The role of clock genes in perinatal depression: the light in the darkness

Buoli, Massimiliano; Grassi, Silvia; Iodice, Simona; Carnevali, Greta Silvia; Esposito, Cecilia Maria; Tarantini, Letizia; Barkin, Jennifer L.; Bollati, Valentina

doi:10.1111/acps.13084

Cited by 16 publications

(12 citation statements)

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“…With regard to severity of depressive symptoms, our data support a dysregulation of the expression of clock genes and this result is not surprising as previous studies showed as specific polymorphisms of CRY1 make subjects more vulnerable to depression [16] and abnormalities of circadian rhythms (e.g., late insomnia) are typical features of patients with depression [15]. However, the most interesting result is perhaps the hypo-methylation of the CLOCK gene in depressed subjects with increased IL-8 levels.…”

Section: Discussionsupporting

confidence: 84%

“…Depression, in particular the melancholic classical type, is associated with a global advance of circadian rhythms [14]. Sleep rhythms are generally deeply disrupted in severe depressed patients, including women with perinatal depression [15] and melancholic subjects that tend to have early sleep and late insomnia [14]. Two recent reviews highlighted that, despite the contrasting results, polymorphisms of Cryptochrome Circadian Regulator 1 (CRY 1) (e.g., the single nucleotide polymorphism-SNP rs2287161) may be potentially associated with an increased risk of Major Depressive Disorder (MDD) [16].…”

Section: Introductionmentioning

confidence: 99%

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The Independent Role of Body Mass Index (BMI) and Severity of Depressive Symptoms on Biological Changes of Women Affected by Overweight/Obesity

Iodice

Ceresa

Esposito

et al. 2021

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Background: Both obesity and depression are medical conditions associated with severe disability and biological abnormalities. Our aim was to study associations between Body Mass Index (BMI), depression and biological changes in women affected by overweight or obesity. Methods: Depressive symptoms were evaluated by the Beck Depression Inventory II (BDI-II) questionnaire in 200 women affected by overweight/obesity (mean age of the sample 52.7 12.9 years, BMI 33.8 5.5 kg/m2). A blood sample was obtained for evaluation of biochemical (oxytocin and vitamin D), inflammatory and epigenetic (methylation of clock genes) parameters. Multivariable linear regression models were used to study the association between BMI or severity of depressive symptoms (BDI-II scores) with different biomarkers. Results: BMI was found to be associated with severity of depressive symptoms (p = 0.050). Severity of obesity resulted to be associated with lower plasma levels of oxytocin (p = 0.053), vitamin D deficiency (p = 0.006) and higher plasma levels of IFN-γ (p = 0.004), IL-6 (p = 0.013), IL-7 (p = 0.013), TNF-alpha (p = 0.036) and chemokine ligand 3 (CCL3) (p = 0.013, R2 = 0.03). Severity of depression was significantly associated with more methylation of clock genes CRY1 (p = 0.034, R2 = 0.16) and CRY2 (p = 0.019, R2 = 0.47). More severe depression together with higher levels of IL-8 strongly predicted lower methylation of CLOCK gene (p = 0.009); Conclusions: Different biological abnormalities have been found to be independently associated with BMI and severity of depressive symptoms in women affected by overweight/obesity. The complex interplay between overweight, depression and biological changes will have to be better clarified by future studies.

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Section: Discussionsupporting

confidence: 84%

Section: Introductionmentioning

confidence: 99%

The Independent Role of Body Mass Index (BMI) and Severity of Depressive Symptoms on Biological Changes of Women Affected by Overweight/Obesity

Iodice

Ceresa

Esposito

et al. 2021

IJERPH

Self Cite

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“…Alternatively, PD is mainly characterized by initial and central insomnia, with a progressive deterioration of sleep quality in the last trimester of pregnancy and first few weeks after delivery ( 29 ). These findings are suggestive of a phase shift in circadian patterns during late pregnancy and postpartum which was demonstrated by recent findings by our group ( 18 ).…”

Section: Discussionsupporting

confidence: 86%

“…All these observations were reinforced by the results from a recent study by Buoli et al which demonstrated hypermethylation of CLOCK and hypomethylation of CRY1, PER1, PER2 in depressed pregnant women compared to controls, suggestive of a disruption in circadian rhythms ( 18 ). Moreover, the dysregulation of clock genes seemed to coincide with potential immunological abnormalities, as depressed women also showed an increased methylation of gene FOXp3 , a transcription factor expressed in a subset of CD4+ T cells that modulates the immune system ( 18 ).…”

Section: Introductionmentioning

confidence: 81%

“…Starting from the results of an our previous article ( 18 ), which supported the evidence of a disruption in circadian rhythms in depressed pregnant women, the aim of the present study is to investigate the role of oxytocin plasma levels in influencing the degree of methylation of different clock genes ( CLOCK, ARNTL, PER1, PER2, PER3, CRY1, CRY2 ) and of other related genes ( OXTR, FOXp3 and HERV-W -which encodes for a protein which plays a fundamental role in maternal immune tolerance during pregnancy) in women affected by PD and healthy controls. Because of its beneficial role in mood regulation and pregnancy outcomes, we hypothesized that oxytocin could exert a protective role over affective symptoms.…”

Section: Introductionmentioning

confidence: 99%

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The Methylation of Clock Genes in Perinatal Depression: Which Role for Oxytocin?

et al. 2021

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Background: Perinatal Depression (PD) is a widespread disabling condition that is hypothesized to be associated with abnormalities in circadian rhythms and neuropeptide release including oxytocin (OXT).Methods: Fourty-four pregnant women (28 with PD, and 16 controls) were evaluated through the Edinburgh Postnatal Depression Scale (EPDS), the State/Trait Anxiety Inventory Form Y (STAI-Y), and the Prenatal Attachment Inventory (PAI). A blood sample was collected from all participants, and OXT plasma levels, DNA methylation of clock genes, as well as of FOXp3 and HERV-W were measured. Linear regression analyses were performed to assess the effect of oxytocin on the methylation of selected genes. Continuous ordinal regression models was further applied to see if the score of rating scales was associated to gene methylation, adjusting for oxytocin-methylation interaction.Results: OXT plasma levels were positively associated with CRY1 methylation. Women with higher OXT plasma levels showed an association between higher degree of CRY2 methylation (thus, reduced expression) and lower EPDS (OR = 0.21; P = 0.043) and STAI-S scores (OR = 6.96; P = 0.019). Finally, with high OXT levels, hypermethylation of CRY1 was associated to higher scores on the PAI (OR = 2.74; P = 0.029) while higher methylation of HERV-W related to lower PAI scores (OR = 0.273; P = 0.019).Conclusion: Our results suggest a possible protective role played by oxytocin in the development of PD by promoting a favorable methylation profile characterized by reduced expression of CRY1 and CRY2. Moreover, oxytocin strengthens the association between maternal prenatal attachment with a favorable pattern of methylation of clock genes and HERV-W, which is essential for pregnancy outcomes.

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