine the direction of this association.

The mechanisms underlying the association between major depressive disorders (MDD) and obesity are still only partially understood. We aimed to explore these mechanisms using two approaches: 1) studying the parent-offspring transmission patterns of MDD and its subtypes and of the adiposity markers BMI and waist circumference, and 2) assessing the associations of parental polygenic risk scores (PRS) for MDD and BMI with MDD and adiposity markers in parents and offspring. Data on parents (N = 467) and their 18 to 35-year-old offspring (N = 592; mean age: 26.5 (s.d. 4.4) years) were derived from a community study conducted in an urban area. Psychiatric DSM-IV disorders including MDD and its atypical and melancholic subtypes were assessed using semi-structured diagnostic interviews. Phenotypic analyses provided evidence for a strong parent-child transmission of BMI (β = 0.33 kg/m2, 95% Confidence Intervals (CI): 0.24;0.42) and waist circumference (β = 0.28 cm, 0.19;0.38), but not for MDD or its subtypes or a cross-transmission of MDD and adiposity markers. Parental PRS for MDD were not only associated with MDD and its subtypes in parents, but also with BMI and waist circumference levels in parents (β = 0.49 kg/m2, 0.11;0.86; β = 2.00 cm, 1.05;3.00, respectively) and offspring (β = 0.54 kg/m2, 0.16;0.91; β = 1.27 cm, 1.17;2.37, respectively), whereas parental PRS for BMI were only associated with adiposity marker levels in parents and offspring. In conclusion, our findings relying on PRS suggest that the associations between atypical MDD and elevated adiposity marker levels may at least be partially attributable to common genetic liability. In contrast, the absence of parent-child transmission of MDD or its subtypes as well as the cross-transmission of MDD and adiposity markers according to our phenotypic analyses could be attributable to the young age of our offspring cohort.

Study Objectives: To investigate the associations of periodic limb movements during sleep (PLMS) and restless legs syndrome (RLS) symptoms with longitudinal changes in cognitive performance among older adults. Methods: We analyzed data from 382 community-dwelling older adults without dementia participating in the HypnoLaus study (mean age: 71.0 ± 4.1 years; 42.9% male). Participants underwent polysomnography and baseline cognitive testing, followed by a second cognitive assessment after 4.7 ± 0.6 years. Individuals were categorized by PLMS index (PLMI) as <15/h (reference), 15–29.9/h, and ≥30/h. Associations between PLMI categories and annualized changes in executive function (Stroop Test), verbal fluency, and verbal memory were examined using multiple linear regression models adjusted for potential confounders. Additional analyses evaluated the role of RLS symptoms and PLMI × RLS symptoms interactions. Results: A PLMI ≥30/h was associated with a steeper deterioration in executive function compared with the reference group (B = −0.06 standard deviations [SD]/year, p = .010), equivalent to −0.3 SD and −1.5 SD declines over 5 years relative to the baseline performance and to the distribution of change scores, respectively. This association was independent of RLS symptoms and other sleep-related conditions. No significant associations were observed between PLMI and changes in verbal fluency or verbal memory. RLS symptoms were not associated with changes in any cognitive outcome, and no PLMI × RLS symptoms interaction was detected. Conclusions: High PLMS frequency was independently associated with accelerated deterioration in executive function, suggesting a link between PLMS and cognitive aging. In contrast, RLS symptoms showed no association with changes in cognitive function. Statement of Significance This study suggests that periodic limb movements during sleep (PLMS) may be related to early cognitive vulnerability and could represent an early marker of accelerated cognitive aging. A higher frequency of PLMS was associated with a steeper deterioration in executive function over about 5 years in community-dwelling older adults, independent of restless legs syndrome symptoms, other sleep conditions, and relevant clinical factors. These findings highlight the need for future research to elucidate the neurobiological mechanisms linking PLMS to accelerated cognitive aging, and to determine whether reducing PLMS could help preserve cognitive health, or whether PLMS primarily represent a marker rather than a direct contributor to cognitive deterioration.

Caffeine metabolic ratios (CMR) following monitored caffeine intake are the gold standard to probe cytochrome P450 (CYP) 1A2 activity, which metabolizes antipsychotics like clozapine and olanzapine. Given caffeine’s ubiquity, we tested whether random CMR from dietary caffeine were associated with (1) clinical, genetic, and epigenetic factors linked to CYP1A2 activity; (2) plasma concentrations of clozapine and olanzapine; and (3) psychotropic treatment response. First, we analyzed two population-based studies (CoLaus|PsyCoLaus, N = 4898; SKIPOGH, N = 2054) to investigate random CMR associations with clinical, genome-wide, and epigenome-wide factors associated with CYP1A2 activity. Second, in psychiatric cohorts, we tested CMR associations with dose-normalized plasma concentrations (C/D) of clozapine (N = 164) and olanzapine (N = 222) and with psychotropic treatment response, including hospital admission risk (N = 1019) and prolonged stays (N = 1349). CMR were positively associated with age, CYP1A2 inducers including smoking, and negatively with female sex. CMR were negatively associated with clozapine C/D, explaining up to 14.9% of the variance; over six-fold the variance explained by genetic factors. A one-unit increase in CMR was associated with a 26% increased likelihood of hospital admission (p = 0.002) and reduced short-stay chance by 11% (p < 10 ⁻³ ). Random CMR provides a useful method to probe CYP1A2 activity, contributing, alongside other variables, to personalizing clozapine doses and identifying psychiatric patients at risk of hospital admission and lengthy stays. Incorporating routine measurement of random CMR before introduction of clozapine could be considered to allow early assessment of CYP1A2 activity, a key determinant of personalized clozapine dose titration.

Introduction: Adverse childhood events (ACEs) have been linked to widespread chronic pain (CP) in various cross-sectional studies, mainly in clinical populations. However, the independent role of different ACEs on the development of different types of CP remains elusive. Accordingly, we aimed to prospectively assess the associations between specific types of ACEs with the development of multisite CP in a large population-based cohort. Methods: Data stemmed from the three first follow-up evaluations of CoLaus|PsyCoLaus, a prospective population-based cohort study of initially 6734 participants (age range: 35–75 years). The present sample included 1537 participants with 2161 analyzable intervals (49.7% men, mean age 57.3 years). Diagnostic criteria for ACEs were elicited using semi-structured interviews and CP was assessed by self-rating questionnaires. Multinomial logistic regressions with generalized estimating equations method analyzed the relationship between the different ACEs measured in the beginning of the interval and the risk of developing multisite CP during the follow-up. Sensitivity analyses were performed to assess the predictive value of ACEs on multisite CP with neuropathic features. Results: Participants with a history of parental divorce or separation had an increased risk of developing multisite CP at during follow-up in comparison to those without (RR1.98; 95% CI 1.13–3.47). A strong association was highlighted between parental divorce or separation and the risk of subsequent CP with neuropathic characteristics (RR 4.21, 95% CI 1.45–12.18). Conclusion: These results highlight the importance of psychotherapeutic management of people experiencing parental separation to prevent CP in the future.

Research on antidepressant-related weight changes over more than 12 months is scarce and adjustment for the effects of depressive episodes has rarely been applied. Accordingly, our aim was to assess the associations of the use of any antidepressants, subclasses of antidepressant and specific compounds prior to baseline and during a 5.5-year follow-up with changes in adiposity markers, and the effect of sex on these associations, with adjustment for multiple confounders including the effects of depressive episodes and their severity. Data stemmed from a prospective cohort study including 2479 randomly selected 35–66 year-old residents of an urban area (mean age 49.9 years, 53.3% women) who underwent physical and psychiatric evaluations at baseline and follow-up. Weight, height, waist circumference, and body fat were measured by trained nurses and information on diagnosis and antidepressant use prior to baseline and during follow-up was collected through standardized interviews. In the fully adjusted models, the number of antidepressants, mainly SSRIs and TCAs, used prior to baseline, was associated with a lower increase of body-mass index (BMI, β (95%CI) = −0.12 (−0.19, −0.05)) and waist circumference (β = −0.28 (−0.56, −0.01)), whereas participants treated with antidepressants during the follow-up had a steeper increase in BMI (β = 0.32 (0.13, 0.50)) and waist circumference (β = 1.23 (0.44, 2.01)). Within the class of SSRIs, the use of fluoxetine, sertraline or escitalopram during follow-up was associated with a steeper increase in adiposity markers. The associations of SSRIs with BMI and waist circumference were only observed when the SSRIs were used during the second period of the follow-up. Sex did not moderate these associations. Our findings suggest an increase of adiposity markers during sustained treatment with TCAs and SSRIs, which however return to normal levels after cessation of treatment. Hence, the benefit of long-term administration of these antidepressants should be carefully weighed against the potential risk of weight gain.