Perinatal depression (PND) refers to the onset of major depression during pregnancy (antenatal depression, AD) and up to 12 months after delivery (postpartum depression, PPD). The estimated prevalence of PND is roughly 12 % [
1] with a three-fold increase in incidence of depression during the postpartum period compared to nullipara [
2]. Up to 80 % of women in the postpartum period report some kind of depressive symptoms, which range from a mild and transient form of sadness that is frequently termed “baby blues” to full diagnoses of major depression [
3]. The Diagnostic and Statistical Manual of Mental Disorders, 4th edition text-revised (DSM-IV-TR) defined a specific subtype of major depressive disorder as post-partum depression (PPD) when the onset of the depressive episode occurs within 4 weeks after delivery [
4]. Indeed, the risk of depression in puerperal women remains high through the first postpartum year [
5], and in around 50 % of the cases the onset of depression occurs already during pregnancy. Based on this, the above mentioned, wider definition of perinatal depression (PND) has been adopted. The revised fifth edition of DSM (DSM-V) does not recognise this entity as a separate diagnosis, but as a specifier of major depression by using the term of “perinatal-onset or peripartum”, where a woman has to meet the criteria for major depressive episode with an onset in pregnancy or within 4 weeks of delivery [
6]. An unrecognized or an untreated PND increases the risk of preterm delivery [
7], smoking and substance use, shortening of breastfeeding [
8], abusive behaviour toward children, suicide [
9], negative effects on the relationship with the partner and cognitive problems in infants [
10]. A significantly higher mean mother-infant daily cost was estimated by the British health system for women with PND compared to women without PND [
11]. The absence of defined objective markers for PND diagnosis, which is purely based on the clinical interview and therefore examiner-dependent, is a significant limit to unequivocal and early recognition of the disease. Moreover, to date, except for a history of depression or positive familiar psychiatric history, no certain medical risk factors are known to predict PND [
12]. With the exception of theoretical abnormalities in hypothalamic-pituitary-adrenal axis activity and possible genetic risk factors that are shared with a variety of psychiatric disorders, the etiopathogenesis of PND is still unknown. Once PND is recognized, no definitely safe pharmacologic treatments are available during pregnancy and breastfeeding [
13], and the concurrent lack of preventive therapies exposes the health of women and children to the PND related risks. Placebo-controlled, randomized trials of antidepressant substances in this population are lacking, and the methodological flaws of available studies limit the generalizability of the findings. A large meta-analysis recently concluded that evidence over benefits/harms of available compounds cannot adequately support informed decisions about the treatment of PND [
14]. Furthermore, teratogenicity concerns commonly influence women’s acceptance of potentially effective treatments. Therefore, a safe and effective treatment remains an urgent, currently unmet, clinical need.
BLT is a well-tested and safe therapy, which is effective in both depression [
17,
18] and circadian/sleep disorders [
19]. BLT is currently the treatment of choice for seasonal depression [
20]. So far, the application of BLT in the treatment of PND has been limited but with overall positive results. BLT for 3 to 6 weeks improved depression and appeared to be a safe therapy for females during pregnancy and postpartum in few small open label trials [
21‐
26].
Sleep disorder, chronobiology and depression
A bidirectional relationship between sleep disorders and depression is well established. Affective disorders, such as major depression, are strongly associated with disruption in circadian rhythms, as demonstrated by the identification of polymorphisms in specific circadian genes that are associated with these disorders. The complex interaction between circadian genes and mood-related neurotransmitter systems, in addition to the impact of chronic stress on rhythms, are considered the mechanisms underlying this relationship [
27]. Further than sleep, other circadian rhythms like hormone secretion (cortisol, prolactin, growth hormone, cortisol), body temperature and cognitive performance are impaired in patients affected by depression [
28]. Sleep deprivation has been demonstrated to be the strongest therapy in the acute phase of depression [
29].
Therefore, it is not surprising that the DSM-V includes changes in sleep duration (insomnia or hypersomnia) among the diagnostic criteria for major depressive disorder as an additional symptom. Mood disorders are commonly associated with subjective complaints of insomnia (difficulty falling asleep, restless sleep, early morning awakening, decrease sleep duration); sleep is less deep and refreshing and a high prevalence of disturbing dreams is reported by depressed patients.
The nocturnal recording of sleep (polysomnography - PSG) provides reliable biomarkers of depression. Objective sleep markers in depressed patients concern sleep disturbances such as prolonged sleep latency (SL), increased wake after sleep onset (WASO), increased early morning wake time, decreased total sleep time (TST), decreased sleep efficiency (SE = percentage of sleep on the total bed time), decreased slow waves sleep (SWS), decreased REM sleep latency, increased REM amount [
30]. Nevertheless, mood disorders are also commonly found in patients affected by sleep disorders (i.e. insomnia [
31], sleep apnoea [
32], and restless legs syndrome [
33]).
Sleep disorders during pregnancy and perinatal depression
Sleep abnormalities are highly prevalent during pregnancy [
34]. In the first trimester of pregnancy women often complain about fatigue and excessive daytime sleepiness. In the third trimester there is a high prevalence of insomnia, sleep related breathing disorders (i.e. obstructive sleep apnea syndrome) [
35,
36], and restless legs syndrome (RLS) [
37]. Several studies demonstrated a solid association between poor sleep quality, sleep disorders and post-partum mental disorders such as psychosis, anxiety and overall depression [
38]. The occurrence of RLS during pregnancy is related to an increased risk of PND [
39]. These findings call for a comprehensive evaluation of sleep and related disorders during pregnancy, suggesting sleep as a black box hiding possible precious candidate features for PND prediction. An early recognition of these sleep-related features during pregnancy would be highly valuable for an accompanying preventive or psychoeducational intervention in affected women, avoiding potential devastating maternal and foetal consequences.
Bright light treatment for perinatal depression
The treatments of choice for major depression are antidepressant drugs. However, no drugs belonging to antidepressant classes (tricyclic, SSRI, SNRI) are unequivocally safe during pregnancy and breastfeeding [
13]. BLT is currently the treatment of choice for seasonal affective disorders [
20,
40] and also well-known as an effective treatment for non-seasonal depression [
41]. Few side effects related to this treatment are reported and include jumpiness/jitteriness, nausea and headache [
42]. In a cohort of untreated patients with normal ocular-retinal status, ophthalmologic evaluations did not document any acute light-induced pathology or long-term sequelae [
43].
There is increasing evidence that depression is associated with misalignment of the circadian rhythm and that the well-established effects of BLT on circadian synchronization are associated with its antidepressant effects [
44]. BLT promotes the resynchronization of the suprachiasmatic nucleus (SCN), the master circadian pacemaker, which is impaired in depressed patients. The firing of SCN neurons is modulated by an endogenous rhythm and by the response to photic/non-photic information received from afferent inputs, which mainly depends on the day-night cycle [
44]. The effect of light on the SCN is mediated by the multisynaptic circuit of the retino-hypotalamic tract, which connects retinal photoreceptors (especially the retinal ganglion cells containing melanopsin) to the anterior hypothalamus where the SCN is located [
45].
The antidepressant effect of BLT is also mediated by biogenic amines, especially serotonin. In patients successfully treated with BLT and in remission, depletion of tryptophan, the amino acid precursor of serotonin, reversed the effects of BLT on mood [
46,
47]. In addition, the mood lowering effect of tryptophan depletion is blocked under bright light conditions [
48] again supporting the notion that BLT affects serotonergic neurotransmission. Since alterations in tryptophan [
49] and the hypothalamic pituitary adrenal (HPA) axis activity [
50,
51] during pregnancy have been implicated in serotonin dysregulation and PND, this provides a possible rationale for the application of BLT in PND. As detailed above, a further rationale is the expectation that BLT’s positive effects on sleep disturbances and alertness during the perinatal period will indirectly improve depressive symptoms.
Because of its well-established antidepressant efficacy and low side-effect profile, the benefit of BLT on mood disorders during pregnancy and post-natal period has been already investigated in small pioneering open label trials [
21‐
25] (Table
1). Overall, 3- to 6-week morning BLT for 30 to 60 min improved several depression scores by close to 50 %. Moreover, in these trials BLT appeared to be a safe treatment for females during pregnancy and puerperium. These positive results pave the way to larger randomized trials with the aim of determining the effectiveness of BLT in perinatal depression, and the safety and feasibility of this therapy [
26].
Table 1
Published studies on the efficacy of bright light therapy in perinatal depression. Adapted from Crowley et Youngstedt [
26]
Antenatal depression |
| n = 16 | OL | 10,000 lux, 60 min morning (10 min after awakening) | SIGH-SAD decreased by 49 % after 3 w, by 59 % after 5 w | 2 patients experienced nausea |
23 ± 7 w | 3–5 w |
| n = 10 | R PC PG | 7,000 lux vs. 500 lux, 60 min morning (10 min after awakening) | no difference vs. placebo, SIGH-SAD improved in both groups by 45 % | Irritable hypomania in one subject resolved after reduction of light exposure |
20 ± 8 w | 5 vs. 5 |
5 w |
Wirz-Justice et al. 2011 [ 25] | n = 26 | R PC DB PG | 7,000 lux vs. 70 lux red light, 60 min morning (10 min after awakening) | significant greater improvement with active treatment (SIGH-HADS 58 % vs. 41 %, HDRS 64 % vs. 38 %) | No clinically meaningful side effects |
~25 w | 16 vs. 10 |
5 w |
Postpartum depression |
| n = 2 | OL | 10,000 lux 30 min morning (7:00–9:30) | HDRS decreased by 38 and 43 % | no adverse side effects |
4 w |
| n = 15 | R PC PG | 10,000 lux vs. 600 lux red light, 30 min morning (7:00–9:00) | no difference vs. placebo, SIGH-SAD improved in both groups by 49 % | no adverse side effects |
10 vs. 5 |
5 w |