Like Mother Like Daughter: Putamen Activation as a Mechanism Underlying Intergenerational Risk for Depression.
Social cognitive and affective neuroscience
Having a depressed mother is one of the strongest predictors for developing depression in adolescence. Given the role of aberrant reward processing in the onset and maintenance of depression, we examined the association between mothers' and their daughters' neural response to the anticipation of reward and loss. Fifteen non-depressed mothers with a history of recurrent depression and their never-disordered daughters, and 23 mothers without past or current depression and their never-disordered daughters, underwent fMRI while performing the monetary incentive delay (MID) task. To assess mother-daughter concordance, we first identified ROIs involved in the anticipation of reward and loss across all mother-daughter pairs. Within each of these ROIs, we examined the association between mothers' and daughters' neural response, and the interaction between group status and mothers' neural response in predicting daughters' neural response. We found a significant association between mothers' and daughters' putamen response to the anticipation of loss, regardless of mother's depression history. Furthermore, pubertal stage moderated the association between mother-daughter putamen concordance. Our findings suggest a unique role of the putamen in the maternal transmission of reward learning and have important implications for understanding disorders characterized by disturbances in reward learning and processing, such as major depression.
View details for DOI 10.1093/scan/nsx073
View details for PubMedID 28575505
Interpretation Bias Training in Depressed Adolescents: Near- and Far-Transfer Effects.
Journal of abnormal child psychology
Depressed adolescents are characterized by negative interpretation biases. Although investigators have used cognitive bias modification for interpretation (CBM-I) to experimentally manipulate interpretation biases in depressed adults, the near- and far-transfer effects are not well understood in adolescents diagnosed with Major Depressive Disorder (MDD). In this study, we extend previous research by investigating the near- and far-transfer effects of 6 sessions of Positive versus Neutral CBM-I on independent measures of interpretation bias (near-transfer effects) and on attention biases and clinical symptoms (far-transfer effects) in a sample of adolescents with MDD (n = 46). At post-training, adolescents who received Positive CBM-I interpreted ambiguous scenarios more positively than did participants who received Neutral CBM-I, providing evidence of training effectiveness. There was no evidence, however, of near- or far-transfer effects. These findings raise concerns about the malleability of interpretation biases in adolescent depression and suggest that further work is needed to establish the clinical utility of CBM-I for adolescents with MDD.
View details for DOI 10.1007/s10802-017-0285-6
View details for PubMedID 28299526
The impact of the severity of early life stress on diurnal cortisol: The role of puberty.
2017; 77: 68-74
Researchers have documented dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in children and adolescents who experienced early life stress (ELS). The precise nature of this dysregulation, however, has been difficult to discern. In fact, both elevated and blunted patterns of diurnal cortisol regulation have been reported in children and adolescents exposed to greater ELS, including both reduced and heightened cortisol levels and change in cortisol across the day. These divergent findings may be due to developmental changes in the relation between ELS and HPA-axis functioning. The present study was designed to examine the role of puberty in the impact of the severity of ELS on the regulation of diurnal cortisol. Boys and girls (N=145) ages 9-13 years recruited from lower-risk communities completed an interview about their ELS experiences and at-home collection of diurnal cortisol. ELS experiences were objectively coded for severity, and children's level of pubertal development was measured using Tanner Staging. Multi-level piecewise mixed-effects models tested the effects of ELS severity and pubertal stage on cortisol levels at waking, the cortisol awakening response (CAR), and the daytime cortisol slope. While we found no significant interactive effects of pubertal stage and ELS severity on cortisol levels at waking or the daytime cortisol slope, findings indicated that pubertal stage interacted with ELS severity to predict the cortisol awakening response (CAR). Specifically, in earlier puberty, higher ELS was associated with a blunted CAR compared to lower ELS; in contrast, in later puberty, higher ELS was associated with a heightened CAR compared to lower ELS. Differences in the relation between ELS severity and the CAR were uniquely determined by puberty, and not by age. By considering and examining the role of puberty, the current study provides a developmental explanation for previous divergent findings of both blunted and heightened patterns of diurnal cortisol following ELS. These results indicate that careful attention should be given to children's pubertal status before drawing conclusions concerning the nature of diurnal cortisol dysregulation.
View details for DOI 10.1016/j.psyneuen.2016.11.024
View details for PubMedID 28024271
View details for PubMedCentralID PMC5336485
Attentional avoidance of fearful facial expressions following early life stress is associated with impaired social functioning.
Journal of child psychology and psychiatry, and allied disciplines
2016; 57 (10): 1174-1182
Early life stress is associated with poorer social functioning. Attentional biases in response to threat-related cues, linked to both early experience and psychopathology, may explain this association. To date, however, no study has examined attentional biases to fearful facial expressions as a function of early life stress or examined these biases as a potential mediator of the relation between early life stress and social problems.In a sample of 154 children (ages 9-13 years) we examined the associations among interpersonal early life stressors (i.e., birth through age 6 years), attentional biases to emotional facial expressions using a dot-probe task, and social functioning on the Child Behavior Checklist.High levels of early life stress were associated with both greater levels of social problems and an attentional bias away from fearful facial expressions, even after accounting for stressors occurring in later childhood. No biases were found for happy or sad facial expressions as a function of early life stress. Finally, attentional biases to fearful faces mediated the association between early life stress and social problems.Attentional avoidance of fearful facial expressions, evidenced by a bias away from these stimuli, may be a developmental response to early adversity and link the experience of early life stress to poorer social functioning.
View details for DOI 10.1111/jcpp.12607
View details for PubMedID 27457566
Ruminative brooding is associated with salience network coherence in early pubertal youth.
Social cognitive and affective neuroscience
Rumination, and particularly ruminative brooding, perpetuates dysphoric mood states and contributes to the emergence of depression. Studies of adults and older adolescents have characterized the association between rumination and intrinsic functional connectivity within default mode (DMN), salience (SN) and executive control (ECN) networks; we know little, however, about the brain network basis of rumination during early puberty, a sensitive period for network reorganization. 112 early puberty boys and girls completed resting-state scans, the Ruminative Response Scale, and the Youth Self-Report questionnaire. Using independent components analysis and dual regression, we quantified coherence for each individual in networks of interest (SN, ECN, DMN) and in non-relevant networks (motor, visual) in which we predicted no correlations with behavioral measures. Boys and girls did not differ in levels of rumination or internalizing symptoms, or in coherence for any network. The relation between SN network coherence and rumination; however, and specifically ruminative brooding, was moderated by sex: greater SN coherence was associated with higher levels of brooding in girls but not in boys. Further, in girls, brooding mediated the relation between SN coherence and internalizing symptoms. These results point to coherence within the SN as a potential neurodevelopmental marker of risk for depression in early pubertal girls.
View details for DOI 10.1093/scan/nsw133
View details for PubMedID 27633394
View details for PubMedCentralID PMC5390708
Neural Aspects of Inhibition Following Emotional Primes in Depressed Adolescents.
Journal of clinical child and adolescent psychology
2016; 45 (1): 21-30
Adults diagnosed with major depressive disorder (MDD) have been found to be characterized by selective attention to negative material and by impairments in their ability to disengage from, or inhibit the processing of, negative stimuli. Altered functioning in the frontal executive control network has been posited to underlie these deficits in cognitive functioning. We know little, however, about the neural underpinnings of inhibitory difficulties in depressed adolescents. We used functional magnetic resonance imaging in 18 adolescents diagnosed with MDD and 15 age- and gender-matched healthy controls (CTLs) while they performed a modified affective Go/No-Go task that was designed to measure inhibitory control in the presence of an emotional distractor. Participants were presented with either a happy or a sad face, followed by a go or a no-go target to which they either made or inhibited a motor response. A group (MDD, CTL) by valence (happy, sad) by condition (go, no-go) analysis of variance indicated that MDD adolescents showed attenuated BOLD response in the right dorsolateral prefrontal cortex (DLPFC) and in the occipital cortex bilaterally, to no-go targets that followed a sad, but not a happy, face. Adolescents diagnosed with MDD showed anomalous recruitment of prefrontal control regions during inhibition trials, suggesting depression-associated disruption in neural underpinnings of the inhibition of emotional distractors. Given that the DLPFC is associated with the maintenance of goal-relevant information, it is likely that sad faces differentially capture attention in adolescents with MDD and interfere with task demands requiring inhibition.
View details for DOI 10.1080/15374416.2014.982281
View details for PubMedID 25635920
Influence of menarche on the relation between diurnal cortisol production and ventral striatum activity during reward anticipation.
Social cognitive and affective neuroscience
2015; 10 (9): 1244-1250
Adolescence is characterized by an increase in risk-taking and reward-seeking behaviors. In other populations, increased risk taking has been associated with tighter coupling between cortisol production and ventral striatum (VS) activation during reward anticipation; this relation has not yet been examined, however, as a function of adolescent development. This study examined the influence of pubertal development on the association between diurnal cortisol production and VS activity during reward anticipation. Pre- and post-menarcheal girls collected diurnal cortisol and completed an functional magnetic resonance imaging-based monetary incentive delay task, from which we extracted estimates of VS activity during the anticipation of reward, anticipation of loss and anticipation of non-incentive neutral trials. Post-menarcheal girls showed greater coupling between the cortisol awakening response and VS activation during anticipation of reward and loss than did their pre-menarcheal counterparts. Post-menarcheal girls did not differ from pre-menarcheal girls in their cortisol-VS coupling during anticipation of neutral trials, suggesting that puberty-related changes in cortisol-VS coupling are specific to affective stimuli. Interestingly, behavioral responses during the task indicate that post-menarcheal girls are faster to engage with affective stimuli than are pre-menarcheal girls. Thus, post-menarcheal girls exhibit neurobiological and behavioral patterns that have been associated with risk taking and that may underlie the dramatic increase in risk-taking behavior documented during adolescence.
View details for DOI 10.1093/scan/nsv016
View details for PubMedID 25678549
HPA-axis reactivity interacts with stage of pubertal development to predict the onset of depression
2015; 55: 94-101
Both elevated and blunted levels of cortisol secretion during childhood and adolescence have been linked to the subsequent onset of major depressive disorder (MDD). These mixed findings may be due to developmental changes in HPA-axis functioning, which have not been previously assessed in the context of risk. In the present study, therefore, we examined whether pubertal development moderated the influence of cortisol secretion on the subsequent development of MDD. Eighty-nine never-disordered girls ages 9-15 years, many of whom were at high risk for depression by virtue of having a maternal history of the disorder, completed a laboratory stress task. To index cortisol reactivity, salivary cortisol samples were collected at baseline and 15min following the onset of the stressor. Girls' levels of pubertal development were measured using Tanner staging. All participants were followed through age 18 in order to assess the subsequent development of MDD. Pubertal stage moderated the effects of cortisol stress reactivity on the development of MDD. Specifically, the onset of MDD was predicted by cortisol hyporeactivity in girls who were earlier in pubertal development (Tanner stage≤2), but by cortisol hyperreactivity in girls who were later in pubertal development (Tanner stage≥3.5).These findings demonstrate that girls' cortisol stress reactivity predicts the subsequent onset of MDD, and further, that the nature of this effect depends on the girls' level of pubertal development. Results are discussed in the context of clarifying previous findings, and directions for future research are offered.
View details for DOI 10.1016/j.psyneuen.2015.02.004
View details for Web of Science ID 000353090100009
Telomere length and cortisol reactivity in children of depressed mothers.
2015; 20 (5): 615-620
A growing body of research demonstrates that individuals diagnosed with major depressive disorder (MDD) are characterized by shortened telomere length, which has been posited to underlie the association between depression and increased instances of medical illness. The temporal nature of the relation between MDD and shortened telomere length, however, is not clear. Importantly, both MDD and telomere length have been associated independently with high levels of stress, implicating dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and anomalous levels of cortisol secretion in this relation. Despite these associations, no study has assessed telomere length or its relation with HPA-axis activity in individuals at risk for depression, before the onset of disorder. In the present study, we assessed cortisol levels in response to a laboratory stressor and telomere length in 97 healthy young daughters of mothers either with recurrent episodes of depression (i.e., daughters at familial risk for depression) or with no history of psychopathology. We found that daughters of depressed mothers had shorter telomeres than did daughters of never-depressed mothers and, further, that shorter telomeres were associated with greater cortisol reactivity to stress. This study is the first to demonstrate that children at familial risk of developing MDD are characterized by accelerated biological aging, operationalized as shortened telomere length, before they had experienced an onset of depression; this may predispose them to develop not only MDD but also other age-related medical illnesses. It is critical, therefore, that we attempt to identify and distinguish genetic and environmental mechanisms that contribute to telomere shortening.
View details for DOI 10.1038/mp.2014.119
View details for PubMedID 25266121
Overreactive Brain Responses to Sensory Stimuli in Youth With Autism Spectrum Disorders
JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
2013; 52 (11): 1158-1172
Sensory over-responsivity (SOR), defined as a negative response to or avoidance of sensory stimuli, is both highly prevalent and extremely impairing in youth with autism spectrum disorders (ASD), yet little is known about the neurological bases of SOR. This study aimed to examine the functional neural correlates of SOR by comparing brain responses to sensory stimuli in youth with and without ASD.A total of 25 high-functioning youth with ASD and 25 age- and IQ-equivalent typically developing (TD) youth were presented with mildly aversive auditory and visual stimuli during a functional magnetic resonance imaging (fMRI) scan. Parents provided ratings of children's SOR and anxiety symptom severity.Compared to TD participants, ASD participants displayed greater activation in primary sensory cortical areas as well as amygdala, hippocampus, and orbital-frontal cortex. In both groups, the level of activity in these areas was positively correlated with level of SOR severity as rated by parents, over and above behavioral ratings of anxiety.This study demonstrates that youth with ASD show neural hyper-responsivity to sensory stimuli, and that behavioral symptoms of SOR may be related to both heightened responsivity in primary sensory regions as well as areas related to emotion processing and regulation.
View details for DOI 10.1016/j.jaac.2013.08.004
View details for Web of Science ID 000326480800007
View details for PubMedID 24157390
Associations Among Pubertal Development, Empathic Ability, and Neural Responses While Witnessing Peer Rejection in Adolescence
2013; 84 (4): 1338-1354
Links among concurrent and longitudinal changes in pubertal development and empathic ability from ages 10 to 13 and neural responses while witnessing peer rejection at age 13 were examined in 16 participants. More advanced pubertal development at age 13, and greater longitudinal increases in pubertal development, related to increased activity in regions underlying cognitive aspects of empathy. Likewise, at age 13 greater perspective taking related to activity in cognitive empathy-related regions; however, affective components of empathy (empathic concern and personal distress) were associated with activity in both cognitive and affective pain-related regions. Longitudinal increases in empathic ability related to cognitive and affective empathy-related circuitry. Findings provide preliminary evidence that physical and cognitive-emotional development relate to adolescents' neural responses when witnessing peer rejection.
View details for DOI 10.1111/cdev.12056
View details for Web of Science ID 000321700600017
View details for PubMedID 23379360
Neural and Behavioral Responses During Self-Evaluative Processes Differ in Youth With and Without Autism
JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS
2013; 43 (2): 272-285
This fMRI study investigated neural responses while making appraisals of self and other, across the social and academic domains, in children and adolescents with and without autism spectrum disorders (ASD). Compared to neurotypical youth, those with ASD exhibited hypoactivation of ventromedial prefrontal cortex during self-appraisals. Responses in middle cingulate cortex (MCC) and anterior insula (AI) also distinguished between groups. Stronger activity in MCC and AI during self-appraisals was associated with better social functioning in the ASD group. Although self-appraisals were significantly more positive in the neurotypical group, positivity was unrelated to brain activity in these regions. Together, these results suggest that multiple brain regions support making self-appraisals in neurotypical development, and function atypically in youth with ASD.
View details for DOI 10.1007/s10803-012-1563-3
View details for Web of Science ID 000313803600003
View details for PubMedID 22760337
COMT genotype affects prefrontal white matter pathways in children and adolescents
2010; 53 (3): 926-934
Diffusion tensor imaging is widely used to evaluate the development of white matter. Information about how alterations in major neurotransmitter systems, such as the dopamine (DA) system, influence this development in healthy children, however, is lacking. Catechol-O-metyltransferase (COMT) is the major enzyme responsible for DA degradation in prefrontal brain structures, for which there is a corresponding genetic polymorphism (val158met) that confers either a more or less efficient version of this enzyme. The result of this common genetic variation is that children may have more or less available synaptic DA in prefrontal brain regions. In the present study we examined the relation between diffusion properties of frontal white matter structures and the COMT val158met polymorphism in 40 children ages 9-15. We found that the val allele was associated with significantly elevated fractional anisotropy values and reduced axial and radial diffusivities. These results indicate that the development of white matter in healthy children is related to COMT genotype and that alterations in white matter may be related to the differential availability of prefrontal DA. This investigation paves the way for further studies of how common functional variants in the genome might influence the development of brain white matter.
View details for DOI 10.1016/j.neuroimage.2010.01.033
View details for Web of Science ID 000282039300015
View details for PubMedID 20083203
View details for PubMedCentralID PMC2902616