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OBJECTIVE: Prenatal stress physiology is often posited as a predictor of birth outcomes, including gestational age at birth and birthweight. However, research has predominantly relied on indicators in the maternal system, with few studies examining hormones of the fetal system. The current study focuses on fetal cortisol in the third trimester, as measured in neonatal hair, as a biological factor that might associate with birth outcomes (gestational age at birth and birthweight). We report findings from two studies: a longitudinal cohort (Study 1), and a meta-analysis of the existing literature (Study 2). METHODS STUDY: Hair was collected for cortisol analysis from 168 neonates (55.95% female) shortly after birth. Gestational age at birth and birthweight were abstracted from medical records. METHODS STUDY: An exhaustive search of four databases was conducted, yielding 155 total studies for screening. Papers reporting neonatal hair cortisol (collection <2 weeks postpartum) and birth outcomes among human neonates were retained for analysis, including Study 1 results (k = 9). RESULTS STUDY: Higher neonatal hair cortisol was related to longer gestation, r = .28, p < .001, and higher birthweight, r = .16, p = .040. Sex did not moderate either association. RESULTS STUDY: Across the nine studies, higher neonatal hair cortisol predicted both longer gestation, r = .35, p < .001, 95% CI [0.24,0.45] and higher birthweight, r = .18, p = .001, 95% CI [0.07,0.28]. Neonatal sex did not moderate these associations. CONCLUSIONS: Fetal cortisol exposure in the third trimester plays a role in normative maturation of the fetus and findings reveal that higher cortisol is associated with positive birth outcomes.
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BACKGROUND: Prenatal glucocorticoids are one of the most widely proposed prenatal programming mechanisms, yet few studies exist that measure fetal cortisol via neonatal hair. Neonatal hair provides a window into the fetal experience and represents cortisol accumulation in the third trimester of pregnancy. In the current study, we test the links between two types of anxiety over the course of gestation (pregnancy-related anxiety and general anxiety) with neonatal hair cortisol. METHOD: Pregnant individuals (N = 107) and their neonates (59.8% female) participated in the current study. Prenatal pregnancy-related anxiety and general anxiety were measured using the Pregnancy Related Anxiety Scale (PRAS) and the State-Trait Anxiety Inventory (STAI), in each trimester of pregnancy. Hierarchical linear modeling was used to model the intercept and slope of each type of anxiety over gestation. Neonatal hair samples were collected shortly after birth (Median days = 1.17, IQR = 0.75-2.00). RESULTS: Both higher pregnancy-related anxiety and general anxiety at the beginning of pregnancy and a flatter decline of pregnancy-related anxiety over gestation were associated with lower neonatal hair cortisol. After inclusion of gestational age at birth and parity as covariates, pregnancy-related anxiety (intercept: ß = -0.614, p =.012; slope: ß = -0.681, p =.006), but not general anxiety (intercept: ß = -0.389, p =.114; slope: ß = -0.302, p =.217) remained a significant predictor. Further, when both general and pregnancy-related anxiety were entered into the same model, only pregnancy-related anxiety (intercept and slope) were significant predictors of neonatal hair cortisol, indicating an association with pregnancy-related anxiety above and beyond general anxiety. CONCLUSION: Cortisol plays a central role in maturation of fetal organ systems, and at the end of gestation, higher cortisol has beneficial effects such as promoting fetal lung maturation. Further, lower maternal cortisol is linked to less optimal cognitive development and altered brain development. As maternal higher anxiety in early pregnancy and a flatter decrease over time are both associated with lower neonatal hair cortisol, maternal pregnancy-related anxiety could be a target of future intervention efforts.
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Ansiedad , Cabello , Hidrocortisona , Humanos , Femenino , Cabello/química , Embarazo , Hidrocortisona/análisis , Hidrocortisona/metabolismo , Ansiedad/metabolismo , Recién Nacido , Adulto , Edad Gestacional , Complicaciones del Embarazo/metabolismo , Masculino , Tercer Trimestre del Embarazo/metabolismoRESUMEN
Background: Shortened gestation is a leading cause of childhood morbidity and mortality with lifelong consequences for health. There is a need for public health initiatives on increasing gestational age at birth. Prenatal maternal depression is a pervasive health problem robustly linked via correlational and epidemiological studies to shortened gestational length. This proof-of-concept study tests the impact of reducing prenatal maternal depression on gestational length with analysis of a randomized clinical trial (RCT). Methods: Participants included 226 pregnant individuals enrolled into an RCT and assigned to receive either interpersonal psychotherapy (IPT) or enhanced usual care (EUC). Recruitment began in July 2017 and participants were enrolled August 10, 2017 to September, 8 2021. Depression diagnosis (Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition; DSM 5) and symptoms (Edinburgh Postnatal Depression Scale and Symptom Checklist) were evaluated at baseline and longitudinally throughout gestation to characterize depression trajectories. Gestational dating was collected based on current guidelines via medical records. The primary outcome was gestational age at birth measured dichotomously (≥39 gestational weeks) and the secondary outcome was gestational age at birth measured continuously. Posthoc analyses were performed to test the effect of reducing prenatal maternal depression on gestational length. This trial is registered with ClinicalTrials.gov (NCT03011801). Findings: Steeper decreases in depression trajectories across gestation predicted later gestational age at birth, specifically an increase in the number of full-term babies born ≥39 gestational weeks (EPDS linear slopes: OR = 1.54, 95% CI 1.10-2.16; and SCL-20 linear slopes: OR = 1.67, 95% CI 1.16-2.42). Causal mediation analyses supported the hypothesis that participants assigned to IPT experienced greater reductions in depression symptom trajectories, which in turn, contributed to longer gestation. Supporting mediation, the natural indirect effect (NIE) showed that reduced depression trajectories resulting from intervention were associated with birth ≥39 gestational weeks (EPDS, OR = 1.65, 95% CI 1.02-2.66; SCL-20, OR = 1.85, 95% CI 1.16-2.97). Interpretation: We used a RCT design and found that reducing maternal depression across pregnancy was associated with lengthened gestation. Funding: This research was supported by the NIH (R01 HL155744, R01 MH109662, R21 MH124026, P50 MH096889).
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Importance: Prenatal depression is prevalent with negative consequences for both the mother and developing fetus. Brief, effective, and safe interventions to reduce depression during pregnancy are needed. Objective: To evaluate depression improvement (symptoms and diagnosis) among pregnant individuals from diverse backgrounds randomized to brief interpersonal psychotherapy (IPT) vs enhanced usual care (EUC). Design, Setting, and Participants: A prospective, evaluator-blinded, randomized clinical trial, the Care Project, was conducted among adult pregnant individuals who reported elevated symptoms during routine obstetric care depression screening in general practice in obstetrics and gynecology (OB/GYN) clinics. Participants were recruited between July 2017 and August 2021. Repeated measures follow-up occurred across pregnancy from baseline (mean [SD], 16.7 [4.2] gestational weeks) through term. Pregnant participants were randomized to IPT or EUC and included in intent-to-treat analyses. Interventions: Treatment comprised an engagement session and 8 active sessions of brief IPT (MOMCare) during pregnancy. EUC included engagement and maternity support services. Main Outcomes and Measures: Two depression symptom scales, the 20-item Symptom Checklist and the Edinburgh Postnatal Depression Scale, were assessed at baseline and repeatedly across pregnancy. Structured Clinical Interview for DSM-5 ascertained major depressive disorder (MDD) at baseline and the end of gestation. Results: Of 234 participants, 115 were allocated to IPT (mean [SD] age, 29.7 [5.9] years; 57 [49.6%] enrolled in Medicaid; 42 [36.5%] had current MDD; 106 [92.2%] received intervention) and 119 to EUC (mean [SD] age, 30.1 [5.9] years; 62 [52.1%] enrolled in Medicaid; 44 [37%] had MDD). The 20-item Symptom Checklist scores improved from baseline over gestation for IPT but not EUC (d = 0.57; 95% CI, 0.22-0.91; mean [SD] change for IPT vs EUC: 26.7 [1.14] to 13.6 [1.40] vs 27.1 [1.12] to 23.5 [1.34]). IPT participants more rapidly improved on Edinburgh Postnatal Depression Scale compared with EUC (d = 0.40; 95% CI, 0.06-0.74; mean [SD] change for IPT vs EUC: 11.4 [0.38] to 5.4 [0.57] vs 11.5 [0.37] to 7.6 [0.55]). MDD rate by end of gestation had decreased significantly for IPT participants (7 [6.1%]) vs EUC (31 [26.1%]) (odds ratio, 4.99; 95% CI, 2.08-11.97). Conclusions and Relevance: In this study, brief IPT significantly reduced prenatal depression symptoms and MDD compared with EUC among pregnant individuals from diverse racial, ethnic, and socioeconomic backgrounds recruited from primary OB/GYN clinics. As a safe, effective intervention to relieve depression during pregnancy, brief IPT may positively affect mothers' mental health and the developing fetus. Trial Registration: ClinicalTrials.gov Identifier: NCT03011801.
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Trastorno Depresivo Mayor , Psicoterapia Breve , Adulto , Humanos , Femenino , Embarazo , Depresión/diagnóstico , Depresión/terapia , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/terapia , Resultado del Tratamiento , Estudios ProspectivosRESUMEN
Background: A large body of research supports the deleterious effects of adverse childhood experiences (ACEs) on disease susceptibility and health for both the exposed individual and the next generation. It is likely that there is an intergenerational transmission of risk from mother to child; however, the mechanisms through which such risk is conferred remain unknown. The current study evaluated the association between maternal ACEs, neonatal brain development of the amygdala and hippocampus, and later infant negative emotionality at six months of age. Methods: The sample included 85 mother-infant dyads (44 female infants) from a longitudinal study. Maternal ACEs were assessed with the Adverse Childhood Experiences Questionnaire (ACE-Q) and neonatal hippocampal and amygdala volume was assessed using structural magnetic resonance imaging (MRI). Infant negative emotionality was assessed at 6 months using the Infant Behavior Questionnaire (IBQ). Results: Multivariate analyses demonstrated that maternal ACEs were associated with bilateral amygdala volume (F(2,78) = 3.697,p = .029). Specifically, higher maternal ACEs were associated with smaller left (ß = -0.220, t(79) = -2.661, p = .009, R2 = 0.494, and right (ß = -0.167, t(79) = -2.043, p = .044, R2 = 0.501) amygdala volume. No significant association between maternal ACEs and bilateral hippocampal volume (F(2,78) = 0.215,p = .0807) was found. Follow-up regression analyses demonstrated that both high maternal ACEs and smaller left amygdala volume were associated with higher infant negative emotionality at six months of age (ß = .232, p = .040, R2 = 0.094, and ß = -0.337, p = .022, R2 = 0.16, respectively) although statistically significant mediation of this effect was not observed (Indirect effect = 0.0187, 95% CI [-0.0016-0.0557]). Conclusions: Maternal ACEs are associated with both newborn amygdala volume and subsequent infant negative emotionality. These findings linking maternal adverse childhood experiences and infant brain development and temperament provide evidence to support the intergenerational transmission of adversity from mother to child.
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BACKGROUND: The rapid maturation of the fetal brain renders the fetus susceptible to prenatal environmental signals. Prenatal maternal sleep quality is known to have important health implications for newborns including risk for preterm birth, however, the effect on the fetal brain is poorly understood. METHOD: Participants included 94 pregnant participants and their newborns (53% female). Pregnant participants (Mage = 30; SDage= 5.29) reported on sleep quality three times throughout pregnancy. Newborn hippocampal and amygdala volumes were assessed using structural magnetic resonance imaging. Multilevel modeling was used to test the associations between trajectories of prenatal maternal sleep quality and newborn hippocampal and amygdala volume. RESULTS: The overall trajectory of prenatal maternal sleep quality was associated with hippocampal volume (left: b = 0.00003, p = 0.013; right: b = 0.00003, p = .008). Follow up analyses assessing timing of exposure indicate that poor sleep quality early in pregnancy was associated with larger hippocampal volume bilaterally (e.g., late gestation left: b = 0.002, p = 0.24; right: b = 0.004, p = .11). Prenatal sleep quality was not associated with amygdala volume. CONCLUSION: These findings highlight the implications of poor prenatal maternal sleep quality and its role in contributing to newborn hippocampal development.
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Nacimiento Prematuro , Efectos Tardíos de la Exposición Prenatal , Recién Nacido , Embarazo , Humanos , Femenino , Adulto , Masculino , Estudios Prospectivos , Efectos Tardíos de la Exposición Prenatal/patología , Nacimiento Prematuro/patología , Amígdala del Cerebelo/patología , Imagen por Resonancia Magnética/métodos , Hipocampo/patología , SueñoRESUMEN
Telomere length (TL) is a biological marker of cellular aging, and shorter TL in adulthood is associated with increased morbidity and mortality risk. It is likely that these differences in TL are established long before adulthood, and there is growing evidence that TL can reflect prenatal experiences. Although maternal prenatal distress predicts newborn TL, it is unknown whether the relation between prenatal exposure to maternal distress and child TL persists through childhood. The purpose of the current longitudinal, prospective study is to examine the relation between prenatal exposure to maternal distress (perceived stress, depressive symptoms, pregnancy-related anxiety) and TL in childhood. Participants included 102 children (54 girls) and their mothers. Mothers' distress was assessed five times during pregnancy, at 12 weeks postpartum, and at the time of child telomere measurement between 6 and 16 years of age. Maternal distress during pregnancy predicted shorter offspring TL in childhood, even after accounting for postnatal exposure to maternal distress and other covariates. These findings indicate that maternal mental health predicts offspring TL biology later in childhood than previously observed. This study bolsters claims that telomere biology is subject to fetal programming and highlights the importance of supporting maternal mental health during pregnancy.
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Efectos Tardíos de la Exposición Prenatal , Distrés Psicológico , Adulto , Niño , Femenino , Humanos , Recién Nacido , Embarazo , Estudios Prospectivos , Telómero , Acortamiento del TelómeroRESUMEN
INTRODUCTION: Research on risk factors for prenatal depression is critical to improve the understanding, prevention, and treatment of women's psychopathology. The current study examines the relation between experiences of racial discrimination and trajectories of depression symptoms over the course of pregnancy. METHOD: Participants completed standardized measures regarding symptoms of depression at four timepoints during pregnancy and reported on experiences of racial discrimination at one timepoint. Latent growth curve modeling was used to examine the relation between discrimination and initial levels (intercept) and trajectories (slope) of depression symptoms over pregnancy. RESULTS: Participants were 129 pregnant individuals recruited from obstetric clinics and oversampled for elevated depression symptoms. Thirty-six percent of the participants were living at or below 200% of the federal poverty line. Fifty-four percent of the sample identified as non-Latinx White, 26% as Latinx, and 13% as non-Latinx Black. An unconditional latent growth curve modeling revealed a negative quadratic trajectory of depression symptoms during pregnancy. When women's report of discrimination was added as a predictor of depression trajectories, discrimination predicted the initial value (intercept) of depression symptoms, but not change over the course of pregnancy (slope). Specifically, higher levels of experiences of discrimination were associated with higher levels of depression symptoms. When sociodemographic and contextual covariates were included in the model, a low family income-to-needs ratio was also related to higher levels of depression symptoms. CONCLUSIONS: These findings provide evidence that women's experiences of racial discrimination and family financial strain are risk factors for prenatal depression, with implications for screening, treatment, and policy.
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Negro o Afroamericano , Racismo , Depresión/diagnóstico , Depresión/etiología , Femenino , Humanos , EmbarazoRESUMEN
The prenatal period represents a critical time for brain growth and development. These rapid neurological advances render the fetus susceptible to various influences with life-long implications for mental health. Maternal distress signals are a dominant early life influence, contributing to birth outcomes and risk for offspring psychopathology. This prospective longitudinal study evaluated the association between prenatal maternal distress and infant white matter microstructure. Participants included a racially and socioeconomically diverse sample of 85 mother-infant dyads. Prenatal distress was assessed at 17 and 29 weeks' gestational age (GA). Infant structural data were collected via diffusion tensor imaging at 42-45 weeks' postconceptional age. Findings demonstrated that higher prenatal maternal distress at 29 weeks' GA was associated with increased fractional anisotropy (b = .283, t(64) = 2.319, p = .024) and with increased axial diffusivity (b = .254, t(64) = 2.067, p = .043) within the right anterior cingulate white matter tract. No other significant associations were found with prenatal distress exposure and tract fractional anisotropy or axial diffusivity at 29 weeks' GA, nor earlier in gestation.
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Sustancia Blanca , Encéfalo/patología , Imagen de Difusión Tensora/métodos , Femenino , Humanos , Lactante , Estudios Longitudinales , Embarazo , Estudios Prospectivos , Sustancia Blanca/diagnóstico por imagenRESUMEN
BACKGROUND: Alcohol use has been reliably associated with smaller subcortical and cortical regional gray matter volumes (GMVs). Whether these associations reflect shared predisposing risk factors or causal consequences of alcohol use remains poorly understood. METHODS: Data came from 3 neuroimaging samples (N = 2423), spanning childhood or adolescence to middle age, with prospective or family-based data. First, we identified replicable GMV correlates of alcohol use. Next, we used family-based and longitudinal data to test whether these associations may plausibly reflect a predispositional liability for alcohol use or a causal consequence of alcohol use. Finally, we used heritability, gene-set enrichment, and transcriptome-wide association study approaches to evaluate whether genome-wide association study-defined genomic risk for alcohol consumption is enriched for genes that are preferentially expressed in regions that were identified in our neuroimaging analyses. RESULTS: Smaller right dorsolateral prefrontal cortex (DLPFC) (i.e., middle and superior frontal gyri) and insula GMVs were associated with increased alcohol use across samples. Family-based and prospective longitudinal data suggest that these associations are genetically conferred and that DLPFC GMV prospectively predicts future use and initiation. Genomic risk for alcohol use was enriched in gene sets that were preferentially expressed in the DLPFC and was associated with replicable differential gene expression in the DLPFC. CONCLUSIONS: These data suggest that smaller DLPFC and insula GMV plausibly represent genetically conferred predispositional risk factors for, as opposed to consequences of, alcohol use. DLPFC and insula GMV represent promising biomarkers for alcohol-consumption liability and related psychiatric and behavioral phenotypes.
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Estudio de Asociación del Genoma Completo , Sustancia Gris , Adolescente , Consumo de Bebidas Alcohólicas/genética , Encéfalo/diagnóstico por imagen , Niño , Sustancia Gris/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
Importance: Previous research indicates that cannabis use is associated with psychotic-like experiences (PLEs). However, it is unclear whether this association results from predispositional (ie, shared genetic) factors or individual-specific factors (eg, causal processes, such as cannabis use leading to PLEs). Objectives: To estimate genetic and environmental correlations between cannabis use and PLEs, and to examine PLEs in twin and nontwin sibling pairs discordant for exposure to cannabis use to disentangle predispositional from individual-specific effects. Design, Setting, and Participants: In this cross-sectional analysis, diagnostic interviews and self-reported data were collected from 2 separate population-based samples of twin and nontwin sibling pairs. Data from the Human Connectome Project were collected between August 10, 2012, and September 29, 2015, and data from the Australian Twin Registry Cohort 3 (ATR3) were collected between August 1, 2005, and August 31, 2010. Data were analyzed between August 17, 2017, and July 6, 2018. The study included data from 1188 Human Connectome Project participants and 3486 ATR3 participants, totaling 4674 participants. Main Outcomes and Measures: Three cannabis-involvement variables were examined: frequent use (ie, ≥100 times), a DSM-IV lifetime cannabis use disorder diagnosis, and current cannabis use. Genetic and environmental correlations between cannabis involvement and PLEs were estimated. Generalized linear mixed models examined PLE differences in twin and nontwin sibling pairs discordant for cannabis use. Results: Among the 4674 participants, the mean (SD) age was 30.5 (3.2) years, and 2923 (62.5%) were female. Data on race/ethnicity were not included as a covariate owing to lack of variability within the ATR3 sample; among the 1188 participants in the Human Connectome Project, 875 (73.7%) were white. Psychotic-like experiences were associated with frequent cannabis use (ß = 0.11; 95% CI, 0.08-0.14), cannabis use disorder (ß = 0.13; 95% CI, 0.09-0.16), and current cannabis use (ß = 0.07; 95% CI, 0.04-0.10) even after adjustment for covariates. Correlated genetic factors explained between 69.2% and 84.1% of this observed association. Within discordant pairs of twins/siblings (Npairs, 308-324), Psychotic-like experiences were more common in cannabis-exposed individuals compared with their relative who used cannabis to a lesser degree (ß ≥ .23, P < .05; eg, frequent and infrequent cannabis-using relatives significantly differed, z = -5.41; P < .001). Conclusions and Relevance: Despite the strong contribution of shared genetic factors, frequent and problem cannabis use also appears to be associated with PLEs via person-specific pathways. This study's findings suggest that policy discussions surrounding legalization should consider the influence of escalations in cannabis use on traitlike indices of vulnerability, such as PLEs, which could contribute to pervasive psychological and interpersonal burden.
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Predisposición Genética a la Enfermedad , Abuso de Marihuana/complicaciones , Psicosis Inducidas por Sustancias/etiología , Adulto , Estudios Transversales , Enfermedades en Gemelos/etiología , Enfermedades en Gemelos/genética , Enfermedades en Gemelos/psicología , Femenino , Humanos , Entrevista Psicológica , Masculino , Abuso de Marihuana/psicología , Psicosis Inducidas por Sustancias/genética , Sistema de Registros , Factores de Riesgo , Hermanos/psicologíaRESUMEN
BACKGROUND: Preclinical models reveal that stress-induced amygdala activity and impairment in fear extinction reflect reductions in anandamide driven by corticotropin-releasing factor receptor type 1 (CRF1) potentiation of the anandamide catabolic enzyme fatty acid amide hydrolase. METHODS: Here, we provide clinical translation for the importance of these molecular interactions using an imaging genetics strategy to examine whether interactions between genetic polymorphisms associated with differential anandamide (FAAH rs324420) and CRF1 (CRHR1 rs110402) signaling modulate amygdala function and anxiety disorder diagnosis. RESULTS: Analyses revealed that individuals with a genetic background predicting relatively high anandamide and CRF1 signaling exhibited blunted basolateral amygdala habituation, which further mediated increased risk for anxiety disorders among these same individuals. CONCLUSIONS: The convergence of preclinical and clinical data suggests that interactions between anandamide and CRF1 represent a fundamental molecular mechanism regulating amygdala function and anxiety. Our results further highlight the potential of imaging genetics to powerfully translate complex preclinical findings to clinically meaningful human phenotypes.
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Amígdala del Cerebelo/patología , Ansiedad , Ácidos Araquidónicos/genética , Hormona Liberadora de Corticotropina/genética , Endocannabinoides/genética , Polimorfismo de Nucleótido Simple/genética , Transducción de Señal/genética , Amidohidrolasas/genética , Amígdala del Cerebelo/diagnóstico por imagen , Amígdala del Cerebelo/metabolismo , Ansiedad/diagnóstico por imagen , Ansiedad/genética , Ansiedad/patología , Hormona Liberadora de Corticotropina/metabolismo , Femenino , Genotipo , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Oxígeno , Alcamidas Poliinsaturadas , Escalas de Valoración Psiquiátrica , Receptores de Hormona Liberadora de Corticotropina/genética , Estudios Retrospectivos , Adulto JovenRESUMEN
Addictions are prevalent psychiatric disorders that confer remarkable personal and social burden. Despite substantial evidence for their moderate, yet robust, heritability (approx. 50%), specific genetic mechanisms underlying their development and maintenance remain unclear. The goal of this selective review is to highlight progress in unveiling the genetic underpinnings of addiction. First, we revisit the basis for heritable variation in addiction before reviewing the most replicable candidate gene findings and emerging signals from genomewide association studies for alcohol, nicotine and cannabis addictions. Second, we survey the modest but growing field of neurogenetics examining how genetic variation influences corticostriatal structure, function, and connectivity to identify neural mechanisms that may underlie associations between genetic variation and addiction. Third, we outline how extant genomic findings are being used to develop and refine pharmacotherapies. Finally, as sample sizes for genetically informed studies of addiction approach critical mass, we posit five exciting possibilities that may propel further discovery (improved phenotyping, rare variant discovery, gene-environment interplay, epigenetics, and novel neuroimaging designs).
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Addiction to cocaine is a chronic condition characterized by high rates of early relapse. This study builds on efforts to identify neural markers of relapse risk by studying resting-state functional connectivity (rsFC) in neural circuits arising from the amygdala, a brain region implicated in relapse-related processes including craving and reactivity to stress following acute and protracted withdrawal from cocaine. Whole-brain resting-state functional magnetic resonance imaging connectivity (6 min) was assessed in 45 cocaine-addicted individuals and 22 healthy controls. Cocaine-addicted individuals completed scans in the final week of a residential treatment episode. To approximate preclinical models of relapse-related circuitry, separate seeds were derived for the left and right basolateral (BLA) and corticomedial (CMA) amygdala. Participants also completed the Iowa Gambling Task, Wisconsin Card Sorting Test, Cocaine Craving Questionnaire, Obsessive-Compulsive Cocaine Use Scale and Personality Inventory. Relapse within the first 30 days post-treatment (n = 24) was associated with reduced rsFC between the left CMA and ventromedial prefrontal cortex/rostral anterior cingulate cortex (vmPFC/rACC) relative to cocaine-addicted individuals who remained abstinent (non-relapse, n = 21). Non-relapse participants evidenced reduced rsFC between the bilateral BLA and visual processing regions (lingual gyrus/cuneus) compared to controls and relapsed participants. Early relapse was associated with fewer years of education but unrelated to trait reactivity to stress, neurocognitive and clinical characteristics or cocaine use history. Findings suggest that rsFC within neural circuits implicated in preclinical models of relapse may provide a promising marker of relapse risk in cocaine-addicted individuals. Future efforts to replicate the current findings and alter connectivity within these circuits may yield novel interventions and improve treatment outcomes.
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UNLABELLED: The neural correlates of response to psychosocial stress and gender differences therein are difficult to model experimentally as this type of stressor is difficult to induce in a brain imaging environment. The Trier Social Stress Test (TSST), a behavioral paradigm that reliably induces moderate levels of stress was thus modified for the MRI environment. To determine the neurobehavioral basis of gender differences in response to observing oneself under social evaluative stress, 26 subjects (14 females) performed the TSST while being videotaped. During fMRI scanning, subjects were shown alternating video clips of two CONDITIONS: SELF or a same-sex OTHER performing the TSST. Subjects rated their stress level immediately after the video clips. GENDER differences in the [SELF-OTHER] contrast were analyzed. There was a GENDER×CONDITION interaction such that only women reported increased subjective stress during video feedback of their TSST session. A whole brain analysis (SELF vs. OTHER) showed activation in the bilateral insula, inferior, middle and superior frontal gyri. Greater recruitment was seen among males in some of these same areas in the context of significantly lower stress ratings. Activation of areas involved in inhibitory control and sensory awareness might contribute to the significantly lower stress ratings in males. Understanding these gender differences is relevant to disorders of stress and self-concept.
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Encéfalo/fisiopatología , Autoimagen , Caracteres Sexuales , Conducta Social , Estrés Psicológico/fisiopatología , Adulto , Mapeo Encefálico , Femenino , Humanos , Juicio , Imagen por Resonancia Magnética , Masculino , Pruebas Neuropsicológicas , Análisis y Desempeño de Tareas , Grabación en VideoRESUMEN
BACKGROUND: Dysregulated striatal functioning coupled with executive control deficits arising from abnormal frontal cortical function are considered key mechanisms in the development and maintenance of cocaine addiction. The same features are thought to underlie high trait impulsivity observed in cocaine-addicted populations. OBJECTIVES: Employing resting state functional connectivity, the current study sought to identify cortico-striatal circuit alterations in cocaine addiction and examine the degree to which circuit connectivity contributes to relapse risk and impulsivity among cocaine-addicted individuals. METHODS: Whole-brain resting-state functional magnetic resonance imaging connectivity was assessed in 45 cocaine-addicted individuals relative to 22 healthy controls using seed volumes in the left and right caudate, putamen and nucleus accumbens. Cocaine-addicted individuals completed scans in the final week of a 2-4 weeks residential treatment episode. Relapse by day 30 post-discharge served to separate cocaine-addicted individuals into relapse and non-relapse groups. All participants completed the Barratt Impulsivity Scale (BIS-11a). RESULTS: Cocaine-addicted individuals exhibited reduced positive connectivity between the bilateral putamen and posterior insula and right postcentral gyrus. Group differences were primarily driven by reduced connectivity in relapse individuals relative to controls. No relapse versus non-relapse differences emerged. Impulsivity (BIS-11a) was higher in cocaine-addicted participants, an effect that was partially mediated by reduced putamen-posterior insula connectivity in this group. CONCLUSION: Cocaine addiction, relapse risk and impulsivity were associated with reduced connectivity in putamen-posterior insula/postcentral gyrus circuits implicated in temporal discounting and habitual responding. Findings provide new insight into the neurobiological mechanisms underlying impulsivity and relapse in cocaine addiction.
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Encéfalo/metabolismo , Trastornos Relacionados con Cocaína/fisiopatología , Conducta Impulsiva/epidemiología , Imagen por Resonancia Magnética , Adulto , Estudios de Casos y Controles , Corteza Cerebral/metabolismo , Trastornos Relacionados con Cocaína/rehabilitación , Cuerpo Estriado/metabolismo , Función Ejecutiva , Femenino , Humanos , Masculino , Persona de Mediana Edad , RecurrenciaRESUMEN
Additional somatosensory contact of preterm human infants improves a variety of developmental assessment scores, but less is known about its lasting consequences. In rodents, maternal contact may influence the programming of juvenile social play behavior. Therefore, we used a paradigm where we can control the levels of somatosensory contact associated with maternal care. We find that additional somatosensory contact of offspring can have lasting consequences on juvenile social play behavior in a sex-dependent manner. Specifically, additional somatosensory stimuli reduced male social play behavior, but did not change female play behavior. We then examined if this additional infant contact altered some neurobiological substrates associated with play within the juvenile amygdala. Control males had lower levels of 5HT2a receptor mRNA levels contrasted to females; however, similar to its sex-dependent effect on juvenile social play, males that received additional somatosensory contact had higher serotonin 5HT2a receptor mRNA levels than control males. No difference was found in females. As serotonin signaling typically opposes juvenile play behavior, these data suggest that maternal touch can program lasting differences in juvenile social play and 5HT2a receptors mRNA levels within the juvenile amygdala.