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1.
Brain ; 143(2): 701-710, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32040562

RESUMO

The efficacy of dopamine agonists in treating major depressive disorder has been hypothesized to stem from effects on ventrostriatal dopamine and reward function. However, an important question is whether dopamine agonists are most beneficial for patients with reward-based deficits. This study evaluated whether measures of reward processing and ventrostriatal dopamine function predicted response to the dopamine agonist, pramipexole (ClinicalTrials.gov Identifier: NCT02033369). Individuals with major depressive disorder (n = 26) and healthy controls (n = 26) (mean ± SD age = 26.5 ± 5.9; 50% female) first underwent assessments of reward learning behaviour and ventrostriatal prediction error signalling (measured using functional MRI). 11C-(+)-PHNO PET before and after oral amphetamine was used to assess ventrostriatal dopamine release. The depressed group then received open-label pramipexole treatment for 6 weeks (0.5 mg/day titrated to a maximum daily dose of 2.5 mg). Symptoms were assessed weekly, and reward learning was reassessed post-treatment. At baseline, relative to controls, the depressed group showed lower reward learning (P = 0.02), a trend towards blunted reward-related prediction error signals (P = 0.07), and a trend towards increased amphetamine-induced dopamine release (P = 0.07). Despite symptom improvements following pramipexole (Cohen's d ranging from 0.51 to 2.16 across symptom subscales), reward learning did not change after treatment. At a group level, baseline reward learning (P = 0.001) and prediction error signalling (P = 0.004) were both associated with symptom improvement, albeit in a direction opposite to initial predictions: patients with stronger pretreatment reward learning and reward-related prediction error signalling improved most. Baseline D2/3 receptor availability (P = 0.02) and dopamine release (P = 0.05) also predicted improvements in clinical functioning, with lower D2/3 receptor availability and lower dopamine release predicting greater improvements. Although these findings await replication, they suggest that measures of reward-related mesolimbic dopamine function may hold promise for identifying depressed individuals likely to respond favourably to dopaminergic pharmacotherapy.

2.
Neuroimage ; : 116656, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32068162

RESUMO

BACKGROUND: Chronic pain and mood disorders share common neuroanatomical substrates involving disruption of the reward system. Although increase in negative affect (NA) and decrease in positive affect (PA) are well-known factors complicating the clinical presentation of chronic pain patients, our understanding of the mechanisms underlying the interaction between pain and PA/NA remains limited. Here, we used a validated task probing behavioral and neural responses to monetary rewards and losses in conjunction with functional magnetic resonance imaging (fMRI) to test the hypothesis that dysfunction of the striatum, a key mesolimbic structure involved in the encoding of motivational salience, relates to mood alterations comorbid with chronic pain. METHODS: Twenty-eight chronic musculoskeletal pain patients (chronic low back pain, n=15; fibromyalgia, n=13) and 18 healthy controls underwent fMRI while performing the Monetary Incentive Delay (MID) task. Behavioral and neural responses were compared across groups and correlated against measures of depression (Beck Depression Inventory) and hedonic capacity (Snaith-Hamilton Pleasure Scale). RESULTS: Compared to controls, patients demonstrated higher anhedonia and depression scores, and a dampening of striatal activation and incentive-related behavioral facilitation (reduction in reaction times) during reward and loss trials of the MID task (ps < 0.05). In all participants, lower activation of the right striatum during reward trials was significantly correlated with lower incentive-related behavioral facilitation and higher anhedonia scores (ps < 0.05). Finally, among patients, lower bilateral striatal activation during loss trials was correlated with higher depression scores (ps < 0.05). CONCLUSIONS: In chronic pain, PA reduction and NA increase are accompanied by striatal hypofunction as measured by the MID task.

3.
Nat Biotechnol ; 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32042166

RESUMO

Antidepressants are widely prescribed, but their efficacy relative to placebo is modest, in part because the clinical diagnosis of major depression encompasses biologically heterogeneous conditions. Here, we sought to identify a neurobiological signature of response to antidepressant treatment as compared to placebo. We designed a latent-space machine-learning algorithm tailored for resting-state electroencephalography (EEG) and applied it to data from the largest imaging-coupled, placebo-controlled antidepressant study (n = 309). Symptom improvement was robustly predicted in a manner both specific for the antidepressant sertraline (versus placebo) and generalizable across different study sites and EEG equipment. This sertraline-predictive EEG signature generalized to two depression samples, wherein it reflected general antidepressant medication responsivity and related differentially to a repetitive transcranial magnetic stimulation treatment outcome. Furthermore, we found that the sertraline resting-state EEG signature indexed prefrontal neural responsivity, as measured by concurrent transcranial magnetic stimulation and EEG. Our findings advance the neurobiological understanding of antidepressant treatment through an EEG-tailored computational model and provide a clinical avenue for personalized treatment of depression.

4.
JAMA Psychiatry ; 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31895437

RESUMO

Importance: Despite the widespread awareness of functional magnetic resonance imaging findings suggesting a role for cortical connectivity networks in treatment selection for major depressive disorder, its clinical utility remains limited. Recent methodological advances have revealed functional magnetic resonance imaging-like connectivity networks using electroencephalography (EEG), a tool more easily implemented in clinical practice. Objective: To determine whether EEG connectivity could reveal neural moderators of antidepressant treatment. Design, Setting, and Participants: In this nonprespecified secondary analysis, data were analyzed from the Establishing Moderators and Biosignatures of Antidepressant Response in Clinic Care study, a placebo-controlled, double-blinded randomized clinical trial. Recruitment began July 29, 2011, and was completed December 15, 2015. A random sample of 221 outpatients with depression aged 18 to 65 years who were not taking medication for depression was recruited and assessed at 4 clinical sites. Analysis was performed on an intent-to-treat basis. Statistical analysis was performed from November 16, 2018, to May 23, 2019. Interventions: Patients received either the selective serotonin reuptake inhibitor sertraline hydrochloride or placebo for 8 weeks. Main Outcomes and Measures: Electroencephalographic orthogonalized power envelope connectivity analyses were applied to resting-state EEG data. Intent-to-treat prediction linear mixed models were used to determine which pretreatment connectivity patterns were associated with response to sertraline vs placebo. The primary clinical outcome was the total score on the 17-item Hamilton Rating Scale for Depression, administered at each study visit. Results: Of the participants recruited, 9 withdrew after first dose owing to reported adverse effects, and 221 participants (150 women; mean [SD] age, 37.8 [12.7] years) underwent EEG recordings and had high-quality pretreatment EEG data. After correction for multiple comparisons, connectome-wide analyses revealed moderation by connections within and between widespread cortical regions-most prominently parietal-for both the antidepressant and placebo groups. Greater alpha-band and lower gamma-band connectivity predicted better placebo outcomes and worse antidepressant outcomes. Lower connectivity levels in these moderating connections were associated with higher levels of anhedonia. Connectivity features that moderate treatment response differentially by treatment group were distinct from connectivity features that change from baseline to 1 week into treatment. The group mean (SD) score on the 17-item Hamilton Rating Scale for Depression was 18.35 (4.58) at baseline and 26.14 (30.37) across all time points. Conclusions and Relevance: These findings establish the utility of EEG-based network functional connectivity analyses for differentiating between responses to an antidepressant vs placebo. A role emerged for parietal cortical regions in predicting placebo outcome. From a treatment perspective, capitalizing on the therapeutic components leading to placebo response differentially from antidepressant response should provide an alternative direction toward establishing a placebo signature in clinical trials, thereby enhancing the signal detection in randomized clinical trials. Trial Registration: ClinicalTrials.gov identifier: NCT01407094.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31931509

RESUMO

Nicotine enhances the reinforcement of non-drug rewards by increasing nucleus accumbens (NAcc) reactivity to anticipatory cues. This anticipatory effect is selective as no clear evidence has emerged showing that nicotine acutely changes reward receipt reactivity. However, repeated rewarding experiences shift peak brain reactivity from hedonic reward outcome to the motivational anticipatory cue yielding more habitual cue-induced behavior. Given nicotine's influence on NAcc reactivity and connectivity, it is plausible that nicotine acutely induces this shift and alters NAcc functional connectivity during reward processing. To evaluate this currently untested hypothesis, a randomized crossover design was used in which healthy non-smokers were administered placebo and nicotine (2-mg lozenge). Brain activation to monetary reward anticipation and outcome was evaluated with functional magnetic resonance imaging. Relative to placebo, nicotine induced more NAcc reactivity to reward anticipation. Greater NAcc activation during anticipation was significantly associated with lower NAcc activation to outcome. During outcome, nicotine reduced NAcc functional connectivity with cortical regions including the anterior cingulate cortex, orbitofrontal cortex, and insula. These regions showed the same negative relationship between reward anticipation and outcome as noted in the NAcc. The current findings significantly improve our understanding of how nicotine changes corticostriatal circuit function and communication during distinct phases of reward processing and critically show that these alterations happen acutely following a single dose. The implications of this work explain nicotinic modulation of general reward function, which offer insights into the initial drive to smoke and the subsequent difficulty in cessation.

6.
Harv Rev Psychiatry ; 28(1): 1-3, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31913977
7.
Brain Behav ; 10(1): e01485, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31773917

RESUMO

BACKGROUND: Childhood maltreatment may contribute to brain alterations in posttraumatic stress disorder (PTSD). We previously found that PTSD was associated with white matter compromise, or lower fractional anisotropy (FA), in the left inferior longitudinal fasciculus (ILF). In this study, including non-PTSD controls, we examined whether ILF FA was associated with maltreatment exposures, including those that meet DSM-IV criterion A (physical abuse, sexual abuse) and those that typically do not (emotional abuse, emotional neglect, physical neglect). We hypothesized that lower FA would be associated with PTSD diagnosis and with both categories of maltreatment. METHODS: Ninety-three participants (51 female), ages 20-50, were enrolled, including 32 with lifetime DSM-IV PTSD, 27 trauma-exposed non-PTSD controls, and 34 healthy controls. Participants completed structured interviews, the Childhood Trauma Questionnaire (CTQ), and diffusion-weighted imaging (36 directions). Probabilistic tractography (using FreeSurfer's TRACULA) was used to assess diffusion metrics in the ILF. RESULTS: Contrary to our hypothesis, there was no significant effect of diagnostic group on FA. In contrast, higher CTQ scores were significantly associated with lower FA in the ILF bilaterally. This association of maltreatment with lower FA remained statistically significant after controlling for diagnostic group, and it was significant for both criterion-A-type and noncriterion-A-type maltreatment categories. CONCLUSIONS: This work contributes to a growing body of literature indicating that different forms of childhood maltreatment are associated with altered white matter microstructure in the ILF, an association pathway involved in integrating visual information from occipital regions with emotion processing functions of the anterior temporal lobe.

8.
Mol Psychiatry ; 25(2): 283-296, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31745239

RESUMO

Adverse posttraumatic neuropsychiatric sequelae (APNS) are common among civilian trauma survivors and military veterans. These APNS, as traditionally classified, include posttraumatic stress, postconcussion syndrome, depression, and regional or widespread pain. Traditional classifications have come to hamper scientific progress because they artificially fragment APNS into siloed, syndromic diagnoses unmoored to discrete components of brain functioning and studied in isolation. These limitations in classification and ontology slow the discovery of pathophysiologic mechanisms, biobehavioral markers, risk prediction tools, and preventive/treatment interventions. Progress in overcoming these limitations has been challenging because such progress would require studies that both evaluate a broad spectrum of posttraumatic sequelae (to overcome fragmentation) and also perform in-depth biobehavioral evaluation (to index sequelae to domains of brain function). This article summarizes the methods of the Advancing Understanding of RecOvery afteR traumA (AURORA) Study. AURORA conducts a large-scale (n = 5000 target sample) in-depth assessment of APNS development using a state-of-the-art battery of self-report, neurocognitive, physiologic, digital phenotyping, psychophysical, neuroimaging, and genomic assessments, beginning in the early aftermath of trauma and continuing for 1 year. The goals of AURORA are to achieve improved phenotypes, prediction tools, and understanding of molecular mechanisms to inform the future development and testing of preventive and treatment interventions.

9.
Psychophysiology ; 57(2): e13473, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31536142

RESUMO

Appropriately adjusting to errors is essential for adaptive behavior. Post-error slowing (PES) refers to the increased reaction times on trials following incorrect relative to correct responses. PES has been used as a metric of cognitive control in basic cognitive neuroscience research as well as clinical contexts. However, calculation of PES varies widely among studies and has not yet been standardized, despite recent calls to optimize its measurement. Here, using behavioral and electrophysiological data from a modified flanker task, we considered different methods of calculating PES, assessed their internal consistency, examined their convergent correlations with behavioral performance and error-related event-related brain potentials (ERPs), and evaluated their sensitivity to task demands (e.g., presence of trial-to-trial feedback). Results indicated that the so-called robust measure of PES, calculated using only error-surrounding trials, provided an estimate of PES that was three times larger in magnitude than the traditional calculation. This robust PES correlated with the amplitude of the error positivity (Pe), an index of attention allocation to errors, just as well as the traditional method. However, all PES estimates had very weak internal consistency. Implications for measurement are discussed.

10.
Psychophysiology ; 57(2): e13483, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31578740

RESUMO

Prior research has identified two resting EEG biomarkers with potential for predicting functional outcomes in depression: theta current density in frontal brain regions (especially rostral anterior cingulate cortex) and alpha power over posterior scalp regions. As little is known about the discriminant and convergent validity of these putative biomarkers, a thorough evaluation of these psychometric properties was conducted toward the goal of improving clinical utility of these markers. Resting 71-channel EEG recorded from 35 healthy adults at two sessions (1-week retest) were used to systematically compare different quantification techniques for theta and alpha sources at scalp (surface Laplacian or current source density [CSD]) and brain (distributed inverse; exact low resolution electromagnetic tomography [eLORETA]) level. Signal quality was evaluated with signal-to-noise ratio, participant-level spectra, and frequency PCA covariance decomposition. Convergent and discriminant validity were assessed within a multitrait-multimethod framework. Posterior alpha was reliably identified as two spectral components, each with unique spatial patterns and condition effects (eyes open/closed), high signal quality, and good convergent and discriminant validity. In contrast, frontal theta was characterized by one low-variance component, low signal quality, lack of a distinct spectral peak, and mixed validity. Correlations between candidate biomarkers suggest that posterior alpha components constitute reliable, convergent, and discriminant biometrics in healthy adults. Component-based identification of spectral activity (CSD/eLORETA-fPCA) was superior to fixed, a priori frequency bands. Improved quantification and conceptualization of frontal theta is necessary to determine clinical utility.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31784354

RESUMO

BACKGROUND: Theoretical models have emphasized systems-level abnormalities in major depressive disorder (MDD). For unbiased yet rigorous evaluations of pathophysiological mechanisms underlying MDD, it is critically important to develop data-driven approaches that harness whole-brain data to classify MDD and evaluate possible normalizing effects of targeted interventions. Here, using an experimental therapeutics approach coupled with machine learning, we investigated the effect of a pharmacological challenge aiming to enhance dopaminergic signaling on whole-brain response to reward-related stimuli in MDD. METHODS: Using a double-blind, placebo-controlled design, we analyzed functional magnetic resonance imaging data from 31 unmedicated MDD participants receiving a single dose of 50 mg amisulpride (MDDAmisulpride), 26 MDD participants receiving placebo (MDDPlacebo), and 28 healthy control subjects receiving placebo (HCPlacebo) recruited through two independent studies. An importance-guided machine learning technique for model selection was used on whole-brain functional magnetic resonance imaging data probing reward anticipation and consumption to identify features linked to MDD (MDDPlacebo vs. HCPlacebo) and dopaminergic enhancement (MDDAmisulpride vs. MDDPlacebo). RESULTS: Highly predictive classification models emerged that distinguished MDDPlacebo from HCPlacebo (area under the curve = 0.87) and MDDPlacebo from MDDAmisulpride (area under the curve = 0.89). Although reward-related striatal activation and connectivity were among the most predictive features, the best truncated models based on whole-brain features were significantly better relative to models trained using striatal features only. CONCLUSIONS: Results indicate that in MDD, enhanced dopaminergic signaling restores abnormal activation and connectivity in a widespread network of regions. These findings provide new insights into the pathophysiology of MDD and pharmacological mechanism of antidepressants at the system level in addressing reward processing deficits among depressed individuals.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31680163

RESUMO

Adolescents strive for peer approval, and an increased sensitivity to peers' opinions is normative. However, among vulnerable adolescents, peer evaluation can be detrimental, contributing to affective disorders. It is, therefore, critical to improve our understanding of neural underpinnings of peer evaluation. Prior research has investigated averaged neural responses to peer acceptance or rejection, neglecting to probe trial-by-trial computations that mirror real-time updating of daily activities. In non-social decision making, a common neural valuation system centered on the medial prefrontal cortex (mPFC) has emerged, which evaluates different reward types on a common scale to guide choices. However, it is unclear whether the mPFC also tracks complex social scenarios involving peer feedback. To address this gap, we acquired fMRI data from 55 healthy adolescents during the Chatroom Task, which probes peer evaluation, and implemented a computational approach to characterize trial-by-trial social value, thereby allowing us to interrogate the neural correlates of social value. Consistent with our hypothesis, social value signals were encoded in the mPFC. Interestingly, analyses also revealed a wider social-specific valuation network including the precuneus and amygdala. Understanding how adolescents make social decisions and neural markers associated with it, may, ultimately, help us clarify promising targets for intervention.

13.
Biol Psychiatry ; 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31672243

RESUMO

BACKGROUND: Maladaptive approach-avoidance behavior has been implicated in the pathophysiology of major depressive disorder (MDD), but the neural basis of these abnormalities in decision making remains unclear. Capitalizing on recent preclinical findings, we adapted an approach-avoidance conflict task from nonhuman primate research for use in human functional magnetic resonance imaging (fMRI). METHODS: Forty-two female participants, including 18 unmedicated individuals with current MDD (mean age 25.2 ± 5.1 years) and 24 psychiatrically healthy control subjects (mean age 26.3 ± 7.6 years) completed the adapted approach-avoidance task during fMRI. To probe potential mechanistic factors underlying the observed behavioral and fMRI findings and to inform interpretation of putative group differences, we examined electrophysiological data from 2 female Macaca mulatta monkeys performing the approach-avoidance conflict task mimicked in the fMRI study. RESULTS: Findings demonstrated congruent neural correlates of approach-avoidance conflict and aversive responsiveness in the anterior cingulate cortex, including the pregenual cortex, of human subjects and macaques (humans: p < .05 whole-brain corrected; macaques: p < .05). The MDD group exhibited aberrant task-related activations in the anterior cingulate cortex, prefrontal cortex, and striatum (all ps < .05). Neural effects in the MDD group were cross-sectionally associated with stress and depressive symptoms. Importantly, they also prospectively predicted stress at 6-month follow-up (all ps < .05). CONCLUSIONS: Findings indicate that there is conservation of anterior cingulate activation across species and that frontal and striatal regions, in unmedicated humans with MDD, are abnormally responsive during cost-benefit decision making. We suggest that these disruptions could be valuable candidates for translational biomarkers.

14.
Psychol Med ; : 1-9, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31615590

RESUMO

BACKGROUND: Preclinical and human studies suggest an association between chronic inflammation and the development of depressive behaviors. This is proposed to occur through downstream effects of inflammatory cytokines on neuroplasticity, neurogenesis and neurotransmitter function, although the neural correlates remain poorly understood in humans. METHODS: In Study 1, structural magnetic resonance imaging and serum inflammatory cytokine data were analyzed from 53 psychiatrically healthy female participants. Correlational analyses were conducted between interleukin-6 (IL-6) and volume in a priori regions implicated in the pathophysiology of major depressive disorder (MDD). In Study 2, medical data [including serum inflammatory acute phase reactants (C-reactive protein)] were analyzed for 12 589 participants. Participants were classified as having (n = 2541) v. not having (n = 10 048) probable lifetime MDD using phenotypes derived using machine-learning approaches. Non-parametric analyses compared inflammation between groups, whereas regression analyses probed whether inflammation predicted probable MDD classification while accounting for other variables. RESULTS: In Study 1, significant negative correlations emerged between IL-6 and hippocampal, caudate, putamen and amygdalar volume. In Study 2, the MDD group showed a higher probability of elevated inflammation than the non-MDD group. Moreover, elevated inflammation was a significant predictor of probable MDD classification. CONCLUSIONS: Findings indicate that inflammation is cross-sectionally related to reduced volume in brain regions implicated in MDD phenotypes among a sample of psychiatrically healthy women, and is associated with the presence of probable MDD in a large clinical dataset. Future investigations may identify specific inflammatory markers predicting first MDD onset.

15.
Transl Psychiatry ; 9(1): 236, 2019 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-31537779

RESUMO

Investigations of pathophysiological mechanisms implicated in vulnerability to depression have been negatively impacted by the significant heterogeneity characteristic of psychiatric syndromes. Such challenges are also reflected in numerous null findings emerging from genome-wide association studies (GWAS) of depression. Bolstered by increasing sample sizes, recent GWAS studies have identified genetics variants linked to MDD. Among them, Okbay and colleagues (Nat. Genet. 2016 Jun;48(6):624-33) identified genetic variants associated with three well-validated depression-related phenotypes: subjective well-being, depressive symptoms, and neuroticism. Despite this progress, little is known about psychopathological and neurobiological mechanisms underlying such risk. To fill this gap, a genetic risk score (GRS) was computed from the Okbay's study for a sample of 88 psychiatrically healthy females. Across two sessions, participants underwent two well-validated psychosocial stressors, and performed two separate tasks probing reward learning both before and after stress. Analyses tested whether GRS scores predicted anhedonia-related phenotypes across three units of analyses: self-report (Snaith Hamilton Pleasure Scale), behavior (stress-induced changes in reward learning), and circuits (stress-induced changes in striatal reward prediction error; striatal volume). GRS scores were negatively associated with anhedonia-related phenotypes across all units of analyses but only circuit-level variables were significant. In addition, the amount of explained variance was systematically larger as variables were putatively closer to the effects of genes (self-report < behavior < neural circuitry). Collectively, findings implicate anhedonia-related phenotypes and neurobiological mechanisms in increased depression vulnerability, and highlight the value of focusing on fundamental dimensions of functioning across different units of analyses.

16.
Neuropsychobiology ; 78(4): 229-237, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31553999

RESUMO

BACKGROUND: Borderline personality disorder (BPD) and bipolar II disorder (BD II) have significant clinical overlap, leaving the potential for diagnostic inaccuracies and inadequate treatment recommendations. However, few studies have probed for clinical and neurobiological differences between the two disorders. Clinically, some prior studies have linked BPD with greater impulsivity and more frequent negative affective shifts than BD II, whereas previous neuroimaging studies have highlighted both similar and distinct neural abnormalities in BPD and BD II. Notably, no prior study has specifically targeted cortico-limbic neural differences, which have been hypothesized to underlie these core clinical differences. METHODS: Individuals with BPD (n = 14) and BD II (n = 15) completed various clinical measures and a resting state functional imaging scan at 3T. Whole-brain amygdala resting state functional connectivity (RSFC) was compared between the two groups. RESULTS: Relative to the BD II group, BPD participants reported significantly higher levels of impulsivity, trait anxiety, more frequent negative affective shifts, greater interpersonally reactive affective instability, lower overall functioning, and were characterized by lower amygdala-middle frontal gyrus RSFC. Lower amygdala-middle frontal gyrus RSFC was associated with greater impulsivity, trait anxiety, affective shifts, interpersonal affective reactivity, and functional impairment. LIMITATIONS: The current study consisted of small sample sizes and lacked a control group. CONCLUSIONS: This preliminary study suggests that amygdala-frontal RSFC may distinguish BPD from BD II. These results may guide future work aimed at identifying neural markers that can help disentangle these two disorders, leading to greater diagnostic accuracy and appropriate treatment implementation.

17.
eNeuro ; 6(4)2019.
Artigo em Inglês | MEDLINE | ID: mdl-31346001

RESUMO

Approach-avoidance conflict arises when the drives to pursue reward and avoid harm are incompatible. Previous neuroimaging studies of approach-avoidance conflict have shown large variability in reported neuroanatomical correlates. These prior studies have generally neglected to account for potential sources of variability, such as individual differences in choice preferences and modeling of hemodynamic response during conflict. In the present study, we controlled for these limitations using a hierarchical Bayesian model (HBM). This enabled us to measure participant-specific per-trial estimates of conflict during an approach-avoidance task. We also employed a variable epoch method to identify brain structures specifically sensitive to conflict. In a sample of 28 human participants, we found that only a limited set of brain structures [inferior frontal gyrus (IFG), right dorsolateral prefrontal cortex (dlPFC), and right pre-supplementary motor area (pre-SMA)] are specifically correlated with approach-avoidance conflict. These findings suggest that controlling for previous sources of variability increases the specificity of the neuroanatomical correlates of approach-avoidance conflict.

18.
Psychol Med ; : 1-10, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31280757

RESUMO

BACKGROUND: Cognitive deficits in depressed adults may reflect impaired decision-making. To investigate this possibility, we analyzed data from unmedicated adults with Major Depressive Disorder (MDD) and healthy controls as they performed a probabilistic reward task. The Hierarchical Drift Diffusion Model (HDDM) was used to quantify decision-making mechanisms recruited by the task, to determine if any such mechanism was disrupted by depression. METHODS: Data came from two samples (Study 1: 258 MDD, 36 controls; Study 2: 23 MDD, 25 controls). On each trial, participants indicated which of two similar stimuli was presented; correct identifications were rewarded. Quantile-probability plots and the HDDM quantified the impact of MDD on response times (RT), speed of evidence accumulation (drift rate), and the width of decision thresholds, among other parameters. RESULTS: RTs were more positively skewed in depressed v. healthy adults, and the HDDM revealed that drift rates were reduced-and decision thresholds were wider-in the MDD groups. This pattern suggests that depressed adults accumulated the evidence needed to make decisions more slowly than controls did. CONCLUSIONS: Depressed adults responded slower than controls in both studies, and poorer performance led the MDD group to receive fewer rewards than controls in Study 1. These results did not reflect a sensorimotor deficit but were instead due to sluggish evidence accumulation. Thus, slowed decision-making-not slowed perception or response execution-caused the performance deficit in MDD. If these results generalize to other tasks, they may help explain the broad cognitive deficits seen in depression.

19.
J Affect Disord ; 256: 8-16, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31158720

RESUMO

BACKGROUND: Our lab has previously found that structural integrity in tracts from the raphe nucleus (RN) to the amygdala, measured by fractional anisotropy (FA), predicts remission to selective serotonin reuptake inhibitors (SSRIs) in major depressive disorder (MDD). This could potentially serve as a biomarker for remission that can guide clinical decision-making. To enhance repeatability and reproducibility, we replicated our study in a larger, more representative multi-site sample. METHODS: 64 direction DTI was collected in 144 medication-free patients with MDD from the Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) study. We performed probabilistic tractography between the RN and bilateral amygdala and hippocampus and calculated weighted FA in these tracts. Patients were treated with either sertraline or placebo, and their change in Hamilton Depression Rating Scale (HDRS) score reported. Pretreatment weighted FA was compared between remitters and nonremitters, and correlation between FA and percent change in HDRS score was assessed. Exploratory moderator and voxel analyses were also performed. RESULTS: Contrary to our hypotheses, FA was greater in nonremitters than in remitters in RN-left and right amygdala tracts (p = 0.02 and 0.01, respectively). Pretreatment FA between the raphe and left amygdala correlated with greater, not reduced, HDRS (r = 0.18, p = 0.04). This finding was found to be greater in the placebo group. Moderator and voxel analyses yielded no significant findings. CONCLUSIONS: We found greater FA in nonremitters between the RN and amygdala than in remitters, and a correlation between FA and symptom worsening, particularly with placebo. These findings may help reveal more about the nature of MDD, as well as guide research methods involving placebo response.

20.
Artigo em Inglês | MEDLINE | ID: mdl-31155512

RESUMO

BACKGROUND: Adolescence is a developmental period in which depression and related mood syndromes often emerge, but few objective markers exist to guide diagnosis or predict symptoms. One potential mood marker is the functioning of frontoinsular networks, which undergo substantial development in adolescence and have been implicated in adult depression. To test this hypothesis, we used task-based neuroimaging to evaluate whether frontoinsular network dysfunction was linked to current and prospective mood health in adolescents. METHODS: Adolescents (n = 40, 13-19 years of age) reporting varying levels of depressive symptom severity performed an emotional working memory task with neuroimaging. Next, teens completed a 2-week follow-up consisting of a daily diary report of negative affect and final report of depressive symptoms (n = 28 adherent). Analyses tested associations between task-related functional connectivity in frontoinsular networks and baseline or prospective measures of mood health over 2-week follow-up. RESULTS: Frontoinsular task response was associated with higher current depression severity (p = .049, ηp2 = .12), increases in future depression severity (p = .018, ηp2 = .23), and more intense and labile negative affect in daily life (ps = .015 to .040, ηp2 = .22 to .30). In particular, hypoconnectivity between insula and lateral prefrontal regions of the frontoparietal network was related to both baseline and prospective mood health, and hyperconnectivity between insula and midline or temporal regions of the default network was related to prospective mood health. CONCLUSIONS: These findings indicate that frontoinsular imbalances are related to both current depression and changes in mood health in the near future and suggest that frontoinsular markers may hold promise as translational tools for risk prediction.

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