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1.
J Psychiatr Res ; 136: 47-53, 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33556904

RESUMO

Social-emotional information processing (SEIP) is critical for appropriate human interaction. It is composed of processes that underlie how we behave towards others, especially in response to adverse social threat. We conducted a study in 26 healthy participants who completed a validated Video-SEIP (V-SEIP) task in the fMRI scanning environment. The V-SEIP phases studied included encoding (ENC) of socially relevant information, hostile attribution (HA) of motive, and the negative emotional response (NER) the participant would have in the context of the video vignettes. The ENC phase was associated with activation of amygdala, left ventrolateral prefrontal cortex, right middle temporal gyrus, and visual cortex, the HA phase associated with activation of several brain regions including frontal and temporal cortex as well as basal ganglia and cerebellum, while the NER phase was associated with activation in the midbrain with regions involving the periaqueductal gray, basal ganglia, and the cerebellum. We suggest that this V-SEIP task represents a novel neuro-biomarker for the study of SEIP and that it can be extended for use in a number of psychiatric conditions in which anger, irritability, and impulsive aggressive are prominent features.

2.
Drug Alcohol Depend ; 221: 108565, 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33592558

RESUMO

BACKGROUND: Few studies have examined how Δ9-Tetrahydrocannabinol (THC), the main psychoactive component of cannabis, impacts brain reward circuitry in humans. In this study, we examined if an acute dose of THC altered resting state functional connectivity between the striatum and prefrontal cortex among healthy young adults with limited cannabis use. METHODS: Participants received THC (n = 24) or placebo (n = 22) in a double-blind, randomized, between-subject design. Participants completed self-report measures of euphoria and drug-liking throughout the visit. Approximately 120 min after drug administration, participants completed an 8-min resting state functional MRI (rs-fMRI) scan. We utilized seed-based connectivity of the striatum (bilateral putamen, caudate, and NAcc seeds) to the frontal cortex. RESULTS: Individuals who received THC demonstrated greater rs-fMRI connectivity between the right NAcc and regions of the medial prefrontal cortex (mPFC) (p-values<0.05, corrected) and higher subjective euphoria ratings (p = .03) compared to compared to individuals who received placebo. Higher ratings of euphoria were related to greater right NAcc-dorsal mPFC (dmPFC) connectivity for the THC group (p=.03), but not for the placebo group (p=.98). CONCLUSIONS: This is one of the first studies to examine rs-fMRI connectivity in healthy young non-users after THC administration. We found individuals receiving THC show greater rs-fMRI connectivity between the NAcc and mPFC, regions implicated in reward, compared to individuals receiving placebo. In addition, individuals receiving THC reported higher subjective euphoria ratings, which were positively associated with NAcc-dmPFC connectivity. Overall, our findings suggest THC may produce subjective and neural reward responses that contribute to the rewarding, reinforcing properties of cannabis.

3.
Int J Psychophysiol ; 161: 13-26, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33450313

RESUMO

Trauma exposure is prevalent, associated with multiple forms of psychopathology, and thought to alter the neurobiological substrates of threat processing. The late positive potential (LPP) is an event-related potential (ERP) that may be a clinically useful probe of the neurobiology of threat processing. Despite evidence that combat-exposed veterans exhibit aberrant threat modulation of the LPP, no studies to date have tested the psychometric properties of the LPP in combat trauma-exposed, symptomatic veterans. The primary aim of the current study was to evaluate the reliability (internal consistency, retest reliability) and convergent validity of LPP modulation by threatening faces and scenes in two common tasks among combat-exposed veterans. Participants included 82 combat-exposed veterans who completed face-matching and emotion regulation tasks during EEG recording at baseline and twelve weeks. Internal consistencies of the early LPP time windows (<1000 ms) were acceptable in both tasks, whereas they were poor in late time windows (>1000 ms). Twelve-week retest reliabilities were fair for the early window LPPs to threatening scenes and fear faces, as well as in the late time window for fear faces. Reliabilities were better for individual condition compared to difference scores. Finally, LPPs modulated by threatening scenes and faces were unrelated. Together, these results suggest that the LPPs to threatening scenes and faces reflect distinct forms of threat processing in combat-exposed veterans, and their reliabilities for the early window indicate potential clinical utility in this population.

4.
Neuropsychopharmacology ; 46(2): 343-350, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32505126

RESUMO

One well-known phenotypic risk factor for the development of alcohol use disorder is sensitivity to the rewarding effects of alcohol. In the present study, we examined whether individuals who are sensitive to alcohol reward are also sensitive to nondrug rewards, thereby reflecting a broader individual difference risk factor. Specifically, we tested the hypothesis that subjective response to acute rewarding effects of alcohol would be related to neural activation during monetary reward receipt relative to loss (in the absence of alcohol). Community-recruited healthy young social drinkers (N = 58) completed four laboratory sessions in which they received alcohol (0.8 g/kg) and placebo in alternating order under double-blind conditions, providing self-report measures of subjective response to alcohol at regular intervals. At a separate visit 1-3 weeks later, they completed a reward-guessing game, the 'Doors' task, during fMRI in a drug-free state. Participants who reported greater motivation (i.e., wanting) to consume more alcohol after a single moderate dose of alcohol also exhibited greater neural activation in the bilateral ventral caudate and the nucleus accumbens during reward receipt relative to loss. Striatal activation was not related to other subjective ratings including alcohol-induced sedation, stimulation, or pleasure (i.e., feeling, liking). Our study is the first to show that measures of alcohol reward are related to neural indices of monetary reward in humans. These results support growing evidence that individual differences in responses to drug and nondrug reward are linked and together form a risk profile for drug use or abuse, particularly in young adults.

5.
Addict Behav ; 113: 106669, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33035810

RESUMO

INTRODUCTION: Disruptions in neural measures of reward responsiveness are implicated in risk for and the development of Substance Use Disorders (SUDs) in general, but it is not clear if this is also true for Cannabis Use Disorder (CUD). To date, no studies have examined neural reward responsiveness in cannabis users using EEG. METHODS: Cannabis users (CU; n = 67) and non-users (n = 60) were drawn from larger studies of individuals with and without internalizing and externalizing psychopathology. Groups were matched on current and lifetime psychopathology. Participants completed a validated monetary reward task during electroencephalogram (EEG). One-way between subject analysis of covariance (ANCOVA) models examined group differences in four EEG indicators of reward responsiveness - the reward positivity (RewP) and feedback negativity (FN) event-related potentials and two time-frequency measures (reward-related delta and loss-related theta). RESULTS: CU demonstrated an enhanced RewP to the attainment of monetary reward compared to non-users (p = .004), even after controlling for relevant covariates. Secondary analyses found that occasional CU, but not current CUD or remitted CUD, showed enhanced RewP compared to non-users. There were no significant differences in FN, reward-related delta, or loss-related theta time-frequency measures between groups. CONCLUSIONS: To our knowledge, this is the first study to show preliminary evidence that CU have an enhanced RewP to reward and the extent of disruption may be related to CUD status. Our findings suggest that greater neural reward responsiveness may only be seen among occasional CU, not necessarily among CU with current or remitted CUD.

6.
Psychol Med ; : 1-11, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33168110

RESUMO

BACKGROUND: Neuroimaging studies have shown variance in brain response to emotional faces predicts cognitive behavioral therapy (CBT) outcome. An important next step is to determine if individual differences in neural predictors of CBT response represent distinct patient groups. METHODS: In total, 90 patients with internalizing disorders completed a face-matching task during functional magnetic resonance imaging before and after 12 weeks of CBT and 45 healthy controls completed the task before and after 12 weeks. Patients exhibiting a pre-to-post CBT >50% reduction in symptom severity on two measures were considered treatment responders. Regions of interest (ROIs) for angry, fearful, and happy faces were submitted to receiver operating characteristic (ROC) curve analysis. Significant ROIs were then submitted to decision tree analysis to classify responder/non-responder subgroups. Psychophysiological interactions (PPI) were used to explore functional connectivity in the region(s) that delineated subgroups. RESULTS: A total of 51 patients were treatment responders and ROC curve results were significant for all face types though specific regions varied. Decision tree results revealed superior occipital response to angry faces identified patient subgroups such that the subgroup with 'high' occipital activity had more responders than the 'low' occipital subgroup. Following CBT, the high, relative to low, occipital subgroup was less symptomatic. Controls exhibited stable superior occipital activation over time. Whole-brain PPI showed reduced baseline superior occipital-postcentral gyrus functional connectivity in responders compared to non-responders. CONCLUSIONS: Preliminary findings indicate patients characterized by relatively more pre-treatment superior occipital gyrus engagement to angry faces and reduced superior occipital-postcentral gyrus connectivity, relative to non-responders, may represent a phenotype likely to benefit from CBT.

7.
Depress Anxiety ; 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33001526

RESUMO

BACKGROUND: Anxiety is associated with aberrant patterns of cortical thickness in regions implicated in emotion regulation. However, few studies have examined cortical thickness differences between individuals with anxiety and healthy controls (HCs) across development, particularly during childhood when cortical thinning begins and anxiety risk increases. A better understanding of age-related changes in cortical thickness patterns among anxious individuals is essential to develop plausible targets for early identification. METHODS: The current study examined how age impacted differences in cortical thickness patterns between HCs and anxious individuals. Participants included 233 individuals (ages 7-35) with a current anxiety disorder (n = 149) or no lifetime history of psychopathology (n = 84). Cortical thickness of regions that are implicated in emotion regulation (ventromedial prefrontal cortex [vmPFC], rostral anterior cingulate [rACC], and insula) were assessed. RESULTS: All regions showed significant thinning with age, except left rACC and right insula. However, rates of thinning differed among anxious and HC participants, with anxious participants demonstrating slower rates of right vmPFC thinning. Regions of significance analyses indicated that anxious, relative to HC, participants exhibited thinner right vmPFC before age 11, but thicker right vmPFC after age 24. CONCLUSIONS: Current findings suggest that anxious individuals do not demonstrate normative right vmPFC cortical thinning, which may lead them to exhibit both thinner vmPFC in middle childhood and thicker vmPFC in adulthood compared with HCs. These findings may provide plausible targets for identification of anxiety risk that differ based on developmental stage.

8.
Dev Psychobiol ; 2020 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-32743851

RESUMO

The error-related negativity (ERN) is an event-related potential that reflects error monitoring. Enhanced ERN indicates sensitivity to performance errors and is a correlate of anxiety disorders. In contrast, youth with externalizing problems exhibit a reduced ERN, suggesting decreased error monitoring. Anxiety and externalizing problems commonly co-occur in youth, but no studies have tested how comorbidity might modulate the ERN. In a sample of youth (N = 46, ages 7-19) with and without anxiety disorders, this preliminary study examined the interactive effect of anxiety and externalizing problems on ERN. Results suggest that externalizing problems moderate the relation between anxiety symptoms and ERN in youth. Anxious youth with less externalizing problems exhibited enhanced ERN response to errors. Conversely, anxious youth with greater externalizing problems demonstrated diminished ERN in response to errors. The regions of significance and proportion affected tests indicated that the moderating the effect of externalizing problems was only significant for youth with anxiety disorders. Findings suggest that enhanced neural error sensitivity could be a specific neurophysiological marker for anxiety disorders, whereas anxious individuals with comorbid externalizing problems demonstrate reduced error monitoring, similar to those with primary externalizing pathology. Results underscore the utility of examining neural correlates of pediatric anxiety comorbidity subtypes.

9.
Artigo em Inglês | MEDLINE | ID: mdl-32725113

RESUMO

OBJECTIVE: The present study explored both embedded symptom (SVT) and performance (PVT) validity test scores within a post-9/11 veteran sample to elucidate the degree to which there is concordance between validity indicators, as well as how frequently one SVT and four PVT indicators were failed in screened mild traumatic brain injury (mTBI) and diagnosed posttraumatic stress disorder (PTSD). METHOD: A total of 114 post-9/11 veterans were evaluated utilizing the Neurobehavioral Symptom Inventory (NSI) Validity-10, four embedded PVTs, mTBI screening, and a diagnostic interview for PTSD. RESULTS: While we found concordance between embedded PVTs and the NSI Validity-10 at select cutoffs (i.e., ≥13, ≥19), symptom and performance validity indicators were clinically dissociable in that only SVT significantly predicted diagnosed PTSD and screened mTBI. CONCLUSIONS: Dissociation between symptom and performance validity may be clinically useful when interpreting neuropsychological evaluation findings in post-9/11 veterans with a history of mTBI or PTSD.

10.
Depress Anxiety ; 37(10): 1037-1046, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32668087

RESUMO

BACKGROUND: Alterations in resting-state functional connectivity (rsFC) have been reported in posttraumatic stress disorder (PTSD). Here, we examined pre- and post-treatment rsFC during a randomized clinical trial to characterize alterations and examine predictors of treatment response. METHODS: Sixty-four combat veterans with PTSD were randomly assigned to prolonged exposure (PE) plus placebo, sertraline plus enhanced medication management, or PE plus sertraline. Symptom assessment and resting-state functional magnetic resonance imaging (fMRI) scans occurred before and after treatment. Twenty-nine trauma-exposed combat veterans without PTSD served as a control group at intake. Seed-based and region of interest (ROI)-to-ROI connectivities, as well as an exploratory connectome-based approach were used to analyze rsFC patterns. Based on previously reported findings, analyses focused on Salience Network (SN) and Default-Mode Network (DMN). RESULTS: At intake, patients with PTSD showed greater DMN-dorsal attention network (DAN) connectivity (between ventromedial prefrontal cortex and superior parietal lobule; family-wise error corrected p = .011), greater SN-DAN connectivity (between insula and middle frontal gyrus; corrected p = .003), and a negative correlation between re-experiencing symptoms and within-DMN connectivity (between posterior cingulate cortex (PCC) and middle temporal gyrus; corrected p < .001). We also found preliminary evidence for associations between rsFC and treatment response. Specifically, high responders (≥50% PTSD symptom improvement), compared with low responders, had greater SN-DMN segregation (i.e., less pre-treatment amygdala-PCC connectivity; p = .011) and lower pre-treatment global centrality (p = .042). CONCLUSIONS: Our findings suggest neural abnormalities in PTSD and may inform future research examining neural biomarkers of PTSD treatment response.

11.
Int J Psychophysiol ; 155: 99-104, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32522512

RESUMO

Identifying neurobehavioral correlates of suicidal ideation can help detect those most vulnerable for suicide among high-risk groups, such as those with internalizing psychopathology. Individuals with elevated sensitivity to uncertain threat (U-threat) have a strong preference for known outcomes relative to unknown outcomes and often experience high levels of chronic distress. We therefore hypothesized that among individuals with internalizing psychopathology, those with heightened reactivity to U-threat would be especially prone to suicidal ideation as a means to escape uncertainty. The present study examined whether in two independent samples suicidal ideation was associated with heightened startle response to U-threat, and whether the effects were specific to responses U-threat relative to predictable threat (P-threat). Study 1 was a sample of treatment-seeking patients (N = 99) and Study 2 was a community sample (N = 102). Participants in both samples met current DSM-5 criteria for an anxiety and/or depressive disorder. In Study 1, current suicidal ideation was positively associated with startle potentiation to U-threat. Similarly, in Study 2, a lifetime history of suicidal ideation was positively associated with startle potentiation to U-threat. The relation between suicidal ideation and startle potentiation to U-threat remained when adjusting for number of internalizing diagnoses. Heightened reactivity to U-threat may therefore characterize those with a propensity for suicidal ideation among individuals with internalizing psychopathology.

12.
Hum Brain Mapp ; 2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32596977

RESUMO

The ENIGMA group on Generalized Anxiety Disorder (ENIGMA-Anxiety/GAD) is part of a broader effort to investigate anxiety disorders using imaging and genetic data across multiple sites worldwide. The group is actively conducting a mega-analysis of a large number of brain structural scans. In this process, the group was confronted with many methodological challenges related to study planning and implementation, between-country transfer of subject-level data, quality control of a considerable amount of imaging data, and choices related to statistical methods and efficient use of resources. This report summarizes the background information and rationale for the various methodological decisions, as well as the approach taken to implement them. The goal is to document the approach and help guide other research groups working with large brain imaging data sets as they develop their own analytic pipelines for mega-analyses.

13.
J Psychiatr Res ; 128: 83-89, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32544774

RESUMO

Structural differences in the amygdala (AMG) are implicated in anxiety and observed among individuals with generalized (GAD) and social anxiety (SAD) disorders. Findings have been mixed, perhaps because studies rarely examine differences between GAD and SAD, test comorbidity, or examine age-related differences. We tested AMG volume differences among a sample of adults and youth with/without SAD and GAD. Participants (N = 242; ages 7-60 years) completed an MRI scan, diagnostic interviews, and anxiety symptom measures. Groups were formed from diagnostic interviews: 1) Typically developing (TD; n = 91); 2) GAD (n = 53); 3) SAD (n = 35); and 4) comorbid SAD/GAD (n = 63). We used analysis of covariance with a bonferroni correction to examine group differences in AMG volume. The SAD and comorbid SAD/GAD groups exhibited increased bilateral AMG volume compared to the TD group. GAD and TD groups did not differ from each other in AMG size. The SAD, but not the comorbid SAD/GAD group, displayed greater right AMG size relative to the GAD group. SAD and comorbid SAD/GAD groups did not differ from the GAD group in left AMG volume. SAD and SAD/GAD groups did not exhibit different bilateral AMG size. Linear regression analyses demonstrated that greater social anxiety but not generalized anxiety symptom severity was associated with enlarged AMG volume. Age was not associated with AMG volume and nor did age moderate any group or symptom effects. Future longitudinal studies should examine whether larger AMG volume is a unique biomarker for SAD across the lifespan.

14.
Depress Anxiety ; 37(7): 670-681, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32306485

RESUMO

BACKGROUND: Posttraumatic stress disorder (PTSD) has been associated with exaggerated threat processing and deficits in emotion modulation circuitry. It remains unknown how neural circuits are associated with response to evidence-based treatments for PTSD. METHOD: We examined associations between PTSD symptoms and indicators of neural response in key emotion processing and modulation regions. Fifty-six military Veterans with PTSD were randomly assigned to one of three evidence-based treatments (prolonged exposure, sertraline, and PE plus sertraline) in a randomized clinical trial ("PROGrESS"; 2018, Contemp Clin Trials, 64, 128-138). Twenty-seven combat-exposed controls (CCs) served as a comparison group at pretreatment. Before and after PTSD treatment, functional magnetic resonance imaging was used to assess brain activation and connectivity during the validated Shifted Attention Emotion Appraisal Task (2003, J Neurosci, 23, 5627-5633; 2013, Biol Psychiatry, 73, 1045-1053). RESULTS: Greater activation in emotion processing (anterior insula) and modulation (prefrontal cortex) regions and increased connectivity between attentional control (dorsolateral prefrontal cortex and superior parietal cortex) and emotion processing (amygdala) regions, at pretreatment, were associated with subsequent PTSD symptom improvement. CONCLUSIONS: This study is one of the first to examine task-based activation and functional connectivity in a PTSD treatment trial, and provides evidence to suggest that activation in and connectivity between emotion processing and modulation regions are important predictors of treatment response.


Assuntos
Transtornos de Estresse Pós-Traumáticos , Tonsila do Cerebelo/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Emoções , Humanos , Imagem por Ressonância Magnética , Transtornos de Estresse Pós-Traumáticos/terapia
15.
Artigo em Inglês | MEDLINE | ID: mdl-32258423

RESUMO

In the following grant report, we describe initial and planned work supported by our National Institute of Mental Health R01-funded, Research Domain Criteria (RDoc) informed project, "Dimensional Brain Behavior Predictors of CBT Outcomes in Pediatric Anxiety". This project examines response to cognitive behavioral therapy (CBT) in a large sample of anxiety-affected and low-anxious youth ages 7 to 18 years using multiple levels of analysis, including brain imaging, behavioral performance, and clinical measures. The primary goal of the project is to understand how brain-behavioral markers of anxiety-relevant constructs, namely acute threat, cognitive control, and their interaction, associate with CBT response in youth with clinically significant anxiety. A secondary goal is to determine whether child age influences how these markers predict, and/or change, across varying degrees of CBT response. Now in its fourth year, data from this project has informed the examination of (1) baseline (i.e., pre-CBT) anxiety severity as a function of brain-behavioral measures of cognitive control, and (2) clinical characteristics of youth and parents that associate with anxiety severity and/or predict response to CBT. Analysis of brain-behavioral markers before and after CBT will assess mechanisms of CBT effect, and will be conducted once the data collection in the full sample has been completed. This knowledge will help guide the treatment of clinically anxious youth by informing for whom and how does CBT work.

16.
Psychiatry Res Neuroimaging ; 299: 111062, 2020 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-32278278

RESUMO

Posttraumatic Stress Disorder (PTSD) is a debilitating condition often associated with difficulty in emotion regulation, including reappraising negative emotions. This study assessed neural mechanisms associated with emotion regulation in veterans prior to and following treatment for PTSD. Participants with PTSD and combat exposed controls (CC) completed diagnostic evaluation and underwent fMRI scanning while completing Emotion Regulation Task (ERT) and Emotional Faces Assessment Task (EFAT). Participants with PTSD were randomly assigned to Prolonged Exposure plus placebo (PE+PLB), Sertraline plus enhanced medication management (SERT+EMM), or PE plus SERT (PE+SERT) and repeated diagnostic evaluation and MRI scanning following treatment. The amygdala, dmPFC, and dlPFC were examined as regions of interest. On ERT, veterans with PTSD showed significantly less dmPFC activation than CCs during reappraisal vs emotional maintenance. Within the PTSD group, results demonstrated a significant association between less activation in the dmPFC during emotion reappraisal vs maintenance trials before treatment and greater reductions in symptoms from pre- to post-treatment. During the EFAT, there were no group differences between participants with PTSD and CCs in brain activation, and no relationships between brain function and PTSD symptoms. These findings suggest that less emotional reactivity might potentially reflect less need for recruitment of prefrontal regions when reappraising negative emotion, and is an individual factor associated with better treatment outcome.


Assuntos
Tonsila do Cerebelo/fisiopatologia , Emoções/fisiologia , Córtex Pré-Frontal/fisiopatologia , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Adulto , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Sertralina/uso terapêutico , Resultado do Tratamento , Veteranos/psicologia
17.
Psychiatry Res Neuroimaging ; 299: 111064, 2020 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-32163837

RESUMO

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.


Assuntos
Conectoma , Transtornos do Humor/patologia , Rede Nervosa/patologia , Substância Branca/patologia , Tonsila do Cerebelo , Estudos de Coortes , Imagem de Tensor de Difusão , Feminino , Humanos , Distribuição Aleatória
18.
Psychoneuroendocrinology ; 114: 104609, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32062371

RESUMO

In major depressive disorder (MDD) and remitted MDD (rMDD) alterations in cortisol and inflammation are associated with cognitive difficulties, but these relationships have not been investigated in HIV. We used secondary data from a placebo-controlled, cross-over study of cognitive performance following a probe of the hypothalamic-pituitary-adrenal (HPA) axis (low dose hydrocortisone; LDH 10 mg) in 65 people with HIV (PWH; 36 women). Using placebo data, we examined sex-specific associations between two biomarkers - basal afternoon salivary cortisol and salivary inflammatory cytokines - cognition, and rMDD. Salivary cortisol and inflammatory biomarkers were sampled across the 5 -h study. The panel of inflammatory markers included interleukin (IL)-6, IL-8, IL-1ß, tumor necrosis factor-(TNF)-α, CRP, interferon gamma-induced protein (IP-10), monocyte chemotactic protein (MCP)-1, monokine induced by interferon (MIG), matrix metalloproteinase MMP-9, and MMP-1. Learning, memory, attention/concentration, and executive function were assessed 30 min and 4 h after the placebo intervention; visuospatial ability was also assessed 30 min after the placebo intervention. For women but not men with HIV, basal cortisol concentrations were higher in rMDD versus noMDD groups, and related to poorer learning and memory. For men and women with HIV, basal inflammatory cytokines were higher in rMDD versus noMDD groups, but were negatively related to cognition independent of rMDD status. Cortisol and cytokines relate to cognition in PWH, but the associations depended on sex, rMDD status, and their interaction.

19.
J Nerv Ment Dis ; 208(5): 397-402, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32053566

RESUMO

Aberrant threat reactivity has been implicated in the pathophysiology of posttraumatic stress disorder (PTSD); however, the literature on this association is mixed. One factor that may contribute to this inconsistent association is differences in severity of posttraumatic stress symptoms (PTSSs) across studies, but no studies have tested this hypothesis. The relation between PTSD and threat reactivity may also differ between unpredictable threats (U-threats) and predictable threats (P-threats), given burgeoning evidence to support a particular role for aberrant responding to U-threat in PTSD. The present study examined how PTSS severity relates to startle potentiation to U-threat and P-threat in a trauma-exposed community sample (N = 258). There was a negative linear, but not quadratic, relation between PTSS severity and startle potentiation to U-threat, but not P-threat. Blunted defensive responding to U-threat may therefore contribute to higher levels of PTSSs and may represent a novel treatment target for higher levels of PTSSs.

20.
Psychol Med ; 50(14): 2324-2334, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31597581

RESUMO

BACKGROUND: Little is known about the neural substrates of suicide risk in mood disorders. Improving the identification of biomarkers of suicide risk, as indicated by a history of suicide-related behavior (SB), could lead to more targeted treatments to reduce risk. METHODS: Participants were 18 young adults with a mood disorder with a history of SB (as indicated by endorsing a past suicide attempt), 60 with a mood disorder with a history of suicidal ideation (SI) but not SB, 52 with a mood disorder with no history of SI or SB (MD), and 82 healthy comparison participants (HC). Resting-state functional connectivity within and between intrinsic neural networks, including cognitive control network (CCN), salience and emotion network (SEN), and default mode network (DMN), was compared between groups. RESULTS: Several fronto-parietal regions (k > 57, p < 0.005) were identified in which individuals with SB demonstrated distinct patterns of connectivity within (in the CCN) and across networks (CCN-SEN and CCN-DMN). Connectivity with some of these same regions also distinguished the SB group when participants were re-scanned after 1-4 months. Extracted data defined SB group membership with good accuracy, sensitivity, and specificity (79-88%). CONCLUSIONS: These results suggest that individuals with a history of SB in the context of mood disorders may show reliably distinct patterns of intrinsic network connectivity, even when compared to those with mood disorders without SB. Resting-state fMRI is a promising tool for identifying subtypes of patients with mood disorders who may be at risk for suicidal behavior.

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