Course of Illness and Treatment Updates for Bipolar Disorder in the Perinatal Period.

PURPOSE OF REVIEW: The perinatal period is a time of increased vulnerability for people with bipolar disorder (BD). The purpose of this review is to provide an update of the literature from the last 3 years regarding course of illness and treatments for BD in the perinatal period to guide clinical care. RECENT FINDINGS: Postpartum manic and depressive episodes are emerging as having a unique presentation that may differentiate them from non-perinatal mood episodes. Many important updates regarding medication treatment in the perinatal period have been published recently that have considered the risks of untreated illness versus treatment risks in this population.' Despite significant research, there are still gaps in knowledge regarding safety and efficacy of medications for the mother and child. Crucial future areas of study include improved screening guidelines, randomized controlled trials examining medication safety in pregnancy and lactation, and efficacy of nonpharmacologic treatments.

Postpartum Stress and Neural Regulation of Emotion among First-Time Mothers.

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.

Associations between stress exposure and new mothers' brain responses to infant cry sounds.

Exposure to severe stress has been linked to negative postpartum outcomes among new mothers including mood disorders and harsh parenting. Non-human animal studies show that stress exposure disrupts the normative adaptation of the maternal brain, thus identifying a neurobiological mechanism by which stress can lead to negative maternal outcomes. However, little is known about the impact of stress exposure on the maternal brain response to infant cues in human mothers. We examined the association of stress exposure with brain response to infant cries and maternal behaviors, in a socioeconomically diverse (low- and middle-income) sample of first-time mothers (N=53). Exposure to stress across socioeconomic, environmental, and psychosocial domains was associated with reduced brain response to infant cry sounds in several regions, including the right insula/inferior frontal gyrus and superior temporal gyrus. Reduced activation in these regions was further associated with lower maternal sensitivity observed during a mother-infant interaction. The findings demonstrate that higher levels of stress exposure may be associated with reduced brain response to an infant's cry in regions that are important for emotional and social information processing, and that reduced brain responses may further be associated with increased difficulties in developing positive mother-infant relationships.

Editorial: Marijuana Legalization and Suicide in Adolescents and Transitional-Age Youth: Important Future Directions for This Line of Research.

Marijuana legalization (ML) processes for medical and recreational use in the United States have been prompted by the potential for positive downstream legal effects of decriminalization, including fewer cannabis-related arrests and prosecutions, which have historically disproportionately impacted minoritized communities. However, ML evolved through primarily political processes, with minimal scientific guidance to inform policies. Commercialization has increased youth cannabis access, diversion of parental cannabis, and proliferation of high-potency products, which, along with early use, are associated with poor mental health outcomes.1 Taken together, these findings raise concerns about the impact of medical (MML) and recreational marijuana legalization (RML) on youth mental health.

Editorial: Adolescent Substance Use Prevention and Treatment Is Our Wheelhouse.

In this issue of the Journal, Welsh et al.5 revise and update the National Institute on Drug Abuse (NIDA) "Principles of Adolescent Substance Use Disorder Treatment,"6 and the practice recommendations based on these principles, published by Winters et al. in 2018.7 These principles and recommendations are solidly grounded in current research and reemphasize individualized, voluntary, readily available, comprehensive, and integrated long-term treatment that is not solely focused on detoxification; that addresses biopsychosocial issues and comorbid psychiatric diagnoses; and that is tailored to specific populations. They also recommend addressing misuse without disorder, using annual routine medical visits as opportunities for screening, and engaging families and legal systems to promote treatment adherence. However, the problem of adolescent substance use has been presented with new challenges.

Maternal Childhood Maltreatment, Internal Working Models, and Perinatal Substance Use: Is There a Role for Hyperkatifeia? A Systematic Review.

The parent-infant relationship is critical for socioemotional development and is adversely impacted by perinatal substance use. This systematic review posits that the mechanisms underlying these risks to mother-infant relationships center on 3 primary processes: (1) mothers' childhood maltreatment experiences; (2) attachment styles and consequent internal working models of interpersonal relationships; and (3) perinatal substance use. Further, the review considers the role of hyperkatifeia, or hypersensitivity to negative affect which occurs when people with substance use disorders are not using substances, and which drives the negative reinforcement in addiction. The authors performed a systematic review of articles (published 2000-2022) related to these constructs and their impact on mother-infant relationships and offspring outcomes, including original clinical research articles addressing relationships between these constructs, and excluding case studies, reviews, non-human animal studies, intervention studies, studies with fewer than 30% female-sex participants, clinical guidelines, studies limited to obstetric outcomes, mechanistic/biological studies, and studies with methodological issues precluding interpretation. Overall 1844 articles were screened, 377 were selected for full text review, and data were extracted from 157 articles. Results revealed strong relationships between mothers' childhood maltreatment experiences, less optimal internal working models, and increased risk for perinatal substance use, and importantly, all of these predictors interacted with hyperkatifeia and exerted a marked impact on mother-infant relationships with less data available on offspring outcomes. These data strongly support the need for future studies addressing the additive impact of maternal childhood maltreatment experiences, suboptimal internal working models, and perinatal substance use, with hyperkatifeia as a potential moderator, and their interacting effects on mother-infant socioemotional outcomes.

Reported maternal childhood maltreatment experiences, amygdala activation and functional connectivity to infant cry.

Maternal childhood maltreatment experiences (CMEs) may influence responses to infants and affect child outcomes. We examined associations between CME and mothers' neural responses and functional connectivity to infant distress. We hypothesized that mothers with greater CME would exhibit higher amygdala reactivity and amygdala-supplementary motor area (SMA) functional connectivity to own infant's cries. Postpartum mothers (N = 57) assessed for CME completed an functional magnetic resonance imaging task with cry and white-noise stimuli. Amygdala region-of-interest and psychophysiological interaction analyses were performed. Our models tested associations of CME with activation and connectivity during task conditions (own/other and cry/noise). Exploratory analyses with parenting behaviors were performed. Mothers with higher CME exhibited higher amygdala activation to own baby's cries vs other stimuli (F1,392 = 6.9, P < 0.01, N = 57) and higher differential connectivity to cry vs noise between amygdala and SMA (F1,165 = 22.3, P < 0.001). Exploratory analyses revealed positive associations between both amygdala activation and connectivity and maternal non-intrusiveness (Ps < 0.05). Increased amygdala activation to own infant's cry and higher amygdala-SMA functional connectivity suggest motor responses to baby's distress. These findings were associated with less intrusive maternal behaviors. Follow-up studies might replicate these findings, add more granular parenting assessments and explore how cue processing leads to a motivated maternal approach in clinical populations.

Neural correlates of taste reward value across eating disorders.

Individuals with eating disorders (ED) make extreme food choices, raising the possibility of altered food-value computation. We utilized an associative taste reward learning paradigm to test whether value signaling differs between participants with EDs vs. healthy controls (HC). We followed up on previous work examining prediction error (PE) signaling, which is a brain response to violation of a learned reward contingency. Expected value (EV) signal is a trial-by-trial assessment of reward significance accounting for error signaling, reward-likelihood, and learning rate. Adult female participants (N = 111) performed a temporal difference (TD) fMRI taste task, which is a specific type of associative reward learning paradigm, to determine EV signal: Anorexia Nervosa-ill (N = 28), Anorexia Nervosa-recovered (N = 20), Bulimia Nervosa (BN) (N = 20), and HC (N= 43). Anatomical region-of-interest (ROI) analyses were performed utilizing EV regressors derived via algorithm, with ROIs based on prior EV analyses: orbitofrontal cortex, anterior cingulate (ACC), amygdala, and striatum. EV signal was elevated in the bilateral ACC in AN-ill vs. HC and BN. Intolerance of uncertainty negatively correlated with EV in AN-ill. BMI and EV were negatively-correlated across groups. Altered ACC EV computation in response to food stimuli could contribute to food restriction in AN-ill.

Neural processing of infant and adult face emotion and maternal exposure to childhood maltreatment.

Face processing in mothers is linked to mother-infant social communication, which is critical for parenting and in turn for child development. Neuroimaging studies of child maltreatment-exposed (CME) mothers are sparse compared to studies of mothers with postpartum depression, which have suggested blunted amygdala reactivity to infant stimuli. We expected to see a similar pattern in CME mothers. Based on broader studies in trauma-exposed populations, we anticipated increased amygdala reactivity to negative adult face stimuli in a comparison task in CME mothers given heightened evaluation of potential threat. We examined Neuroimaging studies of mothers with childhood maltreatment exposure (CME) (18-37 years old), who performed infant (N = 45) and/or adult (N = 46) face processing tasks. CME mothers exhibited blunted bilateral amygdala reactivity to infant faces. There was no between-group difference in amygdala reactivity to adult faces. In infant and adult face processing tasks regardless of CME, superior temporal gyrus activation was increased for negative-valence stimuli. Our preliminary findings suggest that childhood maltreatment alters maternal processing of infant social cues, a critical skill impacting infant socioemotional development.

Indiscriminate amygdala response to mothers and strangers after early maternal deprivation.

BACKGROUND: In altricial species, maternal stimuli have powerful effects on amygdala development and attachment-related behaviors. In humans, maternal deprivation has been associated with both "indiscriminate friendliness" toward non-caregiving adults and altered amygdala development. We hypothesized that maternal deprivation would be associated with reduced amygdala discrimination between mothers and strangers and increased parent report of indiscriminate friendliness behaviors. METHODS: Sixty-seven youths (33 previously institutionalized; 34 comparison; age-at-scan 4-17 years) participated in a functional magnetic resonance imaging experiment designed to examine amygdala response to mother versus stranger faces. In-scanner behavior was measured. Indiscriminate friendliness was assessed with parental report. RESULTS: Comparison youth showed an amygdala response that clearly discriminated mother versus stranger stimuli. Previously institutionalized youths, by contrast, exhibited reduced amygdala discrimination between mothers and strangers. Reduced amygdala differentiation correlated with greater reports of indiscriminate friendliness. These effects correlated with age-at-adoption, with later adoptions being associated with reduced amygdala discrimination and more indiscriminate friendliness. CONCLUSIONS: Our results suggest that early maternal deprivation is associated with reduced amygdala discrimination between mothers and strangers, and reduced amygdala discrimination was associated with greater reports of indiscriminate friendliness. Moreover, these effects increased with age-at-adoption. These data suggest that the amygdala, in part, is associated with indiscriminate friendliness and that there might be a dose-response relationship between institutional rearing and indiscriminate friendliness.

Abnormal fusiform activation during emotional-face encoding assessed with functional magnetic resonance imaging.

This functional magnetic resonance imaging study shows that children and adults with bipolar disorder (BD), compared with healthy subjects, exhibit impaired memory for emotional faces and abnormal fusiform activation during encoding. Fusiform activation abnormalities in BD were correlated with mania severity and may therefore represent a trait and state BD biomarker.

Amygdala hyperactivation during face emotion processing in unaffected youth at risk for bipolar disorder.

OBJECTIVE: Youth at familial risk for bipolar disorder (BD) show deficits in face emotion processing, but the neural correlates of these deficits have not been examined. This preliminary study tests the hypothesis that, relative to healthy comparison (HC) subjects, both BD subjects and youth at risk for BD (i.e., those with a first-degree BD relative) will demonstrate amygdala hyperactivation when viewing fearful and happy faces. The at-risk youth were unaffected, in that they had no history of mood disorder. METHOD: Amygdala activity was examined in 101 unrelated participants, 8 to 18 years old. Age, gender, and IQ-matched groups included BD (N = 32), unaffected at-risk (N = 13), and HC (N = 56). During functional magnetic resonance imaging, participants attended to emotional and nonemotional aspects of fearful and happy faces. RESULTS: While rating their fear of fearful faces, both BD and unaffected at-risk subjects exhibited amygdala hyperactivity versus HC. There were no between-group differences in amygdala activity in response to happy faces. Post-hoc comparisons revealed that, in at-risk youth, familial risk status (offspring versus sibling), presence of Axis I diagnosis (n = 1 attention-deficit/hyperactivity disorder [ADHD], n = 1 social phobia), and history of medication exposure (n = 1) did not influence imaging findings. CONCLUSIONS: We found amygdala hyperactivation in both unaffected at-risk and BD youth while rating their fear of fearful faces. These pilot data suggest that both face emotion labeling deficits and amygdala hyperactivity during face processing should receive further study as potential BD endophenotypes. Longitudinal studies should test whether amygdala hyperactivity to fearful faces predicts conversion to BD in at-risk youth.