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1.
Nutrients ; 16(14)2024 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-39064701

RESUMEN

Effective food fortification strategies using elemental iron powders (EIPs) are needed to combat iron deficiency anemia. The purpose of this study was to determine hemoglobin regeneration efficiency (HRE) and relative iron bioavailability (RBV) of four food-grade EIPs (El-Lyte (EL), Hi-Sol (HS), H-325 (H3), and A-131 (A1)) by treating anemic rats with 14 d iron repletion diets (uncooked and cooked), fortified with a 12, 24, or 36 mg iron/kg diet of the EIPs, ferrous sulfate monohydrate (FS, FeSO4•H2O), or no added iron (control), n = 9-12/group. The ability of EL and HS to maintain hemoglobin for 6 weeks on the 6 mg iron/kg diet was also studied. The dissolution rate of iron from the EIPs was measured in hydrochloric acid at pH 1.0. Compared to FS, the EL, HS, and A1 EIPs had >50% overall RBV, with the following order: HS > A1 > EL > H3 (p ≤ 0.05); the effect of cooking was not significant (p > 0.05). Dissolution testing revealed that the mean RBV of the EIPs was positively associated with the percentage of iron solubility. In the 6-week maintenance study, EL and HS maintained hemoglobin as well as FS. Overall, the findings show that at the concentrations of iron tested, these EIPs are effective fortification agents to replenish hemoglobin and correct iron deficiency anemia.


Asunto(s)
Anemia Ferropénica , Disponibilidad Biológica , Alimentos Fortificados , Hemoglobinas , Hierro , Polvos , Ratas Sprague-Dawley , Animales , Hemoglobinas/metabolismo , Anemia Ferropénica/tratamiento farmacológico , Hierro/sangre , Ratas , Masculino , Hierro de la Dieta/administración & dosificación , Hierro de la Dieta/farmacocinética , Compuestos Ferrosos/administración & dosificación
2.
Brain Lang ; 252: 105414, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38640643

RESUMEN

Childhood poverty is related to deficits in multiple cognitive domains including adult language function. It is unknown if the brain basis of language is disrupted in adults with childhood poverty backgrounds, controlling for current functioning. Fifty-one adults (age 24) from an existing longitudinal study of childhood poverty, beginning at age 9, were examined on behavioral phonological awareness (LP) and completed an event-related fMRI speech/print processing LP task. Adults from childhood poverty backgrounds exhibited lower LP in adulthood. The middle-income group exhibited greater activation of the bilateral IFG and hippocampus during language processing. In psychophysiological interaction (PPI) analyses, the childhood poverty group exhibited greater coupling between ventral Broca's and the middle temporal gyrus (MTG) as well as coupling between Wernicke's region and bilateralization. Childhood poverty disrupts language processing neural networks in adulthood, after controlling for LP, suggesting that poverty in childhood influences the neurophysiological basis for language processing into adulthood.


Asunto(s)
Encéfalo , Lenguaje , Imagen por Resonancia Magnética , Pobreza , Humanos , Femenino , Masculino , Adulto Joven , Encéfalo/fisiología , Encéfalo/diagnóstico por imagen , Niño , Adulto , Estudios Longitudinales , Red Nerviosa/fisiología , Red Nerviosa/diagnóstico por imagen , Mapeo Encefálico
3.
Child Maltreat ; 29(1): 3-7, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-36154501

RESUMEN

Adults with histories of childhood maltreatment (CM) are more likely to display problematic parenting behaviors. The goal of this study was to examine changes in maternal brain activation to negative infant cues over the early postpartum period among new mothers with and without histories of CM, as this is a period of immense neuroplasticity in the maternal brain. CM was measured using the Adverse Childhood Experiences Scale. Functional magnetic resonance imaging (fMRI) conducted at approximately 5 and 13 weeks postpartum measured brain responses to own and unfamiliar infant cues in primiparous women. Women with histories of CM displayed increasing activation in the anterior cingulate cortex, and greater increases in anterior cingulate cortex activation was associated with maternal reports of less regulatory capacity in their infants. Preliminary results suggest that new mothers with CM histories display greater brain responses to negative infant cues compared to new mothers without CM histories. Women with CM histories may benefit from additional supports during the transition to parenthood.


Asunto(s)
Maltrato a los Niños , Señales (Psicología) , Adulto , Lactante , Femenino , Humanos , Niño , Madres , Periodo Posparto , Encéfalo/diagnóstico por imagen , Responsabilidad Parental , Relaciones Madre-Hijo
4.
J Neuroendocrinol ; 35(7): e13316, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37491982

RESUMEN

Opioid-induced deficits in maternal behaviors are well-characterized in rodent models. Amid the current epidemic of opioid use disorder (OUD), prevalence among pregnant women has risen sharply. Yet, the roles of buprenorphine replacement treatment for OUD (BT/OUD) in the brain functions of postpartum mothers are unclear. Using functional magnetic resonance imaging (fMRI), we have developed an evolutionarily conserved maternal behavior neurocircuit (MBN) model to study human maternal care versus defensive/aggressive behaviors critical to mother-child bonding. The anterior cingulate gyrus (ACC) is not only involved in the MBN for mother-child bonding and attachment, but also part of an opioid sensitive "pain-matrix". The literature suggests that prescription opioids produce physical and emotional "analgesic" effects by disrupting specific resting-state functional connectivity (rs-FC) of ACC to regions related to MBN. Thus, in this longitudinal study, we report findings of overlapping MBN and pain matrix circuits, for mothers with chronic exposure of BT/OUD. A total of 32 mothers were studied with 6 min rs-FC at 1 month (T1) and 4 months postpartum (T2), including seven on BT/OUD and 25 non-BT/OUD mothers as a comparison group. We analyzed rs-FC between the insula, putamen, and the dorsal anterior cingulate cortex (DACC) and rostral ACC (RACC), as the regions of interest that mediate opioid analgesia. BT/OUD mothers, as compared to non-BT/OUD mothers, showed less left insula-RACC rs-FC but greater right putamen-DACC rs-FC at T1, with these between-group differences diminished at T2. Some of these rs-FC results were correlated with the scores of postpartum parental bonding questionnaire. We found time-by-treatment interaction effects on DACC and RACC-dependent rs-FC, potentially identifying brain mechanisms for beneficial effects of BT, normalizing dysfunction of maternal brain and behavior over the first four months postpartum. This study complements recent studies to ascertain how BT/OUD affects maternal behaviors, mother-child bonding, and intersubjectivity and reveals potential MBN/pain-matrix targets for novel interventions.


Asunto(s)
Buprenorfina , Trastornos Relacionados con Opioides , Embarazo , Humanos , Femenino , Giro del Cíngulo , Buprenorfina/uso terapéutico , Madres , Analgésicos Opioides/uso terapéutico , Analgésicos Opioides/farmacología , Estudios Longitudinales , Trastornos Relacionados con Opioides/tratamiento farmacológico , Encéfalo , Dolor , Imagen por Resonancia Magnética/métodos
5.
Front Psychol ; 14: 1099800, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36968746

RESUMEN

Conflicts are increasingly intensified among the members of the community, making it almost impossible to extend compassion-defined as a wish to relieve others from suffering-from one side to the other, especially when both sides believe that "life is a battle of us the good vs. them the evil." Is compassion even relevant to conflicts? The answer depends on how a conflict is framed in one's perception. If a conflict is perceived in a frame of zero-sum competition, then compassion is meaningless in such a "tug-of-war" mindset. Conversely, if perceived in a non-zero-sum frame-as demonstrated in reiterated prisoner's dilemma (rPD) in which two players may interdependently render win-win, lose-lose, win-lose, or lose-win scenarios by their actions-then compassion can help achieve the most preferable outcomes for all in a "dyadic dance" mindset. In this article, we present a path of intuitive compassion by pointing to symmetry across three distinct domains of rPD, dyadic active inference, and Mahayana Buddhism. In each of these domains, conflicts serve as points of bifurcation on a bidirectional path, and compassion as a conflict-proof commitment to carrying out the best strategies-even if assessed for one's own sake only-that consistently produce optimal payoffs in rPD, minimal stress in dyadic active inference, and limitless joy of ultimate enlightenment in Mahayana Buddhism. Conversely, a lack of compassion is caused by invalid beliefs that obscure the nature of reality in these domains, causing conflicts to produce even more conflicts. These invalid beliefs are produced by mistakes of over-reduction, over-separation, and over-compression in the mind, and therefore, a person's mindset is overly compressed from a multidimensional frame to a one-dimensional frame. Taken together, intuitive compassion is not about how to balance one's self-serving goals with altruistic ones. Rather, it is a conflict-proof commitment to transforming conflicts into enduring peace and prosperity according to the ultimate nature of reality. The work presented here may serve as a preliminary science-informed introduction to a genre of time-tested compassion meditations, i.e., lojong mind training, for the world laden with conflicts, starting from the conflicts in close relationships to those in geopolitics.

6.
J Perinat Educ ; 31(4): 206-215, 2022 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-36277228

RESUMEN

Mothers are concerned about their firstborn children's acceptance of a baby sibling. Observing children's reactions to mothers interacting with an infant doll simulator has been offered as one means of seeing how children will react to the baby sibling. A longitudinal pilot study with 30 pregnant mothers and their firstborn children was conducted comparing children's behaviors to mother-doll interaction in the laboratory before birth with behaviors during home observations of mother-sibling interaction 1 month after birth. Children responded to mother-doll and mother-sibling interaction differently, with no significant associations across children's behaviors in mother-doll and mother-sibling interactions. The use of an infant doll simulator before birth did not reliably predict children's behavioral adjustment after the birth of a baby sibling.

7.
Front Psychol ; 13: 806755, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35967689

RESUMEN

Intersubjectivity refers to one person's awareness in relation to another person's awareness. It is key to well-being and human development. From infancy to adulthood, human interactions ceaselessly contribute to the flourishing or impairment of intersubjectivity. In this work, we first describe intersubjectivity as a hallmark of quality dyadic processes. Then, using parent-child relationship as an example, we propose a dyadic active inference model to elucidate an inverse relation between stress and intersubjectivity. We postulate that impaired intersubjectivity is a manifestation of underlying problems of deficient relational benevolence, misattributing another person's intentions (over-mentalizing), and neglecting the effects of one's own actions on the other person (under-coupling). These problems can exacerbate stress due to excessive variational free energy in a person's active inference engine when that person feels threatened and holds on to his/her invalid (mis)beliefs. In support of this dyadic model, we briefly describe relevant neuroimaging literature to elucidate brain networks underlying the effects of an intersubjectivity-oriented parenting intervention on parenting stress. Using the active inference dyadic model, we identified critical interventional strategies necessary to rectify these problems and hereby developed a coding system in reference to these strategies. In a theory-guided quantitative review, we used this coding system to code 35 clinical trials of parenting interventions published between 2016 and 2020, based on PubMed database, to predict their efficacy for reducing parenting stress. The results of this theory-guided analysis corroborated our hypothesis that parenting intervention can effectively reduce parenting stress if the intervention is designed to mitigate the problems of deficient relational benevolence, under-coupling, and over-mentalizing. We integrated our work with several dyadic concepts identified in the literature. Finally, inspired by Arya Nagarjuna's Buddhist Madhyamaka Philosophy, we described abstract expressions of Dependent Origination as a relational worldview to reflect on the normality, impairment, and rehabilitation of intersubjectivity.

8.
Behav Brain Sci ; 45: e110, 2022 07 07.
Artículo en Inglés | MEDLINE | ID: mdl-35796356

RESUMEN

Benevolent intersubjectivity developed in parent-infant interactions and compassion toward friend and foe alike are non-violent interventions to group behavior in conflict. Based on a dyadic active inference framework rooted in specific parental brain mechanisms, we suggest that interventions promoting compassion and intersubjectivity can reduce stress, and that compassionate mediation may resolve conflicts.


Asunto(s)
Encéfalo , Empatía , Humanos , Lactante
9.
PLoS One ; 17(4): e0265676, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35472058

RESUMEN

BACKGROUND: The quality of a child's attachment to its primary caregiver plays an important role for its long-term socioemotional development. While 'secure' attachment is associated with better outcomes, 'insecure' attachment is associated with a higher risk of externalizing and internalizing symptoms. Children referred to mental health services show much higher rates of insecure attachment than the general population, yet the parent-child relationship is rarely in treatment focus. Attachment quality is closely associated with parental sensitive responsiveness that is target of attachment-based interventions like Circle of Security (COS). COS has shown to improve attachment quality and the well-being of both children and parents. No randomized controlled trials have investigated the effect of COS on parental sensitivity and child psychiatric symptoms in child mental health services. OBJECTIVES: To investigate whether COS-Parenting (COS-P) can increase observed maternal sensitivity and decrease children's psychiatric symptoms as an add on to treatment as usual (TAU). METHODS: In a randomized controlled parallel superiority trial COS-P is compared with TAU for parents of children referred to child mental health services (n = 186). Families are randomized 2:1 to intervention or control group, if their child is between 3 and 8 years old and scores ≥ 93d percentile on both the CBCL total score and the oppositional defiant disorder or conduct disorder subscale. Primary outcome is maternal sensitivity, secondary and exploratory outcomes include, among others, child psychiatric symptoms, parental stress and coping with children's negative emotions. Outcomes and adverse events are assessed before (T0) and after 10 weeks of treatment (T1) and 6 months later (T2). Regression analysis and /or ANOVA will be used for all outcomes. PERSPECTIVES: Targeting the parent-child relation has the potential to reduce psychiatric symptoms in children. This trial will provide valuable information if attachment-based interventions like COS-P can enhance treatment as usual in child mental health services. TRAIL REGISTRATION: ClinicalTrials.gov Identifier: NCT03578016.


Asunto(s)
Trastorno de la Conducta , Servicios de Salud Mental , Niño , Preescolar , Humanos , Relaciones Padres-Hijo , Responsabilidad Parental , Padres/psicología , Ensayos Clínicos Controlados Aleatorios como Asunto
10.
Handb Clin Neurol ; 182: 63-82, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34266612

RESUMEN

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.


Asunto(s)
Trastornos Mentales , Periodo Periparto , Niño , Femenino , Humanos , Lactante , Conducta Materna , Relaciones Madre-Hijo , Periodo Posparto , Embarazo
11.
Neurosci Biobehav Rev ; 128: 592-620, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34089764

RESUMEN

Social feelings have conceptual and empirical connections with affect and emotion. In this review, we discuss how they relate to cognition, emotion, behavior and well-being. We examine the functional neuroanatomy and neurobiology of social feelings and their role in adaptive social functioning. Existing neuroscience literature is reviewed to identify concepts, methods and challenges that might be addressed by social feelings research. Specific topic areas highlight the influence and modulation of social feelings on interpersonal affiliation, parent-child attachments, moral sentiments, interpersonal stressors, and emotional communication. Brain regions involved in social feelings were confirmed by meta-analysis using the Neurosynth platform for large-scale, automated synthesis of functional magnetic resonance imaging data. Words that relate specifically to social feelings were identfied as potential research variables. Topical inquiries into social media behaviors, loneliness, trauma, and social sensitivity, especially with recent physical distancing for guarding public and personal health, underscored the increasing importance of social feelings for affective and second person neuroscience research with implications for brain development, physical and mental health, and lifelong adaptive functioning.


Asunto(s)
Neurociencias , Interacción Social , Cognición , Emociones , Humanos , Conducta Social
12.
Obesity (Silver Spring) ; 29(6): 1014-1021, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33893721

RESUMEN

OBJECTIVE: This study tested whether substrate concentrations or fatty acid storage proteins predict storage of endogenous lipids in visceral adipose tissue (VAT) and upper body subcutaneous adipose tissue (UBSQ) fat. METHODS: The day prior to surgery, 25 patients undergoing bariatric procedures received an infusion of autologous [1-14 C]triolein-labeled very low-density lipoprotein (VLDL) particles, and during surgery, they received a continuous [U-13 C]palmitate infusion/bolus [9,10-3 H]palmitate tracer. VAT and UBSQ fat were collected to measure VLDL-triglyceride (TG) storage, direct free fatty acid (FFA) storage rates, CD36 content, lipoprotein lipase (LPL), acyl-CoA synthetase, diacylglycerol acetyl-transferase, and glycerol-3-phosphate acyltransferase activities. RESULTS: Storage of VLDL-TG and FFA-palmitate in UBSQ and VAT was not different. Plasma palmitate concentrations correlated with palmitate storage rates in UBSQ and VAT (r = 0.46, P = 0.02 and r = 0.46, P = 0.02, respectively). In VAT, VLDL-TG storage was correlated with VLDL concentrations (r = 0.53, P < 0.009) and LPL (r = 0.42, P < 0.05). In UBSQ, VLDL-TG storage was correlated with LPL (r = 0.42, P < 0.05). CD36, acyl-CoA synthetase, glycerol-3-phosphate acyltransferase, and diacylglycerol acetyl-transferase were not correlated with VLDL-TG or palmitate storage. CONCLUSIONS: Adipose storage of VLDL-TG is predicted by VLDL-TG concentrations and LPL; FFA concentrations predict direct adipose tissue FFA storage rates.


Asunto(s)
Ácidos Grasos/metabolismo , Grasa Intraabdominal/metabolismo , Obesidad Mórbida/metabolismo , Grasa Subcutánea/metabolismo , Adipocitos/metabolismo , Adipocitos/patología , Tejido Adiposo/metabolismo , Tejido Adiposo/patología , Adolescente , Adulto , Cirugía Bariátrica , Ácidos Grasos no Esterificados/metabolismo , Femenino , Humanos , Grasa Intraabdominal/patología , Lipoproteínas VLDL/metabolismo , Masculino , Persona de Mediana Edad , Obesidad Mórbida/patología , Obesidad Mórbida/cirugía , Grasa Subcutánea/patología , Triglicéridos/metabolismo , Adulto Joven
13.
Dev Psychobiol ; 63(5): 1589-1596, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33432574

RESUMEN

Childhood socioeconomic status (SES) has been associated with brain cortex surface area in children. However, the extent to which childhood SES is prospectively associated with brain morphometry in adulthood is unclear. We tested whether childhood SES (income-to-needs ratio averaged across ages 9, 13, and 17) is prospectively associated with cortical surface morphometry in adulthood. Average childhood income-to-needs ratio had a positive, prospective association with cortical thickness in adulthood in the precentral gyrus, postcentral gyrus, and caudal middle frontal gyrus (p < .05, FWE corrected). Childhood income-to-needs ratio also had a positive, prospective association with cortical surface area in adulthood in multiple regions, including the rostral and caudal middle frontal gyri and superior frontal gyrus (p < .05, FWE corrected). Concurrent income-to-needs ratio (measured at age 24) was not associated with cortical thickness or surface area in adulthood. The results underscore the importance of addressing poverty in childhood for brain morphological development.


Asunto(s)
Imagen por Resonancia Magnética , Corteza Motora , Adulto , Encéfalo , Niño , Humanos , Imagen por Resonancia Magnética/métodos , Pobreza , Clase Social , Adulto Joven
15.
Front Psychol ; 12: 770093, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-35185679

RESUMEN

While the prevalence of opioid use disorder (OUD) among pregnant women has multiplied in the United States in the last decade, buprenorphine treatment (BT) for peripartum women with OUD has been administered to reduce risks of repeated cycles of craving and withdrawal. However, the maternal behavior and bonding in mothers with OUD may be altered as the underlying maternal behavior neurocircuit (MBN) is opioid sensitive. In the regulation of rodent maternal behaviors such as licking and grooming, a series of opioid-sensitive brain regions are functionally connected, including the ventral pallidum (VP). In humans, these brain regions, interact with the supplementary motor area (SMA) to regulate maternal behaviors and are functionally dysregulated by opioids. It is unclear how these brain regions respond to the emotions of their child for mothers receiving BT. In this functional magnetic resonance imaging (fMRI) pilot study in 22 mothers within the first postpartum year, including six mothers receiving BT and 16 non-OUD mothers as a comparison group (CG), we devised a child face mirroring task in fMRI settings to assess maternal responses to pictures of facial expressions of own child and an unknown child in an empathic mirroring condition (Join) and a non-mirroring observation condition (Observe). In each condition, faces of neutral, ambiguous, distressed, and joyful expressions of each child were repeatedly displayed in a random order. The response of SMA during empathic mirroring (Join) vs. non-mirroring (Observe) of own child was reduced among BT/OUD vs. CG. Within MBN, the left VP, critical for parental sensitivity, had a similar deficit. This study outlines potential mechanisms for investigating the risks of deficits in the neural responses to actual maternal sensitivity and parenting behavior in mothers with OUD, and potential targets for interventions that reduce stress and augment maternal behavior and child outcome.

16.
Front Psychiatry ; 11: 568824, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33363481

RESUMEN

Stress resilience in parenting depends on the parent's capacity to understand subjective experiences in self and child, namely intersubjectivity, which is intimately related to mimicking other's affective expressions (i. e., mirroring). Stress can worsen parenting by potentiating problems that can impair intersubjectivity, e.g., problems of "over-mentalizing" (misattribution of the child's behaviors) and "under-coupling" (inadequate child-oriented mirroring). Previously we have developed Mom Power (MP) parenting intervention to promote maternal intersubjectivity and reduce parenting stress. This study aimed to elucidate neural mechanisms underlying the effects of MP with a novel Child Face Mirroring Task (CFMT) in functional magnetic-resonance-imaging settings. In CFMT, the participants responded to own and other's child's facial pictures in three task conditions: (1) empathic mirroring (Join), (2) non-mirroring observing (Observe), and (3) voluntary responding (React). In each condition, each child's neutral, ambiguous, distressed, and joyful expressions were repeatedly displayed. We examined the CFMT-related neural responses in a sample of healthy mothers (n = 45) in Study 1, and MP effects on CFMT with a pre-intervention (T1) and post-intervention (T2) design in two groups, MP (n = 19) and Control (n = 17), in Study 2. We found that, from T1 to T2, MP (vs. Control) decreased parenting stress, decreased dorsomedial prefrontal cortex (dmPFC) during own-child-specific voluntary responding (React to Own vs. Other's Child), and increased activity in the frontoparietal cortices, midbrain, nucleus accumbens, and amygdala during own-child-specific empathic mirroring (Join vs. Observe of Own vs. Other's Child). We identified that MP effects on parenting stress were potentially mediated by T1-to-T2 changes in: (1) the left superior-temporal-gyrus differential responses in the contrast of Join vs. Observe of own (vs. other's) child, (2) the dmPFC-PAG (periaqueductal gray) differential functional connectivity in the same contrast, and (3) the left amygdala differential responses in the contrast of Join vs. Observe of own (vs. other's) child's joyful vs. distressed expressions. We discussed these results in support of the notion that MP reduces parenting stress via changing neural activities related to the problems of "over-mentalizing" and "under-coupling." Additionally, we discussed theoretical relationships between parenting stress and intersubjectivity in a novel dyadic active inference framework in a two-agent system to guide future research.

17.
Lancet Diabetes Endocrinol ; 8(12): 960-970, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33137293

RESUMEN

BACKGROUND: The melanocortin 4 receptor (MC4R), a component of the leptin-melanocortin pathway, plays a part in bodyweight regulation. Severe early-onset obesity can be caused by biallelic variants in genes that affect the MC4R pathway. We report the results from trials of the MC4R agonist setmelanotide in individuals with severe obesity due to either pro-opiomelanocortin (POMC) deficiency obesity or leptin receptor (LEPR) deficiency obesity. METHODS: These single-arm, open-label, multicentre, phase 3 trials were done in ten hospitals across Canada, the USA, Belgium, France, Germany, the Netherlands, and the UK. Participants aged 6 years or older with POMC or LEPR deficiency obesity received open-label setmelanotide for 12 weeks. Participants with at least 5 kg weight loss (or ≥5% if weighing <100 kg at baseline) entered an 8-week placebo-controlled withdrawal sequence (including 4 weeks each of blinded setmelanotide and placebo treatment) followed by 32 additional weeks of open-label treatment. The primary endpoint, which was assessed in participants who received at least one dose of study medication and had a baseline assessment (full analysis set), was the proportion of participants with at least 10% weight loss compared with baseline at approximately 1 year. A key secondary endpoint was mean percentage change in the most hunger score of the 11-point Likert-type scale at approximately 1 year on the therapeutic dose, which was assessed in a subset of participants aged 12 years or older in the full analysis set who demonstrated at least 5 kg weight loss (or ≥5% in paediatric participants if baseline bodyweight was <100 kg) over the 12-week open-label treatment phase and subsequently proceeded into the placebo-controlled withdrawal sequence, regardless of later disposition. These studies are registered with ClinicalTrials.gov, NCT02896192 and NCT03287960. FINDINGS: Between Feb 14, 2017, and Sept 7, 2018, ten participants were enrolled in the POMC trial and 11 participants were enrolled in the LEPR trial, and included in the full analysis and safety sets. Eight (80%) participants in the POMC trial and five (45%) participants in the LEPR trial achieved at least 10% weight loss at approximately 1 year. The mean percentage change in the most hunger score was -27·1% (n=7; 90% CI -40·6 to -15·0; p=0·0005) in the POMC trial and -43·7% (n=7; -54·8 to -29·1; p<0·0001) in the LEPR trial. The most common adverse events were injection site reaction and hyperpigmentation, which were reported in all ten participants in the POMC trial; nausea was reported in five participants and vomiting in three participants. In the LEPR trial, the most commonly reported treatment-related adverse events were injection site reaction in all 11 participants, skin disorders in five participants, and nausea in four participants. No serious treatment-related adverse events occurred in both trials. INTERPRETATION: Our results support setmelanotide for the treatment of obesity and hyperphagia caused by POMC or LEPR deficiency. FUNDING: Rhythm Pharmaceuticals.


Asunto(s)
Insuficiencia Suprarrenal/complicaciones , Fármacos Antiobesidad/uso terapéutico , Obesidad/tratamiento farmacológico , Proopiomelanocortina/deficiencia , Receptor de Melanocortina Tipo 4/agonistas , Receptores de Leptina/deficiencia , alfa-MSH/análogos & derivados , Adolescente , Adulto , Niño , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Masculino , Obesidad/complicaciones , Obesidad/etiología , Obesidad/patología , Pronóstico , Adulto Joven , alfa-MSH/uso terapéutico
18.
Hum Brain Mapp ; 41(13): 3580-3593, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32529772

RESUMEN

The association between childhood socioeconomic status (SES) and brain development is an emerging area of research. The primary focus to date has been on SES and variations in gray matter structure with much less known about the relation between childhood SES and white matter structure. Using a longitudinal study of SES, with measures of income-to-needs ratio (INR) at age 9, 13, 17, and 24, we examined the prospective relationship between childhood SES (age 9 INR) and white matter organization in adulthood using diffusion tensor imaging. We also examined how changes in INR from childhood through young adulthood are associated with white matter organization in adult using a latent growth mixture model. Using tract-based spatial statistics (TBSS) we found that there is a significant prospective positive association between childhood INR and white matter organization in the bilateral uncinate fasciculus, bilateral cingulum bundle, bilateral superior longitudinal fasciculus, and corpus callosum (p < .05, FWE corrected). The probability that an individual was in the high-increasing INR profile across development compared with the low-increasing INR profile was positively associated with white matter organization in the bilateral uncinate fasciculus, left cingulum, and bilateral superior longitudinal fasciculus. The results of the current study have potential implications for interventions given that early childhood poverty may have long-lasting associations with white matter structure. Furthermore, trajectories of socioeconomic status during childhood are important-with individuals that belong to the latent profile that had high increases in INR having greater regional white matter organization in adulthood.


Asunto(s)
Experiencias Adversas de la Infancia , Pobreza , Clase Social , Sustancia Blanca/anatomía & histología , Adolescente , Adulto , Niño , Imagen de Difusión Tensora , Femenino , Humanos , Estudios Longitudinales , Masculino , Sustancia Blanca/diagnóstico por imagen , Adulto Joven
19.
Infant Behav Dev ; 59: 101430, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32146254

RESUMEN

This study explored the impact of infant temperament and maternal stress on the development of the infant medial prefrontal cortex (mPFC) among sixteen 6-8-month-old infants. Functional Near Infrared Spectroscopy (fNIRS) was used to measure activation of the infant mPFC in response to angry, happy, and sad faces. Infant temperament and dimensions of maternal stress were measured with the Infant Behavior Questionnaire and the Parenting Stress Index Respectively. Infants with high negative emotionality demonstrated increased mPFC activation in association with all emotion face conditions. Negative emotionality moderated the effect of total maternal stress on mPFC activation to angry and sad faces. Mother-infant dysfunctional interaction was related to increased mPFC activation associated with happy faces, supporting the "novelty hypothesis", in which the mPFC responds more strongly to unique experiences. Therefore, this study provides additional evidence that infant temperament and the quality of the mother-infant relationship influence the development of the mPFC and how infants process emotions.


Asunto(s)
Desarrollo Infantil/fisiología , Emociones/fisiología , Expresión Facial , Relaciones Madre-Hijo/psicología , Corteza Prefrontal/fisiología , Femenino , Humanos , Lactante , Conducta del Lactante/fisiología , Conducta del Lactante/psicología , Masculino , Estimulación Luminosa/métodos , Corteza Prefrontal/metabolismo , Espectroscopía Infrarroja Corta/métodos , Temperamento/fisiología
20.
Front Psychol ; 11: 603385, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33505336

RESUMEN

As interpersonal, racial, social, and international conflicts intensify in the world, it is important to safeguard the mental health of individuals affected by them. According to a Buddhist notion "if you want others to be happy, practice compassion; if you want to be happy, practice compassion," compassion practice is an intervention to cultivate conflict-proof well-being. Here, compassion practice refers to a form of concentrated meditation wherein a practitioner attunes to friend, enemy, and someone in between, thinking, "I'm going to help them (equally)." The compassion meditation is based on Buddhist philosophy that mental suffering is rooted in conceptual thoughts that give rise to generic mental images of self and others and subsequent biases to preserve one's egoism, blocking the ultimate nature of mind. To contextualize compassion meditation scientifically, we adopted a Bayesian active inference framework to incorporate relevant Buddhist concepts, including mind (buddhi), compassion (karuna), aggregates (skandhas), suffering (duhkha), reification (samaropa), conceptual thoughts (vikalpa), and superimposition (prapañca). In this framework, a person is considered a Bayesian Engine that actively constructs phenomena based on the aggregates of forms, sensations, discriminations, actions, and consciousness. When the person embodies rigid beliefs about self and others' identities (identity-grasping beliefs) and the resulting ego-preserving bias, the person's Bayesian Engine malfunctions, failing to use prediction errors to update prior beliefs. To counter this problem, after recognizing the causes of sufferings, a practitioner of the compassion meditation aims to attune to all others equally, friends and enemies alike, suspend identity-based conceptual thoughts, and eventually let go of any identity-grasping belief and ego-preserving bias that obscure reality. We present a brain model for the Bayesian Engine of three components: (a) Relation-Modeling, (b) Reality-Checking, and (c) Conflict-Alarming, which are subserved by (a) the Default-Mode Network (DMN), (b) Frontoparietal Network (FPN) and Ventral Attention Network (VAN), and (c) Salience Network (SN), respectively. Upon perceiving conflicts, the strengthening or weakening of ego-preserving bias will critically depend on whether the SN up-regulates the DMN or FPN/VAN, respectively. We propose that compassion meditation can strengthen brain regions that are conducive for suspending prior beliefs and enhancing the attunements to the counterparts in conflicts.

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