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Abstract

While contemporary diagnostic nosology characterizes postpartum depression (PPD) as a specifier of a major depressive disorder (MDD), this classification continues to be questioned. Functional magnetic resonance imaging (fMRI) holds the promise of helping to characterize the neuroanatomical dysfunction associated with dysregulated emotion after childbirth. Twenty postpartum women underwent fMRI in the presence of emotionally valenced stimuli. The observation of relative amygdala non-responsivity in subjects demonstrating greater depression symptomotology stands in contrast to imaging studies of MDD and provides insight into possible phenotypic differences of PPD.

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... Bebi bluz (baby blues) je posleporođajna tuga, najčešći i najbezazleniji vid pospartalne depresije. Obično traje nekoliko dana posle porođaja, a prate je razdražljiviost, tuga i bezrazložan plač (8). U tim danima najbitnija je podrška porodice, kako emotivna tako i kada je u pitanju briga o detetu. ...
... Ovaj vid depresije se ne javlja uvek odmah nakon porođaja, već je moguće da se pojavi posle nekoliko meseci. Simptomi pospartalne depresije su: izrazite promene raspoloženja, od vrlo dobrog raspoloženja do velike tuge, preterano spavanje ili nesanica (nevezano za potrebe deteta), promene u apetitu, hronično iscrpljivanje ili hiperaktivnost, osećaj nemogućnosti suočavanja sa svakodnevnim problemima, razdražljivost, negativne misli, teškoće u pamćenju i koncentraciji, gubitak samopouzdanja, osećaji krivice, nemoći, usamljenost, plakanje bez razloga, strah od kontakata s drugim ljudima, osećaj nepostojanja ljubavi prema detetu ili porodici, teskoba i napadi panike, tuga i preterani plač, gubitak interesa za hobije i druge svakodnevne aktivnosti (8). ...
... Posleporođajna psihoza je izuzetno retka, jer se javlja tek kod oko 0,5% trudnica (8). Ovo je najteži i najozbiljniji oblik posleporođajnog stanja i zahteva medicinsku pomoć. ...
... For approximately 15% of mothers, this time period is accompanied by severe mood disturbance that meets the criteria for depression and includes symptoms such as irritability, uncontrollable crying, extreme sadness/hopelessness, and sometimes thoughts of harm to self and to the baby (American Psychiatric Association, 2000;Beck, 2001;Cox, Murray, & Chapman, 1993;Dennis, Heaman, & Vigod, 2012;Halbreich & Karkun, 2006;O'Hara & Swain, 1996). Despite its prevalence and pervasive impact on the developing infant (Halligan, Murray, Martins, & Cooper, 2007;Murray, 1992;Pawlby, Sharp, Hay, & O'Keane, 2008), our understanding of the neural bases of PPD relies on only a few recent studies (Moses-Kolko et al., 2010Silverman et al., 2007Silverman et al., , 2011Moses-Kolko et al., 2012;Chase, Moses-Kolko, Zevallos, Wisner, & Phillips, 2013;Laurent & Ablow, 2013, 2012; see Barrett & Fleming, 2011;Swain et al., 2014;Moses-Kolko, Horner, Phillips, Hipwell, & Swain, 2014; for reviews). These studies have identified an inverse relation between PPD symptom severity and amygdala (AMY) response (Moses-Kolko et al., 2010;Silverman et al., 2011), and suggest that this AMY hyporesponsiveness may be pathognomonic for PPD. ...
... Despite its prevalence and pervasive impact on the developing infant (Halligan, Murray, Martins, & Cooper, 2007;Murray, 1992;Pawlby, Sharp, Hay, & O'Keane, 2008), our understanding of the neural bases of PPD relies on only a few recent studies (Moses-Kolko et al., 2010Silverman et al., 2007Silverman et al., , 2011Moses-Kolko et al., 2012;Chase, Moses-Kolko, Zevallos, Wisner, & Phillips, 2013;Laurent & Ablow, 2013, 2012; see Barrett & Fleming, 2011;Swain et al., 2014;Moses-Kolko, Horner, Phillips, Hipwell, & Swain, 2014; for reviews). These studies have identified an inverse relation between PPD symptom severity and amygdala (AMY) response (Moses-Kolko et al., 2010;Silverman et al., 2011), and suggest that this AMY hyporesponsiveness may be pathognomonic for PPD. ...
... To date, negative non-infant stimuli have primarily been used to examine the neural correlates of PPD (e.g., Moses-Kolko et al., 2011Silverman et al., 2011Silverman et al., , 2007. Laurent and Ablow (2012) used negative infant stimuli for the first time, choosing to examine the brain response in mothers with depressive symptomology in the late postpartum stage (15-18 months) to infant cries. ...
Article
Recent evidence suggests that postpartum depression (PPD) is associated with reduced amygdala (AMY) response to negative stimuli. However, given the anhedonic features of PPD, it is important to consider mothers' brain response specifically to positive infant and to other positive stimuli. Mothers with (n=28) and without (n=17) clinically determined PPD (n=28) viewed smiling pictures of infants (Own and Other), and positive non-infant stimuli (NonInfant). First, we examined group differences in AMY response across conditions. Next, psychophysiological interaction was used to examine group differences in AMY connectivity across conditions. Connectivity estimates were then correlated with measures of maternal mood and anxiety. PPD, compared to Non-PPD mothers, showed overall increased AMY response across conditions in the right AMY. Despite this, PPD mothers demonstrated decreased bilateral AMY-right insular cortex (IC) connectivity as compared to Non-PPD mothers when they view Own-Other infants. Furthermore, decreasing AMY-IC connectivity was associated with increasing symptoms of depression and anxiety. These differences were evident only for infant stimuli and did not apply to all positively-valenced stimuli. Thus, PPD mothers show altered brain response and connectivity in regions strongly implicated in the processing of socially and emotionally relevant stimuli, as well as interoception and the evaluation of subjective emotional experience.
... Using fMRI the study focused on four women with PPD and four euthymic mothers that were subjected to a visual presentation task consisting of words with either a positive, negative, or neutral valence. The small sample was later increased to include six women with PPD and 11 euthymic mothers [40]. The analysis of data, obtained with the same paradigm, was aimed at the study of the amygdala. ...
... Overall, brain MRI findings in PPD appear to replicate those obtained in MDD. Two exceptions, a reduced activation of the right amygdala after exposure to words with the meaning of threat [40], rather than the hyperactivity observed in comparable MDD studies, and a slight increase in spectroscopy-detected glutamate concentration in the frontal cortex [49], which contrasts with an opposite finding in most MRS studies in MDD, are not sufficient to delineate a distinct neurobiological profile for PPD, due to the small samples used to make these assessments and the lack of direct comparisons with MDD subjects. However, it seems reasonable to expect that MR studies conducted in larger populations of mothers with PPD might allow for the identification of MRI signatures for this condition. ...
... Overview of brain structures playing a role in the neurobiological mechanisms of postpartum depression as disclosed by BOLD activation fMRI studies[39][40][41][42][43][44]. Insula (INS), dorsolateral prefrontal cortex (DLPFC), dorsomedial prefrontal cortex (DMPFC), orbitofrontal cortex (OFC), thalamus (T), nucleus accumbens (NA), amygdala (AMY), ventral striatum (VS), fusiform gyrus (FG), anterior cingulate cortex (ACC), and posterior cingulate cortex (PCC). ...
Article
Full-text available
Postpartum depression is a frequent and disabling condition whose pathophysiology is still unclear. In recent years, the study of the neural correlates of mental disorders has been increasingly approached using magnetic resonance techniques. In this review we synthesize the results from studies on postpartum depression in the context of structural, functional, and spectroscopic magnetic resonance studies of major depression as a whole. Compared to the relative wealth of data available for major depression, magnetic resonance studies of postpartum depression are limited in number and design. A systematic literature search yielded only eleven studies conducted on about one hundred mothers with postpartum depression overall. Brain magnetic resonance findings in postpartum depression appear to replicate those obtained in major depression, with minor deviations that are not sufficient to delineate a distinct neurobiological profile for this condition, due to the small samples used and the lack of direct comparisons with subjects with major depression. However, it seems reasonable to expect that studies conducted in larger populations, and using a larger variety of brain magnetic resonance techniques than has been done so far, might allow for the identification of neuroimaging signatures for postpartum depression.
... Baby blues is postpartum sorrow, the most common and most innocent form of postpartum depression. It usually lasts a few days after birth, followed by irritability, sadness and causeless crying (8). In those days, the most important is firm family support when it comes to child care. ...
... This type of depression does not always occur immediately after birth, it is possible to appear after a few months. Symptoms of postpartum depression are: extreme mood swings, ranging from very good mood to great sadness, excessive sleeping or insomnia (not related to the needs of the child), changes in appetite, chronic exhaustion or hyperactivity, feeling unable to cope with everyday problems, irritability, negative thoughts, difficulty with memory and concentration, loss of confidence, feelings of guilt, helplessness, loneliness, crying without reason, fear of contact with other people, feeling the lack of love for the child or family, anxiety and panic attacks, grief and excessive crying, loss of interest in hobbies and other daily activities (8). ...
... Postpartum psychosis is extremely rare because it occurs at about 0.5% of pregnant women (8). This is the hardest and most serious form of postpartum condition and requires medical attention. ...
Article
Full-text available
According to the definition of the fourth version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), postpartum depression may include any non-psychotic depressive disorder during the first four weeks of postpartum, according to research criteria during the first year after birth. The exact cause of postpartum depression is not yet known, and most researchers believe that postpartum depression is a bio-psycho-social problem. So far, the biological aspect of the disease is explained by changing the levels of estrogen and progesterone during pregnancy, and by decrease of hormone levels after birth. Psychological correlates are often associated with low self-esteem, pessimism as a personality trait, bad strategies of coping with stress, mood swings and emotional reactions. The social aspect of the disease is associated with the existential conditions of pregnant woman, support of partners and education level. This paper will include issues like hereditary causes and possible psychological factors of postpartum depression prevention. Nowadays, it is estimated that on average 15% of women, regardless of the pregnancy outcome, are suffering from postpartum depression. However, this information includes only those women who were diagnosed with postpartum depression and who themselves reported about it. Almost every woman receives basic care during pregnancy to prevent complications in the physiological level. This paper has shown possible psychological factors of postpartum depression prevention, the impact of optimism, self-esteem and coping skills. Acta Medica Medianae 2011;50(4):62-68.
... Although research into the neurobiology of PPD is in the early stages, dampened amygdala response and corticolimbic activity, both in early and late PPD, is emerging as a distinct feature (Moses-Kolko et al., 2014;Stickel et al., 2019). While MDD involves a heightened amygdala response to negative stimuli (Fales et al., 2008), PPD is associated with a blunted amygdala response to negative (non-infant related) stimuli (Silverman et al., 2011), which predicts greater self-reported maternal hostility towards the infant (Moses-Kolko et al., 2010). Reduced activation of corticolimbic circuitry involved in emotional salience and threat processing is also a distinct feature of PPD, and is thought to underlie the decreased maternal sensitivity and increased self-reported hostility towards the infant seen in PPD (Moses-Kolko et al., 2014;Pechtel et al., 2013). ...
... In summary, PPD, even in the late postpartum period, appears to have distinct features to MDD with dampened corticolimbic circuitry and amygdala response (Moses-Kolko et al., 2014;Silverman et al., 2011), in addition to the unique aspect of the mother-infant relationship. Current treatment options for PPD, with the exception of brexanolone, assume similarities with MDD and disregard the differences, leading to poor efficacy and treatment resistance. ...
Article
Full-text available
Background Postpartum depression (PPD) is a major public health concern and has, at its core, a sense of maternal ‘disconnection’ – from the self, the infant, and the support system. While PPD bears similarities with MDD, there is increasing evidence for its distinct nature, especially with the unique aspect of the mother-infant relationship. Current treatment modalities for PPD, largely based on those used in major depressive disorder (MDD), have low remission rates with emerging evidence for treatment resistance. It is, therefore, necessary to explore alternative avenues of treatment for PPD. Objective In this narrative review, we outline the potential therapeutic rationale for serotonergic psychedelics in the treatment of PPD, and highlight safety and pragmatic considerations for the use of psychedelics in the postpartum period. Methods We examined the available evidence for the treatment of PPD and the evidence for psychedelics in the treatment of MDD. We explored safety considerations in the use of psychedelics in the postpartum period. Results There is increasing evidence for safety, and encouraging signals for efficacy, of psilocybin in the treatment of MDD. Psilocybin has been shown to catalyse a sense of ‘reconnection’ in participants with MDD. This effect in PPD, by fostering a sense of ‘reconnection’ for the mother, may allow for improved mood and maternal sensitivity towards the infant, which can positively impact maternal role gratification and the mother-infant relationship. Conclusion Psychedelic assisted therapy in PPD may have a positive effect on the mother-infant dyad and warrants further examination.
... In that pilot study, four mothers with PPD and four healthy mothers were tasked with distinguishing emotionally valenced words from non-words while undergoing BOLD fMRI. Silverman et al. expanded the study in 2011 [55]. Both studies report decreased right amygdala activation with threatening words in PPD. ...
... This prospective preliminary study evaluated women across the peripartum period for mood symptoms and then completed cross-sectional neuroimaging within 9 weeks of delivery. ROIs were selected based on results of published activation fMRI studies in PPD [55][56][57]71••] and included the ACC, and bilateral amygdalae, hippocampi, and DLPFC [27•]. Healthy postpartum women had stronger connectivity between the ACC and the left DLPFC and bilateral amygdalae. ...
Article
Full-text available
Purpose of review: Imaging research has sought to uncover brain structure, function, and metabolism in women with postpartum depression (PPD) as little is known about its underlying pathophysiology. This review discusses the imaging modalities used to date to evaluate postpartum depression and highlights recent findings. Recent findings: Altered functional connectivity and activity changes in brain areas implicated in executive functioning and emotion and reward processing have been identified in PPD. Metabolism changes involving monoamine oxidase A, gamma-aminobutyric acid, glutamate, serotonin, and dopamine have additionally been reported. To date, no studies have evaluated gray matter morphometry, voxel-based morphometry, surface area, cortical thickness, or white matter tract integrity in PPD. Recent imaging studies report changes in functional connectivity and metabolism in women with PPD vs. healthy comparison women. Future research is needed to extend these findings as they have important implications for the prevention and treatment of postpartum mood disorders.
... Clinical evidence supports disturbances in task-and nontask-oriented brain function/connectivity in PPD relative to healthy postpartum women with fMRI. Amygdala response to threat-related emotional cues is blunted in PPD relative to healthy postpartum women (Moses-Kolko et al, 2010;Silverman et al, 2011). Further, resting-state fMRI studies have shown that patients with PPD have attenuated amygdala rs-FC to DMN hubs (Chase et al, 2013) and disrupted rs-FC in several regions known to be affected in depression (eg, anterior cingulate, amygdala, hippocampus, and dorsolateral prefrontal cortex) (Deligiannidis et al, 2013). ...
... It is perhaps surprising that GnRHa and the emergence of depressive symptoms were not associated with amygdalaprefrontal rs-FC, given its critical role in processing emotionally salient stimuli. However, previous studies of depression, including PPD, did not report differences in amygdala-mPFC rs-FC relative to controls (Anand et al, 2005;Chase et al, 2014) but evidence for differences in amygdala reactivity and connectivity to tasks (Moses-Kolko et al, 2010;Silverman et al, 2011). Thus, our null observation coincides with literature indicating that depression-related amygdala-mPFC alterations are identifiable during emotionally salient tasks rather than in resting-state. ...
Article
Women are at relatively greater lifetime risk for depression than men. This elevated risk in women is partly due to heightened risk during time periods characterized by marked fluctuations in sex hormones, including postpartum and perimenopausal periods. How sex hormone fluctuations contribute to heightened risk is not fully understood but may involve intrinsic functional connectivity. We induced a biphasic ovarian sex hormone fluctuation using the gonadotropin-releasing hormone agonist (GnRHa) goserelin to determine, with a randomized placebo-controlled design, intervention effects on or GnRHa-provoked depressive symptoms associations with change in resting-state functional connectivity (rs-FC) in 58 healthy women for six seeds (amygdala, hippocampus, anterior cingulate cortex, dorsal raphe, median raphe, and posterior cingulate cortex). GnRHa intervention did not significantly affect rs-FC in any seeds. Considering the GnRHa group only, the emergence of depressive symptoms following intervention was positively associated with amygdala-right temporal cortex and negatively associated with hippocampus–cingulate rs-FC. A test for mediation suggested that rs-FC changes in these networks marginally mediated the association between decrease in estradiol and increase in depressive symptoms in the GnRHa group (p=0.07). Our findings provide novel evidence-linking changes in rs-FC networks, the emergence of depressive symptoms and sex hormone fluctuations. Notably, we observed evidence that changes in rs-FC may represent a key neurobiological intermediary between molecular changes induced by hormone fluctuations and the emergence of depressive symptoms. Taken together, our findings indicate that sex hormone fluctuations may contribute to heightened risk for developing depressive symptoms by affecting intrinsic functional connectivity of key limbic brain structures.Neuropsychopharmacology advance online publication, 19 October 2016; doi:10.1038/npp.2016.208.
... Relative to patients with major depressive disorder, patients with PPD exhibit decreased activation of many neural regions (64). Whereas patients with major depressive disorder have been shown to have a heightened amygdala response to negative stimuli (65), mothers with PPD demonstrate a blunted amygdala response to (non-infant related) negative stimuli (66,67), with more severe anxiety and depressive symptoms corresponding to further blunting of amygdala activation (68). This blunted amygdala response has relevance for maternal behavior: in one study, decreased amygdala response predicted greater self-reported hostility toward the infant among mothers with depression (68). ...
... Amygdala response to negative stimuli is heightened for major depressive disorder but blunted for PPD (65)(66)(67)(68)(69). ...
Article
Whether a major depressive episode occurring in the postpartum period (i.e., postpartum depression [PPD]) is sufficiently distinct from major depressive episodes occurring at other times (i.e., major depressive disorder) to warrant a separate diagnosis is a point of debate with substantial clinical significance. The evidence for and against diagnostic distinction for PPD is reviewed with respect to epidemiology, etiology, and treatment. Overall, evidence that PPD is distinct from major depressive disorder is mixed and is largely affected by how the postpartum period is defined. For depression occurring in the early postpartum period (variably defined, but typically with onset in the first 8 weeks), symptom severity, heritability, and epigenetic data suggest that PPD may be distinct, whereas depression occurring in the later postpartum period may be more similar to major depressive disorder occurring outside of the perinatal period. The clinical significance of this debate is considerable given that PPD, the most common complication of childbirth, is associated with immediate and enduring adverse effects on maternal and offspring morbidity and mortality. Future research investigating the distinctiveness of PPD from major depressive disorder in general should focus on the early postpartum period when the rapid decline in hormones contributes to a withdrawal state, requiring profound adjustments in central nervous system function.
... Here we investigated whether chronic Citalopram administration during the postpartum period would reverse the adverse effects of gestational stress on postpartum mood and structural plasticity in the NAc shell and the mPFC. Given findings demonstrating amygdala dysregulation in PPD (Moses-Kolko et al., 2010;Silverman et al., 2011), we also investigated the effects of gestational stress as well as postpartum administration of Citalopram on structural complexity of neurons within the basolateral amygdala (BLA), another stress sensitive brain region that interconnects with both the NAc and mPFC to form a critical network involved in mood and emotion processing (Mitra et al., 2005;Stevenson and Gratton, 2003;Vialou et al., 2014). ...
... We also show that in contrast to the NAc shell and mPFC, gestational stress increased spine density in the BLA, an effect which was not reversed by postpartum administration of Citalopram. Although neuroimaging work has previously linked these brain regions to PPD (Laurent and Ablow, 2012;McEwen et al., 2012;Moses-Kolko et al., 2010Sacher et al., 2015;Silverman et al., 2011), our data provide evidence that stress-induced neuroplastic changes in the postpartum mPFC and NAc shell may contribute to the pathophysiology of PPD and its pharmacologically induced recovery while structural changes in the BLA might underlie separate PPD symptomology beyond behavioral despair. ...
Article
Postpartum depression (PPD) is a common complication following childbirth experienced by one in every five new mothers. Although the neural basis of PPD remains unknown previous research in rats has shown that gestational stress, a risk factor for PPD, induces depressive-like behavior during the postpartum period. Moreover, the effect of gestational stress on postpartum mood is accompanied by structural modifications within the nucleus accumbens (NAc) and the medial prefrontal cortex (mPFC) - limbic regions that have been linked to PPD. Mothers diagnosed with PPD are often prescribed selective serotonin reuptake inhibitor (SSRI) antidepressant medications and yet little is known about their effects in models of PPD. Thus, here we investigated whether postpartum administration of Citalopram, an SSRI commonly used to treat PPD, would ameliorate the behavioral and morphological consequences of gestational stress. In addition, we examined the effects of gestational stress and postpartum administration of Citalopram on structural plasticity within the basolateral amygdala (BLA) which together with the mPFC and NAc forms a circuit that is sensitive to stress and is involved in mood regulation. Our results show that postpartum rats treated with Citalopram do not exhibit gestational stress-induced depressive-like behavior in the forced swim test. In addition, Citalopram was effective in reversing gestational stress-induced structural alterations in the postpartum NAc shell and mPFC. We also found that gestational stress increased spine density within the postpartum BLA, an effect which was not reversed by Citalopram treatment. Overall, these data highlight the usefulness of gestational stress as a valid and informative translational model for PPD. Furthermore, they suggest that structural alterations in the mPFC-NAc pathway may underlie stress-induced depressive-like behavior during the postpartum period and provide much needed information on how SSRIs may act in the maternal brain to treat PPD. Copyright © 2015. Published by Elsevier Inc.
... Adequate emotion processing in the postpartum period is of immediate importance for maternal-infant bonding and involves attention, appropriate infant emotion recognition, reward/ motivation, preoccupation of thought, and parental empathy [11][12][13][14]. Because of the relevance for short-and long-term offspring health, human imaging studies conducted in the postpartum period have focused predominantly on the neural correlates of postpartum depression [15][16][17][18], maternal behavior and attachment (using images of mothers' own infants or infant cries as stimuli) [19][20][21][22][23][24], and changes in parental brain volume associated with maternal-infant bonding [25][26]. However, to enhance the understanding of the maternal brain, and to allow comparison with non-pregnant states, it is also important to investigate emotional processing in the postpartum period that is unrelated to motherhood. ...
... While increased insular reactivity in our healthy postpartum women may represent an adaptation in emotion processing that supports effective parenting, it could also, hypothetically, contribute to the increased risk of depression observed postpartum. Even though participants in the present study reported sub-clinical levels of depressive symptoms, and previous studies have reported women with postpartum depression to have reduced emotion-induced left dorsomedial prefrontal cortex activation [16] and amygdala reactivity [16,18,56], areas that were not observed to be affected in the present study, the observed positive correlation between insular reactivity and depression scores at 4-6 weeks postpartum leaves preliminary support to the later theory. In addition, the observed early postpartum correlations with emotional reactivity and anxiety may reflect hormonal withdrawn manifested as "postpartum blues" with heightened emotionality, but may be important as postpartum blues is a strong risk factor for later development of depression [57] which may also account for the slightly higher depressive scores at the early assessment. ...
Article
Full-text available
Marked endocrine alterations occur after delivery. Most women cope well with these changes, but the postpartum period is associated with an increased risk of depressive episodes. Previous studies of emotion processing have focused on maternal-infant bonding or postpartum depression (PPD), and longitudinal studies of the neural correlates of emotion processing throughout the postpartum period in healthy women are lacking. In this study, 13 women, without signs of post partum depression, underwent fMRI with an emotional face matching task and completed the MADRS-S, STAI-S, and EPDS within 48 h (early postpartum) and 4-6 weeks after delivery (late postpartum). Also, data from a previous study including 15 naturally cycling controls assessed in the luteal and follicular phase of the menstrual cycle was used. Women had lower reactivity in insula, middle frontal gyrus (MFG), and inferior frontal gyrus (IFG) in the early as compared to the late postpartum assessment. Insular reactivity was positively correlated with anxiety in the early postpartum period and with depressive symptoms late postpartum. Reactivity in insula and IFG were greater in postpartum women than in non-pregnant control subjects. Brain reactivity was not correlated with serum estradiol or progesterone levels. Increased reactivity in the insula, IFG, and MFG may reflect normal postpartum adaptation, but correlation with self-rated symptoms of depression and anxiety in these otherwise healthy postpartum women, may also suggest that these changes place susceptible women at increased risk of PPD. These findings contribute to our understanding of the neurobiological aspects of the postpartum period, which might shed light on the mechanisms underlying affective puerperal disorders, such as PPD.
... This finding is more pronounced in women with PMDD (Protopopescu et al., 2008). Interestingly, women diagnosed with postpartum depression exhibit hypoactivity within the amygdala (Silverman et al., 2011). In summary, the relationship between estrogens, spinal density, and neuronal activity within this region is likely highly complex. ...
... The difference noted between these two research groups may reflect the different task subjects completed during functional magnetic resonance imaging (fMRI) scanning. Suprisingly, amygdalar activity is decreased during the postpartum period and decreased further in woman with postpartum depression, in contrast to both PMDD and MDD patients (Godlewska et al, 2012;Rupp et al., 2014;Silverman et al., 2011). This decrease in activity in women with postpartum depression is unexpected, and may be reflective of an aberrant evolutionary mechanism designed for maternal protection of offspring. ...
... When investigating brain responses to an emotional stimulus, an infant-related or non-infant-related cue (i.e., emotional word), research is showing that neural activation in mothers with depressive symptoms differs from nondepressed mothers and this difference is dependent on the type of cue used (Pawluski et For example, when exposed to an emotional cue such as a negative word or adult face, a decrease in the activation of the right amygdala has been reported in women with postpartum depression compared to healthy controls (Silverman et al., 2007(Silverman et al., , 2011. This work also found an increase in the activation of the insula as well as a decrease in striatal activity in postpartum depressed mothers (Silverman et al., 2007(Silverman et al., , 2011). ...
... When investigating brain responses to an emotional stimulus, an infant-related or non-infant-related cue (i.e., emotional word), research is showing that neural activation in mothers with depressive symptoms differs from nondepressed mothers and this difference is dependent on the type of cue used (Pawluski et For example, when exposed to an emotional cue such as a negative word or adult face, a decrease in the activation of the right amygdala has been reported in women with postpartum depression compared to healthy controls (Silverman et al., 2007(Silverman et al., , 2011. This work also found an increase in the activation of the insula as well as a decrease in striatal activity in postpartum depressed mothers (Silverman et al., 2007(Silverman et al., , 2011). When exposed to an infant cue, depressed mothers compared to healthy control mothers show an increase in the activation of the right amygdala and a decrease in the amygdala to insular cortex connectivity with own infant vs other infant smiling pictures (Wonch et al., 2016). ...
Chapter
At least one in seven pregnant or recently postpartum women will experience a mental illness such as an anxiety disorder, depressive disorder, or substance use disorder. These mental illnesses have detrimental effects on the health of the mother, child, and family, but little is known about the hypothalamic and other neural correlates of maternal mental health concerns. The transition to parenthood alone is a time of remarkable neural plasticity, so it is perhaps not surprising that current research is showing that maternal mental illness has unique neural profiles. Furthermore, the neural systems affected by peripartum mental illness overlap and interact with the systems involved in maternal caregiving behaviors, and mother–infant interactions are, therefore, highly susceptible to disruption. This review discusses what we know about the unique neural changes occurring during peripartum mental illness and the role of the hypothalamus in these illnesses. With an improved understanding of the neural correlates of maternal mental health and disease, we will be better equipped to predict risk, develop effective treatments, and ultimately prevent suffering for millions of parents during this critical time in life.
... When investigating brain responses to an emotional stimulus, an infant-related or non-infant-related cue (i.e., emotional word), research is showing that neural activation in mothers with depressive symptoms differs from nondepressed mothers and this difference is dependent on the type of cue used (Pawluski et For example, when exposed to an emotional cue such as a negative word or adult face, a decrease in the activation of the right amygdala has been reported in women with postpartum depression compared to healthy controls (Silverman et al., 2007(Silverman et al., , 2011. This work also found an increase in the activation of the insula as well as a decrease in striatal activity in postpartum depressed mothers (Silverman et al., 2007(Silverman et al., , 2011). ...
... When investigating brain responses to an emotional stimulus, an infant-related or non-infant-related cue (i.e., emotional word), research is showing that neural activation in mothers with depressive symptoms differs from nondepressed mothers and this difference is dependent on the type of cue used (Pawluski et For example, when exposed to an emotional cue such as a negative word or adult face, a decrease in the activation of the right amygdala has been reported in women with postpartum depression compared to healthy controls (Silverman et al., 2007(Silverman et al., , 2011. This work also found an increase in the activation of the insula as well as a decrease in striatal activity in postpartum depressed mothers (Silverman et al., 2007(Silverman et al., , 2011). When exposed to an infant cue, depressed mothers compared to healthy control mothers show an increase in the activation of the right amygdala and a decrease in the amygdala to insular cortex connectivity with own infant vs other infant smiling pictures (Wonch et al., 2016). ...
Article
At least 1 in 7 pregnant or recently postpartum women will experience a mental illness such as an anxiety disorder, depressive disorder or substance use disorder. These mental illnesses have detrimental effects on the health of the mother, child, and family but little is known about the hypothalamic and other neural correlates of these maternal mental health concerns. The transition to parenthood alone is a time of remarkable neural plasticity, so it is perhaps not surprising that current research is showing that maternal mental illnesses have unique neural profiles. Furthermore, the neural systems affected by peripartum mental illness overlap and interact with the systems involved in maternal caregiving behaviors and mother-infant interactions are, therefore, highly susceptible to disruption. This review discusses what we know about the unique neural changes occurring during peripartum mental illnesses and the role of the hypothalamus in these illnesses. With improved understanding of the neural correlates of maternal mental illnesses, we will be better equipped to predict risk, develop effective treatments, and ultimately prevent suffering for millions of parents during this critical time in life.
... Studies report reduced connectivity between the default mode network and the salience network, particularly between the posterior cingulate cortex and right amygdala [16] and reduced connectivity between regions of the prefrontal cortex and amygdala [17]. In PPD, studies report less engagement of neurocircuitry involved in emotional salience and fear processing of negative stimuli, including the amygdala [18,19], with one study indicating increased amygdala engagement with positive stimuli [20], a pattern differing from that reported in non-peripartum depression [21]. A few PPD studies note changes in the salience network, including attenuation of ventral striatal activity after receipt of a reward and reduced ventral striatal activation with positive stimuli [22]. ...
Article
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Diffusion tensor imaging (DTI) studies in depression show decreased structural connectivity in the left anterior limb of the internal capsule and the genu of the corpus callosum but no such studies exist in peripartum depression (PPD), which affects 1 in 8 women. We analyzed fractional anisotropy (FA) as a measure of white matter integrity of these two tracts using tract-based spatial statistics (TBSS). We then conducted an exploratory whole-brain analysis to identify additional regions implicated in PPD. Seventy-five pregnant, medication-free women were evaluated with the Edinburgh Postnatal Depression Scale (EPDS) and Structured Clinical Interview (SCID) for DSM-IV-TR in pregnancy and in the postpartum. Structural MRI and DTI sequences were acquired in forty-four women within 2-8 weeks postpartum. TBSS data were analyzed between healthy comparison postpartum women (HCW) and women who developed PPD to determine differences in white matter integrity within the left anterior limb of the internal capsule and the genu of the corpus callosum, then analyzed across participants to explore correlation between FA and the EPDS score. An exploratory whole-brain analysis was also conducted to identify other potential regions showing differences in white matter integrity between groups, as well as correlation between EPDS and FA across groups. All results were corrected for multiple comparisons and analyses conducted using FSL, p < 0.05, K > 10. In comparison to HCW, women with PPD had significantly lower FA in left anterior limb of the internal capsule (p = 0.010). FA was negatively correlated with EPDS scores in the left anterior limb of the internal capsule (p = 0.019). In the whole-brain analysis, FA in the right retrolenticular internal capsule (p = 0.03) and two clusters within the body of the corpus callosum (p = 0.044, p = 0.050) were negatively correlated with EPDS; there were no between-group differences in FA. Reduced FA in the left anterior limb of the internal capsule suggests disruption of fronto-subcortical circuits in PPD. A negative correlation between FA within the body of the corpus callosum and EPDS total score could additionally reflect disrupted interhemispheric structural connectivity in women with depressive symptoms.
... Future studies should also aim to identify a reliable biological marker for PPD. In this context, two independent fMRI studies have found that women with PPD have blunted activation of the amygdala in response to negative emotional stimuli (Moses-Kolko et al., 2010;Silverman et al., 2011), which is the opposite of what has been widely found in nonpostpartum depressed samples. The finding that women with PPD have a blunted affect to negative stimuli provides important insight into the potentially different neurophysiologic mechanisms responsible for depression in the postpartum period. ...
Article
Postpartum depression (PPD) is associated with debilitating effects on mothers and their infants. A previous history of depression is considered the strongest risk factor for PPD. Depressed individuals recall more negative than positive content and higher levels of stress hormones released during encoding are associated with enhanced recall of emotional stimuli. This study examined the impact of a previous history of major depressive disorder (MDD) and pregnancy on emotional memory. Seventy-seven participants completed the study [44 pregnant women in the second trimester of pregnancy with and without a lifetime history of MDD and 33 non-pregnant women with and without a lifetime history of MDD]. All completed an encoding task and provided salivary cortisol (sCORT) and alpha-amylase (sAA) samples. Participants returned one week later for a surprise incidental recognition memory task. Women with a history of MDD had worse recognition than women without a history of MDD for negative, but not positive images; this effect was independent of sCORT and sAA levels. Pregnancy did not affect emotional memory. Considering that several previous studies found enhanced memory bias for negative content during depressive states, our results suggest that clinical remission may be associated with an opposite cognitive processing of negative emotional content.
... Although neuroimaging studies in PPD are few, depressive symptomatology in the postpartum period is associated with reduced amygdala responsivity to positive stimuli (Barrett, J et al., 2011), threat-related stimuli (Silverman, ME et al., 2011) and negatively valenced stimuli (Moses-Kolko, EL et al., 2010;Silverman, ME et al., 2007). Additional studies have shown abnormalities in ventral striatal response to reward (Moses-Kolko, EL et al., 2011), increased glutamate levels in the medial prefrontal cortex (McEwen, AM et al., 2012) and reduced postsynaptic serotonin-1A receptor binding, in particular in the ACC and mesiotemporal cortices (Moses-Kolko, EL et al., 2008). ...
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Postpartum depression (PPD) affects up to 1 in 8 women. The early postpartum period is characterized by a downward physiological shift from relatively elevated levels of sex steroids during pregnancy to diminished levels after parturition. Sex steroids influence functional brain connectivity in healthy non-puerperal subjects. This study tests the hypothesis that PPD is associated with attenuation of resting-state functional connectivity (rs-fc) within corticolimbic regions implicated in depression and alterations in neuroactive steroid concentrations as compared to healthy postpartum women. Subjects (n = 32) were prospectively evaluated during pregnancy and in the postpartum with repeated plasma neuroactive steroid measurements and mood and psychosocial assessments. Healthy comparison subjects (HCS) and medication-free subjects with unipolar PPD (PPD) were examined using functional magnetic resonance imaging (fMRI) within 9 weeks of delivery. We performed rs-fc analysis with seeds placed in the anterior cingulate cortex (ACC), and bilateral amygdala (AMYG), hippocampi (HIPP) and dorsolateral prefrontal cortices (DLPFCs). Postpartum rs-fc and perinatal neuroactive steroid plasma concentrations, quantified by liquid chromatography/mass spectrometry, were compared between groups. PPD subjects showed attenuation of connectivity for each of the tested regions (i.e. ACC, AMYG, HIPP and DLPFC) and between corticocortical and corticolimbic regions vs. HCS. Perinatal concentrations of pregnanolone, allopregnanolone and pregnenolone were not different between groups. This is the first report of a disruption in the rs-fc patterns in medication-free subjects with PPD. This disruption may contribute to the development of PPD, at a time of falling neuroactive steroid concentrations.
... oxidase A (MAO-A) activity [5], decreased cortical -butyric acid (GABA) concentrations [6], and activation of the inflammatory response [7,8] . However, human imaging studies in the postpartum period have thus far predominantly focused on the neural correlates of maternal behavior9101112131415 or postpartum depression161718. Longitudinal studies on neural correlates of cognitive function and emotional processing across the postpartum period in healthy women are lacking. ...
Article
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The postpartum period is characterized by complex hormonal changes, but human imaging studies in the postpartum period have thus far predominantly focused on the neural correlates of maternal behavior or postpartum depression, whereas longitudinal studies on neural correlates of cognitive function across the postpartum period in healthy women are lacking. The aim of this study was to longitudinally examine response inhibition, as a measure of executive function, and its neural correlates in healthy postpartum women and non-postpartum controls. Thirteen healthy postpartum women underwent event-related functional magnetic resonance imaging while performing a Go/NoGo task. The first assessment was made within 48hours of delivery, and the second at 4-7 weeks postpartum. In addition, 13 healthy women examined twice during the menstrual cycle were included as non-postpartum controls. In postpartum women region of interest analyses revealed task-related decreased activations in the right inferior frontal gyrus, right anterior cingulate, and bilateral precentral gyri at the late postpartum assessment. Generally, postpartum women displayed lower activity during response inhibition in the bilateral inferior frontal gyri and precentral gyri compared to non-postpartum controls. No differences in response inhibition performance were found between time-points or between groups. In conclusion, this study has discovered that brain activity in prefrontal areas during a response inhibition task decreases throughout the course of the first postpartum weeks and is lower than in non-postpartum controls. Further studies on the normal adaptive brain activity changes that occur during the postpartum period are warranted.
... This avoidant presentation was then linked to maternal depressive symptoms across the first six months. While preliminary, study findings are consistent with a recent systematic review on neural endophenotypes of postpartum psychopathology (Moses-Kolko et al., 2014), which summarizes a body of literature in which mothers with postpartum depression tend to show reduced amygdala activation and amygdala-related connectivity in response to negative infant-related stimuli as compared to non-depressed mothers (Barrett et al., 2012;Silverman et al., 2011Silverman et al., , 2007. It is suggested by Moses-Kolko et al. (2014) and other sources (Laurent and Ablow, 2012) that blunted cortico-limbic responses among depressed mothers may reflect a tendency to disengage from distressing stimuli (Gollan et al., 2013;Webb and Ayers, 2015) that would otherwise be emotionally salient for non-depressed mothers in facilitating normative mother-infant attachment. ...
... 16,45 Finally, the hypothesis that amygdala activation in mothers is indicative of 'personal relevance' 44 seems less likely in view of our lack of findings about the role of amygdala activation in differentiating mothers with preterm infants versus mothers with full-term infants-which was unexpected, especially for emotional faces. Another atypical motherhood condition such as postpartum depression showed inconsistent results in depicting the role of the amygdala, to the extent that its activation seems both blunted 14,46 and augmented. 47 Thus, while our results seem to suggest less specificity in amygdala activation related to infant identity and emotional expression, further research is needed to disentangle the amygdala's role in perceiving stimuli from infants. ...
Article
Objective: The birth of a preterm infant and Neonatal Intensive Care Unit hospitalization constitute a potentially traumatic experience for mothers. Although behavioral studies investigated the parenting stress in preterm mothers, no study focused on the underlying neural mechanisms. We examined the effect of preterm births in mothers, by comparing brain activation in mothers of preterm and full-term infants. Study design: We used functional magnetic resonance imaging to measure the cerebral response of 10 first-time mothers of preterm infants (gestational age <32 weeks and/or birth weight <1500) and 11 mothers of full-term infants, viewing happy-, neutral- and distress-face images of their own infant, along with a matched unknown infant. Results: While viewing own infant's face preterm mothers showed increased activation in emotional processing area (i.e., inferior frontal gyrus) and social cognition (i.e., supramarginal gyrus) and affiliative behavior (i.e., insula). Conclusion: Differential brain activation patterns in mothers appears to be a function of the atypical parenthood transition related to prematurity.Journal of Perinatology advance online publication, 2 February 2017; doi:10.1038/jp.2017.2.
... Avoidant strategies also influence the availability of attentional resources for detecting threatening stimuli (Stein et al., 2012;Williams et al., 1996), and this can negatively impact a mother's attentiveness and responsiveness to her infant's signals (Stein et al., 2012). Similarly, emotional dysregulation in postpartum women is believed to impair the increased sensitivity to threat that is evolutionarily advantageous in helping to protect a young infant (Silverman et al., 2011). This has implications for child development, as maternal attentiveness to affective stimuli signals information to young children about their early environment, which can incur risk for the intergenerational transmission of emotional disorders (Waters et al., 2015). ...
... Third, there is emerging evidence that impaired activation of serotonergically targeted circuits may be involved in the pathophysiology of PPD [46,47], which could be corrected with bright light treatment. For example, there is recent fMRI evidence that activation in these areas is abnormal in depressed vs. non-depressed mothers when responding to their newborns' cries [48,49]. ...
Article
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Perinatal depression is an important public health problem affecting 10-20% of childbearing women. Perinatal depression is associated with significant morbidity, and has enormous consequences for the well-being of the mother and child. Treatment of depression during the perinatal period poses a complex problem for both mother and clinician, as antidepressant treatment strategies must consider the welfare of both mother and child during pregnancy and lactation. Bright light therapy may be an attractive treatment for perinatal depression because it is low cost, home-based, and has a much lower side effect profile than pharmacotherapy. The antidepressant effects of bright light are well established, and there are several rationales for expecting that bright light might also be efficacious for perinatal depression. This review describes these rationales, summarizes the available evidence on the efficacy of bright light therapy for perinatal depression, and discusses future directions for investigation of bright light therapy as a treatment for perinatal depression.
... tional dysregulation hinders the increased sensitivity to threat that is evolutionarily advantageous in helping to protect a newborn (Silverman et al., 2011). Although maternal attentiveness and responsiveness are a crucial component of the mother-infant relationship, maternal attentional disturbances and their clinical implications have not been systematically evaluated (Stein et al., 2012(Stein et al., , 2009). ...
Article
Child abuse and neglect can lead to difficulties regulating responses to threatening and emotional situations. Exposure to childhood maltreatment has been linked to conflicting findings of both attention biases toward and away from threat-related information. The aim of the current study was to investigate whether emotion regulation moderated the association between history of childhood maltreatment and attention bias in a sample of postpartum women. One hundred forty women participated in the study at 7 months postpartum. Selective attention to both negative emotional and attachment-related negative emotional words was assessed using the Emotional Stroop task. The latent variable of difficulties with emotion regulation was found to significantly moderate the association between history of childhood maltreatment and attention bias to both negative emotional (β = −0.15, t = −2.04, p < .05) and attachment-related negative emotional stimuli (β = −0.16, t = −2.98, p < .05). In women with higher childhood trauma scores, those with greater emotion regulation difficulties displayed decreased attention to negative emotional and attachment-related emotional stimuli. In contrast, women reporting higher exposure to childhood maltreatment with greater emotion regulation capacity, displayed increased attention toward negative emotional and attachment-related emotional stimuli. This study provides evidence for attentional avoidance of emotional material in postpartum women with greater experiences of maltreatment and difficulties with emotion regulation. As the postpartum period has significant implications for maternal well-being and infant development, these findings are discussed in terms of maternal responsiveness, sensitivity to threat, and the intergenerational transmission of risk.
... 23 However, this classification continues to be questioned as there is evidence to suggest differential amygdala activation in postpartum compared to non-postpartum (unipolar) depression. Two independent studies found an association between blunted amygdala activation and PPD in response to emotional stimuli, 24,25 which suggests that depression in the postpartum period may be qualitatively different than depression outside the postpartum period. ...
Article
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Introduction: Postpartum depression (PPD) is a common disorder that substantially decreases quality of life for both mother and child. In this longitudinal study, we investigated whether emotional memory, salivary cortisol (sCORT) or alpha-amylase during pregnancy predict postpartum depressive symptoms. Methods: Forty-four pregnant women (14 euthymic women with a diagnosis of major depressive disorder [MDD] and 30 healthy women) between the ages of 19 and 37 years (mean age = 29.5±4.1 years) were longitudinally assessed in the 2nd trimester of pregnancy (12-22 weeks of gestational age) and again at 14-17 weeks postpartum. Depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS). Results: Follow-ups were completed for 41 women (7% attrition). Postpartum EPDS scores were predicted by sCORT collected immediately after an incidental encoding memory task during pregnancy (b=-0.78, t -2.14, p=0.04). Postpartum EPDS scores were not predicted by positive (p=0.27) or negative (p=0.85) emotional memory. Conclusions: The results of this study indicate that higher levels of sCORT during a memory encoding task in the 2nd trimester of pregnancy are associated with lower postpartum EPDS scores. While the hypothalamus-pituitary-adrenal (HPA) axis has long been associated with the neurobiology of MDD, the role of the HPA axis in perinatal depression deserves more attention.
... Attenuated activity of the orbitofrontal cortex in response to neutral stimuli, decreased amygdala activity in response to negative words, and attenuated activity in the striatum in response to positive words have been associated with increased depression scores in women with postpartum depression [203]. Women with postpartum depression also exhibited decreased amygdala responsiveness in response to emotionally valenced stimuli [204]. Decreased activity in the ventral striatum in a monetary reward task has also been demonstrated in women with postpartum depression [205]. ...
Article
This review aims to summarize the diverse proposed pathophysiological mechanisms contributing to postpartum depression, highlighting both clinical and basic science research findings. The risk factors for developing postpartum depression are discussed, which may provide insight into potential neurobiological underpinnings. The evidence supporting a role for neuroendocrine changes, neuroinflammation, neurotransmitter alterations, circuit dysfunction, and the involvement of genetics and epigenetics in the pathophysiology of postpartum depression are discussed. This review integrates clinical and preclinical findings and highlights the diversity in the patient population, in which numerous pathophysiological changes may contribute to this disorder. Finally, we attempt to integrate these findings to understand how diverse neurobiological changes may contribute to a common pathological phenotype. This review is meant to serve as a comprehensive resource reviewing the proposed pathophysiological mechanisms underlying postpartum depression.
... Indeed, this finding is consistent with the possibility that depression in the perinatal period is a complex and heterogeneous disorder (Postpartum Depression: Action Towards Causes and Treatment (PACT) Consortium 2015) occurring via multiple pathways (O'Hara and Wisner 2014;Di Florio and Meltzer-Brody 2015). While the intent of this study was to test the association between childbirth and depression in new mothers, because of the repeatedly observed rarity of clinically ascertained PPD absent of a depression history (Fisher et al. 2012;Räisänen et al. 2014;Silverman et al. 2017;Rasmussen et al. 2017), future studies should consider the possibility that PPD in women with and without a depression history may in fact represent different phenotypes of depression (Navarro et al. 2008;Silverman et al. 2011;Altemus et al. 2012). 296.21,296.22,296.23,296.3,296.31,296.32,296.33,296.34,296.99,301.1,309.0,311,311.0,648.40,648.42,F320,F321,F322,F32.3,F32.4,F32.8,F32.9,F33,F33.0,F33.1,F33.2,F33.3,F33.4,F33.8,F33.9,F34.0,F34.1,F34.8,F34.9,F38.0,F38.1,F38.8,F39,F53,F530,F53.1,F53.8,F53.9 ...
Article
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Postpartum depression (PPD) is characterized as a depressive episode conditional on childbirth. We examined whether the risk of depression is higher following childbirth than that at a randomly generated time unrelated to childbirth. In a prospective cohort of all women with live singleton births in Sweden, 1997–2008, we first calculated the relative risk (RR) of PPD for mothers with a history of depression compared to mothers without such a history. Next, we repeated the calculations, but now for depression following a computer-generated arbitrary “phantom delivery” date, unrelated to the true date of delivery. For this phantom delivery date, we used the average expected date of delivery for all women of the same age. For the analyses of each group, women were followed for a full calendar year. We fitted Poisson regression and calculated RR and two-sided 95% confidence intervals (CI). Among a total of 707,701 deliveries, there were 4397 PPD cases and 4687 control depression cases. The RR of PPD was 21.0 (CI 19.7–22.4). The RR of depression in the control group was 26.2 (CI 24.7–27.9). We provide evidence that the risk for PPD is no greater following childbirth than following a random date unrelated to childbirth. This finding suggests that the postpartum period may not necessarily represent a time of heightened vulnerability for clinically significant depression and that the well-established observation of depression covarying with childbirth does not necessarily equate to causation, but rather may be a secondary effect of postpartum women representing a medically captured population.
... Tasking-state fMRI was performed to explore the effects of emotional responses on neural activity and functional connectivity during PPD. Clinical depressive symptoms are related to reduced amygdala responsivity with positive stimuli (Barrett et al., 2012) in the postpartum stage, threat-related stimuli (Silverman et al., 2011), and negatively valenced stimuli (Silverman et al., 2007;Moses-Kolko et al., 2010). Several abnormalities in ventral striatal activity after reward (Moses-Kolko et al., 2011), increased amygdala activity in positive emotional stimuli (Wonch et al., 2016), and reduced inferior frontal gyrus with negative stimuli were observed (Bannbers et al., 2013). ...
Article
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Abnormalities related to peripartum depression (PPD) have been detected in several brain regions through tasking-state functional magnetic resonance imaging (fMRI). In this study, we used the two markers of resting-state fMRI (rs-fMRI) to investigate changes in spontaneous neural activity of PPD and their correlation with depression severity. A total of 16 individuals with PPD were compared with 16 age- and education-matched healthy controls (HCs) by using rs-fMRI. Two-sample t-test was used to compare the fractional amplitudes of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo) values between groups. Pearson correlation analysis was used to determine the correlation between the fALFF and ReHo of the abnormal brain region and the Hamilton Depression Scale (HAMD) and Edinburgh Postnatal Depression Scale scores. The spontaneous neural activity of the PPD group significantly increased mainly in the left middle frontal gyrus, left precuneus, left inferior parietal lobule, and left dorsolateral prefrontal cortex (DLPFC) and decreased mainly in the bilateral precentral gyrus and right inferior occipital gyrus compared with those of the HCs. The fALFF value of the left DLPFC was negatively correlated with the HAMD score in PPD. This rs-fMRI study suggests that changes in the spontaneous neural activity of these regions are related to emotional responses. PPD cases with low fALFF values in the left DLPFC have severe depression.
... In contrast, two studies explored activations at the whole-brain level (121,122). Studies usually compare the pattern of brain activation while exposing mothers to cues of their baby vs. of unrelated babies (121)(122)(123)(124)(125), although some studies have also used as stimuli unrelated infants crying (120), images of adult faces (119), and emotionally valenced words (126,127). These studies also vary in the proportion of primiparous and unmedicated mothers, diagnosis criteria, and postpartum time-points assessed. ...
Article
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Women that become mothers face notable physiological adaptations during this life-period. Neuroimaging studies of the last decade have provided grounded evidence that women's brains structurally change across the transition into motherhood. The characterization of this brain remodeling is currently in its early years of research. The current article reviews this scientific field by focusing on our longitudinal (pre-to-post pregnancy) Magnetic Resonance Imaging (MRI) studies in first-time parents and other longitudinal and cross-sectional studies of parents. We present the questions that are currently being answered by the parental brain literature and point out those that have not yet been explored. We also highlight potential confounding variables that need to be considered when analyzing and interpreting brain changes observed during motherhood.
... Although some regions, such as the IFG were consistent with prior work, others like the SFG were unexpected. Much of the preexisting literature examining peripartum affective disorders has focused on functional masking or regionof-interest analyses to target hypothesized brain structures (for example, see the work of [54][55][56][57][58]). While this has the advantage of increased statistical power, it also means that many of the potential changes in neural activity across the postpartum brain have been left unexamined. ...
Article
It is currently unknown whether differences in neural responsiveness to infant cues observed in postpartum affective disturbance are specific to depression/anxiety or are better attributed to a common component of internalizing distress. It is also unknown whether differences in mothers' brain response can be accounted for by effects of past episodes, or if current neural processing of her child may serve as a risk factor for development of future symptoms. Twenty-four mothers from a community-based sample participated in an fMRI session viewing their 3-month- old infant during tasks evoking positive or negative emotion. They were tracked across the ensuing 15 months to monitor changes in affective symptoms. Past and current episodes of depression and anxiety, as well as future symptoms, were used to predict differences in mothers' hemodynamic response to their infant in positive compared to negative emotion contexts. Lower relative activation in largely overlapping brain regions involving frontal lobe structures to own infant positive vs. negative emotion was associated with concurrent (3-month) depression diagnosis and prospective (3-18 month) depression and anxiety symptoms. There was little evidence for impacts of past psychopathology (more limited effect of past anxiety and nonsignificant effect of past depression). Results suggest biased maternal processing of infant emotions during postpartum depression and anxiety is largely accounted for by a shared source of variance (internalizing distress). Furthermore, differential maternal responsiveness to her infant's emotional cues is specifically associated with the perpetuation of postpartum symptoms, as opposed to more general phenotypic or scarring effects of past psychopathology.
... Neuroimaging tools have the potential to elucidate the neurological pathologies of psychiatric disorders (21). Fundamental studies have revealed the function and functional connectivity (FC) alterations of the brain during resting-state (22,23) and different task performances in PPD (24)(25)(26)(27)(28). ...
Article
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Purpose: The COVID-19 epidemic has been a threat to the health of people all over the world. Various precautions during COVID-19 in China have kept a large number of people in isolation, and this has inconvenienced and placed enormous stress on pregnant women. Pregnant women are more likely to suffer from antenatal depression (ANDP) with social isolation or low social support. This research aims to investigate the neurobiological mechanisms underlying ANDP, which impedes early detection and intervention in this disorder. Methods: A total of 43 singleton pregnant women who experienced isolation were recruited, including 21 treatment-naïve ANDP patients and 22 healthy pregnant women (HPW). To explore the intrinsic cerebral activity alternations in ANDP using resting-state functional MRI (rsfMRI), we assessed the local regional homogeneity (ReHo) differences in two groups using the voxel-based whole-brain analysis. The correlation between the regional functional abnormalities and clinical variables in ANDP patients was also examined. Results: Compared with HPW, ANDP patients showed decreased ReHo in the left dorsolateral prefrontal cortex, right insular and the cluster coving the right ventral temporal cortex (VTC), amygdala (AMG), and hippocampus (HIP). The Edinburgh Postnatal Depression Scale (EPDS) scores of ANDP patients negatively correlated with the ReHo in the right VTC, AMG, and HIP. Conclusion: Elucidating the neurobiological features of ANDP patients during COVID-19 is crucial for evolving adequate methods for early diagnosis, precaution, and intervention in a future epidemic.
... Only one electroencephalogram (EEG) study identified that ATDP patients with greater right frontal EEG activation have severe depression symptoms and lower prenatal and postnatal dopamine levels (Field et al., 2002). In contrast, a considerable number of PPD studies have revealed cerebral functional activity and connectivity alterations during the resting state (Deligiannidis et al., 2013;Wang et al., 2011) and brain activation changes during the performance of different tasks (Laurent and Ablow, 2013a;Moses-Kolko et al., 2011;Silverman et al., 2011;Silverman et al., 2007;Wonch et al., 2016). In particular, these functional abnormalities were mainly involved in some frequently discussed cerebral regions of the prefrontal-limbic circuit related to multiple neural network/loop abnormalities, including the dorsolateral prefrontal cortex (DLPFC), medial prefrontal cortex (MPFC), anterior/ posterior cingulate cortex (ACC/PCC), temporal cortices, amygdala, parahippocampus (PHP) and striatal structures (Deligiannidis, Sikoglu, 2013;Morgan et al., 2017;Moses-Kolko et al., 2014;Wang et al., 2011). ...
Article
Background : Antenatal depression (ATDP) is one of the most common mental disorders that occur during the antenatal period. As a serious problem in households around the world, ATDP has adverse consequences for both mothers and offspring and heavily burdens their families and society. However, until recently, the neurobiological mechanisms underlying ATDP remained unclear, which impeded early detection and interventions for this disorder. Methods : To explore the intrinsic cerebral activity alternations in ATDP, we investigated fractional amplitude of low-frequency fluctuation (fALFF) differences in 20 treatment-naïve ATDP patients and 22 healthy pregnant women (HPW) using voxel-based whole-brain analysis by resting-state functional magnetic resonance imaging. The correlation between the regional functional abnormalities and clinical variables in ATDP patients was also examined. Results : Compared with HPW, ATDP patients showed increased fALFF in the left medial prefrontal cortex, dorsolateral prefrontal cortex and anterior cingulate cortex, as well as decreased fALFF values in the bilateral orbitofrontal cortex, the right insula, the cluster covering the right ventral temporal cortex (VTC) and the parahippocampus (PHP). The Edinburgh Postnatal Depression Scale scores of ATDP patients were negatively correlated with fALFF values in the right VTC and PHP. Limitations : The study is limited by a small sample size and the fact that only antenatal maternal women in the second and third trimesters were assessed. Conclusion : The aberrant regional functional activities of ATDP patients were mainly located within the prefrontal-limbic circuit related to multiple neural system abnormalities. This finding provides insight into the potential psychopathology of ATDP.
... Multiple fMRI studies have improved our understanding of the neural mechanisms of patients with PPD. Task-related fMRI studies have indicated that during exposure to emotional stimuli, patients with PPD have increased activity in the amygdala (15) and reduced activity in the middle frontal gyrus (MFG) and inferior frontal gyrus (IFG). Resting-state fMRI studies have reported significant disruption of the posterior cingulate cortex (PCC)-right amygdala functional coupling in patients with PPD (16). ...
Article
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Postpartum depression (PPD) is a depressive condition that is associated with a high risk of stressful life events, poor marital relationships, and even suicide. Neuroimaging techniques have enriched our understanding of cerebral mechanisms underlying PPD; namely, abnormalities in the amygdala-insula-frontal circuit might contribute to the pathogenesis of PPD. Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) is a recently validated neuroscience-informed accelerated intermittent theta-burst stimulation repetitive transcranial magnetic stimulation (rTMS) protocol. It has been shown to be effective, safe, tolerable, and rapid acting for treating treatment-resistant depression, and may be a valuable tool in the treatment of PPD. The purpose of the current study was to detect inter-hemispheric connectivity changes and their relationship with the clinical treatment effects of rTMS. Resting-state fMRI data from 32 patients with PPD treated with SAINT were collected and compared with findings from 32 age matched healthy controls. Voxel-mirrored homotopic connectivity (VMHC) was used to analyze the patterns of interhemispheric intrinsic functional connectivity in patients with PPD. Scores on the 17-item Hamilton Depression Rating Scale, Edinburgh Postnatal Depression Scale (EPDS) scores, and the relationships between these clinical characteristics and VMHC were the primary outcomes. Patients with PPD at baseline showed reduced VMHC in the amygdala, insula, and medial frontal gyrus compared with the HCs. These properties showed a renormalization after individualized rTMS treatment. Furthermore, increased connectivity between the left and right insula after SAINT was significantly correlated with the improvement of EPDS scores. Our results reveal the disruptions in the intrinsic functional architecture of interhemispheric communication in patients with PPD, and provide evidence for the pathophysiological mechanisms and the effects of rTMS.
... Another fMRI study identified blunted striatal activation in response to positive words as well as blunted amygdala activation in response to negative (i.e. threatening) words, which were associated with greater PPD symptomatology in mothers (Silverman et al., 2007;Silverman et al., 2011). These results were supported by other fMRI studies showing decreased activity in the PFC and amygdala in response to negative emotional faces as well as decreased PFC-amygdala resting state connectivity in mothers with PPD (Moses- Kolko et al., 2010;Deligiannidis et al., 2013;Chase et al., 2014). ...
Article
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Initiation and maintenance of maternal behavior is driven by a complex interaction between the physiology of parturition and offspring stimulation, causing functional changes in maternal brain and behavior. Maternal behaviors are among the most robust and rewarding motivated behaviors. Mesolimbic dopamine (DA) system alterations during pregnancy and the postpartum enable enhanced reward-related responses to offspring stimuli. Here, we review behavioral evidence demonstrating postpartum rodents exhibit a bias towards pups and pup-related stimuli in reward-related tasks. Next, we provide an overview of normative adaptations in the mesolimbic DA system induced by parturition and the postpartum, which likely mediate shifts in offspring valence. We also discuss a causal link between dopaminergic dysfunction and disrupted maternal behaviors, which are recapitulated in postpartum depression (PPD) and relevant rodent models. In sum, mesolimbic DA system activation drives infant-seeking behavior and strengthens the mother-infant bond, potentially representing a therapeutic target for reward-related deficits in PPD.
... ,22and negative adult faces (vs | 3 of 20NGUYEN Et al.TA B L E 1 Functional magnetic resonance imaging (fMRI) studies comparing maternal brain responses in mothers with and without postpartum depression (PPD) ...
Article
Postpartum depression is a common but complex condition that is poorly understood and multifactorial in etiology. It is a condition that can compromise the mother's care for her infant, which may pose challenges to the formation of the mother‐infant bond and the infant's overall development. Past research has looked at abnormalities in the brain circuitry and hormonal profiles of mothers with postpartum depression compared to non‐depressed mothers. However, abnormalities in postpartum depression that may specifically affect the mother's care of her infant have not been clearly assessed. Thus, the aim of this review is to synthesize studies of altered brain and hormonal responses in mothers with postpartum depression in relation to their care of their infant. First, we will review maternal brain responses and their relation to postpartum depression symptomatology, focusing on the salience/fear network, reward/attachment network and default mode network. Next, we will discuss oxytocin and hypothalamic‐pituitary‐adrenal (HPA) axis hormones in the context of maternal behavior and postpartum depression. Finally, we will synthesize these findings and propose how future studies may benefit from the combined study of both neural and hormonal activity to better understand the underlying neurobiology of maternal care in postpartum depression.
... 17,42 These studies have identified an inverse relationship between amygdala responsiveness to negative stimuli (including infant faces in distress) and symptom severity in PPD. 43,44 Thus, in comparison to non-depressed mothers, depressed mothers show reduced amygdalar responses to negative infant-related stimuli. 43 By contrast, the more extensive fMRI literature on MDD 10 points to a hyper-responsive amygdala to negative stimuli. ...
Article
In many mammalian species, new mothers show heightened positive responsiveness to infants and their cues when they give birth. As evident from non‐human and human studies, the amygdala is a brain region implicated in both the maternal and affective neural circuitry, and is involved in processing socioemotionally salient stimuli. In humans, infants are socially salient stimuli to women, and mothers in particular. Neuroimaging studies investigating the maternal response to infant cues have identified infant‐related amygdala function as an important factor in maternal anxiety/depression, in quality of mothering, and in individual differences in the motivation to mother. This study investigated the effects of maternal status and depression on the subjective affective response and amygdala responsiveness to Unfamiliar infants using fMRI. Smiling infant pictures were used in a 2x2 design comparing four groups of women: mothers and non‐mothers, with and without depression (total of 101 women: PPD=32, non‐PPD=25, MDD=15, non‐MDD=29). We undertook an anatomically defined ROI analysis of the amygdala response for a priori defined group comparisons. We found that mothers rated infants more positively than non‐mothers and non‐mothers rated non‐infant stimuli (scenery) more positively than mothers. In the amygdala, we found that depression elevated response to smiling Unfamiliar infants in mothers but had no effect in non‐mothers. Within the depressed groups, mothers (PPD) showed an elevated amygdala response to unfamiliar smiling infants compared to depressed non‐mothers. Hence, our results indicate that women with PPD show an enhanced amygdala response to affectively positive infant pictures, but not to affectively positive (but non‐salient) pictures of scenery. Women with depression outside of the postpartum period show no change in amygdala responsiveness to either stimulus categories. This article is protected by copyright. All rights reserved.
... Because cued fear relies heavily on LAT and fear extinction involves the BA, these changes in the pattern of behaviors over estrous caused by repeated stress may be related to the parallel changes of LAT and BA neuronal function. Most studies of amygdala activation in humans after stress or depression find increased activity in males and females 68,69 . However, those studies usually lack the resolution to separate nuclei of the amygdala and seldom track ovarian phase. ...
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Stress is a precipitating factor in depression and anxiety disorders. Patients with these disorders often show amygdala abnormalities. The basolateral amygdala (BLA) is integral in mood and emotion, and is sensitive to stress. While much is known about effects of stress on BLA neuron activity and morphology in males, less is known in females. We tested whether repeated stress exerts distinct effects on BLA in vivo neuronal activity and morphology of Golgi-stained BLA neurons [lateral (LAT) and basal (BA) nuclei] in adult female rats. Repeated restraint stress increased BLA neuronal firing and caused hypertrophy of BLA neurons in males, while it decreased LAT and BA neuronal firing and caused hypotrophy of neurons in the LAT of females. BLA neuronal activity and function, such as fear conditioning, shifts across the estrous cycle. Repeated stress disrupted this pattern of BLA activity and fear expression over the estrous cycle. The disruptive effects of stress on the pattern of BLA function across estrous may produce behavior that is non-optimal for a specific phase of the estrous cycle. The contrasting effects of stress may contribute to sex differences in the effects of stress on mood and psychiatric disorders.
... As recently reviewed, (Duan C et al., 2017) the main functional MRI imaging studies in women with PND show differences in activity and connectivity between different brain regions compared to those in healthy postnatal women. Task-based, or BOLD activation, fMRI studies show differences between healthy postnatal and postnatal depressed women in the activity of the right(Moses- Kolko et al., 2010;Silverman et al., 2011;Silverman et al., 2007;Wonch et al., 2016) and left(Moses-Kolko et al., 2010) amygdala (Barrett et al., 2012), posterior orbitofrontal cortex (Silverman et al., 2007), insula (Silverman et al., 2007), striatum (Moses-Kolko et al., 2011;Silverman et al., 2007), left dorsomedial prefrontal cortex(Moses-Kolko et al., 2010), thalamus (Barrett et al., 2012), and temporal cortex (Barrett et al., 2012). Task-based fMRI studies also show differences in functional connectivity between the left dorsomedial prefrontal cortex and the left amygdala (Moses-Kolko et al., 2010), as well as between the amygdala and the right insular cortex (Wonch et al., 2016), for postnatal depressed women. ...
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Depression is the most common perinatal psychiatric disorder, but little is known about how it may impact offspring neurodevelopment, as well as the mechanisms by which it may confer transgenerational psychiatric risk. This review presents imaging studies conducted to evaluate the relationship between perinatal depression (PND) and infant and child neurodevelopment. Altered structural and functional connectivity is implicated in children exposed to PND and anxiety. Overall, there are changes in connectivity between amygdala and the prefrontal cortex. Studies suggest decreased hippocampal growth in the first 6 months after birth, decreased cortical thickness in children, and increased amygdala volumes, that are more pronounced in female offspring. Future research is needed to understand the impact of PND on development so that early interventions which promote mother–infant bonding and cognitive development may improve developmental outcomes in children exposed to PND, reducing later risk of psychopathology.
... However, in the reviewed studies, amygdalar reactivity seems to be deactivated in pubertal depression and PPD, and in PMDD results are highly inconsistent throughout the menstrual cycle. In PPD, explanations for the hypoactivation aim at the dulled empathic responsiveness towards the child (Moses-Kolko et al., 2010;Silverman et al., 2011). In PMDD fluctuation of sex steroids, especially progesterone, are hold liable for the unusual activation pattern Henningsson et al., 2015). ...
... Despite the current classification of postpartum depression, doctors and clinicians with experience treating depressed mothers often note specific differences between unipolar depression and the depression that occurs immediately after childbirth. Silverman et al. (Silverman et al., 2011) recently used state-of-the-art brain imaging technology, functional magnetic resonance imaging (fMRI), to assess the neuroanatomical responsivity of the amygdala in women six to eight weeks postpartum and to understand how the brains of women with postpartum depression differ from non-depressed postpartum woman. While contemporary diagnostic nosology characterizes postpartum depression (PPD) as a specifier of a major depressive disorder (MDD), this traditional classification continues to be questioned. ...
Article
The aim of this study is to investigate the alterations of interhemispheric functional connectivity in patients with postpartum depression (PPD) during resting state, and their potential correlations with clinical severity. Twenty- eight patients with PPD and twenty-five matched healthy postpartum (HP) women within 4 weeks after delivery were recruited and performed resting-state functional magnetic resonance imaging(fMRI) scans. Voxel-mirrored homotopic connectivity (VMHC), which is useful for exploring interhemispheric functional connectivity, and has been widely utilized to identify abnormal functional connectivity between the symmetrical brain regions in many diseases, was calculated in the present study, and intergroup VMHC differences in the voxel manner were analyzed. Correlations between VMHC values and clinical variables were also analyzed. Compared with HP, patients with PPD exhibited significantly decreased VMHC values in bilateral dorsomedial prefrontal cortex (dmPFC), dorsal anterior cingulate cortex (dACC) and orbitofrontal cortex (OFC). Furthermore, VMHC values within the dmPFC negatively correlated with the Edinburgh postpartum depression scale (EPDS) score. These findings suggested that functional coordination between several homotopic brain regions were impaired in patients with PPD. This study provided evidences of aberrant interhemispheric connectivity within brain regions involved in the maternal care network in PPD, and may contribute to the further understanding of the neural mechanism underlying PPD.
Chapter
Women’s mental health seems to be affected by different factors and present with particular epidemiology when compared to men’s mental health. In terms of mood disorders, these include the age of onset, seasonal features, incidence of suicidal attempts, and typicality of features. One hypothesis is that the difference in sex hormones is considered to impact the epidemiology and the course of psychiatric disorders in women. For example, changes in the hormonal milieu that occur in the end of pregnancy have been linked to peripartum depression, and the fluctuations of sex hormones during the menstrual cycle have been linked to premenstrual dysphoric disorder (PMDD). Neuroimage research has contributed to identifying potential biomarkers in respect to these disorders. For instance, peripartum depression has been associated with a decreased activation of the limbic structures, as well as a decreased functional connectivity between frontal cortex and limbic structures, which seems to point out different pathophysiologic mechanisms for postpartum depression. Regarding PMDD, being diagnosed with bipolar disorder while experiencing this comorbidity is related to a more challenging course of bipolar disorder. This seems to be related to female sex hormones’ neuroactivity, since they were shown to affect the glutamatergic and GABAergic systems. According to the phase of the menstrual cycle, women with PMDD seem to exhibit different brain activation in the motor and somatosensory cortices. Complementarily, a cortical thickness study showed that PMDD women with bipolar disorder present with an increased cortical thickness of the left superior temporal gyrus, a decreased cortical thickness of the left parietal, and superior frontal and left pericalcarine cortices, including, resting-state functional connectivity (rs-FC) between the left hippocampus and right frontal cortex, as well as decreased rs-FC between right hippocampus and right premotor cortex. Although there are not many neuroimaging studies investigating the influence of “female” sex hormones in the brain, and therefore, their relationship with psychiatric symptoms in transgender women/transgender person should also be considered a population vulnerable to female sex neuroactive steroids influence.
Article
Ten to twenty percent of postpartum women experience anxiety or depressive disorders, which can have detrimental effects on the mother, child, and family. Little is known about the neural correlates of these affective disorders when they occur in mothers, but they do have unique neural profiles during the postpartum period compared with when they occur at other times in a woman's life. Given that the neural systems affected by postpartum anxiety and depression overlap and interact with the systems involved in maternal caregiving behaviors, mother-infant interactions are highly susceptible to disruption. Thus, there is an intricate interplay among maternal mental health, the mother-infant relationship, and the neurobiological mechanisms mediating them that needs to be the focus of future study.
Article
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.
Article
Background : Postpartum depression (PPD) is a common mental disorder among women. However, the brain information flow alteration in patients with PPD remains unclear. This study investigated the brain information flow characteristics of patients with PPD and their value for clinical evaluation by using support vector regression (SVR). Methods : Structural and resting-state functional magnetic resonance imaging data were acquired from 21 patients with PPD and 23 age-, educational level-, body mass index-, and menstruation-matched healthy controls. The preferred information flow direction between local brain regions and the preferred information flow direction index within local brain regions based on non-parametric multiplicative regression granger causality analysis were calculated to determine the global and local brain functional characteristics of the patients with PPD. Pearson's correlation analyses were performed to evaluate the relationship of the information flow characteristics with clinical scales. A predictive model for the mental state of the patients with PPD was established using SVR based on information flow characteristics. Results : The information flow patterns in the amygdala, cingulum gyrus, insula, hippocampus, frontal lobe, parietal lobe, and occipital lobe changed significantly in the patients with PPD. The preferred information flow direction between the amygdala and the temporal and frontal lobes significantly correlated with clinical scales. Prediction analysis shows that the information flow patterns can be used to assess depression in patients with PPD. Limitation : This exploratory study has a small sample size with no longitudinal research. Conclusion : The change in information flow pattern in the amygdala may play an important role in the neuropathological mechanism of PPD and may provide promising markers for clinical evaluation.
Article
Background: Postpartum depression (PPD) is a serious postpartum mental health problem worldwide. However, the cortical structural alterations in patients with PPD remain unclear. This study investigated the cortical structural alterations of PPD patients through multidimensional structural patterns and their potential correlations with clinical severity. Methods: High-resolution 3D T1 structural images were acquired from 21 drug-naive patients with PPD and 18 healthy postpartum women matched for age, educational level, and body mass index. The severity of PPD was assessed by using the Hamilton Depression Scale (HAMD) and Edinburgh Postnatal Depression Scale (EPDS) scores. Cortical morphological parameters including cortical thickness, surface area, and mean curvature were calculated using the surface-based morphometric (SBM) method. General linear model (GLM) analyses were performed to evaluate the relationship of cortical morphological parameters with clinical scales. Results: In the present study, PPD patients showed a thinner cortical thickness in the right inferior parietal lobule compared with the healthy controls. Increased surface area was observed in the left superior frontal gyrus, caudal middle frontal gyrus, middle temporal gyrus, insula, and right supramarginal cortex in PPD patients. Likewise, PPD patients exhibited a higher mean curvature in the left superior and right inferior parietal lobule. Furthermore, increased cortical surface area in the left insula had a positive correlation with EPDS scores, and higher mean curvature in the left superior parietal lobule was negatively correlated with EPDS scores. Limitations: First, SBM cannot reflect the changes of subcortical structures that are considered to play a role in the development of PPD. Second, the sample size of this study is small. These positive results should be interpreted with caution. Third, this cross-sectional study does not involve a comparison of structural MRI before and after pregnancy. Conclusions: The complex cortical structural alterations of patients with PPD mainly involved the prefrontal and parietal regions. The morphometric alterations in these specific regions may provide promising markers for assessing the severity of PPD.
Article
Background Postpartum depression (PPD) is a serious postpartum mental health problem worldwide. To date, minimal is known about the alteration of topographical organization in the brain structural covariance network of patients with PPD. This study investigates the brain structural covariance networks of patients with PPD by using graph theoretical analysis. Methods High-resolution 3D T1 structural images were acquired from 21 drug-naive patients with PPD and 18 healthy postpartum women. Cortical thickness was extracted from 64 brain regions to construct the whole-brain structural covariance networks by calculating the Pearson correlation coefficients, and their topological properties (e.g., small-worldness, efficiency, and nodal centrality) were analyzed by using graph theory. Nonparametric permutation tests were further used for group comparisons of topological metrics. A node was set as a hub if its betweenness centrality (BC) was at least two standard deviations higher than the mean nodal centrality. Network-based statistic (NBS) was used to determine the connected subnetwork. Results The PPD and control groups showed small-worldness of group networks, but the small-world network was more evidently in the PPD group. Moreover, the PPD group showed increased network local efficiency and almost similar network global efficiency. However, the difference of the network metrics was not significant across the range of network densities. The hub nodes of the patients with PPD were right inferior parietal lobule (BC = 13.69) and right supramarginal gyrus (BC = 13.15), whereas those for the HCs were left cuneus (BC = 14.96), right caudal anterior-cingulate cortex (BC = 15.51), and right precuneus gyrus (BC = 15.74). NBS demonstrated two disrupted subnetworks that are present in PPD: the first subnetwork with decreased internodal connections is mainly involved in the cognitive-control network and visual network, and the second subnetwork with increased internodal connections is mainly involved in the default mode network, cognitive-control network and visual network. Conclusions This study demonstrates the alteration of topographical organization in the brain structural covariance network of patients with PPD, providing in sight on the notion that PPD could be characterized as a systems-level disorder.
Article
Early parenting relies on emotion regulation capabilities, as mothers are responsible for regulating both their own emotional state and that of their infant during a time of new parenting-related neural plasticity and potentially increased stress. Previous research highlights the importance of frontal cortical regions in facilitating effective emotion regulation, but few studies have investigated the neural regulation of emotion among postpartum women. The current study employed a functional neuroimaging (fMRI) approach to explore the association between perceived stress, depressive symptoms, and the neural regulation of emotion in first-time mothers. Among 59 postpartum mothers, higher perceived stress during the postpartum period was associated with less self-reported use of cognitive reappraisal in everyday life, and greater use of emotion suppression. While viewing standardized aversive images during the Emotion Regulation Task (ERT), mothers were instructed to experience their natural emotional state (Maintain) or to decrease the intensity of their negative emotion by using cognitive reappraisal (Reappraise). Whole-brain analysis revealed a two-way interaction of perceived stress x condition in the right dorsolateral prefrontal cortex (DLPFC) at p < .05 cluster-wise corrected, controlling for postpartum months and scanner type. Higher levels of perceived stress were associated with heightened right DLPFC activity while engaging in cognitive reappraisal versus naturally responding to negative stimuli. Higher right DLPFC activity during Reappraise versus Maintain was further associated with elevated parenting stress. Findings suggest that stress and everyday reappraisal use is reflected in mothers’ neural regulation of emotion and may have important implications for their adaptation to parenthood.
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Postpartum major depression is a significant public health problem that strikes 15% of new mothers and confers adverse consequences for mothers, children, and families. The neural mechanisms involved in postpartum depression remain unknown, but brain processing of affective stimuli appears to be involved in other affective disorders. The authors examined activity in response to negative emotional faces in the dorsomedial pre-frontal cortex and amygdala, key emotion regulatory neural regions of importance to both mothering and depression. Postpartum healthy mothers (N=16) and unmedicated depressed mothers (N=14) underwent functional magnetic resonance imaging blood-oxygen-level-dependent acquisition during a block-designed face versus shape matching task. A two-way analysis of variance was performed examining main effects of condition and group and group-by-condition interaction on activity in bilateral dorsomedial prefrontal cortical and amygdala regions of interest. Depressed mothers relative to healthy mothers had significantly reduced left dorsomedial prefrontal cortical face-related activity. In depressed mothers, there was also a significant negative correlation between left amygdala activity and postpartum depression severity and a significant positive correlation between right amygdala activity and absence of infant-related hostility. There was reliable top-down connectivity from the left dorsomedial prefrontal cortex to the left amygdala in healthy, but not depressed, mothers. Significantly diminished dorsomedial prefrontal cortex activity and dorsomedial prefrontal cortical-amygdala effective connectivity in response to negative emotional faces may represent an important neural mechanism, or effect, of postpartum depression. Reduced amygdala activity in response to negative emotional faces is associated with greater postpartum depression severity and more impaired maternal attachment processes in postpartum depressed mothers.
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Research on postpartum mood disorders has focused primarily on major depressive disorder, bipolar I disorder, and puerperal psychosis and has largely ignored or neglected bipolar II disorder. Hypomanic symptoms are common after delivery but frequently unrecognized. DSM-IV does not consider early postpartum hypomania as a significant diagnostic feature. Although postpartum hypomania may not cause marked impairment in social or occupational functioning, it is often associated with subsequent, often disabling depression. Preliminary evidence suggests that bipolar II depression arising in the postpartum period is often misdiagnosed as unipolar major depressive disorder. The consequences of the misdiagnosis can be particularly serious because of delayed initiation of appropriate treatment and the inappropriate prescription of antidepressants. Moreover, no pharmacological or psychotherapeutic studies of bipolar postpartum depression are available to guide clinical decision making. Also lacking are screening instruments designed specifically for use before or after delivery in women with suspected bipolar depression. It is recommended that the treatment of postpartum bipolar depression follow the same guidelines as the treatment of nonpuerperal bipolar II depression, using medications that are compatible with lactation.
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The neural networks that putatively modulate aspects of normal emotional behavior have been implicated in the pathophysiology of mood disorders by converging evidence from neuroimaging, neuropathological and lesion analysis studies. These networks involve the medial prefrontal cortex (MPFC) and closely related areas in the medial and caudolateral orbital cortex (medial prefrontal network), amygdala, hippocampus, and ventromedial parts of the basal ganglia, where alterations in grey matter volume and neurophysiological activity are found in cases with recurrent depressive episodes. Such findings hold major implications for models of the neurocircuits that underlie depression. In particular evidence from lesion analysis studies suggests that the MPFC and related limbic and striato-pallido-thalamic structures organize emotional expression. The MPFC is part of a larger "default system" of cortical areas that include the dorsal PFC, mid- and posterior cingulate cortex, anterior temporal cortex, and entorhinal and parahippocampal cortex, which has been implicated in self-referential functions. Dysfunction within and between structures in this circuit may induce disturbances in emotional behavior and other cognitive aspects of depressive syndromes in humans. Further, because the MPFC and related limbic structures provide forebrain modulation over visceral control structures in the hypothalamus and brainstem, their dysfunction can account for the disturbances in autonomic regulation and neuroendocrine responses that are associated with mood disorders. This paper discusses these systems together with the neurochemical systems that impinge on them and form the basis for most pharmacological therapies.
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With approximately 4 million births each year in the United States, an estimated 760,000 women annually suffer from a clinically significant postpartum depressive illness. Yet even though the relationship between psychiatric disorders and the postpartum period has been documented since the time of Hippocrates, fewer than half of all these cases are recognized. Because postpartum depression (PPD), the most common complication of childbearing, remains poorly characterized, and its etiology remains unclear, we attempted to address a critical gap in the mechanistic understanding of PPD by probing its systems-level neuropathophysiology, in the context of a specific neurobiological model of fronto-limbic-striatal function. Using emotionally valenced word probes, with linguistic semantic specificity within an integrated functional magnetic resonance imaging (fMRI) protocol, we investigated emotional processing, behavioral regulation, and their interaction (functions of clinical relevance to PPD), in the context of fronto-limbic-striatal function. We observed attenuated activity in posterior orbitofrontal cortex for negative versus neutral stimuli with greater PPD symptomatology, increased amygdala activity in response to negative words in those without PPD symptomotology, and attenuated striatum activation to positive word conditions with greater PPD symptomotology. Identifying the functional neuroanatomical profile of brain systems involved in the regulation of emotion and behavior in the postpartum period will not only assist in determining whether the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition psychiatric diagnostic specifier of PPD has an associated, unique, functional neuroanatomical profile, but a neurobiological characterization in relation to asymptomatic (postpartum non-depressed) control subjects, will also increase our understanding of the affective disorder spectrum, shed additional light on the possible mechanism(s) responsible for PPD and provide a necessary foundation for the development of more targeted, biologically based diagnostic and therapeutic strategies for PPD.
Article
Difficulties in emotion processing and poor social function are common to bipolar disorder (BD) and major depressive disorder (MDD) depression, resulting in many BD depressed individuals being misdiagnosed with MDD. The amygdala is a key region implicated in processing emotionally salient stimuli, including emotional facial expressions. It is unclear, however, whether abnormal amygdala activity during positive and negative emotion processing represents a persistent marker of BD regardless of illness phase or a state marker of depression common or specific to BD and MDD depression. Sixty adults were recruited: 15 depressed with BD type 1 (BDd), 15 depressed with recurrent MDD, 15 with BD in remission (BDr), diagnosed with DSM-IV and Structured Clinical Interview for DSM-IV Research Version criteria; and 15 healthy control subjects (HC). Groups were age- and gender ratio-matched; patient groups were matched for age of illness onset and illness duration; depressed groups were matched for depression severity. The BDd were taking more psychotropic medication than other patient groups. All individuals participated in three separate 3T neuroimaging event-related experiments, where they viewed mild and intense emotional and neutral faces of fear, happiness, or sadness from a standardized series. The BDd-relative to HC, BDr, and MDD-showed elevated left amygdala activity to mild and neutral facial expressions in the sad (p < .009) but not other emotion experiments that was not associated with medication. There were no other significant between-group differences in amygdala activity. Abnormally elevated left amygdala activity to mild sad and neutral faces might be a depression-specific marker in BD but not MDD, suggesting different pathophysiologic processes for BD versus MDD depression.
Article
Neuroimaging studies of bipolar disorder (BD) have provided evidence of brain functional abnormalities during both the states of mania and remission. However, the differences in brain function between these two states are still poorly known. In the current study, we aimed to use a longitudinal design to examine the functional changes associated with symptomatic remission from mania within the brain network underlying motor response inhibition. Using event-related functional magnetic resonance imaging (fMRI), 10 BD patients and 10 healthy subjects were imaged twice while performing a Go/NoGo task. Patients were in a manic state when they underwent the first scan and fully remitted during the second scan. A mixed-effect ANOVA was used to identify brain regions showing differences in activation change over time between the two groups. The left amygdala was the only brain region to show a time-dependent change in activation that was significantly different between BD patients and healthy subjects. Further analyses revealed that this difference arose from the patient group, in which amygdala activation was decreased between mania and subsequent remission. This finding suggests that a decrease in left amygdala responsiveness is a critical phenomenon associated with remission from mania. It emphasizes the relevance of longitudinal approaches for identifying neurofunctional modifications associated with mood changes in BD.
Article
The development of a 10-item self-report scale (EPDS) to screen for Postnatal Depression in the community is described. After extensive pilot interviews a validation study was carried out on 84 mothers using the Research Diagnostic Criteria for depressive illness obtained from Goldberg's Standardised Psychiatric Interview. The EPDS was found to have satisfactory sensitivity and specificity, and was also sensitive to change in the severity of depression over time. The scale can be completed in about 5 minutes and has a simple method of scoring. The use of the EPDS in the secondary prevention of Postnatal Depression is discussed.
Article
The amygdala has a central role in processing emotions, particularly fear. During functional magnetic resonance imaging (fMRI) amygdala activation has been demonstrated outside of conscious awareness using masked emotional faces. We applied the masked faces paradigm to patients with major depression (n = 11) and matched control subjects (n = 11) during fMRI to compare amygdala activation in response to masked emotional faces before and after antidepressant treatment. Data were analyzed using left and right amygdala a priori regions of interest, in an analysis of variance block analysis and random effects model. Depressed patients had exaggerated left amygdala activation to all faces, greater for fearful faces. Right amygdala did not differ from control subjects. Following treatment, patients had bilateral reduced amygdala activation to masked fearful faces and bilateral reduced amygdala activation to all faces. Control subjects had no differences between the two scanning sessions. Depressed patients have left amygdala hyperarousal, even when processing stimuli outside conscious awareness. Increased amygdala activation normalizes with antidepressant treatment.
Article
According to cognitive theories, negative cognitions including negative attitudes towards the future are key factors associated with depressive disorder. We investigated the neural correlates of anticipation of emotional stimuli in patients with unipolar depression to reveal influences of future thinking on brain activity. We used functional magnetic resonance imaging (fMRI) to study 12 female patients with stable antidepressant medication and 12 healthy women. Subjects were presented with positive, negative and neutral pictures that were announced by a congruent cue. Subjects were instructed to expect and subsequently watch the pictures. After scanning, subjects filled the Emotion Regulation Questionnaire (ERQ) to assess the regulation strategies suppression and reappraisal. Compared to the healthy control group, during expectation of negative vs. neutral or positive stimuli the patients showed significantly more activation within the sublenticular extended dorsal amygdala (SLEA) bilaterally but did not differ from controls upon expecting positive stimuli. Hamilton depression scores of the patients correlated positively with activation of the left and right ventral amygdala during expectation of negative stimuli. Furthermore, we found a negative correlation of ventral amygdala activation in the patients with reappraisal scores comprising the ability to limit emotional responding by re-interpreting emotion-eliciting situations. We interpret enhanced activation in the amygdala/SLEA as a possible consequence of altered future thinking in patients suffering from depression. Supporting cognitive theories, this finding does represent evidence that altered cognitions as potentially involved in expectation result in differences in brain activity.
Article
The relationship of postnatal (postpartum) depression (PND) to episodes of depression occurring at other times is not well understood. Despite a number of studies of clinical presentation, there is little consistency in the literature. We have undertaken within- and between-individual comparisons of the clinical presentation of postnatal (PN) and non-postnatal (NPN) depressive episodes in women with recurrent depression. In a sample of well-characterized, parous women meeting DSM-IV and ICD-10 criteria for recurrent major depressive disorder, the clinical presentation of episodes of major depression with onset within 4 weeks of giving birth (PND group, n=50) were compared with (i) the non-postnatal episodes of women with PND, and (ii) episodes of major depression in parous women who had not experienced episodes of mood disorder in relation to childbirth (NPND group, n=132). In addition, the non-postnatal episodes of the PND group of women were compared with the depressive episodes of the NPND group. The small number of differences found between PN and NPN depressive episodes, such as reduced early morning wakening in postnatal episodes, are likely to be explicable by the context of having a new baby rather than by any difference in the nature of the underlying depression. The results do not point to substantial differences in clinical presentation between episodes of major depression occurring in relation to childbirth and at other times. Other avenues of research are therefore required to demonstrate a specific relationship between childbirth and depression.
Bipolar II postpartum depression: detection, diagnosis, and treatment Increased amygdala response to masked emotional faces in depressed subjects resolves with antidepressant treatment: an fMRI study Neural dysfunction in postpartum depres-sion: an fMRI pilot study
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  • A Snyder
  • Mintun
  • Me Silverman
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  • M Safier
  • X Protopopescu
  • G Leiter
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Professional Manual. Odessa, Psychological Assessment Resources Sharma V , Burt VK, Ritchie HL (2009) Bipolar II postpartum depression: detection, diagnosis, and treatment. Am J Psychiatry 166:1217–1221 Sheline Y , Barch D, Donnelly J, Ollinger J, Snyder A, Mintun M (2001) Increased amygdala response to masked emotional faces in depressed subjects resolves with antidepressant treatment: an fMRI study. Biol Psychiatry 50:651–658 Silverman ME, Loudon H, Safier M, Protopopescu X, Leiter G, Goldstein M (2007) Neural dysfunction in postpartum depres-sion: an fMRI pilot study. CNS Spectr 12:853–862 The neural processing of negative emotion postpartum 359
Remission from mania is associated with a decrease in amygdala activation during motor response inhibi-tion Abnormally reduced dorsomedial prefrontal cortical activity and effective connectivity with amygdala in response to negative emotional faces in postpartum depression
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Hamilton Depression Inventory: a self-report version of the Hamilton Depression Rating Scale Bipolar II postpartum depression: detection, diagnosis, and treatment
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Hamilton Depression Inventory: a self-report version of the Hamilton Depression Rating Scale. Professional Manual. Odessa
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Structured clinical interview for DSM-IV, research version (SCID-RV)
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Increased amygdala response to masked emotional faces in depressed subjects resolves with antidepressant treatment: an fMRI study
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  • M Mintun
Sheline Y, Barch D, Donnelly J, Ollinger J, Snyder A, Mintun M (2001) Increased amygdala response to masked emotional faces in depressed subjects resolves with antidepressant treatment: an fMRI study. Biol Psychiatry 50:651–658