# Sex differences in insomnia and hypersomnia complaints during major depressive episode: Results from a national sample

Pierre A. Geoffroy, Alejandro Edán-Sánchez, Sibylle Mauries, Michel Lejoyeux, Julia Maruani, Marina Sánchez-Rico, Nicolas Hoertel, Laura Palagini, Hugo Peyre

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## ► To cite this version:

Pierre A. Geoffroy, Alejandro Edán-Sánchez, Sibylle Mauries, Michel Lejoyeux, Julia Maruani, et al. "Sex differences in insomnia and hypersomnia complaints during major depressive episode: Results from a national sample." Journal of Affective Disorders, 2025, 369, pp.202-210. 10.1016/j.jad.2024.09.163. hal-05029336

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Research paper

# Sex differences in insomnia and hypersomnia complaints during major depressive episode: Results from a national sample

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Pierre A. Geoffroy<sup>a,b,c,*</sup>, Alejandro Edán-Sánchez<sup>a,d</sup>, Marina Sánchez-Rico<sup>b,g</sup>, Sibylle Mauries<sup>a,b,c</sup>, Laura Palagini<sup>h</sup>, Hugo Peyre<sup>i,j</sup>, Michel Lejoyeux<sup>a,b,c</sup>, Julia Maruani<sup>a,b,c</sup>, Nicolas Hoertel<sup>d,e,f</sup>

## ARTICLE INFO

**Keywords:**

Major depressive episode

Mood disorders

Major depressive disorder

Gender differences

Insomnia

Hypersomnia

Hypersomnolence

Sleep disorders

## ABSTRACT

**Background:** Sex differences in sleep disturbances during major depressive episodes (MDE) have been suggested. This study compares the prevalence, sociodemographic characteristics, and psychiatric comorbidity associated with sleep complaints specific to each sex among adults with MDE. These findings are crucial for precise diagnosis, personalized treatment, and improved clinical outcomes.

**Methods:** In a large nationally representative prospective survey, we used multi-adjusted logistic regression models including sociodemographic characteristics, psychiatric comorbidity, and depression severity to examine whether associations differ between men and women.

**Results:** Among women, 93.3 % reported at least one type of sleep complaints (i.e., trouble falling asleep, early morning awakening or hypersomnia) while 91.0 % of men did, with respectively 78.3 % and 77.2 % of insomnia complaints, and 46.2 % and 41.3 % of hypersomnia complaints. Women with sleep complaints were more likely to be black, with lower individual incomes, have histrionic personality disorder or a specific phobia. Conversely, men with sleep complaints were more likely to have a lifetime diagnosis of mania spectrum disorder, generalized anxiety disorder, drug use disorder, as well as dependent and schizotypal personality disorders. Surprisingly, being "never married" has emerged as a protective factor against sleep complaints in women, while posing as a risk factor in men compared to other marital statuses. Differences and specificities were also noted concerning subtypes of insomnia and hypersomnia complaints.

**Limitations:** The cross-sectional design means the associations found do not imply causality.

**Conclusions:** These findings provide insights into the complex relationship between sleep and depression in men and women, highlighting the need for personalized interventions.

## 1. Introduction

Major depressive episode (MDE) affects up to 20 % of the general

population and can result in severe impairments that interfere with one's ability to carry out major life activities (Bakish, 2001; Hoertel et al., 2018, 2017; Kessler et al., 2005; Malhi and Mann, 2018). Women are at

<footnote><sup>a</sup> Département de psychiatrie et d'addictologie, AP-HP, GHU Paris Nord, DMU Neurosciences, Hôpital Bichat - Claude Bernard, F-75018 Paris, France</footnote>

<footnote><sup>b</sup> Centre ChronoS, GHU Paris - Psychiatry & Neurosciences, 1 rue Cabanis, 75014 Paris, France</footnote>

<footnote><sup>c</sup> Université Paris Cité, NeuroDiderot, Inserm, FHU I2-D2, F-75019 Paris, France</footnote>

<footnote><sup>d</sup> Université Paris Cité, Paris, France</footnote>

<footnote><sup>e</sup> Assistance Publique-Hôpitaux de Paris, Hôpital Corentin-Celton, DMU Psychiatrie et Addictologie, Département de Psychiatrie, Issy-les-Moulineaux, France</footnote>

<footnote><sup>f</sup> INSERM, Institut de Psychiatrie et Neurosciences de Paris (IPNP), UMR_S1266, Paris, France</footnote>

<footnote><sup>g</sup> Department of Psychobiology and Behavioural Sciences Methods, Faculty of Psychology, Universidad Complutense de Madrid, Pozuelo de Alarcón, Madrid, Spain</footnote>

<footnote><sup>h</sup> Department of Experimental and Clinical Medicine, Section of Psychiatry, University of Pisa, Pisa, Italy</footnote>

<footnote><sup>i</sup> Autism Reference Centre of Languedoc-Roussillon CRA-LR, Excellence Centre for Autism and Neurodevelopmental disorders CeAND, Montpellier University Hospital, MUSE University, France</footnote>

<footnote><sup>j</sup> Université Paris-Saclay, UVSQ, Inserm, CESP, Team DevPsy, 94807 Villejuif, France</footnote>

<footnote>* Corresponding author at: University Hospital Bichat-Claude Bernard, Department of Psychiatry and Addictive Medicine, 46 rue Henri Huchard, 75018 Paris, France.</footnote>

<footnote>E-mail address: pierre.a.geoffroy@gmail.com (P.A. Geoffroy).</footnote>
higher risk, and it is estimated that one-in-three women and one-in-five men would suffer from a MDE by the age of 65 (Kuehner, 2003). A tremendous variability in symptoms may occur within MDE, which complicates the identification of reliable biomarkers and limits tailored treatment recommendations (Geoffroy and Gottlieb, 2020; Malhi and Mann, 2018). In this context, some authors proposed a return to fundamental dimensional pillars, approaching the core features and natural presentations of mood disorders (Geoffroy and Gottlieb, 2020; Malhi et al., 2018). The “sleep” domain is considered as one of these dimensional pillars, as it is a core symptom of MDE occupying a primary position in the pathophysiology, phenomenology, historical accounts, and evolution of episodes in mood disorders (Geoffroy, 2018; Geoffroy and Gottlieb, 2020; Lee, 2019; McClung, 2013; Palagini et al., 2019; Wirz-Justice and Benedetti, 2019). Indeed, sleep alterations are part of DSM-5 criteria of MDE (American Psychiatric Association, 2013), with more than 90 % of depressed patients reporting sleep complaints (Geoffroy et al., 2018a; Tsuno et al., 2005). These sleep disturbances worsen the severity of depressive symptoms (O'Brien et al., 2011) and are associated with poorer treatment response (Pigeon et al., 2008). Their persistence during remitted phases increases the risk of relapses and recurrences (Li et al., 2012). Furthermore these sleep complaints are known to predict suicidal behaviors (Geoffroy et al., 2021) as well as the emergence of comorbid psychiatric and addictive disorders and non-psychiatric comorbidities, predominantly cardiovascular diseases in patients with MDE (Barbotin et al., 2022; Brochard et al., 2016; Franco et al., 2015). Bidirectional associations have been observed between MDE and sleep disturbances (Franzen and Buysse, 2008; Geoffroy, 2018).

Importantly, recent research suggests that sex differences may exist in the presentation of these sleep disturbances during MDE (Geoffroy et al., 2018a; Soehner et al., 2014a). Previous studies have provided evidence of sex disparities in the prevalence of insomnia and hyper-somnia complaints within the general population (Matza et al., 2003; Morin et al., 2006; Ohayon, 2012). Furthermore, higher prevalence of sleep complaints are also observed in women, with several factors affecting sleep that could be argued to contribute to sex differences (Ulander et al., 2021). This female predisposition appears to be consis-tent and progressive across age (Zhang and Wing, 2006). Moreover, men in adulthood tend to have a more frequent evening chronotype of sleep-wake rhythms (Randler and Engelke, 2019; Roenneberg et al., 2007), which is also known to be associated with depressive disorders (Boudebesse et al., 2013; Etain et al., 2014; Romo-Nava et al., 2020) and to influence antidepressant response of chronotherapeutics (Dallaspezia et al., 2018). Despite clear evidence of an intimate connection between sleep, mood and sex, few studies have explored sex differences in sleep disturbances among individuals experiencing MDE (Armitage and Hoffmann, 2001; Reynolds et al., 1990). Indeed, limited research has focused specifically on sex differences in sleep microstructure and macrostructure abnormalities associated with MDE, such as sex effects on slow wave sleep and delta-wave density (Armitage and Hoffmann, 2001; Reynolds et al., 1990). These results already provide substantial support for a sex-difference pathophysiology of MDE, but no study to our knowledge has indicated whether sleep complaints associated with MDE differ for men and women. Addressing this gap in knowledge is impor-tant for elucidating the unique patterns of sleep disturbances and their associations with MDE specific to each sex.

In this context, this study aims to investigate sex differences in the prevalence, sociodemographic characteristics, and psychiatric comor-bidity associated with sleep complaints among adults with MDE. Such understandings appear important for accurate diagnosis, tailored treat-ment approaches, and improved clinical outcomes.

## 2. Methods

### 2.1. Participants

Data were drawn from the Wave 1 and Wave 2 NESARC, a nationally representative survey of the US adult population, conducted in 2001–2002 (Wave 1) and 2004–2005 (Wave 2) by the National Institute on Alcoholism and Alcohol Abuse (NIAAA) and described in detail elsewhere (Blanco et al., 2023; Grant et al., 2009). The target population included the civilian population, aged 18 years and older, residing in households and group quarters. Face-to-face interviews were conducted with 43,093 respondents. The overall survey response rate for Wave 1 was 81 %. In Wave 2, attempts were made to conduct second interviews with all 43,093 respondents. Excluding respondents ineligible for the Wave 2 interview because they were deceased, deported, on active military duty throughout the follow-up period, or mentally or physically impaired, the cumulative response rate at Wave 2 was 70.2 %, reflecting 34,653 completed Wave 2 interviews.

Adjustment for nonresponse across sociodemographic characteristics and the presence of any lifetime Wave 1 NESARC substance use disorder or other psychiatric disorder was performed at the household and person levels (Grant et al., 2007). Weighted data were then adjusted to be representative of the civilian population of the United States on socio-economic variables based on the 2000 Decennial Census (Grant et al., 2009). The Wave 2 NESARC weights include a component that adjusts for nonresponse for sociodemographic factors and psychiatric diagnoses (Grant et al., 2009), to ensure that the sample approximates the target population, i.e., the original sample minus attrition between the two waves. In order to test whether this nonresponse adjustment was suc-cessful, Wave 2 respondents were compared with the target population (comprising Wave 2 respondents and eligible non-respondents) in terms of number of baseline (Wave 1) sociodemographic and diagnostic measures (Grant et al., 2009). The resulting comparison indicated that there were no significant differences between the Wave 2 respondents and the target population on socioeconomic status, age, race-ethnicity, sex or the presence of any lifetime drug, mood, anxiety or personality disorder (each examined separately) (Grant et al., 2009). The research protocol, including informed consent procedures, received full human subjects review and approval from the US Census Bureau and the Office of Management and Budget (Grant et al., 2009).

### 2.2. Diagnostic interview

The NIAAA Alcohol Use Disorder and Associated Disabilities Inter-view Schedule, DSM-IV Version (AUDADIS-IV) (Grant et al., 2003), a fully structured diagnostic interview designed for administration by lay professional interviewers, was used to assess lifetime DSM-IV-TR dis-orders (Guze, 1995). Consistent with DSM-IV-TR, a MDE was diagnosed when an individual reported at least 2 weeks of persistent depressed mood or anhedonia, accompanied by a total of at least 5 of the 9 DSM-IV-TR symptoms of MDE during the episode. To reduce participants' burden, the diagnosis of MDE focused on the most severe episode (Hasin et al., 2005). Test-retest reliability (Grant et al., 2003; Hasin et al., 2005) and validity (Canino et al., 1999) of the AUDADIS-IV diagnoses of MDE (Canino et al., 1999; Grant et al., 2003) are good (k = 0.64–0.67), and a clinical reappraisal study (Grant et al., 2004) of major depressive episode indicated good agreement between AUDADIS-IV and psychia-trist diagnoses (k = 0.64–0.68).

In this study, we examined the sleep complaints of men and women respectively with a DSM-IV-TR diagnosis of MDE between the two Waves, in order to increase our confidence that all MDE symptoms co-occurred and to reduce the risk of recall bias. The sum of all 8 DSM-IV-TR MDE criteria (after excluding the criterion assessing sleep com plaints) was used to estimate MDE severity.

Other axis I diagnoses included substance use disorders (alcohol use disorder, drug use disorder and nicotine dependence), mood disorders
(dysthymic disorder, hypomania and mania), anxiety disorders (panic disorder with and without agoraphobia, agoraphobia, social anxiety disorder, specific phobia, generalized anxiety disorder and post-traumatic stress disorder) and attention deficit hyperactivity disorder. For all Axis I disorders, diagnoses were made on a lifetime basis. Axis II disorders (including avoidant, dependent, obsessive-compulsive, hysteronic, paranoid, schizoid, schizotypal, borderline, narcissistic and antisocial personality disorders) were also assessed on a lifetime basis. The test-retest reliability and validity of AUDADIS-IV measures of DSM-IV-TR mental disorders are good to excellent for substance use disorders and fair to good for other disorders.

Sociodemographic characteristics included sex, age, education, marital status, race-ethnicity, individual income, family income and nativity.

## 2.3. Sleep complaints among participants with MDE

Three types of sleep complaints were assessed among participants with a diagnosis of MDE at Wave 2 (Trouble falling asleep, Woke up too early and Hypersomnia) with the three following questions: (i) "Since last interview, did you have trouble falling asleep nearly every day for 2 (or more) weeks?"; (ii) "Since last interview, did you wake up too early nearly every day for 2 (or more) weeks?"; and (iii) "Since last interview, did you sleep more than usual nearly every day for 2 (or more) weeks?". Because these different sleep complaints may co-occur during a depressive episode (Geoffroy et al., 2018a; Soehner et al., 2014b), we distinguished the 8 following groups of individuals with MDE: "Trouble falling asleep + Woke up too early + Hypersomnia", "Trouble falling asleep + Woke up too early", "Trouble falling asleep + Hypersomnia", "Trouble falling asleep", "Woke up too early + Hypersomnia", Woke up too early", "Hypersomnia" and "No sleep problems".

## 2.4. Statistical analyses

Percentages and their standard errors (SE) were calculated to provide descriptive information on the sociodemographic characteristics and psychiatric comorbidity within each group of individuals with a MDE. Multinomial logistic regression analyses were performed to compare sociodemographic characteristics and lifetime psychiatric comorbidity across the 8 groups of individuals with MDE with each type of sleep disturbances in both men and women. To disentangle factors that are independently associated with each pattern of sleep disturbance, we performed a single multi-adjusted multinomial logistic regression model including sociodemographic characteristics, psychiatric comorbidity and depression severity (estimated using the sum of all DSM-IV MDE criteria, except for the criterion assessing sleep complaints). These models were then repeated including interaction terms between each variable and sex to study if the main effects differed between men and women. We performed statistical analyses using R version 4.1.3 with the survey package (version 4.0) (Lumley, 2020, 2004) to take into account the complex design of the NESARC. Because our approach was both semi-confirmatory and semi-exploratory, and in order to limit type I error inflation, statistical significance was evaluated using a two-sided design with alpha set a priori at 0.05.

# 3. Results

## 3.1. Prevalence of sleep complaints in participants with MDE

Among the 954 men [median age at Wave 2 (interquartile range (IQR)) = 43 (32–57) years] with MDE between the two waves of the NESARC, 864 (91.0 %) reported at least one type of sleep complaints, whereas 90 (9.0 %) had no sleep problems. Among those with sleep complaints, 732 (77.2 %) had insomnia, while 390 (41.3 %) reported hypersomnia. More specifically, within the whole population, 105 (11.7 %) had trouble falling asleep, 68 (6.6 %) woke up too early, 301 (31.5 %) had both trouble falling asleep and woke up too early, 132 (13.8) had hypersomnia only, 92 (9.5 %) had both trouble falling asleep and hypersomnia, 37 (4.4 %) woke up too early and had hypersomnia, and 129 (13.5 %) had all three types of sleep complaints between the 2 waves (Fig. 1).

Among the 2619 women (median age at Wave 2 (interquartile range (IQR)) = 44 (32–61) years] with MDE between the two waves, 2435 (93.3 %) reported at least one type of sleep complaints, whereas 184 (6.7 %) had no sleep problems. Among those with sleep complaints, 2077 (78.3 %) had insomnia, while 1176 (46.2 %) reported hypersomnia. More specifically, within the whole population, 243 (9.7 %) had trouble falling asleep, 161 (5.8 %) woke up too early, 855 (31.6 %) had both trouble falling asleep and woke up too early, 358 (15.0 %) had hypersomnia only, 319 (13.5 %) had both trouble falling asleep and hypersomnia, 97 (3.4 %) woke up too early and had hypersomnia, and 402 (14.3 %) had all three types of sleep complaints between the 2 waves (Fig. 1).

No statistically significant differences were observed in the comparison of the prevalence of different types of sleep complaints between men and women with major depressive disorder (Table S1).

## 3.2. Sociodemographic characteristics and psychiatric comorbidity in men with MDE by type of sleep complaints (tables S2 and S4, Fig. 2)

### 3.2.1. Characteristics of men who had trouble falling asleep and/or woke up too early

Men with MDE who had trouble falling asleep, compared to men with MDE and no sleep problems, were less likely to be black, to have low individual incomes, to be married or living with someone, and were more likely to have a lifetime history of drug use disorder and hypomania or mania.

Based on the same comparison group, men with MDE who woke up too early were less likely to have a diagnosis of histrionic personality disorder.

Men with MDE and both trouble falling asleep and woke up too early, compared to men with MDE and no sleep problems, were less likely to be black, to have lower individual incomes and were more likely to report a lifetime history of post-traumatic stress disorder.

### 3.2.2. Characteristics of men with hypersomnia

Compared to men with MDE and no sleep problems, men with MDE and hypersomnia were less likely to be black, married or widowed, to have low individual incomes, and to report a lifetime history of specific phobia and dependent personality disorder, but were more likely to have a lifetime history of hypomania and mania.

### 3.2.3. Characteristics of men who complained of both trouble falling asleep and hypersomnia

Compared to men with MDE and no sleep problems, those who complained of both trouble falling asleep and hypersomnia were less likely to be married or widowed and to have a lifetime history of avoi-dant personality disorder.

### 3.2.4. Characteristics of men who complained of both waking up too early and hypersomnia

Compared to men with MDE and no sleep problems, those with MDE who complained of both waking up too early and hypersomnia were less likely to have lower individual incomes, and more likely to report a lifetime history of post-traumatic stress disorder.

### 3.2.5. Characteristics of men with MDE and multiple sleep complaints

Compared to men with MDE and no sleep problems, those with MDE and multiple sleep complaints (i.e., had trouble falling asleep and hypersomnia and woke up too early) were older and less likely to be married. They also reported less frequently a lifetime history of alcohol use disorder and of avoidant personality disorder, whereas they had
<figure><img src="image_4.png" /><figcaption>Fig. 1. Prevalence of sleep complaints in men (N = 954) and women (N = 2619) participants with major depressive disorder between the two waves of the NESARC.</figcaption></figure>

higher rates of drug use disorder, hypomania and mania, generalized anxiety disorder, and schizotypal personality disorder.

### 3.3. Sociodemographic characteristics and psychiatric comorbidity in women with MDE by type of sleep complaints (Tables S2 and S5, Fig. 2)

#### 3.3.1. Characteristics of women who had trouble falling asleep and/or woke up too early

Women with MDE who had trouble falling asleep, compared to women with MDE and no sleep problems, were more likely to be Native American and to have a lifetime history of panic disorder with or without agoraphobia, and less likely to report a lifetime history of agoraphobia.

Based on the same comparison group, women with MDE who woke up too early were less likely to be Asian and have a lifetime history of agoraphobia, and more likely to report a lifetime history of panic disorder.

Women with MDE and both trouble falling asleep and woke up too early, compared to women with MDE and no sleep problems, were more likely to be married and to report a lifetime history of hypomania and mania, panic disorder and post-traumatic stress disorder.

#### 3.3.2. Characteristics of women with hypersomnia

Compared to women with MDE and no sleep problems, women with MDE and hypersomnia were more likely to report a lifetime history of panic disorder with or without agoraphobia.

#### 3.3.3. Characteristics of women who complained of both trouble falling asleep and hypersomnia

Compared to women with MDE and no sleep problems, women who complained of both trouble falling asleep and hypersomnia were less likely to be black and have lower education levels, and less likely to have a lifetime history of social anxiety disorder. On the other hand, these women were more likely to have a lifetime history of hypomania or mania, dysthymic disorder, panic disorder with or without agoraphobia and post-traumatic stress disorder.

#### 3.3.4. Characteristics of women who complained of both waking up too early and hypersomnia

Compared to women with MDE and no sleep problems, women with MDE who complained of both waking up too early and hypersomnia were less likely to be white and more likely to have lower individual incomes. They were also less likely to have a lifetime history of agoraphobia and schizotypal disorders, and more likely to have a lifetime history of panic disorder and of borderline disorders.

#### 3.3.5. Characteristics of women with MDE and multiple sleep complaints

Compared to women with MDE and no sleep problems, women with MDE and multiple sleep complaints (i.e., had trouble falling asleep and hypersomnia and woke up too early) had higher rates of hypomania and mania, panic disorder and post-traumatic stress disorder, and lower rates of alcohol use disorder.

### 3.4. Sociodemographic characteristics and psychiatric comorbidity comparison between women and men with major depressive episode (MDE) by type of sleep complaints (Table S2 and Table S3)

#### 3.4.1. Characteristics of participants who had trouble falling asleep and/or woke up too early

Compared to women with MDE and trouble falling asleep, men with MDE and trouble falling asleep were more likely to report a lifetime diagnosis of a mania spectrum disorder, agoraphobia or generalized anxiety disorder. In the other hand, they were less likely to be black, married or to report a lifetime history of specific phobia.

Compared to women with MDE who woke up too early, men with MDE who woke up showed no significant differences.

Compared to women with MDE and both trouble falling asleep and woke up too early, men were more likely to present a lifetime diagnosis of dependent or schizotypal personality disorders, and less likely to have an individual income lower than $70,000. They were also less likely to be married.
<figure><img src="image_5.png" /><figcaption>**Fig. 2.** Frequency of sleep complaints per psychiatric comorbidity in men (N = 954) and women (N = 2619) patients with major depressive disorder. Abbreviations: SAD, social anxiety disorder; GAD, generalized anxiety disorder; PTSD, post-traumatic stress disorder; ADHD, attention deficit-hyperactivity disorder; PD, personality disorder; OCPD, obsessive-compulsive personality disorder.</figcaption></figure>
### 3.4.2. Characteristics of participants with hypersomnia

Compared to women with MDE and hypersomnia, men with MDE and hypersomnia were less likely to be black, and to be married. They were also less likely to show a lifetime history of specific phobia. They were more likely to present a lifetime diagnosis of dependent personality disorder.

### 3.4.3. Characteristics of participants who complained of both trouble falling asleep and hypersomnia

In comparison with depressed women with complaints of both trouble falling asleep and hypersomnia, depressed men with the same sleep complaints were more likely to have a lifetime diagnosis of dependent personality disorder. They were less likely to be married, divorced or separated, and widowed.

### 3.4.4. Characteristics of participants who complained of both waking up too early and hypersomnia

Men with MDE who complained of both waking up too early and hypersomnia, when compared with women with MDE and the same sleep complaints, were more likely to have an income lower than $70,000. They were less likely to be married or have a lifetime history of histrionic personality disorder.

### 3.4.5. Characteristics of participants with MDE and multiple sleep complaints

Compared to women with MDE and all three sleep complaints, men were more likely to be US-born, to report a lifetime history of drug use disorder, generalized anxiety disorder, and schizotypal personality disorder. They were less likely to be married.

## 4. Discussion

This study investigated the sociodemographic characteristics and psychiatric comorbidity in men and women with MDE based on different types of sleep complaints. First, we found in both sexes a very high prevalence of all sleep complaints among patients suffering from MDE, with a prevalence of any type of sleep complaints of 93% of women and 91% of men with MDE. Sex differences were observed and provide insights into the distinctive characteristics associated with sleep complaints in MDE for men and women, which are summarized in detail in Table 1. Interestingly, women with MDE and insomnia complaint (trouble falling asleep and wake up too early) were more likely to be black, married, and low individual incomes; while men were more likely to present with an history of mania spectrum and schizotypal or dependent personality disorders. The hypersomnia complaint in women were more likely to be associated with a lifetime history of specific phobia, while men were more likely to have a dependent personality

disorder like for those with insomnia complaints. Surprisingly, being “never married” seems to be a protective factor in women against sleep complaints, while posing as a risk factor in men, compared to other marital statuses. Additionally, histrionic personality disorder is associated with these sleep issues in women. On the other hand, men experiencing multiple sleep complaints are more prone to having a drug use disorder, generalized anxiety, as well as a schizotypal or dependent personality disorder. These findings shed light on distinct characteristics and risk factors associated with sleep complaints in MDE for women and men, enhancing our understanding of the complex relationship between sleep and depression.

The higher prevalence of sleep complaints reported by both men and women in our study further emphasizes the significance of investigating the interplay between sleep disturbances and depressive symptoms. These results may be generalized beyond clinical samples and indicate that the sex-difference in the prevalence might have been overestimated in prior clinical samples, especially through the potential underestimation of their prevalence in men (Crimmins et al., 2011; Kuehner, 2003). Moreover, understanding the factors contributing to this sex difference can provide valuable insights for the development of targeted interventions and preventive strategies to address the specific needs of women affected by depressive disorders. The observed sex differences in sociodemographic characteristics and psychiatric comorbidity among individuals with MDE and different types of sleep complaints have important implications for clinical practice and treatment interventions. The findings highlight the need for tailored approaches when addressing sleep complaints in patients with MDE, screening for specific comorbidities and considering the unique clinical profiles associated with each sex.

Among women with MDE and multiple insomnia or hypersomnia complaints, the higher likelihood of specific phobia and histrionic personality disorder, and on the other hand the lower likelihood of being never married (versus married, divorced or widowed), suggest potential other underlying psychopathological mechanisms. Of note, being “never married” has been identified as a protective factor against sleep complaints in women, but poses as a risk factor in men compared to other marital statuses. Additionally, it is recognized that higher mental workload, or cognitive load, is associated with lower overall sleep quality (Jansen et al., 2020). Moreover, it is observed that women experience a greater mental workload than men, juggling responsibilities both at home and in the labor market (Fleche et al., 2018). To potentially elucidate the opposing trends observed in women and men, one could hypothesize that the heightened mental workload in women becomes more pronounced after marriage or cohabitation, possibly exacerbated by the presence of children, consequently affecting sleep quality. Additionally, previous findings reported that women may be more vulnerable to insomnia symptoms as sequelae of trauma (Short

<caption>**Table 1**</caption>

Summary of statistically significant differences for sociodemographic characteristics and psychiatric comorbidities between Men and Women participants with MDE by type of sleep complaints.

<table><thead><tr><th></th><th>Trouble falling asleep</th><th>Woke up too early</th><th>Trouble falling asleep + Woke up too early</th><th>Hypersomnia</th><th>Trouble falling asleep + Hypersomnia</th><th>Woke up too early + Hypersomnia</th><th>Trouble falling asleep + Woke up too early + Hypersomnia</th></tr></thead><tbody><tr><td>Women increased adjusted risk compared to Men</td><td>Black<br>Married<br>Widowed<br>Individual income lower than $30,000</td><td>None</td><td>Individual income lower than $70,000</td><td>Black<br>Married<br>Specific phobia</td><td>Married<br>Divorced or separated<br>Widowed</td><td>Married<br>Histrionic personality disorder</td><td>Married</td></tr><tr><td>Men increased adjusted risk compared to Women</td><td>Mania spectrum<br>Dependent personality disorder</td><td>None</td><td>Schizotypal personality disorder<br>Dependent personality disorder</td><td>Dependent personality disorder</td><td>Dependent personality disorder</td><td>Individual income lower than $70,000</td><td>US-born<br>Drug use disorder<br>Generalized anxiety disorder<br>Schizotypal personality disorder</td></tr></tbody></table>

Note: All marital statuses are compared to “never married”.
et al., 2022; Tekin et al., 2016). This finding is also consistent with a higher prevalence of nightmares among women (Schredl and Reinhard, 2011). This finding aligns with our own observations, which indicate an elevated risk of PTSD in women with MDE and multiple sleep complaints. It's noteworthy that both genders faced an increased risk of PTSD when experiencing sleep complaints, yet the risk was similar in women and men. The vulnerability to the effects of traumatic events may be greater in women than in men (as we previously shown (Blanco et al., 2018)), thus possibly contributing to explain that PTSD and MDE are more prevalent in women generally, and that trauma-related sleep alterations are more prevalent in women in our study. However, because all participants included do have MDE, this vulnerability to traumatic events may not confer additional risk once a major mental health consequence already occurred, such as MDE. Future studies should further study the specific mechanisms underlying these associations -such as neuroimaging, genetic, hormonal, immune-inflammation, psychological and psychosocial risk factor studies (Dai et al., 2016; Krishnan and Collop, 2006; Kuehner, 2003; Tu et al., 2022; Zhang et al., 2023), which may help in the development of personalized treatment strategies for individuals with MDE and sleep complaints. Furthermore, different antidepressant and sleep treatments may work somewhat differently in men and women (Khan et al., 2005; Yonkers and Brawman-Mintzer, 2002). Finally, these findings are in line with previous research indicating that personality disorders may contribute to the development and maintenance of sleep disturbances in patients with mood disorder (Kuehner, 2003). Understanding in each sex the interplay between personality traits, sleep disturbances, and depressive symptoms could inform the development of targeted interventions that address both the mood and personality disorders.

Among men with MDE and specific sleep complaints, the increased probability of mania spectrum disorder (mania or hypomania), schizotypal and dependent personality disorders, generalized anxiety, and drug use disorder, highlights the importance of comprehensive assessments that encompass both depressive symptoms and related psychiatric disorders. Notably, these findings may be associated with the observation that men often exhibit more externalizing symptoms during MDE, which can have significant repercussions such as excessive substance use, aggression, and risk-taking behaviors (Rice et al., 2015). Therefore, a comprehensive clinical assessment is warranted for men experiencing MDE with sleep complaints, considering the potential impact of these comorbidities on their overall mental health and treatment needs. Additionally, the higher prevalence of drug use disorder, schizotypal and dependent personality disorders among men with MDE and multiple sleep complaints highlights the importance of comprehensive assessments to identify and address the complexity of their clinical presentations. These findings are consistent with existing literature, which consistently demonstrates a heightened risk of these psychiatric disorders in men compared to women, irrespective of sleep disturbances (Bardenstein and McGlashan, 1990; Carter et al., 2022; Crane et al., 2015; Martin et al., 2013; van Os and Kapur, 2009). Therefore, it appears imperative to recognize the potential co-occurrence of these conditions in men with MDE and multiple sleep complaints, to propose tailored treatment approaches and improve outcomes for these individuals.

Some limitations should be acknowledged. Firstly, the NESARC has a cross-sectional design, the associations reported in this study should not be interpreted as implying causality. Secondly, sleep symptoms were assessed on qualitative reports that are not as accurate as quantitative (Boudebesse et al., 2014; Geoffroy et al., 2014; Kaplan et al., 2011; Lichstein et al., 2003) and objective assessments (Arfken et al., 2014; Geoffroy et al., 2015; Lopez et al., 2010; Murray et al., 2020). Additionally, it is worth noting that there are currently no established sex-specific guidelines for measuring sleep in individuals with MDE. However, future studies could focus on validating or comparing existing sleep assessment tools to determine whether any potential differences between sexes may exist (Ulander et al., 2021). Furthermore, depressive

disorders are highly heterogeneous conditions, and studies indicate that the characteristics of psychiatric disorders also differ according to sex (Chotai et al., 2004). For instance, seasonal affective disorders are more prevalent in women than in men. Therefore, the examination of sleep disorders based on gender should also be evaluated within the subtypes of depression. Thirdly, given the growing recognition of sleep apnea as a significant contributor to both insomnia and hypersomnia, particularly in older adults, individuals with a high BMI, and certain demographic groups, such as Black males, it is important to consider its potential impact on our findings (Geoffroy et al., 2018b; Gottlieb and Punjabi, 2020; Lee et al., 2014). While our study was unable to directly assess sleep apnea due to data limitations, we recognize that this condition could confound the associations we observed between sleep disturbances and other variables. Future studies should aim to incorporate measures of sleep apnea to provide a more comprehensive understanding of these relationships. Moreover, details regarding medication including their class, dosage, and adherence, were not available in our study. This limitation suggests the need for further investigation to understand their potential impact on sleep. Therefore, further studies are warranted to investigate these aspects. Finally, the NESARC was conducted twenty years ago and some of the measures, such as the prevalence of sleep problems psychiatric disorders, and sociodemographic characteristics, may be slightly different nowadays. Nevertheless, it is unlikely that the pattern of associations between men and women of sleep complaints would have appreciably changed during the past two decades.

In conclusion, this study identified specific sex differences in socio-demographic characteristics and psychiatric comorbidities associated with different types of sleep complaints among adults with MDE. These findings may contribute to a better understanding of the relationship between sleep and depression in men and women, paving the way for future sex-specific research and tailored prevention and treatment approaches.

## Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

## Disclaimer

The views and opinions expressed in this report are those of the authors and should not be construed to represent the views of any of the sponsoring organizations, agencies, or the US government.

Use of AI-assisted technologies in the writing process: In the writing of this manuscript, the authors used ChatGPT 4.0 for English editing, given their non-native English speaking background. The authors have reviewed the content and takes full responsibility for the content of the publication.

## CRediT authorship contribution statement

**Pierre A. Geoffroy:** Writing – original draft, Visualization, Validation, Supervision, Methodology, Formal analysis, Conceptualization.
**Alejandro Edán-Sánchez:** Formal analysis, Data curation.
**Marina Sánchez-Rico:** Writing – review & editing, Supervision, Formal analysis, Data curation.
**Sibylle Mauries:** Writing – review & editing.
**Laura Palagini:** Writing – review & editing.
**Hugo Peyre:** Writing – review & editing.
**Michel Lejoyeux:** Writing – review & editing.
**Julia Maruani:** Writing – review & editing.
**Nicolas Hoertel:** Writing – review & editing, Visualization, Validation, Supervision, Resources, Project administration, Methodology, Investigation, Formal analysis.

## Declaration of competing interest

Authors report no conflicts of interest related to this work.
# Data availability

The original data set for the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) is available from the National Institute on Alcohol Abuse and Alcoholism (http://www.niaaa.nih.gov).

# Acknowledgements

None.

# Appendix A. Supplementary data

Supplementary data to this article can be found online at https://doi.org/10.1016/j.jad.2024.09.163.

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