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1.
Stress Health ; 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33049110

RESUMO

Individuals vary greatly in their mental health and these differences may play a critical role in stress resistance, risk reduction and illness recovery. Here we ask how these differences may be related to normal variation in personality and genotype. One hundred healthy college students completed measures of mental health (Mental Health Continuum-Short Form [MHC-SF]), personality (NEO Five Factor Inventory) and adverse childhood experiences. Participants also provided saliva samples, genotyped for both the serotonin transporter (5-HTTLPR) and the brain-derived neurotrophic factor (BDNF), each assayed for naturally occurring polymorphisms, 5-HTTLPR (short/long) and BDNF (valine/methionine). Mental health correlated strongly with the NEO triad of conscientiousness-extraversion-neuroticism, with largest contributions to MHC-SF scores for conscientiousness, followed by extraversion and then neuroticism. The personality trait interaction of extraversion × conscientiousness uniquely accounted for approximately 44.22% 44.62% of the variance in MHC-SF scores. Polygenic comparisons showed a significant gene × gene interaction, with highest mental health for 5-HTTLPR-S, Met carriers. Together these results provided support for distinct yet interacting roles of personality and genetics in the phenotypical expression of mental health.

2.
Horm Behav ; 126: 104822, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32730760

RESUMO

Oxytocin is important for postnatal developmental experiences for mothers, infants, and transactions between them. Oxytocin is also implicated in adult affiliative behaviors, including social buffering of stress. There is evidence for connections between early life experience and adult oxytocin system functioning, but effects of early experience on behavioral, endocrine, and neurophysiological outcomes related to adult social buffering are not well explored. We use a limited bedding and nesting (LBN) material paradigm as an environmental disruption of early experiences and assessed central oxytocin systems in brain regions related to hypothalamic-pituitary-adrenal (HPA) axis regulation (paraventricular nucleus of the hypothalamus, amygdala, hippocampus). We also assessed developmentally-appropriate social behaviors and HPA reactivity during social buffering testing in adulthood. LBN litters had larger huddles and more pups visible compared to control litters during the first two weeks of life. LBN also altered the developmental trajectory of oxytocin-expressing cells and oxytocin receptor cells, with increases in oxytocin receptor cells at P15 in LBN pups. By adulthood, LBN females had more and LBN males had fewer oxytocin and oxytocin receptor cells in these areas compared to sex-matched controls. Adult LBN females, but not LBN males, had behavioral changes during social interaction and social buffering testing. The sex-specific effects of early experience on central oxytocin systems and social behavior may contribute to female resilience to early life adversity.

3.
Physiol Behav ; 222: 112957, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32387121

RESUMO

A quality nest can buffer pups from the cold climate in typical laboratory housing by insulating them from cool ambient air and facilitating pup huddling during early life when many thermal regulation strategies are not yet developed. The limited nesting material (LBN) manipulation prevents the dam from constructing a quality nest. In the present study, we investigate whether LBN presents a thermal challenge to pups across the first two postnatal weeks. Behavioral thermal regulation (huddling), physiological thermogenesis (activation of brown adipose tissue; BAT), changes in cellular metabolism (mitochondrial biogenesis) in peripheral and central tissues, and maternal behavior were measured in environments with LBN or abundant bedding on postnatal day (P) 2, P6, P10, and P14. The huddle of LBN litters had greater area, greater perimeter, and reduced circularity, and more pups visible. Control male pups were visible longer than control female pups during home cage recordings and LBN pups were visible longer than control pups. Heart weight relative to body weight was higher in LBN pups after P2. LBN affected BAT, but not white adipose tissue (WAT), activation in a sex and age-specific manner, with reductions in UCP1 expression after P2. Pups appear especially affected by LBN on P6, when mitochondrial DNA copy number was reduced in WAT. Mitochondrial DNA copy number was reduced in LBN pups in the hippocampus but not the brainstem. Our data provide evidence of changes in indices of thermal regulation and cellular metabolism in LBN pups which may be indicative of changes in energy allocation during development.

4.
Dev Psychobiol ; 62(5): 684-692, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32072622

RESUMO

Intergenerational patterns of parental behavior, especially maternal behavior, have been observed across mammalian species including humans, non-human primates, and rodents. These patterns are largely experience-dependent as opposed to genetically induced, with experiences in early-life serving an essential role in directing maternal behavior expressed later in life. Environmental conditions can also alter maternal behavior with consequences for offspring neurodevelopment and interactions with the next generation. Here, we describe effects of lineage during developmental environmental disruption using a limited bedding and nesting material manipulation during the first 2 weeks of life. Dams from three lineages were placed in environments containing either abundant nesting material or reduced nesting material. Environmental condition affected eight measures of maternal behavior and dam lineage affected 12 measures of maternal behavior during the first two postnatal weeks. Lineage, condition, and pup sex predicted pup body weight immediately following the manipulation, with lineage accounting for the largest portion of variance in body weight. Although from a limited sample, these data are the first to examine effects of lineage and environment simultaneously and suggest dam lineage may be a better predictor of maternal behavior than current environmental conditions with important implications for pup outcomes.

5.
Dev Psychobiol ; 62(1): 116-122, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31342518

RESUMO

Neonatal abstinence syndrome (NAS) after in-utero opioid exposure remains a poorly understood condition with multiple factors contributing to severity. Exposure to maternal stress may be one contributing factor. Hair cortisol measurement represents a novel technique for assessing prenatal stress. In this pilot study, the association between maternal hair cortisol levels and NAS severity was examined in 70 postpartum women with opioid use disorder within 72 hr of delivery. Infants were monitored for NAS and treated according to institutional protocol. Forty-four (63%) of the infants were pharmacologically treated for NAS, with a mean length of hospital stay (LOS) for all infants of 14.2 (SD 9.0) days. The mean cortisol level in the mothers was 131.8 pg/mg (SD 124.7). In bivariate analysis, higher maternal hair cortisol levels were associated with shorter infant LOS (R = -.26, p = .03) and fewer infant opioid treatment days (R = -.28, p = .02). Results were no longer statistically significant in regression models after adjusting for maternal opioid and smoking. In conclusion, we demonstrated the feasibility of hair cortisol assaying within the first few days after delivery in mothers with opioid use disorder as a novel marker for NAS. The findings suggest that maternal stress may impact the severity of infant opioid withdrawal.


Assuntos
Cabelo/metabolismo , Hidrocortisona/metabolismo , Mães , Síndrome de Abstinência Neonatal/diagnóstico , Síndrome de Abstinência Neonatal/terapia , Transtornos Relacionados ao Uso de Opioides/complicações , Efeitos Tardios da Exposição Pré-Natal , Estresse Psicológico/metabolismo , Adulto , Estudos de Viabilidade , Feminino , Humanos , Recém-Nascido , Projetos Piloto , Gravidez , Índice de Gravidade de Doença , Adulto Jovem
6.
Front Neuroendocrinol ; 56: 100802, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31738947

RESUMO

The ability to adapt to stressful circumstances, known as emotional resilience, is a key factor in the maintenance of mental health. Several individual biomarkers of the stress response (e.g., corticosterone) that influence an animal's position along the continuum that ranges from adaptive allostasis to maladaptive allostatic load have been identified. Extending beyond specific biomarkers of stress responses, however, it is also important to consider stress-related responses relative to other relevant responses for a thorough understanding of the underpinnings of adaptive allostasis. In this review, behavioral, neurobiological, developmental and genomic variables are considered in the context of emotional resilience [e.g., explore/exploit behavioral tendencies; DHEA/CORT ratios and relative proportions of protein-coding/nonprotein-coding (transposable) genomic elements]. As complex and multifaceted relationships between pertinent allostasis biomediators are identified, translational applications for optimal resilience are more likely to emerge as effective therapeutic strategies.

7.
Trends Endocrinol Metab ; 30(11): 807-818, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31699238

RESUMO

The glucocorticoid receptor (GR) has been shown to be important for mediating cellular responses to stress and circulating glucocorticoids. Ligand-dependent transcriptional changes induced by GR are observed across numerous tissues. However, the mechanisms by which GR achieves cell and tissue-specific effects are less clear. Epigenetic mechanisms have been proposed to explain some of these differences as well as some of the lasting, even transgenerational, effects of stress and glucocorticoid action. GR functions in tandem with epigenetic cellular machinery to coordinate transcription and shape chromatin structure. Here, we describe GR interactions with these effectors and how GR acts to reshape the epigenetic landscape in response to the environment.


Assuntos
Epigênese Genética/genética , Receptores de Glucocorticoides/metabolismo , Animais , Metilação de DNA/fisiologia , Glucocorticoides/metabolismo , Humanos , RNA não Traduzido/genética , RNA não Traduzido/metabolismo
8.
Neurobiol Stress ; 11: 100186, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31440532

RESUMO

We focused on individual risk by examining childhood adversity and current psychiatric symptoms in a sample of 100 college students genotyped for both the serotonin transporter (5-HTTLPR) and the brain-derived neurotrophic factor (BDNF). Naturally occurring allelic variation in 5-HTTLPR (short/long) and BDNF (valine/methionine) have been strongly implicated in stress-related psychiatric risk, but the combined effects of these alleles on psychological functioning have yet to be fully elucidated. Univariate analysis revealed gene-environment correlations linking heightened psychiatric risk with past childhood adversity for short but not long 5-HTTLPR allelic carriers and for valine (Val) but not methionine (Met) BDNF allelic carriers. Multivariate analyses revealed a significant gene x gene interaction with results showing that risk varied systematically depending on both 5-HTTLPR and BDNF alleles, independent of childhood adversity. Hierarchical regression analyses indicated that approximately 11% of the variance in symptoms of depression could be specifically accounted for by the epistatic interaction of 5-HTTLPR and BDNF val66Met polymorphisms. Allelic group analyses indicated lowest risk, as measured by depression and anxiety, for allelic carriers of 5-HTTLPR-short and BDNF Met, followed by 5-HTTLPR-long and BDNF-Val, 5-HTTLPR-short and BDNF-Val, and 5-HTTLPR-long and BDNF-Met. Results suggest that protective or risk-enhancing effects on stress-related psychiatric functioning may depend on specific allelic combinations of 5-HTTLPR and BDNF.

9.
Brain Sci ; 9(8)2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31349644

RESUMO

One source of information we glean from everyday experience, which guides social interaction, is assessing the emotional state of others. Emotional state can be expressed through several modalities: body posture or movements, body odor, touch, facial expression, or the intonation in a voice. Much research has examined emotional processing within one sensory modality or the transfer of emotional processing from one modality to another. Yet, less is known regarding interactions across different modalities when perceiving emotions, despite our common experience of seeing emotion in a face while hearing the corresponding emotion in a voice. Our study examined if visual and auditory emotions of matched valence (congruent) conferred stronger perceptual and physiological effects compared to visual and auditory emotions of unmatched valence (incongruent). We quantified how exposure to emotional faces and/or voices altered perception using psychophysics and how it altered a physiological proxy for stress or arousal using salivary cortisol. While we found no significant advantage of congruent over incongruent emotions, we found that changes in cortisol were associated with perceptual changes. Following exposure to negative emotional content, larger decreases in cortisol, indicative of less stress, correlated with more positive perceptual after-effects, indicative of stronger biases to see neutral faces as happier.

10.
Neurobiol Stress ; 11: 100174, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31193573

RESUMO

Transposable elements make up a much larger portion of the genome than protein-coding genes, yet we know relatively little about their function in the human genome. However, we are beginning to more fully understand their role in brain development, neuroinflammation, and adaptation to environmental insults such as stress. For instance, glucocorticoid receptor activation regulates transposable elements in the brain following acute stress. Early life is a period of substantial brain development during which transposable elements play a role. Environmental exposures and experiences during early life that promote abnormal regulation of transposable elements may lead to a cascade of events that ultimately increase susceptibility to disorders later in life. Recent attention to transposable elements in psychiatric illness has begun to clarify associations indicative of dysregulation of different classes of transposable elements in stress-related and neurodevelopmental illness. Though individual susceptibility or resiliency to psychiatric illness has not been explained by traditional genetic studies, the wide inter-individual variability in transposable element composition in the human genome make TEs attractive candidates to elucidate this differential susceptibility. In this review, we discuss evidence that regulation of transposable elements in the brain are stage-specific, sensitive to environmental factors, and may be impacted by early life perturbations. We further present evidence of associations with stress-related and neurodevelopmental psychiatric illness from a developmental perspective.

11.
Horm Behav ; 113: 38-46, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31047887

RESUMO

Gonadal steroids play an integral role in male sexual behavior, and in most rodent models, this relationship is tightly coupled. However, many other species, including humans, continue to demonstrate male sex behavior in the absence of gonadal steroids, and the mechanisms that regulate steroid-independent male sex behavior are not well understood. Approximately 30% of castrated male B6D2F1 hybrid mice display male sex behavior many months after castration, allowing for the investigation of individual variation in steroidal regulation of male sex behavior. During both the perinatal and peripubertal periods of development, the organizational effects of gonadal steroids on sexual differentiation of the neural circuits controlling male sex behavior are well-documented. Several factors can alter the normal range of gonadal steroids or their receptors which may lead to the disruption of the normal processes of masculinization and defeminization. It is unknown whether the organizational effects of gonadal hormones during puberty are necessary for steroid-independent male sex behavior. However, gonadal steroids during puberty were not necessary for either testosterone or estradiol to activate male sex behavior in adulthood. Furthermore, activation of male sex behavior was initiated sooner in hybrid male mice castrated prior to puberty that were administered estradiol in adulthood compared to those that were provided testosterone. The underlying mechanisms by which gonadal hormones, during both the perinatal and peripubertal developmental periods of sexual differentiation, organize the normal maturation of neural circuitry that regulates steroid-independent male sex behavior in adult castrated B6D2F1 male mice warrants further investigation.


Assuntos
Hormônios Esteroides Gonadais/fisiologia , Comportamento Sexual Animal , Maturidade Sexual/fisiologia , Animais , Estradiol/farmacologia , Feminino , Hormônios Esteroides Gonadais/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Orquiectomia , Diferenciação Sexual/efeitos dos fármacos , Comportamento Sexual Animal/efeitos dos fármacos , Maturidade Sexual/efeitos dos fármacos , Esteroides/farmacologia , Esteroides/fisiologia , Testosterona/farmacologia , Testosterona/fisiologia
12.
Neurotoxicol Teratol ; 71: 41-49, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29475055

RESUMO

Histories of early life stress (ELS) or social discrimination can reach levels of severity characterized as toxic to mental and physical health. Such toxic social stress during development has been linked to altered acute hypothalamic-pituitary-adrenal (HPA) response to social stress in adulthood. However, there are important individual differences in the size and direction of these effects. We explored developmental, genetic, epigenetic, and contextual sources of individual differences in the relationship between ELS, discrimination, and adult responses to acute social stress in a standard laboratory test. Additional measures included perceived status, social support, background activity of HPA axis, and genetic variants in aspects of the stress response system. Participants (n = 90) answered questions about historical and ongoing stress, provided a DNA sample to examine genetic polymorphisms and epigenetic marks, and underwent the Trier Social Stress Test (TSST) during which three saliva samples were collected to assess HPA function. Individuals who reported high levels of childhood adversity had a blunted salivary cortisol response to the TSST. Childhood adversity, discrimination experiences, and FKBP5 genotype were found to predict pretest cortisol levels. Following up on recent observations that the glucocorticoid receptor directly interacts with the mitochondrial genome, particularly the NADH dehydrogenase 6 (MT-ND6) gene, individuals who reported high childhood adversity were also found to have higher percent methylation across six CpG sites upstream of MT-ND6. These findings suggest multiple contributions across psychological, genetic, epigenetic, and social domains to vulnerability and resilience in hypothalamic-pituitary-adrenal axis regulation. Further study to examine how these multiple contributors affect developmental endpoints through integrated or independent pathways will be of use.


Assuntos
Epigênese Genética , Hidrocortisona/sangue , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Estresse Psicológico/genética , Adulto , Feminino , Genótipo , Humanos , Sistema Hipotálamo-Hipofisário/fisiopatologia , Masculino , Sistema Hipófise-Suprarrenal/fisiopatologia , Saliva/química , Estresse Psicológico/sangue , Estresse Psicológico/fisiopatologia , Inquéritos e Questionários
13.
J Mol Endocrinol ; 62(2): R121-R128, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30082335

RESUMO

Glucocorticoids have long been recognized for their role in regulating the availability of energetic resources, particularly during stress. Furthermore, bidirectional connections between glucocorticoids and the physiology and function of mitochondria have been discovered over the years. However, the precise mechanisms by which glucocorticoids act on mitochondria have only recently been explored. Glucocorticoids appear to regulate mitochondrial transcription via activation of glucocorticoid receptors (GRs) with elevated circulating glucocorticoid levels following stress. While several mechanistic questions remain, GR and other nuclear transcription factors appear to have the capacity to substantially alter mitochondrial transcript abundance. The regulation of mitochondrial transcripts by stress and glucocorticoids will likely prove functionally relevant in many stress-sensitive tissues including the brain.


Assuntos
Regulação da Expressão Gênica , Mitocôndrias/genética , Receptores de Glucocorticoides/metabolismo , Estresse Fisiológico/genética , Animais , Humanos , Modelos Biológicos , Transcrição Genética
14.
Epigenomics ; 8(2): 237-49, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26791965

RESUMO

Classically thought as genomic clutter, the functional significance of transposable elements (TEs) has only recently become a focus of attention in neuroscience. Increasingly, studies have demonstrated that the brain seems to have more retrotransposition and TE transcription relative to other somatic tissues, suggesting a unique role for TEs in the central nervous system. TE expression and transposition also appear to vary by brain region and change in response to environmental stimuli such as stress. TEs appear to serve a number of adaptive roles in the nervous system. The regulation of TE expression by steroid, epigenetic and other mechanisms in interplay with the environment represents a significant and novel avenue to understanding both normal brain function and disease.


Assuntos
Genoma , Genômica , Adaptação Biológica , Animais , Sistema Nervoso Central/metabolismo , Elementos de DNA Transponíveis , Meio Ambiente , Epigênese Genética , Evolução Molecular , Regulação da Expressão Gênica , Interação Gene-Ambiente , Aptidão Genética , Genômica/métodos , Humanos , Sistema Nervoso/metabolismo , Retroelementos , Estresse Fisiológico/genética
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