Internalizing Psychopathology Research Articles

Differentiating Performance on the Connors Continuous Performance Test (CPT-3) as a Function of Comorbid Internalizing Psychopathology.

Internalizing psychopathology commonly co-occurs with attention-deficit/hyperactivity disorder (ADHD). Attention concerns are present in both ADHD and internalizing disorders, yet the neuropsychological functioning of those with comorbid ADHD and internalizing psychopathology is underexamined. This study compared Conners' Continuous Performance Test-Third Edition (CPT-3) profiles across ADHD (n = 141), internalizing psychopathology (n = 78), and comorbid (ADHD/internalizing psychopathology; n = 240) groups. Compared to the internalizing psychopathology group, the comorbid group had higher mean T-scores on CPT-3 indices indicative of inattentiveness and impulsivity and more clinically elevated T-scores (T>60) on indices measuring inattentiveness and impaired sustained attention. Patients in the comorbid group were also more likely to have abnormal overall CPT-3 profiles (>2 elevated T-scores) than the ADHD and psychopathology only groups. Patients with comorbid ADHD/internalizing psychopathology may evidence a more impaired attentional performance on the CPT-3, which could aid in more tailored treatment planning.

Neural reactivity to neutral and aversive stimuli: Evidence for altered precuneus function in internalizing psychopathologies

Individuals with internalizing psychopathologies (IPs) demonstrate a negativity bias in emotion and self-related processing that contributes to negative interpretation of neutral information. However, most neuroimaging studies of emotional experience in IPs do not specifically investigate reactivity to neutral stimuli. Thus, little is known about the neural processes underlying emotional experience for neutral stimuli and how those processes may differ between groups and during neutral versus negative stimuli. To address this gap, we asked: (1) does neural reactivity to neutral and negative stimuli differ between IPs and control groups in brain regions associated with emotional and self-referential processing, and (2) does neural activity during neutral condition relate to clinical symptoms? Adults with IPs (n = 103) and healthy volunteers (HVs; n = 40) completed a well-validated fMRI task probing neural responses to neutral and negative images. A flexible factorial model revealed a significant group-by-condition interaction, such that individuals with IPs had less precuneus activation during the neutral condition relative to HVs. In IPs, precuneus activation during the neutral condition was negatively correlated with depression symptom severity. Individuals with IPs demonstrate abnormal precuneus reactivity to neutral stimuli that is associated with depression symptoms. This may reflect altered default mode network activity and/or self-referential processing in IPs.

Neuromodulatory effects of transcranial electrical stimulation on emotion regulation in internalizing psychopathologies

ObjectiveWe hypothesize offset theta-tACS (transcranial alternating current stimulation) improves emotion regulation (ER) and psychopathology more than transcranial direct current stimulation (tDCS) in participants with internalizing psychopathologies (IPs). MethodsThis pilot study utilized a double-blind, pseudo-counterbalanced, sham-controlled design with participants with IPs. Participants were assigned to receive tDCS or tACS, underwent four stimulation sessions (two sham), and completed an emotion regulation task (ERT) during or after stimulation. Participants completed the Beck Depression Inventory before/after the study, the Spielberger State and Trait Anxiety Index after each ERT, and rated their arousal, valence, and perceived reappraisal ability during the ERT. ResultsParticipants receiving either stimulation type showed a reduction in anxiety, depression, and valence and arousal ratings. We additionally discovered an effect demonstrating those who received sham stimulation first displayed little-to-no change in any score across the study, but tACS participants who received verum stimulation first showed significant improvements in each metric. ConclusionsImproving ER capabilities via theta tACS has the potential to yield beneficial clinical effects. SignificanceThis study adds validity to the use of non-invasive neuromodulatory methods, especially tACS, to alleviate IPs. Additional research is needed to better understand the effects of sham stimulation. Careful consideration of sham incorporation should be made in future studies.

Neural reactivity to affective stimuli and internalizing symptom dimensions in a transdiagnostic patient sample.

Internalizing psychopathologies (IPs) are highly comorbid and exhibit substantial overlap, such as aberrant affective reactivity. Neural reactivity to emotional images, measured via the late positive potential (LPP) event-related potential (ERP) component, has been utilized to index affective reactivity in IPs. The LPP is often examined in isolation with a specific disorder, ignoring overlap between IPs. The current study examined how transdiagnostic IP symptom dimensions relate to neural affective reactivity in a highly comorbid patient sample. Participants (N = 99) completed a battery of IP symptom assessments as well as a target categorization task while viewing pleasant, unpleasant, and neutral images during electroencephalography recording. ERPs to each image valence were averaged from 400 to 1000 ms following picture onset at pooled centroparietal and occipital electrodes to calculate the LPP. A principal components analysis performed on the IP symptom measures resulted in two factors: affective distress/misery and fear-based anxiety. Fear-based anxiety was associated with enhanced LPP reactivity to unpleasant, but not pleasant, images. Distress/misery was related to attenuated average LPP reactivity across images. Results revealed a dissociable effect of IP symptom factors in a transdiagnostic sample such that enhanced reactivity to negative images was specific to enhanced fear-based anxiety symptoms while distress/misery symptoms predicted blunted affective reactivity. Neural affective reactivity may serve as an objective biological marker to elucidate the nature of psychological concerns in individuals with comorbid IPs.

Electrocortical measures of win and loss processing are associated with mesocorticolimbic functional connectivity: A combined ERP and rs-fMRI study.

The reward positivity (RewP) event-related potential is a well-validated measure of reward processing implicated in internalizing psychopathologies. The RewP is thought to reflect reward reactivity in the mesocorticolimbic system; however, it is not clear how the RewP is related to the functional connectivity of reward-related brain regions. The current study examined associations between the RewP (Win and Loss residuals) and resting-state fMRI (rs-fMRI), among adults with internalizing psychopathology (IP) and healthy controls (HC). All participants (N=102) completed a validated monetary reward task during electroencephalogram and rs-fMRI. Regression analyses were conducted with (1) RewP-Win residual amplitude and striatal seeds (caudate, putamen, nucleus accumbens) and (2) RewP-Loss residual amplitude and anterior cingulate cortex (ACC) seeds. Overall, individuals with greater RewP-Win residual amplitude demonstrated increased rs-fMRI connectivity between striatal regions and the medial prefrontal cortex, as well as the parahippocampal gyrus, but decreased connectivity between striatal regions and regions involved in cognitive control and sensorimotor processing. Greater RewP-Loss residual was related to greater connectivity between the ACC and regions involved in reward/loss processing and motor control, but decreased connectivity between the ACC and regions involved in cognitive control. Relationships between the RewP and rs-fMRI were generally consistent across IP and HC. However, a few patterns were unique to IP. Results indicate the RewP is associated with resting-state functional connectivity of reward- and loss-related brain regions, suggesting connectivity of the mesocorticolimbic system may be an important individual difference factor in dimensions of attainment of reward and loss.

P230. Neural Reactivity to Neutral and Aversive Stimuli: Evidence for Altered Precuneus Function in Internalizing Psychopathologies

Internalizing psychopathologies (IP) demonstrate a negativity bias that contributes to negative interpretation of neutral information. However, most neuroimaging studies of emotional experience in IPs do not specifically investigate reactivity to neutral stimuli. Thus, little is known about the neural processes underlying emotional experience for neutral stimuli and how those processes may differ between groups and during neutral versus negative stimuli. To address this gap, we asked: (1) do patterns of neural reactivity to neutral and negative stimuli differ between IP and control groups, and (2) does neural activity during neutral condition relate to clinical symptoms?

P301. Default Mode Network Hypoalignment of Function to Structure Correlates With Depression and Rumination

Recent studies have begun to examine the extent to which signals in the brain correspond to the underlying white matter structure by using tools from the field of graph signal processing to quantify brain function ‘alignment’ to network topology. Here, we apply this framework towards an internalizing psychopathology (IP) cohort to uncover how such alignment within the default mode network (DMN) is related to depression and rumination symptoms.

Maternal Error-Related Negativity Relationship With Offspring Error-Related Negativity and Negative Parenting Styles: A Novel Model of Internalizing Psychopathology Risk

BackgroundEnhanced error-related negativity (ERN), an event-related potential component reflecting neural sensitivity to errors and threat, has been theorized to represent an endophenotype of internalizing psychopathologies (IPs). We tested whether intergenerational transmission of ERN patterns may confer risk for internalizing symptoms. We examined associations among maternal and offspring ERN and offspring internalizing symptoms. Given the role of parenting in IP risk, we also explored how maternal negative parenting styles related to maternal ERN and offspring internalizing symptoms. MethodsParticipants included 117 biological mother-child dyads (ages 9–16 years, 70.9% female). Of these, 72 mothers had a history of major depression (32 with lifetime anxiety), and 45 had no history of psychiatric illness. Dyads completed psychiatric interviews, parenting questionnaires, and a flanker task to elicit the ERN while an electroencephalogram was recorded. ResultsPath analyses revealed that maternal ERN was significantly associated with enhanced offspring ERN and greater negative parenting styles. Enhanced offspring ERN and maternal negative parenting styles were significantly related to greater internalizing symptoms in offspring. Maternal ERN had a significant indirect effect on offspring internalizing symptoms through offspring ERN and maternal negative parenting styles, above the effects of self-reported maternal internalizing symptoms. Maternal IP history did not moderate pathways. ConclusionsStudy findings suggest that enhanced maternal ERN is indirectly associated with greater offspring internalizing symptoms through its relationship to offspring ERN and negative parenting styles. Future longitudinal work is needed to evaluate the temporal timing and directionality of these tested pathways and their clinical implications for the prevention of IPs.

Network Diffusion Embedding Reveals Transdiagnostic Subnetwork Disruption and Potential Treatment Targets in Internalizing Psychopathologies.

Network diffusion models are a common and powerful way to study the propagation of information through a complex system and they offer straightforward approaches for studying multimodal brain network data. We developed an analytic framework to identify brain subnetworks with perturbed information diffusion capacity using the structural basis that best maps to resting state functional connectivity and applied it towards a heterogeneous dataset of internalizing psychopathologies (IPs), a set of psychiatric conditions in which similar brain network deficits are found across the swath of the disorders, but a unifying neuropathological substrate for transdiagnostic symptom expression is currently unknown. This research provides preliminary evidence of a transdiagnostic brain subnetwork deficit characterized by information diffusion impairment of the right area 8BM, a key brain region involved in organizing a broad spectrum of cognitive tasks, which may underlie previously reported dysfunction of multiple brain circuits in the IPs. We also demonstrate that models of neuromodulation involving targeting this brain region normalize IP diffusion dynamics towards those of healthy controls. These analyses provide a framework for multimodal methods that identify both brain subnetworks with disrupted information diffusion and potential targets of these subnetworks for therapeutic neuromodulatory intervention based on previously well-characterized methodology.

Mediational Pathways From Genetic Risk to Alcohol Use Disorder in Swedish Men and Women

The purpose of this study was to clarify the mediational pathways from genetic risk for alcohol use disorder (AUD) to AUD itself. Using information on AUD status from first- through fourth-degree relatives obtained from national registries, we created a genetic risk score for AUD for the Swedish population. We first tested a simple mediational path model in males and females separately, with early onset externalizing psychopathology (EPP), internalizing psychopathology (IPP), and poor educational attainment (EA). We then tested a more complex model in a smaller, older sample of males that contained additional self-report measures from late adolescence. In our basic model, the largest mediational pathway from AUD genetic risk to AUD in both sexes was via high EPP followed by low EA and high IPP. The EPP pathway was considerably stronger in males, the low EA pathway was modestly stronger in females, and the IPP pathway was identical in both sexes. Our more complex model replicated the strong externalizing pathway to AUD, showing that it connected to key downstream risk factors such as early drug and alcohol use and low resilience. Our models concurred in showing that the strongest mediational pathway for genetic risk to AUD includes externalizing symptoms and disorders, which in turn predict further key downstream risk factors. Pathways through lower EA and IPP had smaller effects. IPP had mixed effects (partly predisposing and partly protective) on downstream risk factors. The largest sex difference was a stronger externalizing pathway to genetic risk to AUD in males than in females.

Infant behavioral inhibition predicts personality and social outcomes three decades later

Does infant temperament predict adult personality and life-course patterns? To date, there is scant evidence examining relations between child temperament and adult outcomes, and extant research has relied on limited methods for measuring temperament such as maternal report. This prospective longitudinal study followed a cohort of infants (n = 165) for three decades to examine whether infant behavioral inhibition, a temperament characterized by cautious and fearful behaviors to unfamiliar situations, shapes long-term personality, social relationships, vocational/education, and mental health outcomes in adulthood. At age 14 mo, behavioral inhibition was assessed using an observation paradigm. In adolescence (15 y; n = 115), error monitoring event-related potentials were measured in a flanker task. In adulthood (26 y; n = 109), personality, psychopathology, and sociodemographics were self-reported using questionnaires. We found that infants with higher levels of behavioral inhibition at 14 mo grew up to become more reserved and introverted adults (β = 0.34) with lower social functioning with friends and family (β = -0.23) at age 26. Infant behavioral inhibition was also a specific risk factor for adult internalizing (i.e., anxiety and depression, β = 0.20) psychopathology, rather than a transdiagnostic risk for general and externalizing psychopathology. We identified a neurophysiologic mechanism underlying risk and resilience for later psychopathology. Heightened error monitoring in adolescence moderated higher levels of adult internalizing psychopathology among behaviorally inhibited individuals. These findings suggest meaningful continuity between infant temperament and the development of adult personality. They provide the earliest evidence suggesting that the foundation of long-term well-being is rooted in individual differences in temperament observed in infancy.

Graph theoretical measures of the uncinate fasciculus subnetwork as predictors and correlates of treatment response in a transdiagnostic psychiatric cohort

The internalizing psychopathologies (IP) are a highly prevalent group of disorders for which little data exists to guide treatment selection. We examine whether graph theoretical metrics from white matter connectomes may serve as biomarkers of disease and predictors of treatment response. We focus on the uncinate fasciculus subnetwork, which has been previously implicated in these disorders. We compared baseline graph measures from a transdiagnostic IP cohort with controls. Patients were randomized to either SSRI or cognitive behavioral therapy and we determined if graph theory metrics change following treatment, and whether these changes correlated with treatment response. Lastly, we investigated whether baseline metrics correlated with treatment response. Several baseline nodal graph metrics differed at baseline. Of note, right amygdala betweenness centrality was increased in patients relative to controls. In addition, white matter integrity of the uncinate fasciculus was decreased at baseline in patients versus controls. The SSRI and CBT cohorts had increased left frontal superior orbital betweenness centrality and left frontal medial orbital clustering coefficient, respectively, suggesting the presence of treatment specific neural correlates of treatment response. This study provides insight on shared white matter network features of IPs and elucidates potential biomarkers of treatment response that may be modality-specific.

Neural correlates of predictable and unpredictable threat in internalizing psychopathology

Converging lines of evidence suggest that heightened responding to unpredictable threat may be an important neurobiological marker of internalizing psychopathology (IP). Prior data also indicate that aversive responding to uncertainty may be mediated by hyperactivation of several brain regions within the frontolimbic circuit, namely the anterior insula (aINS) and the dorsal anterior cingulate cortex (dACC). To date, however, the majority of this research has been focused on individual diagnoses and it is unclear whether abnormal neural reactivity to unpredictable threat is observed within heterogeneous, transdiagnostic IP patient populations, as theory would suggest. The aim of the current study was to therefore examine the neural correlates of temporally unpredictable (U) and predictable (P) threat in a sample of healthy controls (n = 24) and patients with a broad range of IP diagnoses (n = 51). We also examined whether symptom severity measures of fear and distress/misery dimensions correlated with neural reactivity to U- and P-threat. All participants completed a modified version of a well-validated threat-of-shock task during functional magnetic resonance imaging (fMRI). Across all participants, U- and P-threat elicited heightened activation in the aINS and brainstem, while P-threat alone also activated the dACC. Relative to healthy controls, patients displayed greater activation in the right aINS during U-threat, and greater right brainstem activation during P-threat. In addition, we found that brainstem activity during U-threat correlated with fear, but not distress/misery, psychopathology. Taken together, these preliminary results suggest that exaggerated aINS reactivity during U-threat and brainstem reactivity during P-threat may have the potential to become important transdiagnostic biomarkers of IP; however, future research efforts are needed to corroborate and expand the present findings.

SU114 - EARLY SEXUAL ASSAULTIVE TRAUMA, POLYGENIC RISK FOR AUD/CUD, AND NEURAL RESPONSE INHIBITION IN ADOLESCENCE AND YOUNG ADULTS: TRAJECTORIES OF FRONTAL OSCILLATIONS DURING A GO/NOGO TASK

Background Trauma, particularly when experienced early in life, may alter brain and concurrent cognitive, affective and behavioral development, thereby increasing risk for substance use disorders and related psychopathology. While research indicates that genetic factors may exacerbate these vulnerabilities, few studies have empirically examined these effects using relatively large longitudinal and genetically informative developmental samples with dense phenotyping in multiple domains. Methods The association of early assaultive, non-assaultive, and sexual-assaultive experiences prior to age 10 with developmental trajectories of neurophysiological functioning during response inhibition (frontal theta and posterior delta activity during an equal probability Go/NoGo task) were examined, using data from the Collaborative Study of the Genetics of Alcoholism (COGA) prospective cohort, comprising offspring from high-risk and comparison families who were aged 12–22 at enrollment and who have been sought for interview every 2 years (only those with 3+ interviews were included in the present analyses, N: 3,030). Interactions with early trauma exposures and polygenic risk for Alcohol and Cannabis Use Disorders (AUD, CUD) based on recently published GWAS data, were examined. Additionally, associations of neurophysiological functioning with AUD, CUD, Externalizing (EXT) and Internalizing (INT) psychopathology measured at each individual's last assessment were examined. Models were adjusted for age, gender, self-reported race/ethnicity, parental alcohol use disorders, and participants' own alcohol and cannabis use. Results Individuals exposed to sexual assaultive trauma prior to age 10 had altered developmental trajectories of NoGo frontal theta; the typical developmental change in frontal theta activity observed throughout adolescence and young adulthood occurred at a slower rate among those who had been exposed to early sexual assault, but not other types of trauma, compared to those who were not exposed (controlling for other types of assaultive and non-assaultive trauma exposure). Importantly, effects remained significant after accounting for parental history of AUD and participants’ own alcohol and cannabis use. Associations were more robust for participants with greater polygenic risk for AUD, but not CUD. Further, changes in NoGo frontal theta development was associated with increased risk for AUD and INT (mood disorders and suicidal ideation), but not CUD or EXT (conduct disorder, oppositional defiant disorder). Post-hoc analyses showed that early sexual assault was associated with higher rates of impulsivity (Barrett Impulsivity Scale) and sensation seeking (Zuckerman's Sensation Seeking Scale). Discussion Findings support the hypothesis that childhood sexual assault may influence young adult AUD and INT via alterations in genetic, brain and behavioral development in adolescence and young adulthood. However, future studies are needed to disentangle complex interactions among genetic and psycho-social influences on neurobiological development.

Developmental changes in resting-state functional networks among individuals with and without internalizing psychopathologies.

Three well-established intrinsic connectivity networks (ICNs) involved in cognitive-affective processing include the cognitive control network (CCN), default mode network (DMN), and salience and emotional network (SEN). Despite recent advances in understanding developmental changes in these ICNs, the majority of research has focused on single seeds or networks in isolation with limited age ranges. Additionally, although internalizing psychopathologies (IPs), such as anxiety and depression, are often characterized by maladaptive cognitive-affective processing styles, it is not clear how IP history influences age-related changes in brain networks. The current study aimed to characterize the normative development of the CCN, DMN, and SEN across a large age-span (7-29year olds) of typically developing (TD) individuals (n=97). We also explore how age may impact differences in network connectivity between TD individuals and patients with IPs (n = 136). Among TD individuals, DMN and CCN connectivity strengthened with age, whereas connectivity between the SEN and ventromedial prefrontal cortex weakened across development. When exploring group (IP vs. TD) differences, the IP group was characterized by greater connectivity between the CCN and cerebellum and between the SEN and caudate from childhood to early adulthood, relative to TD individuals. In addition, patients with IPs, versus TD individuals, exhibited reduced connectivity between the SEN and medial frontal gyrus from adolescence to adulthood. The current findings shed light on differential age-related changes in brain network patterns among psychiatrically free, TD individuals and those with internalizing disorders, and may provide plausible targets for novel mechanism-based treatments that differ based on developmental stage.

The roles of early-life adversity and rumination in neural response to emotional faces amongst anxious and depressed adults.

Early-life adversity (ELA) is a risk factor for internalizing psychopathology (IP). ELA is also linked to alterations in neural phenotypes of emotion processing and maladaptive emotion regulatory strategies, such as ruminative brooding, in adulthood. We therefore expected that ELA would predict cortical brain activation to emotional faces in transdiagnostic IP and in turn, mediate the extent of rumination amongst patients with IPs and ELA (IP + ELA). One hundred and thirty-two individuals, including 102 treatment-seeking adults with heterogeneous IPs and 30 healthy controls (HCs) performed an Emotional Face-Matching Task during functional magnetic resonance imaging. Whole-brain analyses compared HC (n = 30), IP (n = 52), and IP + ELA (n = 50) neural responses to emotional (angry, fearful, happy, and sad) faces v. shapes, controlling for depression and anxiety symptoms. Parameter estimates of activation were extracted for significant between-group differences and tested as a mediator of ruminative brooding in IP + ELA. IP + ELA demonstrated increased activation in the superior frontal gyrus and anterior cingulate cortex (fear), superior parietal lobule, precuneus, posterior cingulate, and inferior temporal gyrus (fear only), and cuneus (fear and angry). These regions were preferentially correlated with ruminative brooding in IP + ELA, many of which mediated the link between IP + ELA and ruminative brooding. Results provide evidence that ELA history amongst IP patients augments engagement of brain regions involved in emotion processing, above and beyond what is accounted for by current symptoms. Though longitudinal designs are needed, alterations in the neural correlates of maladaptive processing of socio-emotional information may be a common pathway by which ELA poses risk for psychopathology.

Principal component analysis and brain-based predictors of emotion regulation in anxiety and depression.

Reappraisal, an adaptive emotion regulation strategy, is associated with frontal engagement. In internalizing psychopathologies (IPs) such as anxiety and depression frontal activity is atypically reduced suggesting impaired regulation capacity. Yet, successful reappraisal is often demonstrated at the behavioral level. A data-driven approach was used to clarify brain and behavioral relationships in IPs. During functional magnetic resonance imaging, anxious [general anxiety disorder (n = 43), social anxiety disorder (n = 72)] and depressed (n = 47) patients reappraised negative images to reduce negative affect ('ReappNeg') and viewed negative images ('LookNeg'). After each trial, the affective state was reported. A cut-point (i.e. values <0 based on ΔReappNeg-LookNeg) demarcated successful reappraisers. Neural activity for ReappNeg-LookNeg, derived from 37 regions of interest, was submitted to Principal Component Analysis (PCA) to identify unique components of reappraisal-related brain response. PCA factors, symptom severity, and self-reported habitual reappraisal were submitted to discriminant function analysis and linear regression to examine whether these data predicted successful reappraisal (yes/no) and variance in reappraisal ability. Most patients (63%) were successful reappraisers according to the behavioral criterion (values<0; ΔReappNeg-LookNeg). Discriminant function analysis was not significant for PCA factors, symptoms, or habitual reappraisal. For regression, more activation in a factor with high loadings for frontal regions predicted better reappraisal facility. Results were not significant for other variables. At the individual level, more activation in a 'frontal' factor corresponded with better reappraisal facility. However, neither brain nor behavioral variables classified successful reappraisal (yes/no). Findings suggest individual differences in regions strongly implicated in reappraisal play a role in on-line reappraisal capability.

A preliminary examination of the relation between neural sensitivity to reward and history of alcohol use disorder among adults with internalizing psychopathologies

Decreased reward responsiveness, as demonstrated utilizing the event-related potential (ERP) component the reward positivity (RewP), is an established correlate of internalizing psychopathologies (IPs), such as depressive and anxiety disorders. Although IPs are highly comorbid with alcohol use disorders (AUDs) and despite evidence that AUDs are also characterized by aberrant reward processing styles, no studies have examined how AUD history impacts the RewP among adults with IPs. The current preliminary study sought to examine this question in a sample of 65 adults with 1) current IPs (i.e., depression, social anxiety, and/or generalized anxiety, 2) current IPs with a history of an AUD (IP + Past AUD), and 3) no history of a DSM-IV disorder. Participants completed a guessing reward task while electroencephalogram (EEG) was recorded. Results indicated that participants in the IP group exhibited a more attenuated RewP relative to IP + Past AUD and healthy control individuals. Findings from this study highlight the importance of examining diagnostic subgroups among adults with anxiety and depressive disorders, and suggest that a history of AUD may enhance reward reactivity at the neural level in individuals with IPs.

Self-Reported Sleep Quality Modulates Amygdala Resting-State Functional Connectivity in Anxiety and Depression.

Sufficient sleep plays an important role in neurocognitive function, yet, problematic sleep is ubiquitous in the general population. It is also frequently predictive of, and concurrent with, internalizing psychopathologies (IPs) such as anxiety and depression suggesting sleep quality is dimensional and transdiagnostic. Along with problematic sleep, IPs are characterized by negative affectivity, therefore, prominent neurobiological models of internalizing conditions involve the amygdala, a region central to emotion. In resting-state studies (independent of sleep considerations), abnormalities in amygdala-frontal functional connectivity are commonly observed suggesting emotion dysregulation may contribute to clinically-relevant phenotypes. In a separate line of research, studies of sleep deprivation, and insomnia disorder suggest sleep loss may alter amygdala-frontal connectivity. Taken together, findings point to shared neurobiology between sleep and emotion systems, however, the impact of sleep quality on the amygdala circuit in anxiety or depression is unclear. Therefore, we evaluated variance in naturalistic sleep quality on amygdala-based circuity in individuals with and without psychiatric illness. Resting-state fMRI data was collected in 87 un-medicated, treatment-seeking adults diagnosed with a primary anxiety disorder (n = 68) or primary depressive disorder (n = 19) in addition to healthy individuals (n = 40). Regression analysis was conducted with bilateral anatomical amygdala as seed regions and self-reported sleep quality was indexed with a validated self-report measure, the Pittsburgh Sleep Quality Index (PSQI). Post-hoc analysis was performed to evaluate whether diagnostic status (primary anxiety, primary depression, healthy) significantly explained functional connectivity results. Whole-brain regression analysis, controlling for anxiety and depression symptoms, revealed worse sleep quality (i.e., higher PSQI total scores) predicted increased left amygdala-subgenual anterior cingulate functional connectivity and reduced connectivity with posterior cerebellar lobe and superior temporal gyrus. For right amygdala, increased coupling with postcentral gyrus corresponded with worse sleep. Post-hoc analysis did not detect a significant relationship between diagnostic status and whole-brain findings. Results expand on previous studies and indicate variance in sleep quality tracks brain pathways involved in cognitive-emotion functions implicated in the neurobiology of IPs that may extend to individuals at risk for clinical anxiety or depression. Altogether, the clinical relevance of identifying phenotypes to improve our understanding of psychopathology may be improved by incorporating sleep quality.

F92. Identification of Biotype in Anxiety and Depression Using Amygdala Response to Threat and Objective and Subjective Measures of Sleep

Anxiety and depression are heterogeneous internalizing psychopathologies (IPs) characterized by exaggerated amygdala reactivity to threat and problematic sleep to varying degrees. Therefore, measures of brain response to threat and sleep could be leveraged to identify novel subtypes of IPs.