Original ArticleAltered sleep architecture during the first months of life in infants born to depressed mothers
Introduction
Major depressive disorder (MDD) is a common, globally pervasive disease with a lifetime prevalence of 16.2% [1] that causes a considerable socioeconomic burden [2]. Notably, women are much more commonly affected than men, and 10–16% of women experience major depression during pregnancy and postpartum [3], [4].
A large portion of the literature has reported that depression in children and adolescents is more likely to occur among the offspring of depressed mothers and that more than half of them develop the disease before adulthood [5], [6]. Many mechanisms have been identified, to date, explaining the transmission of risk from mothers to children, thereby reflecting the complexity of its underlying aetiology [7]. Among these, genetic factors and environmental exposure are prevalent [8], [9].
Several studies [10], [11] have found a need to identify early markers of mother-child transmission of depressive disorders, so that mental illness predictors can be evaluated before the development of pathology. In this context, sleep disturbances have recently been proposed to serve as these types of predictors because they are a common feature of mood spectrum disorders. Indeed, alterations at a macro-structural level, including a reduction in rapid eye movement (REM) sleep latency and slow-wave sleep, and an increase in sleep latency, wakefulness and sleep fragmentation have been reported in depressed adults [12], [13], [14], [15], [16].
Although less studied, micro-architectural sleep features are regarded as even more accurate predictive markers of vulnerability to pathology [17], [18]. Micro-architectural sleep studies have reported decreased slow-wave activity and reduced temporal coherence [12], [15], as well as increased rapid eye movements (REMs) density [19] in depressed patients compared with non-depressed individuals. As such, these micro-architectural indices have been considered to be fundamental markers of depression.
Moreover, a micro-structural sleep correlate of depression has been found in the delta sleep ratio, which is typically decreased in depressed individuals [20], [21]. Furthermore, a reduced delta sleep ratio can be regarded as a predictor of early recurrence, mood worsening and negative therapeutic outcome in major depressive disorders [22], [23].
Despite the unquestionable link between sleep disturbances and mood disorders in adults, studies on depressed children and adolescents have produced inconsistent findings [18], [24]. These inconsistencies originate from age-related or sex-related differences in sleep parameters. Indeed, recent studies have found significant sex differences in the sleep macro-architecture of depressed children and adolescents, with the greatest alterations being observed in adolescent males [25], [26], [27]. These alterations comprised lower sleep efficiency [26], reduced N2 sleep and slow-wave sleep (SWS) durations [27].
Furthermore, micro-architectural sleep alterations have been reported in 8–15-year-onset depression, with, in particular, reduced spindle activity [25], inter-hemispheric and intra-hemispheric coherence [26] and a higher REMs density [10] in depressed children and adolescents. Conversely, the delta sleep ratio has not yet been investigated in this age range.
Nonetheless, few studies have investigated sleep disturbances in never-depressed but high-risk children. Yet, the offspring of depressed mothers are likely to develop mood disorders, particularly unipolar depression. In this perspective, early predictors of pathology are relevant to these children, in order to evaluate their actual risk of developing depression.
At a macro-structural level of sleep, Armitage et al. [10] found that infants from depressed mothers exhibited a longer sleep latency, lower sleep efficiency and more sleep bouts (expression of sleep fragmentation) than controls from two weeks to six months of age. Additionally, Bat-Pitault et al. [11] found that wake after sleep onset (WASO) and sleep efficiency were, respectively, increased and reduced in high-risk adolescents relative to controls.
As for the micro-architectural sleep features, low temporal coherence and reduced sleep spindle activity (SPA) were reported in adolescent females who were at high risk of depression [25], [28]. However, because of the genetic susceptibility of depression and the need to establish early programs of prevention, it appears to be important to assess whether infants at high risk of mood disorders exhibit early onset sleep disturbances. It is believed that, to date, no data are available on the micro-architectural characteristics of this population.
Therefore, the aim of the present study was to compare the macro sleep structure between high-risk and low-risk infants at zero and six months of age. Microstructure was only studied at six months of age, which is an age when architectural features, such as spindles, are settled. The first hypothesis was that the sleep structure in the offspring of depressed mothers was already modified at birth due to the prenatal environment. Second, it was postulated that these sleep disturbances in high-risk children would trace those in adolescence and adulthood depression and, if correct, that these alterations would reflect a vulnerability to depressive mood since childhood and, hence, could be considered to be an early vulnerability marker of depression.
Section snippets
Participants
Sixty-four newborn infants (32 males, 32 females) were separated into two groups: a group of high-risk infants born from mothers with a major depressive disorder (MDD, see Diagnostic procedures and Fig. 1) (N = 32) and a group of low-risk infants born from non-MDD mothers (N = 32). Mothers were drawn from the AuBE cohort (Autonomic Baby Evaluation) [29], in which 302 women whose infants were born in the maternity ward of the University Hospital Centre of Saint-Etienne, France, were recruited
Demographic and clinical data
The HAD depression score values, corresponding to the means of HAD depression score at 0, 6, 12, 18 and 24 months, were significantly different between the two groups and were higher in the high-risk group relative to the low-risk group. No significant differences were found in the other clinical or demographic data of quantitative and categorical variables between the high-risk and low-risk groups (see Table 1).
Macro-architectural features of sleep
At M0 and M6, the high-risk infants showed more awake time and fewer arousals than
Discussion
The purpose of the present study was to assess early onset sleep disturbances in infants born from mothers with a history of major depressive disorder, which confers a considerable risk for mood disorder in their offspring [6], [7], [8], [9]. To that purpose, macro- and micro-architectural sleep indices were recorded and compared between high-risk and low-risk infants. The results revealed striking between-group differences at both levels. Because the two groups were matched on the infants' and
Conclusions
In summary, the findings largely confirm, but more importantly characterize, the findings from older children and adolescents at high risk of depression and from depressed young and adult individuals in very young infants. Moreover, the samples were composed of high risk but non-depressed individuals, indicating that the abnormal sleep pattern that was found in these infants is not due to the presence of the pathology, but rather to a vulnerability to depression. Because macro-, and especially
Acknowledgments
This work was supported in part by the French National Research Agency, Contrat ANR n° 08-MNPS-033-01.
The AuBE study was allowed through consecutive grants from the French Ministry of Health: Programmes Hospitaliers de Recherche Clinique – PHRC interrégional, 2009 and AOL 2010.
We especially acknowledge Mrs. Sophie Foucat and all of the parents of the association SA VIE (www.sa-vie.fr; Nantes-France), Dr Elisabeth Briand-Huchet and Mrs. Myriam Morinay, president of the French national
References (55)
- et al.
Major depressive in women: a review of the literature
J Am Pharm Assoc (Wash)
(2000) Epidemiology of women and depression
J Affect Disord
(2003)- et al.
Heritability of anxious-depressive and withdrawn behavior: age-related changes during adolescence
J Am Acad Child Adolesc Psychiatry
(2010) - et al.
The sleep macroarchitecture of children at risk for depression recruited in sleep centers
Eur Psychiatry
(2013) Microarchitectural findings in sleep EEG in depression: diagnostic implications
Biol Psychiatry
(1995)- et al.
Sleep EEG, depression and gender
Sleep Med Rev
(2001) - et al.
Slow-wave activity in NREM sleep: sex and age effects in depressed outpatients and healthy controls
Psychiatry Res
(2000) - et al.
A meta-analysis of electroencephalographic sleep in depression: evidence for genetic biomarkers
Biol Psychiatry
(2011) - et al.
Polysomnographic features of early-onset depression: a meta-analysis
J Affect Disord
(2014) - et al.
REM sleep dysregulation in depression: state of the art
Sleep Med Rev
(2013)
Delta sleep ratio as a predictor of sleep deprivation response in major depression
J Psychiatr Res
Sleep and depression in children and adolescents
Sleep Med Rev
Reduced sleep spindle activity in early-onset and elevated risk for depression
J Am Acad Child Adolesc Psychiatry
Ultradian rhythms and temporal coherence in sleep EEG in depressed children and adolescents
Biol Psychiatry
Temporal coherence in ultradian sleep EEG rhythms in a never-depressed, high-risk cohort of female adolescents
Biol Psychiatry
What psychometric scales can be used to assess psychologic distress of pregnant women?
J Gynecol Obstet Biol Reprod
Coordinated interactions between hippocampal ripples and cortical spindles during slow-wave sleep
Neuron
Topography of sleep slow wave activity in children with attention-deficit/hyperactivity disorder
Cortex
New insights into the mechanisms of antidepressant therapy
Pharmacol Ther
Alterations of neuroplasticity in depression: the hippocampus and beyond
Eur Neuropsychopharmacol
The HPA axis in major depression: classical theories and new developments
Trends Neurosci
Paternal transmission of stress-induced pathologies
Biol Psychiatry
The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R)
JAMA
Socioeconomic burden of subsyndromal depressive symptoms and major depression in a sample of the general population
Am J Psychiatry
Families at high and low risk for depression: a 3-Generation Study
Arch General Psychiatry
Severity, chronicity, and timing of maternal depression and risk for adolescent offspring diagnoses in a community sample
Arch Gen Psychiatry
Risk for psychopathology in the children of depressed mothers: a developmental model for understanding mechanism of transmission
Psychol Rev
Cited by (0)
- 1
These authors contributed equally to this work.