Pregnancy Denial: Toward a New Understanding of the Underlying Mechanisms.

PURPOSE OF REVIEW: Pregnancy denial is the lack of awareness of being pregnant. The aim of the review is to understand why the affected women do not recognize the signs of pregnancy. RECENT FINDINGS: Twelve case reports of pregnancy denial were published in the last ten years. While in five cases the women had an underlying mental disorder, the rest of the cases involved women who either exhibited no physical symptoms or perceived themselves to be not pregnant despite the symptoms (i.e., repression mechanisms). Pregnancy denial is considered to be a pathological issue, a likely consequence of trauma, the wish to not have a child, or a psychiatric problem. However, it appears that the majority of cases cannot be linked to any of the above reasons. We argue, therefore, that, in most cases, pregnancy denial is not associated with mental or physiological problems. Under certain circumstances, it can affect any woman.

The expectant brain-pregnancy leads to changes in brain morphology in the early postpartum period.

There is growing evidence that pregnancy may have a significant impact on the maternal brain, causing changes in its structure. To investigate the patterns of these changes, we compared nulliparous women (n = 40) with a group of primiparous women (n = 40) and multiparous mothers (n = 37) within 1-4 days postpartum, using voxel-based and surface-based morphometry (SBM). Compared with the nulliparous women, the young mothers showed decreases in gray matter volume in the bilateral hippocampus/amygdala, the orbitofrontal/subgenual prefrontal area, the right superior temporal gyrus and insula, and the cerebellum. These pregnancy-related changes in brain structure did not predict the quality of mother-infant attachment at either 3 or 12 weeks postpartum nor were they more pronounced among the multiparous women. SBM analyses showed significant cortical thinning especially in the frontal and parietal cortices, with the parietal cortical thinning likely potentiated by multiple pregnancies. We conclude that, compared with the brain of nulliparous women, the maternal brain shows widespread morphological changes shortly after childbirth. Also, the experience of pregnancy alone may not be the underlying cause of the adaptations for mothering. As regards the exact biological function of the changes in brain morphology, longitudinal research will be needed to draw any definitive conclusions.

A case report involving the experience of pervasive pregnancy denial: detailed observation of the first 12 postpartum weeks.

BACKGROUND: Pervasive pregnancy denial is a rare condition associated with distress and unassisted delivery. CASE PRESENTATION: The case involves a 38-year-old woman (NN), with two older children (ages 8 and 11), who was unaware, until delivery, that she had been pregnant. The case is discussed in the context of a 12-week observation of postpartum mood, stress, and mother-child attachment. NN and other 558 non-depressed women (mean age 32.41 years) were selected from the pool of participants in the RIPOD (risk of postpartum depression) study. All participants were recruited within 1-6 days of delivery. In addition to surveying depressed mood at childbirth, remote assessments of mood, mother-child attachment, and perceived stress were conducted at 3, 6, 9, and 12 weeks postpartum. Every other day, the participants also reported their current perceived stress levels based on a scale from 1 (low) to 10 (high). During the entire period of postpartum observation, NN reported no symptoms on the Edinburgh Postpartum Depression Scale, similar to only 1.6% of the sample, no stress as 0.7% of the sample, and above-average mother-infant bonding akin to only 4.6% of the sample. Her daily stress levels showed no disturbance, which was the case for only 3.32% of the total sample. On the day of delivery, NN reported a stress level of 1 (the minimum possible level), which was reported by only 4.2% of the total sample. However, NN reported the experience of delivery to be traumatic given that the child had fallen to the floor. CONCLUSION: The experience of a denied pregnancy did not appear to disturb NN at any time point, not even on the day of delivery. Compared to NN, the other non-depressed participants reported wide fluctuations in stress levels during the observation period. NN did not report any risk factors for denied pregnancy. Thus, she belonged neither to any group of typical pregnancy deniers, as reported in the literature, nor to a typical postpartum group. We postulate, therefore, that the extent to which pregnancy denial can be deemed a normal variation, unrelated to a psychological or physiological condition, depends largely on personal traits.

Male brain processing of the body odor of ovulating women compared to that of pregnant women.

Female chemical signals underlie the advertising of sexual receptivity and fertility. Whether the body odor of a pregnant woman also has a signaling function with respect to male behavior is yet to be conclusively established. This study examines how the body odors of ovulating and pregnant women differentially affect the behavior of heterosexual men. Body odor samples were collected from 5 pregnant women and 5 matched controls during ovulation. In a double-blind functional magnetic resonance imaging design, 18 heterosexual men were exposed to female body odors during ovulation (OV) and pregnancy (PRG) while being required to indicate the attractiveness of concurrently presented female portrait images. The participants were also required to indicate whether they assumed a depicted woman was pregnant. While neither OV nor PRG altered the perceived attractiveness of a presented face, the men tended to identify the women as pregnant while exposed to a PRG body odor. On the neural level, OV activated a network of the frontotemporal and limbic regions, while PRG activated the superior medial frontal gyrus. The results suggest that the detection of sexual availability activates the male brain regions associated with face processing and reward/motivation, whereas sensing pregnancy activates a region responsible for empathy and prosocial behavior. Thus, the female body odor during pregnancy likely helps foster circumstances conducive to the future care of offspring while the body odor advertising sexual availability promotes mating behavior. The brains of heterosexual men may be capable of unconsciously discriminating between these two types of olfactory stimuli.

The peripartum human brain: Current understanding and future perspectives.

The peripartum period offers a unique opportunity to improve our understanding of how dramatic fluctuations in endogenous ovarian hormones affect the human brain and behavior. This notwithstanding, peripartum depression remains an underdiagnosed and undertreated disorder. Here, we review recent neuroimaging findings with respect to the neuroplastic changes in the maternal brain during pregnancy and the postpartum period. We seek to provide an overview of multimodal neuroimaging designs of current peripartum depression models of hormone withdrawal, changes in monoaminergic signaling, and maladaptive neuroplasticity, which likely lead to the development of a condition that puts the lives of mother and infant at risk. We discuss the need to effectively integrate the available information on psychosocial and neurobiological risk factors contributing to individual vulnerability. Finally, we propose a systematic approach to neuroimaging the peripartum brain that acknowledges important co-morbidities and variation in disease onset.

Self-enucleation of the right eye by a 38-year-old woman diagnosed with schizoaffective disorder: a case report.

BACKGROUND: Autoenucleation is a rare form of self-mutilation typically associated with psychiatric disorders such as schizophrenia, substance-induced psychosis and bipolar disorder. The act is usually unilateral, although bilateral attempts are also well documented in the literature. CASE PRESENTATION: It is a case study involving a female patient (NN) diagnosed with schizoaffective disorder who self-enucleated her right eye following sexual intercourse with a fellow patient, and was forcefully prevented by staff from enucleating the second eye. We report recurrent episodes of her illness culminating in this severe act of self-mutilation. The motivational reasons behind this form of self-harm along with differential diagnosis and potential treatment options are discussed in the context of the available literature. CONCLUSION: Autoenucleation is commonly associated with religious and sexual delusions, and patients are thought to be at a greater risk of further self-harm. Timely antipsychotic treatment is likely to reduce the risk of such extreme forms of self-harm, although they can occur despite robust therapeutic intervention and treatment attempts. While self-inflicted eye injuries are rare, their prevention in what is typically a difficult patient group is fraught with challenges.

Effects of overnight fasting on working memory-related brain network: an fMRI study.

Glucose metabolism serves as the central source of energy for the human brain. Little is known about the effects of blood glucose level (BGL) on higher-order cognitive functions within a physiological range (e.g., after overnight fasting). In this randomized, placebo-controlled, double blind study, we assessed the impact of overnight fasting (14 h) on brain activation during a working memory task. We sought to mimic BGLs that occur naturally in healthy humans after overnight fasting. After standardized periods of food restriction, 40 (20 male) healthy participants were randomly assigned to receive either glucagon to balance the BGL or placebo (NaCl). A parametric fMRI paradigm, including 2-back and 0-back tasks, was used. Subclinically low BGL following overnight fasting was found to be linked to reduced involvement of the bilateral dorsal midline thalamus and the bilateral basal ganglia, suggesting high sensitivity of those regions to minimal changes in BGLs. Our results indicate that overnight fasting leads to physiologically low levels of glucose, impacting brain activation during working memory tasks even when there are no differences in cognitive performance.

Do Parental Hormone Levels Synchronize During the Prenatal and Postpartum Periods? A Systematic Review.

Physiological synchrony is the phenomenon of linked physiological processes among two or more individuals. Evidence of linkage between dyads has been found among a broad range of physiological indices, including the endocrine systems. During the transition to parenthood, both men and women undergo hormonal changes that facilitate parenting behavior. The present review sought to address the question as to whether hormonal synchronization occurs among expecting or new parents. A systematic literature search yielded 13 eligible records. The evidence of cortisol synchrony during the prenatal period, with additional testosterone, prolactin, and progesterone covariations in the time leading up to childbirth, was found to be most significant. During the postpartum period, parental synchrony was reported for oxytocin, testosterone, and cortisol levels. The implications of these covariations were found to translate into adaptive parenting behaviors and the facilitation of romantic bond. Associations with infant development were also reported, suggesting far-reaching effects of hormonal synchrony outside the parental dyad. The results highlight the importance of physiological interrelatedness during this sensitive period, underscoring the need for further research in this field. In view of the limited data available in this research domain, we have put forward a framework for future studies, recommending the adoption of standardized research protocols and repeated collections of specimens.

Time-sensitive changes in the maternal brain and their influence on mother-child attachment.

Pregnancy and the postpartum period are characterized by an increased neuroplasticity in the maternal brain. To explore the dynamics of postpartum changes in gray matter volume (GMV), magnetic resonance imaging was performed on 20 healthy postpartum women immediately after childbirth and at 3-week intervals for 12 postpartum weeks. The control group comprised 20 age-matched nulliparous women. The first 6 postpartum weeks (constituting the subacute postpartum period) are associated with decreasing progesterone levels and a massive restructuring in GMV, affecting the amygdala/hippocampus, the prefrontal/subgenual cortex, and the insula, which approach their sizes in nulliparous women only around weeks 3-6 postpartum. Based on the amygdala volume shortly after delivery, the maternal brain can be reliably distinguished from the nulliparous brain. Even 12 weeks after childbirth, the GMV in the dorsomedial prefrontal cortex, and the cortical thickness of the subgenual and lateral prefrontal cortices do not reach the pre-pregnancy levels. During this period, a volume decrease is seen in the cerebellum, the thalamus, and the dorsal striatum. A less hostile behavior toward the child at 6-12 weeks postpartum is predicted by the GMV change in the amygdala, the temporal pole, the olfactory gyrus, the anterior cingulate, the thalamus and the cerebellum in the same period. In summary, the restructuring of the maternal brain follows time-dependent trajectories. The fact that the volume changes persist at 12 weeks postpartum indicates that the maternal brain does not fully revert to pre-pregnancy physiology. Postpartum neuroplasticity suggests that these changes may be particularly significant in the regions important for parenting.

Neural responses to monetary incentives in postpartum women affected by baby blues.

Up to 50% of new mothers experience baby blues (BB) within a week of delivery, with affective disturbances being the central symptoms. Because reward processing is known to be affected in depression, this study sought to investigate whether incentive processing during the experience of BB can be altered through the monetary incentive delay (MID) task. The MID task allows reward processing to be investigated based on responses to 'anticipation' and 'feedback of reward or loss'. 60 women participated in the fMRI-based MID task within 1-6 days of delivery, and 50% of them developed BB within the first few postpartum weeks. Over a 12-week observation period, a greater number of women in the BB group (52% vs. 13%) developed psychiatric conditions, with 24% of women with BB developing postpartum depression compared to only 3% of those without BB. During the feedback trials of the MID task, women with BB, compared to those without, showed increased activation in both the winning and losing trials (the temporal areas, the insula, the midbrain, and the inferior frontal gyrus). During the anticipation trials, however, subjects affected by BB showed reduced activation in the pregenual and the subgenual anterior cingulate cortices (pg/sg ACC). Our results demonstrate, for the first time, that the BB-related time window overlaps with alterations in the brain networks associated with incentive processing. Given the involvement of pg/sgACC in the development of depressive mood, the weaker involvement of these brain regions during anticipation in participants affected by BB is of particular interest.

Baby blues, premenstrual syndrome and postpartum affective disorders: intersection of risk factors and reciprocal influences.

BACKGROUND: The aetiology and consequences of 'baby blues' (lower mood following childbirth) are yet to be sufficiently investigated with respect to an individual's clinical history. AIMS: The primary aim of the study was to assess the symptoms of baby blues and the relevant risk factors, their associations with clinical history and premenstrual syndrome (PMS), and their possible contribution to the early recognition of postpartum depression (PPD). METHOD: Beginning shortly after childbirth, 369 mothers were followed up for 12 weeks. Information related to their clinical history, PMS, depression, stress and mother-child attachment was collected. At 12 weeks, mothers were classified as non-depressed, or with either PPD or adjustment disorder. RESULTS: A correlation was found between the severity of baby blues and PMS (r = 0.397, P < 0.001), with both conditions increasing the possibility of adjustment disorder and PPD (baby blues: OR = 6.72, 95% CI 3.69-12.25; PMS: OR = 3.29, 95% CI 2.01-5.39). Baby blues and PMS independently predicted whether a mother would develop adjustment disorder or PPD after childbirth (χ2(64) = 198.16, P < 0.001). Among the non-depressed participants, baby blues were found to be associated with primiparity (P = 0.012), family psychiatric history (P = 0.001), PMS (P < 0.001) and childhood trauma (P = 0.017). CONCLUSIONS: Baby blues are linked to a number of risk factors and a history of PMS, with both conditions adding to the risk of PPD. The neuroendocrine effects on mood need be understood in the context of individual risk factors. The assessment of both baby blues and PMS symptoms within the first postpartum days may contribute to an early identification of PPD.

Characterization of Depressive Symptom Trajectories in Women between Childbirth and Diagnosis.

The inhomogeneity of postpartum mood and mother-child attachment was estimated from immediately after childbirth to 12 weeks postpartum in a cohort of 598 young mothers. At 3-week intervals, depressed mood and mother-child attachment were assessed using the EPDS and the MPAS, respectively. The diagnosis was based on clinical interviews at the end of the 12-week follow-up. The latent class mixed model estimated multiple distinct patterns in depressed mood and mother-child attachment. The baseline EPDS cluster contained 72% of the study population and showed low EPDS values during the follow-up period, while the five remaining clusters showed either deterioration or improvement of the EPDS levels. The majority of women with postpartum depression showed deteriorating, and the majority of adjustment disorder cases improving, behavior. While the cases with more pronounced EPDS values were found to constitute more homogeneous clusters in terms of diagnosis, subclinical or only temporarily increased EPDS levels represented less homogeneous clusters. Higher EPDS levels correlated with the higher risk factor profiles. The four MPAS/EPDS clusters demonstrated that higher EPDS lead to lower mother-child attachment, and vice versa.

Examining early structural and functional brain alterations in postpartum depression through multimodal neuroimaging.

Postpartum depression (PPD) affects approximately 1 in 10 women after childbirth. A thorough understanding of a preexisting vulnerability to PPD will likely aid the early detection and treatment of PPD. Using a within-sample association, the study examined whether the brain's structural and functional alterations predict the onset of depression. 157 euthymic postpartum women were subjected to a multimodal MRI scan within the first 6 days of childbirth and were followed up for 12 weeks. Based on a clinical interview 12 weeks postpartum, participants were classified as mentally healthy or having either PPD or adjustment disorder (AD). Voxel-based morphometry and resting-state functional connectivity comparisons were performed between the three groups. 13.4% of women in our study developed PPD (n = 21) and 12.1% (n = 19) adjustment disorder (AD). The risk factors for PPD were a psychiatric history and the experience and severity of baby blues and the history of premenstrual syndrome. Despite the different risk profiles, no differences between the PPD, AD and control group were apparent based on structural and functional neuroimaging data immediately after childbirth. At 12 weeks postpartum, a significant association was observed between Integrated Local Correlation (LCor) and the Edinburgh Postnatal Depression Score (EPDS). Our findings do not support the notion that the brain's structural and resting-state functional alterations, if present, can be used as an early biomarker of PPD or AD. However, effects may become apparent if continuous measures of symptom severity are chosen.

The early postpartum period - Differences between women with and without a history of depression.

Depression is a highly recurrent disorder. When in remission, it affords an important opportunity to understand the state-independent neurobiological alterations, as well as the socio-demographic characteristics, that likely contribute to the recurrence of major depressive disorder (MDD). The present study examined 110 euthymic women in their early postpartum period. A comparison was made between participants with (n = 20) and without (n = 90) a history of MDD by means of a multimodal approach including an fMRI experiment, assessment of hair cortisol concentration (HCC) and a clinical anamnestic interview. Women with a personal history of MDD were found to have decreased resting-state functional connectivity (RSFC) between the lateral parietal cortex (LPC) and the posterior cingulate cortex (PCC), and their Edinburgh Postnatal Depression Scale (EPDS) scores were significantly higher shortly after childbirth. More often than not, these women also had a family history of MDD. While women with no history of depression showed a negative association between hair cortisol concentration (HCC) and gray matter volume (GMV) in the medial orbitofrontal cortex (mOFC), the opposite trend was seen in women with a history of depression. This implies that women with remitted depression show distinctive neural phenotypes with subclinical residual symptoms, which likely predispose them to later depressive episodes.

Predicting Hair Cortisol and Cortisone Concentration in Postpartum Women through Repeated Measurements of Perceived Stress.

To investigate whether hair cortisol (HCC) and hair cortisone (HCNC) can be predicted by repeated stress reports from postpartum women in different mental health conditions (non-depressed, ND, adjustment disorder, AD, postpartum depression, PPD), 240 mothers (mean age 31.8 years; SD = 4.7) were monitored from within 1 to 6 days of childbirth over a period of three months. HCC and HCNC in 3 cm hair samples were assessed via triple mass spectrometry after liquid chromatographic separation. Every second day, participants reported their stress levels online. The summed perceived stress scores were not found to be predictive of HCC. However, perceived stress predicted a decrease in HCNC (rSpearman = -0.153, p = 0.035) and an increase in the HCC/HCNC ratio (rSpearman = 0.304, p < 0.001) in the ND group. With AD in the first few weeks after childbirth, an inverse effect appeared for HCNC (rSpearman = 0.318, p = 0.011), suggesting an overall downregulation of the HPA axis owing to the stressful experience of adjusting to the new situation. No effects were found for mothers developing PPD. The indirect results of HPA-axis activity are better indicators of the experience of psychological stress in postpartum women than the absolute HCC value.

Phenotypical predictors of pregnancy-related restless legs syndrome and their association with basal ganglia and the limbic circuits.

Restless legs syndrome (RLS) in pregnancy is a common disorder with a multifactorial etiology. A neurological and obstetrical cohort of 308 postpartum women was screened for RLS within 1 to 6 days of childbirth and 12 weeks postpartum. Of the 308 young mothers, 57 (prevalence rate 19%) were identified as having been affected by RLS symptoms in the recently completed pregnancy. Structural and functional MRI was obtained from 25 of these 57 participants. A multivariate two-window algorithm was employed to systematically chart the relationship between brain structures and phenotypical predictors of RLS. A decreased volume of the parietal, orbitofrontal and frontal areas shortly after delivery was found to be linked to persistent RLS symptoms up to 12 weeks postpartum, the symptoms' severity and intensity in the most recent pregnancy, and a history of RLS in previous pregnancies. The same negative relationship was observed between brain volume and not being married, not receiving any iron supplement and higher numbers of stressful life events. High cortisol levels, being married and receiving iron supplements, on the other hand, were found to be associated with increased volumes in the bilateral striatum. Investigating RLS symptoms in pregnancy within a brain-phenotype framework may help shed light on the heterogeneity of the condition.

Early identification of postpartum depression using demographic, clinical, and digital phenotyping.

Postpartum depression (PPD) and adjustment disorder (AD) affect up to 25% of women after childbirth. However, there are no accurate screening tools for either disorder to identify at-risk mothers and enable them to benefit from early intervention. Combinations of anamnestic, clinical, and remote assessments were evaluated for an early and accurate identification of PPD and AD. Two cohorts of mothers giving birth were included in the study (N = 308 and N = 193). At baseline, participants underwent a detailed sociodemographic-anamnestic and clinical interview. Remote assessments were collected over 12 weeks comprising mood and stress levels as well as depression and attachment scores. At 12 weeks postpartum, an experienced clinician assigned the participants to three distinct groups: women with PPD, women with AD, and healthy controls (HC). Combinations of these assessments were assessed for an early an accurate detection of PPD and AD in the first cohort and, after pre-registration, validated in a prospective second cohort. Combinations of postnatal depression, attachment (for AD) and mood scores at week 3 achieved balanced accuracies of 93 and 79% for differentiation of PPD and AD from HC in the validation cohort and balanced accuracies of 87 and 91% in the first cohort. Differentiation between AD and PPD, with a balanced accuracy of 73% was possible at week 6 based on mood levels only with a balanced accuracy of 73% in the validation cohort and a balanced accuracy of 76% in the first cohort. Combinations of in clinic and remote self-assessments allow for early and accurate detection of PPD and AD as early as three weeks postpartum, enabling early intervention to the benefit of both mothers and children.

Restless Legs Syndrome During Pregnancy and 12 Weeks Postpartum and its Links to Cardiovascular Diseases, Stressful Life Events, and Psychiatric History.

Restless legs syndrome (RLS) is highly prevalent among pregnant women. In the present study, a neurological-obstetrical sample of 561 postpartum women was retrospectively screened for RLS symptoms during pregnancy and in the first 12 weeks postpartum. The first screening took place within 1 to 6 days of delivery (T0) and the second 12 weeks after childbirth (T1). The pregnancy-related RLS prevalence rate was found to be 21% (n = 119), with the women suffering from RLS being more often affected by psychiatric history and having been more exposed to stressful life events. They were also found to have experienced baby blues more frequently shortly after childbirth. However, RLS in pregnancy did not appear to have any effect on the development of postpartum depression. Additionally, a positive trend was observed toward an association between pregnancy-related RLS and gestational diabetes and hypertension. Of the 119 women, 23 (19.3%) remained affected by RLS 12 weeks postpartum. Body mass index (BMI), weight gain, parity, childbearing history, or chronic stress exposure in pregnancy as measured by hair cortisol were not found to be linked to RLS. In summary, a comprehensive understanding of the interaction of clinical, environmental, and anamnestic factors can help shed valuable light on this pregnancy-related condition.

Neural correlates of depression in women across the reproductive lifespan - An fMRI review.

INTRODUCTION: Depressive disorders in women emerge largely during transitions in their reproductive aging cycle, which can be attributed to internal endocrine possesses that affect emotion-associated brain circuits. A review was performed to outline the neural basis in depression during female puberty, premenstrual dysphoric disorder (PMDD), postpartum depression disorder (PPD) and perimenopausal depression disorder. METHODS: For this review, Web of science, Pubmed and PsychInfo databases were searched for functional brain imaging studies addressing reproductive cycle-related mood disorder. The results are summarized and discussed within a broader theoretical framework of major depression disorder (MDD) to determine how reproductive-sensitive phases contribute to affective symptoms and how they relate to the neurobiology of MDD. RESULTS: Neural activation patterns of all depressive disorders related to female reproductive cycle, except for puberty depression, differ from these observed in MDD. While the PMDD results are widely divergent, the activation patterns in PPD show general hypoactivation in all respects. LIMITATIONS: Systematic comparisons between the diverse depression disorders are impeded by the heterogeneous experimental protocols used on different samples, reproductive aging stages and depression types. CONCLUSION: Given that hormonal fluctuations strongly influence the development of a reproductive cycle-related depression, it is possible that the hormonal and neural patterns are indicative of distinct mood disorder with phase specific biotypes, that only show behavioral similarities to MDD. Understanding the similarities and differences in the neural functioning of female cycle-related mood disorders evaluated against MDD might help elucidate the role of neuroendocrine involvement in development of depression in women, and potentially facilitate the search for prevention and treatment approaches for women' reproductive-related depressions.