[Show abstract][Hide abstract] ABSTRACT: This is the first study to date to examine volumetric alterations in the anterior insula (AI) as a potential biomarker for the course of childhood major depressive disorder (MDD).
[Show abstract][Hide abstract] ABSTRACT: Major Depressive Disorder (MDD) is often characterized by impaired emotional functioning, which can vary drastically based on the cluster of symptoms exhibited and symptom severity. This study examined the relationship between the two gateway symptoms for diagnosis of MDD, anhedonia and depressed mood, and emotional reactivity within a large non-clinical sample. Participants (N=107) were asked to complete an Emotional Picture Rating Task (EPRT). In the EPRT participants rated the valence and arousal level of emotional responses to 100 pictures (40 negative, 20 neutral, and 40 positive pictures) from the International Affective Picture System. Participants also completed self-report questionnaires assessing hedonic capacity, general affect, and depressive symptomology. We found that elevated levels of anhedonia (i.e. decreased hedonic capacity) predicted blunted emotional reactivity to both positive (p<0.001) and negative (p<0.001) pictures, while elevated depressive symptoms predicted potentiated negative emotional reactivity to negative pictures (p=0.017). These findings are consistent with literature suggesting depressive symptoms relate to emotional processing, but extend this literature by suggesting that different types of depressive symptoms, anhedonia and depressed mood, affect emotional processing in different ways. Future studies taking such a dimensional approach and including different symptoms as predictors of emotional function may help rectify inconsistencies in the MDD literature and the heterogeneity in behavioral manifestations of mood pathology.
Midstates Consortium for Math and Science Undergraduate Research Symposium in the Biological Sciences and Psychology, University of Chicago; 11/2014
[Show abstract][Hide abstract] ABSTRACT: Structural and functional alterations in a variety of brain regions have been associated with depression and risk for depression across the life span. A majority of
these regions are associated with emotion reactivity and/or regulation. However, it is generally unclear what mechanistic role these alterations play in the
etiology of depression. A first step toward understanding this is to characterize the relationships between variation in brain structure/function and individual
differences in depression severity and related processes, particularly emotion regulation. To this end, the current study examines how brain structure and
function predict concurrent and longitudinal measures of depression symptomology and emotion regulation skills in psychiatrically healthy school-age
children (N ¼ 60). Specifically, we found that smaller hippocampus volumes and greater responses to sad faces in emotion reactivity regions predict increased
depressive symptoms at the time of scan, whereas larger amygdala volumes, smaller insula volumes, and greater responses in emotion reactivity regions
predict decreased emotion regulation skills. In addition, larger insula volumes predict improvements in emotion regulation skills even after accounting for
emotion regulation at the time of scan. Understanding brain–behavior relationships in psychiatrically healthy samples, especially early in development,
will help inform normative developmental trajectories and neural alterations in depression and other affective pathology.
Development and Psychopathology 11/2014; 26:1289–1303. · 4.40 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Heritability of fractional anisotropy (FA) was compared in individuals with schizophrenia and their siblings versus controls.•FA was nonsignificantly reduced in a portion of the fornix in schizophrenia.•FA in siblings did not differ from that in controls.
Psychiatry Research Neuroimaging 10/2014; · 2.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Major Depressive Disorder (MDD) is an extremely disabling disease that affects physiological, cognitive, and emotional functioning. The literature has been conflicted regarding the relationship between MDD and emotional responsivity, particularly to negative stimuli. However, in prior work, we showed that individual differences in MDD's gateway symptoms, anhedonia (loss of pleasure) and depressed mood, predicted differential effects on emotional response to affective stimuli in a non-clinical sample. Furthermore, we found that current mood predicted emotional responsivity above and beyond anhedonia and depressed mood. The current study aims to induce moods in a large non-clinical sample to examine whether induced mood can affect emotion responsivity. The following is data from a pilot study used to determine the efficacy of different film clips for inducing negative, positive, and neutral mood.
Washington University in St. Louis Undergraduate Research Symposium, Washington University in St. Louis; 10/2014
[Show abstract][Hide abstract] ABSTRACT: Decades of research have provided robust evidence of cognitive impairments in psychotic disorders. Individuals with schizophrenia appear to be impaired on the majority of neuropsychological tasks, leading some researchers to argue for a “generalized deficit”, in which the multitude of cognitive impairments are the result of a common neurobiological source. One such common mechanism may be an inability to actively represent goal information in working memory as a means to guide behavior, with the associated neurobiological impairment being a disturbance in the function of the dorsolateral prefrontal cortex. Here, we provide a discussion of the evidence for such impairment in schizophrenia, and how it manifests in domains typically referred to as cognitive control, working memory and episodic memory. We also briefly discuss cognitive impairment in affective psychoses, reporting that the degree of impairment is worse in schizophrenia than in bipolar disorder and psychotic major depression, but the profile of impairment is similar, possibly reflecting common mechanisms at the neural level. Given the recent release of the DSM-5, we end with a brief discussion on assessing cognition in the context of diagnosis and treatment planning in psychotic disorders.
[Show abstract][Hide abstract] ABSTRACT: To determine if late preterm (LP) children differ from full term (FT) children in volumes of the cortex, hippocampus, corpus callosum, or amygdala and whether these differences are associated with anxiety symptoms at school-age.
Journal of Pediatrics 08/2014; · 3.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In this study, we examined the morphology of the basal ganglia and thalamus in bipolar disorder (BP), schizophrenia-spectrum disorders (SCZ-S), and healthy controls (HC) with particular interest in differences related to the absence or presence of psychosis. Volumetric and shape analyses of the basal ganglia and thalamus were performed in 33 BP individuals [12 without history of psychotic features (NPBP) and 21 with history of psychotic features (PBP)], 32 SCZ-S individuals [28 with SCZ and 4 with schizoaffective disorder], and 27 HC using FreeSurfer-initiated large deformation diffeomorphic metric mapping. Significant volume differences were found in the caudate and globus pallidus, with volumes smallest in the NPBP group. Shape abnormalities showing inward deformation of superior regions of the caudate were observed in BP (and especially in NPBP) compared with HC. Shape differences were also found in the globus pallidus and putamen when comparing the BP and SCZ-S groups. No significant differences were seen in the nucleus accumbens and thalamus. In summary, structural abnormalities in the caudate and globus pallidus are present in BP and SCZ-S. Differences were more apparent in the NPBP subgroup. The findings herein highlight the potential importance of separately examining BP subgroups in neuroimaging studies.
Psychiatry Research Neuroimaging 08/2014; · 2.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Pharmacological enhancement of prefrontal D1 dopamine receptor function remains a promising therapeutic approach to ameliorate schizophrenia-spectrum working memory deficits, but has yet to be rigorously evaluated clinically. This proof-of-principle study sought to determine whether the active enantiomer of the selective and full D1 receptor agonist dihydrexidine (DAR-0100A) could attenuate working memory impairments in unmedicated patients with schizotypal personality disorder (SPD). We performed a randomized, double-blind, placebo-controlled trial of DAR-0100A (15 mg/150 ml of normal saline administered intravenously over 30 min) in medication-free patients with SPD (n=16) who met criteria for cognitive impairment (i.e., scoring below the 25(th) percentile on tests of working memory). We employed two measures of verbal working memory that are salient to schizophrenia-spectrum cognitive deficits, and clinical data implicate as being associated with prefrontal D1 availability: 1) the Paced Auditory Serial Addition Test (PASAT); and 2) the N-back test (ratio of 2-back:0-back scores). Study procedures occurred over four consecutive days with working memory testing on Days 1 and 4, and DAR-0100A/placebo administration on Days 2-4. Treatment with DAR-0100A was associated with significantly improved PASAT performance relative to placebo, with a very large effect size (Cohen's d=1.14 for both tests). Performance on the N-back ratio was also significantly improved, however, this effect rested on both a non-significant enhancement and diminution of 2-back and 0-back performance, respectively; therefore interpretation of this finding is more complicated. DAR-0100A was generally well tolerated, with no serious medical or psychiatric adverse events; common side-effects were mild-to-moderate and transient, consisting mainly of sedation, lightheadedness, tachycardia, and hypotension; however, we were able to minimize these effects, without altering the dose, with supportive measures, e.g., co-administered normal saline. Although preliminary, these findings lend further clinical support to the potential of D1 receptor agonists to treat schizophrenia-spectrum working memory impairments. These data suggest a need for further studies with larger group sizes, serum DAR-0100A levels, and a more comprehensive neuropsychological battery.Neuropsychopharmacology accepted article preview online, 30 July 2014; doi:10.1038/npp.2014.192.
Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 07/2014; · 8.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The development of reward-related neural systems, from adolescence through adulthood, has received much recent attention in the developmental neuroimaging literature. However, few studies have investigated behavioral and neural responses to both gains and losses in pre-pubertal child populations. To address this gap in the literature, in the present study healthy children aged 7-11 years and young-adults completed an fMRI card-guessing game using candy pieces delivered post-scan as an incentive. Age differences in behavioral and neural responses to candy gains/losses were investigated. Adults and children displayed similar responses to gains, but robust age differences were observed following candy losses within the caudate, thalamus, insula, and hippocampus. Interestingly, when task behavior was included as a factor in post-hoc mediation analyses, activation following loss within the caudate/thalamus related to task behavior and relationships with age were no longer significant. Conversely, relationships between response to loss and age within the hippocampus and insula remained significant even when controlling for behavior, with children showing heightened loss responses within the dorsal/posterior insula. These results suggest that both age and task behavior influence responses within the extended reward circuitry, and that children seem to be more sensitive than adults to loss feedback particularly within the dorsal/posterior insula.
[Show abstract][Hide abstract] ABSTRACT: Objective
Previous studies have examined the relationships between structural brain characteristics and early life stress in adults. However, there is limited evidence for functional brain variation associated with early life stress in children. We hypothesized that early life stress and trauma would be associated with increased functional brain activation to negative emotional faces in children with and without a history of depression.
Psychiatric diagnosis and life events in children (starting at ages 3-5) were assessed in a longitudinal study. A follow-up magnetic resonance imaging (MRI) study acquired data (N = 115 at ages 7-12, 51% female) on functional brain response to fearful, sad, and happy faces relative to neutral faces. We used a region of interest (ROI) mask within cortico-limbic areas and conducted regression analyses and repeated-measures analysis of covariance (ANCOVA).
Greater activations to fearful, sad, and happy faces in the amygdala and its neighboring regions were found in children with higher life stress. Moreover, an association between life stress and left hippocampal and globus pallidus activity depended on children’s diagnostic status. Finally, all children with higher life trauma showed greater bilateral amygdala and cingulate activity specific to sad faces, but not the other emotional faces, although right amygdala activity was moderated by psychiatric status.
These findings may suggest that limbic hyperactivity is a biomarker of early life stress and trauma in children and may have implications in the risk trajectory for depression and other stress-related disorders. However, this pattern varied based on emotion type and history of psychopathology.
Journal of the American Academy of Child and Adolescent Psychiatry 07/2014; 53(7):800-813.e10. · 6.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recent years have seen a rejuvenation of interest in studies of motivation-cognition interactions arising from many different areas of psychology and neuroscience. The present issue of Cognitive, Affective, & Behavioral Neuroscience provides a sampling of some of the latest research from a number of these different areas. In this introductory article, we provide an overview of the current state of the field, in terms of key research developments and candidate neural mechanisms receiving focused investigation as potential sources of motivation-cognition interaction. However, our primary goal is conceptual: to highlight the distinct perspectives taken by different research areas, in terms of how motivation is defined, the relevant dimensions and dissociations that are emphasized, and the theoretical questions being targeted. Together, these distinctions present both challenges and opportunities for efforts aiming toward a more unified and cross-disciplinary approach. We identify a set of pressing research questions calling for this sort of cross-disciplinary approach, with the explicit goal of encouraging integrative and collaborative investigations directed toward them.
[Show abstract][Hide abstract] ABSTRACT: Major Depressive Disorder (MDD) is an extremely debilitating disorder with respect to physical, psychological, and emotional functioning. However, impairment in people with MDD may vary drastically based on the cluster of symptoms that people exhibit and the severity of those symptoms. The present study examines the relationship between the two gateway symptoms for diagnosis of MDD, anhedonia and depressed mood, and emotional reactivity within a large non-clinical sample. To this end, participants (N=107) were asked to complete an Emotional Picture Rating Task (EPRT). The EPRT required participants to rate the valence and arousal level of their emotional response to 100 pictures (40 negative, 20 neutral, and 40 positive pictures) from the International Affective Picture System. In addition, participants completed self-report questionnaires used to assess levels of hedonic capacity, general affect, and depressive symptomology. We found that elevated levels of anhedonia (i.e. decreased hedonic capacity) predicted blunted emotional reactivity to both positive and negative pictures, while elevated depressive symptoms predicted potentiated negative emotional reactivity to negative pictures. These findings are consistent with current literature that suggests that MDD affects emotional processing, but suggests that different symptoms affect emotional processing in different ways. These findings could suggest that treatment of MDD should be approached at a symptomatic level rather than at a generalized level.
Washington University in St. Louis Undergraduate Research Symposium, Washington University in St. Louis; 04/2014
[Show abstract][Hide abstract] ABSTRACT: The relationship between Major Depressive Disorder (MDD) and reduced reward response is well documented in adult and adolescent MDD literatures [1-2]. Conversely, adults and adolescents with MDD show enhanced responses to loss/negative stimuli [1,3]. However, as reward-related behaviors and adaptive responses to negative feedback undergo dramatic changes across puberty [4-5], key questions remain regarding how altered gain and loss processing relates to depressive and anhedonic symptoms in pre-pubertal child populations. Twenty-four pre-pubertal children aged 7-10 years completed two signal detection tasks that assessed behavioral responsivity to candy gain and loss feedback, respectively. These tasks were based on Pizzagalli's probabilistic reward task where asymmetric feedback leads to greater response bias in more hedonic/non-depressed adults. We further modified the task to create a version where incorrect responses could result in loss feedback [6,7]. Children and parents also completed individual difference questionnaires to assess child depressive symptomology, general affect, and approach motivation/hedonic capacity. Hierarchical regressions indicated a relationship between approach motivation/hedonic capacity and response bias in both gain and loss tasks, even when controlling for depressive and externalizing symptoms. No relationships between depressive symptoms and bias were observed. Results suggest that reduced approach motivation/hedonic capacity is associated with blunted responses to both gain and loss feedback in pre-pubertal children, independent of other depressive symptoms.