@article{pmid42247738,

title = {Low levels of organization and consistency in the home in middle childhood predicts cortisol levels and internalizing symptoms 12 years later among the offspring of parents with bipolar disorder},

author = {Mark A Ellenbogen and Lisa Serravalle and Sheilagh Hodgins and Claire-Dominique Walker and Elaine F Walker},

doi = {10.1016/j.psyneuen.2026.107904},

issn = {1873-3360},

year  = {2026},

date = {2026-09-01},

journal = {Psychoneuroendocrinology},

volume = {191},

pages = {107904},

abstract = {The offspring of parents with bipolar disorder (OBD) are at high risk for developing affective disorders. Low levels of organization and consistency in the home (parenting structure) is associated with increased behavioral problems and hypothalamic-pituitary-adrenal (HPA) reactivity in the OBD and thus may be an important developmental risk factor. We also examined whether the cortisol response following awakening (CAR) is increased in the OBD who developed an affective disorder relative to OBD with no affective disorder. The sample (19.3 ± 3.4 years) consisted of 68 OBD and 64 offspring (61 female) of parents with no affective disorder (controls). As predicted, offspring who developed an affective disorder had higher CAR than OBD who did not have an affective disorder (Cohen's d= 0.423) and controls (Cohen's d= 0.468). Bootstrapping serial mediation analyses revealed that parenting structure in middle childhood and the CAR in offspring significantly mediated the relationship between risk status and offspring depressive and anxiety symptoms 12 years later (CI:.01,.66). Low parenting structure in the OBD leads to changes in the HPA axis that increases the risk of developing symptoms of an affective disorder. Suboptimal childrearing may have enduring consequences on mental health outcomes in the OBD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid42005377,

title = {Early adversity alters neurodevelopmental milestones in male and female rat pups and motor cortex morphology and gait in juveniles},

author = {Annie Phan and Michael Ru and Brianna Latremouille and Hong Long and Claire-Dominique Walker},

doi = {10.1016/j.ynstr.2026.100814},

issn = {2352-2895},

year  = {2026},

date = {2026-06-01},

journal = {Neurobiol Stress},

volume = {42},

pages = {100814},

abstract = {Early life stress (ELS) and adversity influences neurodevelopmental trajectories and affects maturation of brain circuits, network connectivity and epigenetic regulation, leading to increased vulnerability to adult psychopathology. ELS timing targets sensitive periods for neural plasticity, which are identified by the ability to reach physical and sensorimotor developmental milestones. In particular, motor development, being highly dependent on coordinated activity across several brain regions, is especially susceptible to environmental challenges, although detailed modifications are unclear. Here we used the limited bedding (LB) paradigm in rats to examine the effects of ELS longitudinally on physical and sensorimotor milestones as well as morphological changes in the motor cortex (M1) and motor behavior in male and female juveniles. Neonates from the LB litters displayed delayed eye opening and reduced weight gain compared to NB pups. Reaching sensory milestones such as cliff avoidance, ear twitch and auditory startle responses was delayed by LB exposure, similarly to surface righting reflex, grasping reflex and orienting behavior that were significantly impaired in both male and female LB pups. In juvenile LB rats, locomotion in the openfield was reduced and hind limb gait was impaired. There were no bedding or sex effects on skilled walking. Morphological analysis of Layer V motor cortex neurons (M1) in juveniles revealed that LB reduced dendritic length and increased spine density, but in females only. These data show that LB exposure during the neonatal period delays the reaching of multiple developmental milestones in several domains associated with the maturation of motor function and coordination.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41125449,

title = {Layer-Specific Glutamatergic Inputs and Parvalbumin Interneurons Modulate Early Life Stress-Induced Alterations in Prefrontal Glutamate Release during Fear Conditioning in Pre-adolescent Rats},

author = {Jiamin Song and Muzammil Younus and Hong Long and Tak Pan Wong and Claire-Dominique Walker},

doi = {10.1523/ENEURO.0073-25.2025},

issn = {2373-2822},

year  = {2025},

date = {2025-11-01},

journal = {eNeuro},

volume = {12},

number = {11},

abstract = {Exposure to early life stress (ELS) can exert long-lasting impacts on emotional regulation. The corticolimbic system including the basolateral amygdala (BLA), ventral hippocampus (vHIP), and the medial prefrontal cortex (mPFC) plays a key role in fear learning. Using the limited bedding paradigm (LB), we examined the functional consequences of ELS on excitatory and inhibitory tone in the prelimbic (PL) mPFC after fear conditioning in rats. In adults, LB exposure enhanced in vivo glutamate release in the PL mPFC during fear conditioning in male, but not female offspring. In contrast, the glutamate response to fear conditioning was diminished in LB-exposed pre-adolescent males, but not females. We investigated whether reduced glutamatergic inputs and/or elevated inhibitory tone might contribute to the diminished glutamate response in the mPFC following LB in pre-adolescent male rats. Indeed, we found that LB exposure specifically increased the activation of PV, but not SST interneurons in layer V, but not layer II/III of the PL mPFC in fear-exposed pre-adolescent males. Presynaptic glutamate release probability was reduced by LB exposure in layer V, but increased in layer II/III of the PL mPFC. These functional changes might be related to the LB-induced alterations in the bilaminar distribution of BLA and vHIP projections to the PL mPFC we observed in pre-adolescent males. Overall, our findings suggest that ELS modifies glutamate release and PL mPFC function during fear conditioning in a sex- and age-dependent fashion, likely through layer-specific shifts in excitation/inhibition balance.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39694537,

title = {Neonatal estradiol and early adversity interact to modify basolateral amygdala morphology and adult behavior in female rats},

author = {Grace Kraatz and Henry Tian Hao Xie and Hong Long and Claire-Dominique Walker},

doi = {10.1111/jne.13483},

issn = {1365-2826},

year  = {2025},

date = {2025-07-01},

journal = {J Neuroendocrinol},

volume = {37},

number = {7},

pages = {e13483},

abstract = {Being raised under adverse conditions during infancy and childhood represents a significant risk factor for developing later psychopathologies and dysfunctions in emotional, affective, and cognitive abilities. Depending on the type, timing, and duration of early adversity, different consequences emerge across the sexes in both human and animal models, although our understanding of the underlying interactions between sex and early life stress (ELS) is still incomplete. In this study, we used the limited bedding (LB) paradigm, a well-described model of ELS in rat pups during the first 10 days of life, and tested whether masculinization of the female brain by neonatal injections of estradiol benzoate (EB) would recapitulate the ELS-induced vulnerability phenotype of males on morphology of the basolateral amygdala (BLA) principal neurons and pre-adolescent and adult behavior. Our results show that LB-induced morphological changes in BLA neurons of weaning female rats were eliminated by EB treatment independently of early changes in estrogen receptor (ERα) expression in this region. EB treatment synergized with LB to enhance play behavior of pre-adolescent females to levels far greater than those observed in control males. In adult offspring, LB reduced time spent in the center in males and EB tended to increase social contact time compared to normal females, but only in LB conditions. Our findings indicate that neonatal masculinization of the female brain modifies specific, but not all aspects of BLA morphology and both pre-adolescent and adult behavior that are altered by ELS.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38129480,

title = {Peripheral clock gene oscillations are perturbed in neonatal and adult rat offspring raised under adverse limited bedding conditions},

author = {Claire-Dominique Walker and Tara C Delorme and Silke Kiessling and Hong Long and Nicolas Cermakian},

doi = {10.1038/s41598-023-47968-y},

issn = {2045-2322},

year  = {2023},

date = {2023-12-01},

journal = {Sci Rep},

volume = {13},

number = {1},

pages = {22886},

abstract = {Circadian (24-h) rhythms in the suprachiasmatic nucleus (SCN) are established in utero in rodents, but rhythmicity of peripheral circadian clocks appears later in postnatal development. Since peripheral oscillators can be influenced by maternal feeding and behavior, we investigated whether exposure to the adverse environmental conditions of limited bedding (LB) during postnatal life would alter rhythmicity in the SCN, adrenal gland and liver in neonatal (postnatal day PND10), juvenile (PND28) and adult rats. We also examined locomotor activity in adults. Limited bedding increased nursing time and slightly increased fragmentation of maternal behavior. Exposure to LB reduced the amplitude of Per2 in the SCN on PND10. Adrenal clock gene expression (Bmal1, Per2, Cry1, Rev-erbα, Dbp) and corticosterone secretion were rhythmic at all ages in NB offspring, whereas rhythmicity of Bmal1, Cry1 and corticosterone was abolished in neonatal LB pups. Circadian gene expression in the adrenal and liver was well established by PND28. In adults, liver expression of several circadian genes was increased at specific daytimes by LB and the microstructure of locomotor behavior was altered. Thus, changes in maternal care and behavior might provide important signals to the maturing peripheral oscillators and modify, in particular their output functions in the long-term.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36420995,

title = {The circadian variation of sleep and alertness of postmenopausal women},

author = {Rafael Pérez-Medina-Carballo and Anastasi Kosmadopoulos and Philippe Boudreau and Manon Robert and Claire-Dominique Walker and Diane B Boivin},

doi = {10.1093/sleep/zsac272},

issn = {1550-9109},

year  = {2023},

date = {2023-02-01},

journal = {Sleep},

volume = {46},

number = {2},

abstract = {STUDY OBJECTIVES: Several factors may contribute to the high prevalence of sleep disturbances occurring in postmenopausal women. However, the contribution of the circadian timing system to their sleep disturbances remains unclear. In the present study, we aim to understand the impact of circadian factors on changes of sleep and alertness occurring after menopause.nnMETHODS: Eight healthy postmenopausal women and 12 healthy young women in their mid-follicular phase participated in an ultradian sleep-wake cycle procedure (USW). This protocol consisted of alternating 60-min wake periods and nap opportunities for ≥ 48 h in controlled laboratory conditions. Core body temperature (CBT), salivary melatonin, self-reported alertness, and polysomnographically recorded sleep were measured across this procedure.nnRESULTS: In both groups, all measures displayed a circadian variation throughout the USW procedure. Compared to young women, postmenopausal women presented lower CBT values, more stage N1 and N2 sleep, and number of arousals. They also showed a reduced amplitude of the circadian variation of melatonin, total sleep time (TST), sleep onset latency (SOL), stage N3 sleep, and alertness levels. Postmenopausal women fell asleep faster and slept more during the biological day and presented higher alertness levels during the biological night than young women.nnCONCLUSION: These results support the hypothesis of a weakened circadian signal promoting sleep and wakefulness in older women. Aging processes including hormonal changes may be main contributors to the increased sleep-wake disturbances after menopause.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34512291,

title = {Effects of Early Life Stress on the Developing Basolateral Amygdala-Prefrontal Cortex Circuit: The Emerging Role of Local Inhibition and Perineuronal Nets},

author = {Angela Guadagno and Claudia Belliveau and Naguib Mechawar and Claire-Dominique Walker},

doi = {10.3389/fnhum.2021.669120},

issn = {1662-5161},

year  = {2021},

date = {2021-01-01},

journal = {Front Hum Neurosci},

volume = {15},

pages = {669120},

abstract = {The links between early life stress (ELS) and the emergence of psychopathology such as increased anxiety and depression are now well established, although the specific neurobiological and developmental mechanisms that translate ELS into poor health outcomes are still unclear. The consequences of ELS are complex because they depend on the form and severity of early stress, duration, and age of exposure as well as co-occurrence with other forms of physical or psychological trauma. The long term effects of ELS on the corticolimbic circuit underlying emotional and social behavior are particularly salient because ELS occurs during critical developmental periods in the establishment of this circuit, its local balance of inhibition:excitation and its connections with other neuronal pathways. Using examples drawn from the human and rodent literature, we review some of the consequences of ELS on the development of the corticolimbic circuit and how it might impact fear regulation in a sex- and hemispheric-dependent manner in both humans and rodents. We explore the effects of ELS on local inhibitory neurons and the formation of perineuronal nets (PNNs) that terminate critical periods of plasticity and promote the formation of stable local networks. Overall, the bulk of ELS studies report transient and/or long lasting alterations in both glutamatergic circuits and local inhibitory interneurons (INs) and their associated PNNs. Since the activity of INs plays a key role in the maturation of cortical regions and the formation of local field potentials, alterations in these INs triggered by ELS might critically participate in the development of psychiatric disorders in adulthood, including impaired fear extinction and anxiety behavior.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32978287,

title = {It Is All in the Right Amygdala: Increased Synaptic Plasticity and Perineuronal Nets in Male, But Not Female, Juvenile Rat Pups after Exposure to Early-Life Stress},

author = {Angela Guadagno and Silvanna Verlezza and Hong Long and Tak Pan Wong and Claire-Dominique Walker},

doi = {10.1523/JNEUROSCI.1029-20.2020},

issn = {1529-2401},

year  = {2020},

date = {2020-10-01},

journal = {J Neurosci},

volume = {40},

number = {43},

pages = {8276--8291},

abstract = {Early-life stress (ELS) is associated with increased vulnerability to mental disorders. The basolateral amygdala (BLA) plays a critical role in fear conditioning and is extremely sensitive to ELS. Using a naturalistic rodent model of ELS, the limited bedding paradigm (LB) between postnatal days 1-10, we previously documented that LB male, but not female preweaning rat pups display increased BLA neuron spine density paralleled with enhanced evoked synaptic responses and altered BLA functional connectivity. Since ELS effects are often sexually dimorphic and amygdala processes exhibit hemispheric asymmetry, we investigated changes in synaptic plasticity and neuronal excitability of BLA neurons  in the left and right amygdala of postnatal days 22-28 male and female offspring from normal bedding or LB mothers. We report that LB conditions enhanced synaptic plasticity in the right, but not the left BLA of males exclusively. LB males also showed increased perineuronal net density, particularly around parvalbumin (PV) cells, and impaired fear-induced activity of PV interneurons only in the right BLA. Action potentials fired from right BLA neurons of LB females displayed slower maximal depolarization rates and decreased amplitudes compared with normal bedding females, concomitant with reduced NMDAR GluN1 subunit expression in the right BLA. In LB males, reduced GluA2 expression in the right BLA might contribute to the enhanced LTP. These findings suggest that LB differentially programs synaptic plasticity and PV/perineuronal net development in the left and right BLA. Furthermore, our study demonstrates that the effects of ELS exposure on BLA synaptic function are sexually dimorphic and possibly recruiting different mechanisms. Early-life stress (ELS) induces long-lasting consequences on stress responses and emotional regulation in humans, increasing vulnerability to the development of psychopathologies. The effects of ELS in a number of brain regions, including the amygdala, are often sexually dimorphic, and have been reproduced using the rodent limited bedding paradigm of early adversity. The present study examines sex differences in synaptic plasticity and cellular activation occurring in the developing left and right amygdala after limited bedding exposure, a phenomenon that could shape long-term emotional behavioral outcomes. Studying how ELS selectively produces effects in one amygdala hemisphere during a critical period of brain development could guide further investigation into sex-dependent mechanisms and allow for more targeted and improved treatment of stress-and emotionality-related disorders.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid31356452,

title = {Sustained efficacy of kangaroo care for repeated painful procedures over neonatal intensive care unit hospitalization: a single-blind randomized controlled trial},

author = {Marsha Campbell-Yeo and C Celeste Johnston and Britney Benoit and Timothy Disher and Kim Caddell and Michael Vincer and Claire-Dominique Walker and Margot Latimer and David L Streiner and Darlene Inglis},

doi = {10.1097/j.pain.0000000000001646},

issn = {1872-6623},

year  = {2019},

date = {2019-11-01},

journal = {Pain},

volume = {160},

number = {11},

pages = {2580--2588},

abstract = {Preterm neonates hospitalized in the neonatal intensive care unit undergo frequent painful procedures daily, often without pain treatment, with associated long-term adverse effects. Maternal-infant skin-to-skin contact, or kangaroo care (KC), and sweet-tasting solutions such as sucrose are effective strategies to reduce pain during a single procedure; however, evidence of sustained efficacy over repeated procedures is limited. We aimed to determine the relative sustained efficacy of maternal KC, administered alone or in combination with 24% sucrose, to reduce behavioral pain intensity associated with routine neonatal procedures, compared with 24% sucrose alone. Stable preterm infants (n = 242) were randomized to receive KC and water, KC and 24% sucrose, or 24% sucrose before all routine painful procedures throughout their neonatal intensive care unit stay. Pain intensity, determined using the Premature Infant Pain Profile, was measured during 3 medically indicated heel lances distributed across hospitalization. Maternal and neonatal baseline characteristics, Premature Infant Pain Profile scores at 30, 60, or 90 seconds after heel lance, the distribution of infants with pain scores suggesting mild, moderate, or severe pain, Neurobehavioral Assessment of the Preterm Infant scores, and incidence of adverse outcomes were not statistically significantly different between groups. Maternal KC, as a pain-relieving intervention, remained efficacious over time and repeated painful procedures without evidence of any harm or neurological impact. It seemed to be equally effective as 24% oral sucrose, and the combination of maternal KC and sucrose did not seem to provide additional benefit, challenging the existing recommendation of using sucrose as the primary standard of care.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid31437474,

title = {Experience of Adversity during a First Lactation Modifies Prefrontal Cortex Morphology in Primiparous Female Rats: Lack of Long Term Effects on a Subsequent Lactation},

author = {Emily A Opala and Silvanna Verlezza and Hong Long and Denisa Rusu and Barbara Woodside and Claire-Dominique Walker},

doi = {10.1016/j.neuroscience.2019.08.022},

issn = {1873-7544},

year  = {2019},

date = {2019-10-01},

journal = {Neuroscience},

volume = {417},

pages = {95--106},

abstract = {Reproductive experience is associated with morphological and functional plasticity in brain areas important for cognitive and emotional responses, including the infralimbic (IL) medial prefrontal cortex (mPFC). Here we examined whether suboptimal conditions during a first lactation could modify lactation-induced morphological IL mPFC changes, leading to alterations in stress responses and attention and whether any observed effects would persist into a second lactation. Reduced availability of bedding and nesting material (LB) was used to induce unfavorable conditions in primiparous (P) mothers. In normal bedding (NB) conditions, P mothers exhibited high spine number and density on postpartum day (PPD)10, which greatly decreased 2 weeks after weaning of their pups. In contrast, P-LB mothers had a lower spine number and density on PPD10, which markedly increased after weaning. LB exposure did not modify stress responsiveness to a ferret odor on PPD5 in primiparous or in multiparous (M) females. Number of errors and trials to criterion in the attention set shifting task were not modified by a history of adversity in multiparous females, although this group tended to exhibit higher attentional abilities than M-NB females. These results suggest that adversity acutely reduces morphological plasticity in the maternal mPFC during lactation, an effect that is not associated with significant changes in stress responses and/or glucocorticoid production. Medial PFC morphological changes induced by LB subside during a subsequent lactation as does the effect of maternity itself.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32082105,

title = {Increased Hypothalamic Projections to the Lateral Hypothalamus and Responses to Leptin in Rat Neonates From High Fat Fed Mothers},

author = {Lyla Kelley and Silvanna Verlezza and Hong Long and Mary Loka and Claire-Dominique Walker},

doi = {10.3389/fnins.2019.01454},

issn = {1662-4548},

year  = {2019},

date = {2019-01-01},

journal = {Front Neurosci},

volume = {13},

pages = {1454},

abstract = {The lateral hypothalamus (LHA) is a central hub in the regulation of food intake and metabolism, as it integrates homeostatic and hedonic circuits. During early development, maturing input to and output from the LHA might be particularly sensitive to environmental dietary changes. We examined the effects of a maternal high fat diet (HFD, 60% Kcal in fat) on the density of hypothalamic projections to the orexin (ORX-A) field of the LHA in 10 day-old (PND10) rat pups using retrograde labeling with fluorescent microspheres. We also compared responsiveness of phenotypically identified LHA neurons to leptin administration (3 mg/kg, bw) between pups from control (CD) or high fat (HFD) fed mothers on PND10 and 15-16, at the onset of independent feeding. HFD pups exhibited a higher density of LHA projections ( = 0.05) from the ventromedial hypothalamus (VMH) compared to CD pups and these originated from both SF-1 and BDNF-positive neurons in the VMH. Increased circulating leptin levels in HFD pups, particularly on PND15-16 was consistent with enhanced pSTAT3 responses to leptin in the orexin (ORX-A) field of the LHA, with some of the activated neurons expressing a GABA, but not CART phenotype. ORX-A neurons colocalizing with pERK were significantly higher in PND15-16 HFD pups compared to CD pups, and leptin-induced increase in pERK signaling was only observed in CD pups. There was no significant effect of leptin on pERK in HFD pups. These results suggest that perinatal maternal high fat feeding increases hypothalamic projections to the ORX-A field of the LHA, increases basal activation of ORX-A neurons and direct responsiveness of LHA neurons to leptin. Since these various LHA neuronal populations project quite heavily to Dopamine (DA) neurons in the ventral tegmental area, they might participate in the early dietary programming of mesocorticolimbic reward circuits and food intake.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid30032360,

title = {Reduced resting-state functional connectivity of the basolateral amygdala to the medial prefrontal cortex in preweaning rats exposed to chronic early-life stress},

author = {Angela Guadagno and Min Su Kang and Gabriel A Devenyi and Axel P Mathieu and Pedro Rosa-Neto and Mallar Chakravarty and Claire-Dominique Walker},

doi = {10.1007/s00429-018-1720-3},

issn = {1863-2661},

year  = {2018},

date = {2018-11-01},

journal = {Brain Struct Funct},

volume = {223},

number = {8},

pages = {3711--3729},

abstract = {Early-life stress (ELS) exposure has long-term consequences for both brain structure and function and impacts cognitive and emotional behavior. The basolateral amygdala (BLA) plays an important role in anxiety and fear conditioning through its extensive anatomical and functional connections, in particular to the medial prefrontal cortex (mPFC). However, how ELS affects amygdala function and connectivity in developing rats is unknown. We used the naturalistic limited bedding/nesting (LB) paradigm to induce chronic stress in the pups between postnatal day (PND) 1-10. Male normal bedding (NB, control) or LB offspring underwent structural and resting-state functional MRI (rs-fMRI) on PND18 and in adulthood (PND74-76). Adult male rats were tested for fear conditioning and extinction behavior prior to scanning. Seed-based functional connectivity maps were generated based on four BLA seeds (left, right, anterior and posterior). At both ages, LB induced different effects on anterior and posterior BLA networks, with significant reductions in rs-fMRI connectivity between the anterior BLA and mPFC in LB compared to NB offspring. BLA connectivity was lateralized by preweaning age, with the right hemisphere displaying more connectivity changes than the left. Weak negative volumetric correlations between the BLA and mPFC were also present, mostly in preweaning LB animals. rs-fMRI connectivity and volumetric changes were associated with enhanced fear behaviors in adult LB offspring. Activation of the LB-exposed neonatal amygdala described previously might accelerate the maturation of BLA-mPFC projections and/or modify the activity of reciprocal connections between these structures, leading to a net reduction in rs-fMRI connectivity and increased fear behavior.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}