Positive and negative valence systems in major depression have distinct clinical features, response to antidepressants, and relationships with immunomarkers

Medeiros, Gustavo C.; Rush, A. John; Jha, Manish K.; Carmody, Thomas; Furman, Jennifer L.; Czysz, Andrew H.; Trombello, Joseph M.; Cooper, Crystal; Trivedi, Madhukar H.

doi:10.1002/da.23006

Cited by 27 publications

(19 citation statements)

References 68 publications

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“…Given the association of the insula with the nucleus accumbens (ACB), a hub for reward, and the role of the salience network in valence mapping, we hypothesized that photostimulation of the insula would lead to positive valence, resulting in conditioned place preference. Aberrant valence mapping is associated with the induction and maintenance of depression [ 45 ]. However, we could not conclude that insula photostimulation leads to positive valence (Fig.…”

Section: Resultsmentioning

confidence: 99%

A triple-network organization for the mouse brain

et al. 2021

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The triple-network model of psychopathology is a framework to explain the functional and structural neuroimaging phenotypes of psychiatric and neurological disorders. It describes the interactions within and between three distributed networks: the salience, default-mode, and central executive networks. These have been associated with brain disorder traits in patients. Homologous networks have been proposed in animal models, but their integration into a triple-network organization has not yet been determined. Using resting-state datasets, we demonstrate conserved spatio-temporal properties between triple-network elements in human, macaque, and mouse. The model predictions were also shown to apply in a mouse model for depression. To validate spatial homologies, we developed a data-driven approach to convert mouse brain maps into human standard coordinates. Finally, using high-resolution viral tracers in the mouse, we refined an anatomical model for these networks and validated this using optogenetics in mice and tractography in humans. Unexpectedly, we find serotonin involvement within the salience rather than the default-mode network. Our results support the existence of a triple-network system in the mouse that shares properties with that of humans along several dimensions, including a disease condition. Finally, we demonstrate a method to humanize mouse brain networks that opens doors to fully data-driven trans-species comparisons.

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Section: Resultsmentioning

confidence: 99%

A triple-network organization for the mouse brain

et al. 2021

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“…A recent clinical trial adopting an RDoC approach to the investigation of a selective κ-opioid receptor blocker for anhedonia across mood and anxiety disorders showed that this compound increased fMRI ventral striatum activation during reward anticipation compared to placebo (70). A study dividing MDD disorder symptoms into positive valence symptoms (impaired motivation, impaired energy, and anhedonia) and negative valence symptoms (anxiety and interpersonal sensitivity) showed that antidepressants were more effective for positive valence symptoms (71).…”

Section: Integrating Psychedelic Therapy and The Research Domain Criteriamentioning

confidence: 99%

Psychedelic Therapy's Transdiagnostic Effects: A Research Domain Criteria (RDoC) Perspective

et al. 2021

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Accumulating clinical evidence shows that psychedelic therapy, by synergistically combining psychopharmacology and psychological support, offers a promising transdiagnostic treatment strategy for a range of disorders with restricted and/or maladaptive habitual patterns of emotion, cognition and behavior, notably, depression (MDD), treatment resistant depression (TRD) and addiction disorders, but perhaps also anxiety disorders, obsessive-compulsive disorder (OCD), Post-Traumatic Stress Disorder (PTSD) and eating disorders. Despite the emergent transdiagnostic evidence, the specific clinical dimensions that psychedelics are efficacious for, and associated underlying neurobiological pathways, remain to be well-characterized. To this end, this review focuses on pre-clinical and clinical evidence of the acute and sustained therapeutic potential of psychedelic therapy in the context of a transdiagnostic dimensional systems framework. Focusing on the Research Domain Criteria (RDoC) as a template, we will describe the multimodal mechanisms underlying the transdiagnostic therapeutic effects of psychedelic therapy, traversing molecular, cellular and network levels. These levels will be mapped to the RDoC constructs of negative and positive valence systems, arousal regulation, social processing, cognitive and sensorimotor systems. In summarizing this literature and framing it transdiagnostically, we hope we can assist the field in moving toward a mechanistic understanding of how psychedelics work for patients and eventually toward a precise-personalized psychedelic therapy paradigm.

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“…Previous studies have shown that patients with CM are twice as likely to have depression compared to patients with EM and that depression is a risk factor for migraine chronification 3,4 . Aspects of depression related to negative valence (aversive and unpleasant) symptoms have been shown to be associated with amygdala function 54 . Recently, a distinct neural ensemble specifically in the BLA amygdala was shown to encode the negative affective valence of pain in mouse models of acute and chronic pain 12 .…”

Section: Discussionmentioning

confidence: 99%

Increased amygdala volume and functional connectivity with cognitive control networks in chronic migraine

DeSouza

Krimmel

Sanjanwala

et al. 2020

Preprint

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Objective: To characterize the role of the amygdala in episodic (EM) and chronic (CM) migraine, we evaluated amygdala volumes, functional connectivity (FC), and associations with clinical and affective measures. Methods: Eighty-eight patients (44 with EM and 44 age- and sex-matched patients with CM) completed anatomical and resting-state functional MRI scans. Amygdala volumes and resting-state FC to three core large-scale cognitive control networks (default mode (DMN), salience (SN), central executive (CEN)) were compared between groups. Associations between amygdala volume and FC, measures of headache severity (frequency and intensity), and cognitive-affective measures (depression, anxiety, pain catastrophizing) were evaluated. Results: Compared to EM, patients with CM had larger amygdala volume bilaterally. Headache frequency and intensity were associated with increased left and right amygdala volume, and depression was associated with increased right amygdala volume. Patients with CM also demonstrated increased left amygdala FC with the DMN, which across patients was related to headache frequency. Left amygdala FC to the SN was correlated with headache intensity while right amygdala FC to the CEN was correlated with pain catastrophizing. Conclusion: Our findings reveal increased amygdala volume and FC with large-scale neurocognitive networks in patients with CM compared to EM. Aberrant amygdala volume and FC measures were associated with increased migraine severity, depression, and pain catastrophizing, pointing to a link between emotion and pain in migraine. Our findings provide novel insights into amygdala involvement in chronic migraine and may inform future interventions aimed at preventing the progression of both headache and its negative cognitive-affective symptoms.

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Positive and negative valence systems in major depression have distinct clinical features, response to antidepressants, and relationships with immunomarkers

Cited by 27 publications

References 68 publications

A triple-network organization for the mouse brain

A triple-network organization for the mouse brain

Psychedelic Therapy's Transdiagnostic Effects: A Research Domain Criteria (RDoC) Perspective

Increased amygdala volume and functional connectivity with cognitive control networks in chronic migraine

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