Anastacia Y. Kudinova

Cross-species evidence for the role of interleukin-33 in depression risk.

Extensive evidence highlights the role of inflammatory processes in major depressive disorder (MDD). However, most studies have examined a consistent set of inflammatory cytokines and there is evidence that other immune-derived products may play a role in MDD. In this article, we present data from 3 complimentary studies that support the role of a novel cytokine, interleukin-33 (IL-33), in depression risk. First, we show that a 2-SNP haplotype in the IL-33 gene (rs11792633 and rs7044343) moderated the link between womens history of childhood abuse and their history of recurrent MDD (rMDD), such that the link between childhood abuse and rMDD was stronger among women with fewer copies of the protective IL-33 CT haplotype. Second, linking these findings to differences in circulating cytokine levels, we show in a separate sample that those with a history of rMDD had higher peripheral levels of IL-33 and IL-1β compared with women with a single MDD episode or no history of MDD. Third, providing initial evidence of brain regions underlying these effects using archival rat brain tissue, we show that an acute stressor increased IL-33 expression in the paraventricular nucleus of the hypothalamus and, to a lesser extent, the prefrontal cortex, key brain regions underlying stress response and emotion regulation. These findings provide converging support for the potential role of IL-33 in risk for recurrent MDD. (PsycINFO Database Record

Influence of maternal depression on children's brooding rumination: Moderation by CRHR1 TAT haplotype

There is growing evidence that brooding rumination plays a key role in the intergenerational transmission of major depressive disorder (MDD) and may be an endophenotype for depression risk. However, less is known about the mechanisms underlying this role. Therefore, the goal of the current study was to examine levels of brooding in children of mothers with a history of MDD (n = 129) compared to children of never depressed mothers (n = 126) and to determine whether the variation in a gene known to influence hypothalamic-pituitary-adrenal axis functioning—corticotropin-releasing hormone receptor 1 (CRHR1) —would moderate the link between maternal MDD and childrens levels of brooding. We predicted children of mothers with a history of MDD would exhibit higher levels of brooding than children of mothers with no lifetime depression history but that this link would be stronger among children carrying no copies of the protective CRHR1 TAT haplotype. Our results supported these hypotheses and suggest that the development of brooding among children of depressed mothers, particularly children without the protective CRHR1 haplotype, may serve as an important mechanism of risk for the intergenerational transmission of depression.

Differences in emotion modulation using cognitive reappraisal in individuals with and without suicidal ideation: An ERP study

Difficulties in emotion regulation have been associated with increased suicidal thoughts and behaviours. The majority of studies have examined self-reported use of emotion regulation strategies. In contrast, the current study focused on a direct measure of individuals’ ability to use a specific emotion regulation strategy, cognitive reappraisal, using the late positive potential (LPP), an event-related potential component that reflects attention to emotional stimuli. Specifically, the cognitive reappraisal ability of 33 undergraduate students was assessed via an image-viewing task during which the participants had to passively view, increase or reduce their emotions in response to looking at neutral, positive or dysphoric images. We found that participants with a history of suicidal ideation (SI) had significantly higher LPP when asked to reduce negative emotion in response to dysphoric images, compared to individuals with no history of SI. These findings suggest that difficulties with using cognitive reappraisal, specifically to decrease negative affect, might be linked to suicide risk.

Increased Neural and Pupillary Reactivity to Emotional Faces in Adolescents with Current and Remitted Major Depressive Disorder

Abstract This study combined multiple levels of analysis to examine whether disrupted neural and pupillary reactivity to emotional faces serves as a state- or trait-like marker of adolescent major depressive disorder (MDD). The study examined differences in pupil dilation and the event-related potential (ERP) late positive potential (LPP) component to emotional faces before and after a negative mood induction between 71 adolescents (age 11–18 years) with (i) a current diagnosis of MDD, (ii) a past episode of MDD currently in full remission and (iii) no lifetime history of any Axis I disorder. Relative to healthy control (HC) youth, adolescents with current or remitted MDD exhibited an enhanced LPP and pupillary response to all emotional facial expressions (fearful, happy and sad). This difference in reactivity between remitted depressed and HC adolescents persisted following the negative mood induction. Results also revealed that LPP and pupillary responses to emotional faces were significantly related, but only among the currently depressed adolescents. This study suggests that increased physiological and neural activation in response to social-emotional stimuli may not only characterize currently depressed adolescents, but also remains following MDD remission, potentially serving as a mechanism of risk for future depression relapse.

Cognitive Reappraisal and Depression in Children with a Parent History of Depression

Although decades of research have documented that children whose parents have a history of Major Depressive Disorder (MDD) are at a higher risk of developing depression themselves, not all of these children go on to develop depression themselves, thus highlighting the need to understand potential moderators of risk. The current study examined whether child emotion regulation, specifically, the use of cognitive reappraisal and suppression, moderated the link between parent and child depression. We recruited 458 parents and their children between the ages of 7–11 from the community. The majority of children were Caucasian (74.2%) and approximately half were girls (46.1%). Among children with a parent history of MDD, those who reported using cognitive reappraisal more frequently were less likely to have a history of depressive diagnoses themselves and had higher current levels of positive affect. Although children’s use of suppression was not associated with their levels of depressive symptoms among children with a parent history of MDD, higher levels of suppression were related to higher levels of depressive symptoms among children with no parent history of MDD. These findings suggest that, among children with a history of parent depression, children’s use of cognitive reappraisal may influence their own risk for developing depression and highlights the potential utility of early interventions that focus on improving the use of emotion regulation strategies like cognitive reappraisal among children of depressed parents.

Pupillary Response to Emotional Stimuli as a Risk Factor for Depressive Symptoms Following a Natural Disaster: The 2011 Binghamton Flood

Understanding pathways of risk following a natural disaster may help create next-generation targeted interventions. The current study examined if a biomarker of cognitive-affective response (pupil dilation) could identify which individuals are at greatest risk for depression following disaster-related stress. A total of 51 women completed a computer-based task assessing pupillary response to facial expressions of emotion and reported their depressive symptoms before the 2011 Binghamton flood. Following the flood, women were assessed for objective levels of flood-related stress and again reported their depressive symptoms. Supporting the proposed diathesis-stress model, decreased pupil dilation to emotional expressions predicted a significant increase in postflood depressive symptoms, but only among women who experienced higher levels of flood-related stress. Findings suggest that reduced cognitive-affective response to emotional stimuli (measured via pupillary response) can increase risk for depression in the context of high levels of objective life stress.

Resting respiratory sinus arrhythmia in suicide attempters

Although suicide attempts (SA) occur across a broad range of diagnoses as well as in the absence of a diagnosable disorder, most studies to date have focused on them within a single, specific disorder. Consistent with the NIMH RDoC initiative to identify biobehavioral vulnerabilities that cut across diagnoses, the goal of the present study was to examine potential differences in resting respiratory sinus arrhythmia (RSA) levels in a large, diagnostically heterogeneous sample of women with and without a history of SA who were matched on a broad range of demographic and clinical variables. Participants were 112 women with (n = 56) and without (n = 56) a history of SA recruited from the community. The two groups were equated on approximate age, race, household income, and lifetime histories of psychiatric diagnoses. Resting electrocardiogram was recorded during a 2-min rest period. RSA was calculated via spectral power analyses with a fast Fourier transform. We found that women with a history of SA exhibited significantly lower resting RSA levels than women with no history of SA, and this difference was maintained even after statistically controlling for the potential influence of womens history of psychiatric diagnoses and their current symptoms of depression and anxiety. These findings suggest the presence of a link between resting RSA and SA history.

Circulating Levels of Brain-Derived Neurotrophic Factor and History of Suicide Attempts in Women

A growing body of research examining biological factors associated with suicidal behaviors highlights the role of brain-derived neurotropic factor (BDNF), involved in neurogenesis and synaptic plasticity. There is evidence suggesting that suicide attempters have lower BDNF levels than those with no history of suicide attempts. The key question addressed in the current investigation is whether differences in circulating BDNF levels persist beyond the current suicidal episode and would be observed in those with a past history of suicide attempts (SA). Plasma levels of BDNF were assessed in 73 women from the community. We found that women with a history of SA exhibited lower levels of BDNF than women with no SA history and this difference was maintained after statistically controlling for the influence of other potential psychiatric or demographic factors. These findings support and extend existing research by suggesting that circulating BDNF levels are decreased among individuals with a history of SA compared to individuals with no history of SA. This relation appeared to be specific to womens history of SA and was not explained by other potential psychiatric or demographic factors, which further highlights the role of BDNF as a promising biomarker for suicidal behavior.

Disrupted physiological reactivity among children with a history of suicidal ideation: Moderation by parental expressed emotion-criticism

OBJECTIVE The goal of this study was to examine physiological reactivity during parent-child interactions in children with and without a history of suicidal ideation (SI), a group known to be at increased risk for suicidal thoughts and behaviors in the future. We also examined the potential moderating role of parental expressed emotion-criticism (EE-Crit) to determine whether the presence of parental criticism may help to identify a subgroup of children with a history of SI most at risk for physiological dysregulation. METHOD Participants were 396 children (age 7-11; 54% male, 71.7% Caucasian) and their biological parent. Childrens levels of high frequency heart rate variability (HF-HRV) were assessed during a resting baseline period followed by a positive and negative discussion with their parent. Additionally, parents completed the Five-Minute Speech Sample to determine levels of EE-Crit toward their child, and children completed an interview assessing their history of SI. RESULTS Consistent with our hypothesis, we found that exposure to parental criticism moderated the relation between a childs history of SI and their HF-HRV reactivity to the discussions. Specifically, while most children exhibited the typical pattern of HF-HRV suppression from baseline to both interactions, the highest risk children (i.e., children with a history of SI who also had highly critical parents) did not display any change in HF-HRV across the tasks, suggesting a failure to engage a typical psychophysiological response during emotional contexts. CONCLUSIONS These results suggest a specific physiological mechanism that may place these children at risk for suicidal thoughts and behaviors in the future.