Showing papers by "Diego A. Pizzagalli published in 2015"
TL;DR: A meta-analysis of rsFC studies provides an empirical foundation for a neurocognitive model in which network dysfunction underlies core cognitive and affective abnormalities in depression.
Abstract: Importance Major depressive disorder (MDD) has been linked to imbalanced communication among large-scale brain networks, as reflected by abnormal resting-state functional connectivity (rsFC). However, given variable methods and results across studies, identifying consistent patterns of network dysfunction in MDD has been elusive. Objective To investigate network dysfunction in MDD through a meta-analysis of rsFC studies. Data Sources Seed-based voxelwise rsFC studies comparing individuals with MDD with healthy controls (published before June 30, 2014) were retrieved from electronic databases (PubMed, Web of Science, and EMBASE) and authors contacted for additional data. Study Selection Twenty-seven seed-based voxel-wise rsFC data sets from 25 publications (556 individuals with MDD and 518 healthy controls) were included in the meta-analysis. Data Extraction and Synthesis Coordinates of seed regions of interest and between-group effects were extracted. Seeds were categorized into seed-networks by their location within a priori functional networks. Multilevel kernel density analysis of between-group effects identified brain systems in which MDD was associated with hyperconnectivity (increased positive or reduced negative connectivity) or hypoconnectivity (increased negative or reduced positive connectivity) with each seed-network. Results Major depressive disorder was characterized by hypoconnectivity within the frontoparietal network, a set of regions involved in cognitive control of attention and emotion regulation, and hypoconnectivity between frontoparietal systems and parietal regions of the dorsal attention network involved in attending to the external environment. Major depressive disorder was also associated with hyperconnectivity within the default network, a network believed to support internally oriented and self-referential thought, and hyperconnectivity between frontoparietal control systems and regions of the default network. Finally, the MDD groups exhibited hypoconnectivity between neural systems involved in processing emotion or salience and midline cortical regions that may mediate top-down regulation of such functions. Conclusions and Relevance Reduced connectivity within frontoparietal control systems and imbalanced connectivity between control systems and networks involved in internal or external attention may reflect depressive biases toward internal thoughts at the cost of engaging with the external world. Meanwhile, altered connectivity between neural systems involved in cognitive control and those that support salience or emotion processing may relate to deficits regulating mood. These findings provide an empirical foundation for a neurocognitive model in which network dysfunction underlies core cognitive and affective abnormalities in depression.
1,385 citations
TL;DR: New evidence of reward processing abnormalities in MDD, bipolar disorder and schizophrenia has led to a greater understanding of the neural processes associated with symptomatology common across these conditions, andsecting various subcomponents of rewardprocessing that map onto partially different neurobiological pathways and investigating their dysregulation in different psychiatric disorders holds promise for developing more targeted, and hopefully efficacious treatment and intervention strategies.
Abstract: Purpose of reviewThis article reviews the recent literature on reward processing dysfunction in major depression (MDD), bipolar disorder and schizophrenia, with a focus on approach motivation, reward learning and reward-based decision-making.Recent findingsEmerging evidence indicates the presence of
549 citations
TL;DR: Findings are consistent with preclinical models suggesting that the dentate gyrus and mPFC are especially vulnerable to stress exposure and provide evidence for morphometric changes that are consistency with stress-sensitization models of recurrence in MDD.
243 citations
TL;DR: Improved understanding of precise reward-related dysfunctions in depression promises to improve diagnostic and therapeutic efforts in depression.
Abstract: Anhedonia - diminished pleasure and/or decreased reactivity to pleasurable stimuli - is a core feature of depression that frequently persists after treatment. As a result, extensive effort has been directed towards characterizing the psychological and biological processes that mediate dysfunctional reward processing in depression. Reward processing can be parsed into sub-components that include motivation, reinforcement learning, and hedonic capacity, which, according to preclinical and neuroimaging evidence, involve partially dissociable brain systems. In line with this, recent findings indicate that behavioral impairments and neural abnormalities in depression vary across distinct reward-related constructs. Ultimately, improved understanding of precise reward-related dysfunctions in depression promises to improve diagnostic and therapeutic efforts in depression.
210 citations
TL;DR: Attentional control appears to impact depression and anxiety symptoms through rumination, and interventions targeting attentional control may decrease maladaptive ruminative processes, leading to improved emotion regulation and reduced clinical symptomatology.
101 citations
TL;DR: Findings suggest that the P1 and LPP reflect biased self-referential processing in female adolescents with depression, which is associated with a more maladaptive self-view and self-criticism.
Abstract: Despite the alarming increase in the prevalence of depression during adolescence, particularly among female adolescents, the pathophysiology of depression in adolescents remains largely unknown. Event-related potentials (ERPs) provide an ideal approach to investigate cognitive-affective processes associated with depression in adolescents, especially in the context of negative self-referential processing biases. In this study, healthy (n = 30) and depressed (n = 22) female adolescents completed a self-referential encoding task while ERP data were recorded. To examine cognitive-affective processes associated with self-referential processing, P1, P2, and late positive potential (LPP) responses to negative and positive words were investigated, and intracortical sources of scalp effects were probed using Low Resolution Electromagnetic Tomography (LORETA). Additionally, we tested whether key cognitive processes (e.g., maladaptive self-view, self-criticism) previously implicated in depression related to ERP components. Relative to healthy female subjects, depressed females endorsed more negative and fewer positive words, and free recalled and recognized fewer positive words. With respect to ERPs, compared to healthy female adolescents, depressed adolescents exhibited greater P1 amplitudes following negative words, which was associated with a more maladaptive self-view and self-criticism. In both early and late LPP responses, depressed females showed greater activity following negative versus positive words, whereas healthy females demonstrated the opposite pattern. For both P1 and LPP, LORETA revealed reduced inferior frontal gyrus activity in response to negative words in depressed versus healthy female adolescents. Collectively, these findings suggest that the P1 and LPP reflect biased self-referential processing in female adolescents with depression. Potential treatment implications are discussed.
98 citations
TL;DR: Enhanced conformity between cross-species tasks will facilitate investigation of the neurobiological mechanisms underlying discrete reward and motivated behaviors and is expected to improve the understanding and treatment of neuropsychiatric disorders characterized by reward and motivation deficits.
Abstract: Deficits in reward and motivation are common symptoms characterizing several psychiatric and neurological disorders. Such deficits may include anhedonia, defined as loss of pleasure, as well as impairments in anticipatory pleasure, reward valuation, motivation/effort, and reward learning. This chapter describes recent advances in the development of behavioral tasks used to assess different aspects of reward processing in both humans and non-human animals. While earlier tasks were generally developed independently with limited cross-species correspondence, a newer generation of translational tasks has emerged that are theoretically and procedurally analogous across species and allow parallel testing, data analyses, and interpretation between human and rodent behaviors. Such enhanced conformity between cross-species tasks will facilitate investigation of the neurobiological mechanisms underlying discrete reward and motivated behaviors and is expected to improve our understanding and treatment of neuropsychiatric disorders characterized by reward and motivation deficits.
87 citations
TL;DR: Striatal hypersensitivity during stress might constitute a trait mark of depression, providing a potential neural substrate for the interaction between stress and reward dysfunction in MDD.
63 citations
TL;DR: The caudate is identified as a region with dissociable incentive-dependent dACC connectivity abnormalities in major depressive disorder, and initial evidence that cortico-striatal circuitry may play a role in MDD treatment response is provided.
Abstract: Background
Individuals with major depressive disorder (MDD) are characterized by maladaptive responses to both positive and negative outcomes, which have been linked to localized abnormal activations in cortical and striatal brain regions However, the exact neural circuitry implicated in such abnormalities remains largely unexplored
62 citations
TL;DR: FMRI captures the acute affective and neural responses to naturalistic positive mood induction, as well as their spontaneous fluctuations during resting states, and suggests that corticostriatal pathways contribute to the natural time course of positive mood fluctuations, while disturbances of those neural interactions may characterize mood disorder.
Abstract: The natural time course of mood includes both acute responses to stimuli and spontaneous fluctuations. To date, neuroimaging studies have focused on either acute affective responses or spontaneous neural fluctuations at rest but no prior study has concurrently probed both components, or how mood disorders might modulate these processes. Here, using fMRI, we capture the acute affective and neural responses to naturalistic positive mood induction, as well as their spontaneous fluctuations during resting states. In both healthy controls and individuals with a history of depression, our manipulation acutely elevates positive mood and ventral striatum activation. Only controls, however, sustain positive mood over time, and this effect is accompanied by the emergence of a reciprocal relationship between the ventral striatum and medial prefrontal cortex during ensuing rest. Findings suggest that corticostriatal pathways contribute to the natural time course of positive mood fluctuations, while disturbances of those neural interactions may characterize mood disorder.
59 citations
TL;DR: The current findings show that the intensity of nicotine craving is linked to lower sensitivity to non-drug rewards, in line with prior theories that suggest reward dysfunction in some clinical populations may facilitate nicotine use.
TL;DR: Melancholia is characterised by a reduced ability to modulate behaviour as a function of reward, and the motivational salience of rewarding stimuli may differ across depressive sub-types.
TL;DR: Executive control was delayed in depression but this was counterbalanced by reduced prepotent response bias, demonstrating how participants with executive function deficits can nevertheless perform accurately in a cognitive control task.
Abstract: Background. Depression is characterized by poor executive function, but – counterintuitively – in some studies, it has been associated with highly accurate performance on certain cognitively demanding tasks. The psychological mechanisms responsible for this paradoxical finding are unclear. To address this issue, we applied a drift diffusion model (DDM) to flanker task data from depressed and healthy adults participating in the multi-site Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for Depression (EMBARC) study. Method. One hundred unmedicated, depressed adults and 40 healthy controls completed a flanker task. We investigated the effect of flanker interference on accuracy and response time, and used the DDM to examine group differences in three cognitive processes: prepotent response bias (tendency to respond to the distracting flankers), response inhibition (necessary to resist prepotency), and executive control (required for execution of correct response on incongruent trials). Results. Consistent with prior reports, depressed participants responded more slowly and accurately than controls on incongruent trials. The DDM indicated that although executive control was sluggish in depressed participants, this was more than offset by decreased prepotent response bias. Among the depressed participants, anhedonia was negatively correlated with a parameter indexing the speed of executive control (r=�0.28, p = 0.007). Conclusions. Executive control was delayed in depression but this was counterbalanced by reduced prepotent response bias, demonstrating how participants with executive function deficits can nevertheless perform accurately in a cognitive control task. Drawing on data from neural network simulations, we speculate that these results may reflect tonically reduced striatal dopamine in depression.
TL;DR: This hypothesis that sensitivity for negative feedback is potentiated in moderate MDD, but reduced in highly anhedonic subjects is tested by analyzing the feedback‐related negativity, frontomedial theta power, and source‐localized anterior midcingulate cortex activity after negative feedback.
Abstract: Background
Although cognitive theories of depression have postulated enhanced processing of negatively valenced information, previous EEG studies have shown both increased and reduced sensitivity for negative performance feedback in MDD. To reconcile these paradoxical findings, it has been speculated that sensitivity for negative feedback is potentiated in moderate MDD, but reduced in highly anhedonic subjects. The goal of this study was to test this hypothesis by analyzing the feedback-related negativity (FRN), frontomedial theta power (FMT), and source-localized anterior midcingulate cortex (aMCC) activity after negative feedback.
Methods
Fourteen unmedicated participants with Major Depressive Disorder (MDD) and 15 control participants performed a reinforcement learning task while 128-channel Electroencephalogram (EEG) was recorded. FRN, FMT, and LORETA source-localized aMCC activity after negative and positive feedback were compared between groups.
Results
The MDD group showed higher FRN amplitudes and aMCC activation to negative feedback than controls. Moreover, aMCC activation to negative feedback was inversely related to self-reported anhedonia. In contrast, self-reported anxiety correlated with feedback-evoked frontomedial theta (FMT) within the depression group.
Conclusions
The present findings suggest that, among depressed and anxious individuals, enhanced processing of negative feedback occurs relatively early in the information processing stream. These results extend prior work and indicate that although moderate depression is associated with elevated sensitivity for negative feedback, high levels of anhedonia may attenuate this effect.
TL;DR: The aim was to identify emotion‐processing biases in depressed adolescents and examine neural abnormalities related to these biases using high‐density resting EEG and source localization.
Abstract: Background: Although theorists have posited that adolescent depression is characterized by emotion-processing biases (greater propensity to identify sad than happy facial expressions), findings have been mixed. Additionally, the neural correlates associated with putative emotion-processing biases remain largely unknown. Our aim was to identify emotion-processing biases in depressed adolescents and examine neural abnormalities related to these biases using high-density resting EEG and source localization. Methods: Healthy (n = 36) and depressed (n = 23) female adolescents, aged 13–18 years, completed a facial recognition task in which they identified happy, sad, fear, and angry expressions across intensities from 10% (low) to 100% (high). Additionally, 128-channel resting (i.e., task-free) EEG was recorded and analyzed using a distributed source localization technique (low-resolution electromagnetic tomography (LORETA)). Given research implicating the dorsolateral prefrontal cortex (DLPFC) in depression and emotion processing, analyses focused on this region. Results: Relative to healthy youth, depressed adolescents were more accurate for sad and less accurate for happy, particularly low-intensity happy faces. No differences emerged for fearful or angry facial expressions. Further, LORETA analyses revealed greater theta and alpha current density (i.e., reduced brain activity) in depressed versus healthy adolescents, particularly in the left DLPFC (BA9/BA46). Theta and alpha current density were positively correlated, and greater current density predicted reduced accuracy for happy faces. Conclusion: Depressed female adolescents were characterized by emotion-processing biases in favor of sad emotions and reduced recognition of happiness, especially when cues of happiness were subtle. Blunted recognition of happy was associated with left DLPFC resting hypoactivity. Depression and Anxiety 32:693–701, 2015. C
TL;DR: Depressed individuals experiencing greater recent life stress recruited the mPFC more under stress when processing rewards, an initial step toward elucidating mechanisms underlying stress sensitization and recurrence in depression.
TL;DR: Low prevalence of smoking in OCD may be familial and unique among psychiatric disorders, and might represent a possible state-independent OCD marker.
TL;DR: It is possible that nicotine normalizes the otherwise blunted reward responsiveness in individuals with rMDD, and therapies aimed at enhancing this reward-based deficit may be beneficial in the treatment of both nicotine dependence and MDD.
TL;DR: Depression has been associated with poor performance following errors, but the clinical implications, response to treatment and neurobiological mechanisms of this post-error behavioral adjustment abnormality remain unclear.
Abstract: Depression has been associated with poor performance following errors, but the clinical implications, response to treatment and neurobiological mechanisms of this post-error behavioral adjustment abnormality remain unclear. To fill this gap in knowledge, we tested depressed patients in a partial hospital setting before and after treatment (cognitive behavior therapy combined with medication) using a flanker task. To evaluate the translational relevance of this metric in rodents, we performed a secondary analysis on existing data from rats tested in the 5-choice serial reaction time task after treatment with corticotropin-releasing factor (CRF), a stress peptide that produces depressive-like signs in rodent models relevant to depression. In addition, to examine the effect of treatment on post-error behavior in rodents, we examined a second cohort of rodents treated with JDTic, a kappa-opioid receptor antagonist that produces antidepressant-like effects in laboratory animals. In depressed patients, baseline post-error accuracy was lower than post-correct accuracy, and, as expected, post-error accuracy improved with treatment. Moreover, baseline post-error accuracy predicted attentional control and rumination (but not depressive symptoms) after treatment. In rats, CRF significantly degraded post-error accuracy, but not post-correct accuracy, and this effect was attenuated by JDTic. Our findings demonstrate deficits in post-error accuracy in depressed patients, as well as a rodent model relevant to depression. These deficits respond to intervention in both species. Although post-error behavior predicted treatment-related changes in attentional control and rumination, a relationship to depressive symptoms remains to be demonstrated.
TL;DR: A gap in the understanding of dysfunctional connectivity in depression engenders several important questions: to what extent are alterations in functional connectivity unique to specific cognitive or emotional processes?
TL;DR: Results indicated that anhedonia was significantly elevated in the depression group, and negatively correlated with agency, suggesting that in spite of considerable phenotypical overlap,Anhedonia and agency may be linked to partially distinct neurobiological markers.
01 Jan 2015
TL;DR: New evidence of reward processing abnormalities in MDD, bipolar disorder and schizophrenia has led to a greater understanding of the neural processes associated with symptomatology common across these conditions, andsecting various subcomponents of rewardprocessing that map onto partially different neurobiological pathways and investigating their dysregulation in different psychiatric disorders holds promise for developing more targeted, and hopefully efficacious treatment and intervention strategies.
Abstract: Purpose of review This article reviews the recent literature on reward processing dysfunction in major depression (MDD), bipolar disorder and schizophrenia, with a focus on approach motivation, reward learning and rewardbased decision-making. Recent findings Emerging evidence indicates the presence of reward processing abnormalities across all three disorders, supporting a transdiagnostic approach. In particular, findings are consistent with a role of abnormal phasic striatal dopamine signaling, which is critical for reinforcement learning, efficient mobilization of effort to obtain reward and allocation of attention to reward-predictive cues. Specifically, reward-related striatal signaling appears blunted in MDD and the negative symptoms of schizophrenia, elevated in bipolar (hypo)mania, and contextually misallocated in the positive symptoms of psychosis. However, whether shared or distinct pathophysiological mechanisms contribute to abnormal striatal signaling across the three disorders remains unknown. Summary New evidence of reward processing abnormalities in MDD, bipolar disorder and schizophrenia has led to a greater understanding of the neural processes associated with symptomatology common across these conditions (e.g., anhedonia). Dissecting various subcomponents of reward processing that map onto partially different neurobiological pathways and investigating their dysregulation in different psychiatric disorders holds promise for developing more targeted, and hopefully efficacious treatment and intervention strategies.
Journal Article•
TL;DR: In this paper, the authors compare striatal DAT nondisplaceable binding potential (BPND) in individuals with Major Depressive Disorder (MD) and healthy controls (HCs) using the high-selective DAT radiotracer [11C]altropane.
Abstract: 527 Objectives Dopamine (DA) plays an important role in learning and motivation. These functions are reduced in Major Depressive Disorder (MDD) signifying the involvement of DA signaling in MDD. The DA transporter (DAT) terminates DA signaling by reuptake of synaptic DA. Post-mortem studies have found decreased DAT in MDD, which has been interpreted as a compensatory down-regulation due to low DA levels; SPECT and PET studies have, however, been inconclusive. The goal of this work was to compare striatal DAT nondisplaceable binding potential (BPND) in individuals with MDD and healthy controls (HCs) using the high-selective DAT radiotracer [11C]altropane. Methods PET data were acquired in 25 unmedicated adults with MDD and 23 HCs using a Siemens HR +. Regional BPND estimates were generated using MRTM2 (cerebellum as a reference) in the caudate (CAU), putamen (PUT), nucleus accumbens (NAc), and ventral tegmental area (VTA). Results A Group (HCs, MDD) x Region (CAU, PUT, NAc) x Hemisphere (left, right) MANCOVA (covariate:age) indicated a significant Group x Region interaction (p .05). For both the PUT (r=-.36) and VTA (r=-0.36), mean DAT BP was negatively correlated with the number of prior major depressive episodes (MDE; p Conclusions Results indicate decreased DAT in the striatum and VTA in MDD. The specificity of this finding highlights the significance of mesolimbic over nigrostriatal pathways in the pathophysiology of MDD. Decreased DAT in MDD may be explained as a compensatory down-regulation due to chronic low DA signaling. These findings have promising implications for understanding the physiological processes underlying MDD as well as potential for interventions. Research Support R01MH068376, R01MH095809, T32EB013180
01 Apr 2015