Biomedical subjects

Diego A Pizzagalli

Publications and source records attributed to Diego A Pizzagalli.

5 recordsLinked to original sources

PubMed2026

Acute effects of AT1 receptor blockade on approach-avoidance of negative emotional faces.

Recent evidence implicates the renin angiotensin system (RAS) in various cognitive markers of depression, including dysfunctional reward processing. Yet, it remains unknown whether these effects extend to other markers implicated in depression and its treatment, such as approach-avoidance motivations that reflect innate drives to approach reward and evade harm. We sought to examine the impact of acute losartan, an angiotensin type 1 (AT1) receptor blocker, on the implicit approach-avoidance of facial expressions and checkerboard controls in healthy adults. In a randomized controlled trial, N = 68 healthy adults aged 18-50 (49 F/19 M) were administered a single 50 mg dose of losartan or placebo before completing an implicit Approach Avoidance Task (AAT) at drug-peak level. On the AAT, participants responded to color-filtered facial stimuli (happy, sad, angry, or neutral) and checkerboard controls using a joystick, and were instructed to pull all gray photos and push all brown photos as quickly as possible. Compared to placebo, losartan induced a significant avoidance bias for sad faces (p = 0.027) and reduced avoidance of angry faces at trend level (p = 0.085). This occurred without significant group differences on blood pressure, overall reaction time, accuracy, and approach-avoidance biases for other stimuli. The response pattern associated with AT1 receptor blockade may counteract previously observed depressive tendencies, suggesting effects possibly consistent with antidepressant treatments. Our findings further highlight the RAS as a mechanistically relevant target for psychiatry, suggesting that AT1 receptor antagonism may have relevance for treating depression and other emotional disorders characterized by aberrant motivational biases (Clincialtrials.gov ID: NCT06624904).

Journal Article↗

PubMed2026

Targeting distinct facets of anhedonia via transcutaneous auricular vagus nerve stimulation: Effects on heart rate variability and reward-based behavior.

Anhedonia, a core feature of major depressive disorder, is associated with disrupted reward processing and may represent a mechanistically relevant target for neuromodulation. This study examined the effects of transcutaneous auricular vagus nerve stimulation (taVNS) on reward-related behavior and autonomic regulation in individuals with higher (n = 34) and lower (n = 34) depressive symptomatology. In a randomized, within-subject crossover design, participants received active taVNS and sham stimulation on two separate days. During each session, incentive motivation and reward learning were assessed using the Effort Expenditure for Rewards Task and the Probabilistic Reward Task (PRT), respectively, with stimulation condition and task order counterbalanced. Findings revealed that taVNS effects on heart rate variability (HRV) were modulated by baseline HRV levels and depressive status; specifically, they enhanced HRV at low baseline levels and reduced it at high baseline levels in participants with lower depressive symptomatology, with opposite patterns in individuals with higher symptoms. Moreover, compared to sham, taVNS enhanced the willingness to exert effort for rewards, particularly at low reward probabilities, with a more pronounced effect in the group characterized by higher depressive symptoms. No significant effects were observed on reward learning, as indexed by the PRT. Additionally, taVNS reduced self-reported anxiety across groups. Despite the limitation of a single stimulation session, these findings suggest that taVNS modulates motivational effort allocation in individuals with higher depressive symptoms, supporting its potential relevance for targeting reward-related dysfunctions in mood disorders.

Anhedonia↗

PubMed2026

Neurophysiological signatures of Stanford Neuromodulation Therapy in treatment resistant depression.

Treatment-resistant depression (TRD) affects approximately 30% of patients with major depressive disorder. Stanford Neuromodulation Therapy (SNT), a high-dose intermittent theta-burst transcranial magnetic stimulation protocol, produces rapid antidepressant effects, but its neurophysiological mechanisms remain unclear. Here, we used longitudinal TMS-EEG to characterize the progressive neurophysiological changes induced by SNT, assess their site-specificity, and explore whether baseline neural markers are associated with clinical response. We conducted a double-blind, randomized, sham-controlled trial at Stanford University (2017-2018; analysis August 2024-October 2025) in 24 TMS-naïve participants with TRD (Montgomery-Åsberg Depression Rating Scale ≥20; ≥1 failed antidepressant trial). Participants were randomized to active (n = 12) or sham (n = 12) SNT, consisting of 10 sessions per day over 5 consecutive days targeting the left dorsolateral prefrontal cortex (90,000 pulses). TMS-EEG was acquired at two baseline sessions, before and after each treatment session, and at 1-month follow-up (14 TMS-EEG sessions in total). Active SNT progressively reduced cortical excitability at the treatment site, with significant decreases by day 3 in the early window component (-27.9%; P < 0.01), while no changes were observed at the vertex control site. Site-specific comparisons confirmed early window reductions only at the left dorsolateral prefrontal cortex (t₂₂ = -3.82; P < 0.001). SNT also selectively decreased estimated medial prefrontal source activity consistent with the subgenual anterior cingulate cortex (sgACC) across sessions (F₁₃,₂₂₂ = 4.93; P < 0.001), with effects persisting at 1-month follow-up. In an exploratory analysis in the active group (n = 12), higher baseline estimated sgACC source activity was associated with greater clinical improvement (r = -0.67; P = 0.023); although promising, the latter preliminary finding requires replication in larger, adequately powered samples before predictive utility can be established. These findings indicate that SNT induces progressive, site-specific cortical modulation and selective downstream effects on estimated sgACC source activity. Early cortical excitability changes represent candidate neurophysiological markers of SNT response, while the observed association between baseline sgACC activity and clinical outcome, while preliminary, motivates prospective investigation of subcortical source activity as a potential predictor of treatment response in larger trials. ClinicalTrials.gov Identifier: NCT03068715.

Journal Article↗

PubMed2026

Research agenda to advance anhedonia assessment, understanding and treatment: an ECNP-GALENOS expert meeting report.

Anhedonia, broadly defined as a reduced ability to experience interest or pleasure, represents an important transdiagnostic neuropsychiatric symptom dimension which may benefit from targeted diagnostics and treatments. Different lines of research have proposed that it comprises multiple facets, including deficits in anticipatory ('wanting') and consummatory ('liking') reward processing as well as reward learning and affects different aspects of life (eg, social, physical, cognitive). Certain facets-more specifically anticipation, motivation and reward learning-likely involve blunted phasic dopaminergic signalling. However, recent meta-analytical evidence of human depression studies indicates that prodopaminergic antidepressants produce relatively small improvements in anhedonia symptoms and suggest that mechanisms beyond dopamine likely contribute to anhedonia. This stimulated an expert meeting to review the literature and define priorities for future research in anhedonia. A central key priority is developing a translational biologically-informed nomenclature and consensus that solves the current mismatch between constructs, paradigms and measures, and mechanisms, which separates discrete reward-related processes such as effort allocation, reward learning and anticipatory interest versus consummatory pleasure. Clinical research priorities are improved multimodal measurement tools, integrating neurobiological frameworks (eg, neuroimaging, electrophysiology and liquid biomarkers capturing dopaminergic, glutamatergic, opioid and immunometabolic pathways) and transdiagnostic studies across neuropsychiatric disorders and developmental stages. Innovative trial designs that explicitly target anhedonic phenotypes as a primary outcome and test mechanism-based interventions are also needed. Translational research recommendations include back-translation strategies that begin with patient-relevant phenotypes followed by the development of comparable human and animal tasks that target reward-related processes, such as effort allocation, reward learning and anticipatory interest versus consummatory pleasure, improve cross-species behavioural paradigms and enhance methodological rigour and reproducibility. Collectively, these recommendations will help refine the conceptualisation of anhedonia and advance its role within precision psychiatry as a mechanistically grounded target across multiple disorders.

Humans↗

PubMed2025

Brain dynamics reflecting an intra-network brain state is associated with increased posttraumatic stress symptoms in the early aftermath of trauma.

Post-traumatic stress (PTS) encompasses a range of psychological responses following trauma, which may lead to more severe outcomes such as post-traumatic stress disorder (PTSD). Identifying early neuroimaging biomarkers that link brain function to PTS outcomes is critical for understanding PTSD risk. This longitudinal study examines the association between brain dynamic functional network connectivity (dFNC) and current/future PTS symptom severity, and the impact of sex on this relationship. By analyzing 275 participants' dFNC data obtained ~2 weeks after trauma exposure, we noted that brain dynamics of an inter-network brain state link negatively with current (r=-0.197, p corrected = 0.0079) and future (r=-0.176, p corrected = 0.0176) PTS symptom severity. Also, dynamics of an intra-network brain state correlated with future symptom intensity (r = 0.205, p corrected = 0.0079). We additionally observed that the association between the network dynamics of the inter-network and intra-network brain state with symptom severity is more pronounced in female group. Our findings highlight a potential link between brain network dynamics in the aftermath of trauma with current and future PTSD outcomes, with a stronger effect in female group, underscoring the importance of sex differences.

Journal Article↗