Biology subjects

Nemeroff, C. B.

Publications and source records attributed to Nemeroff, C. B..

4 recordsLinked to original sources

bioRxiv2025

Early Brain Functional Connectivity Changes Induced by Antidepressants and Placebo

Major depressive disorder (MDD) is a common and debilitating condition with limited treatment precision. While brain imaging has linked neural features to MDD diagnosis and treatment response, the underlying circuits and their early modulation by treatment remain unclear. To examine changes in functional connectivity within the first two weeks of treatment, we analyzed two independent cohorts of MDD patients receiving antidepressants or placebo. Across patients, a visual-precuneus-thalamus network showed increased functional connectivity regardless of treatment arm or clinical outcome. Placebo response involved attention and striatal systems, while drug-specific effects were localized to the amygdala, mid-cingulate, orbitofrontal cortex, and cerebellum, emerging only in a subset of medicated patients. Notably, the responses of those without drug-specific changes can be predicted with a placebo response prediction model. These early functional connectivity changes reveal common and distinct mechanisms of treatment effects, offering insights that could inform more personalized interventions for MDD.

neuroscience↗

bioRxiv2025

Enhanced Episodic Memory Following Putative Inhibition of the Amygdala via Transcranial Low-Intensity Focused Ultrasound

The amygdala is considered crucial to the formation of emotional episodic memories, but causal evidence in humans is limited due to challenges in non-invasive neuromodulation of deep brain structures. In a double-blind, sham-controlled, repeated measures study, we examined whether transcranial low-intensity focused ultrasound (tFUS) targeting the left amygdala prior to the encoding of emotional and neutral pictures impacted memory for these pictures 24 hours later. We used a putative inhibitory tFUS protocol shown to attenuate amygdala blood-oxygenation- level-dependent signal, thus testing the hypothesis that pre-encoding amygdala inhibition diminishes emotional memory. Surprisingly, active vs. sham sonication enhanced multiple measures of neutral and emotional memory across two memory tests. A secondary test of amygdala function found that active sonication enhanced fear recognition in faces. Computational modeling further supported these results. These findings motivate a novel conceptualization of the amygdalas role in emotional episodic memory. Rather than enhancing memory via amplification of salient stimuli, the amygdala may instead act as a filter that attenuates the maintenance of non-salient stimuli in long-term memory. Finally, the potential to enhance memory serves as an impetus to test tFUS of the amygdala in disorders such as depression and posttraumatic disorder that exhibit comorbid hyperreactive amygdalae and memory impairments.

neuroscience↗

bioRxiv2024

Contrastive functional connectivity defines neurophysiology-informed symptom dimensions in major depression

BackgroundMajor depressive disorder (MDD) is a prevalent psychiatric disorder characterized by substantial clinical and neurobiological heterogeneity. Conventional studies that solely focus on clinical symptoms or neuroimaging metrics often fail to capture the intricate relationship between these modalities, limiting their ability to disentangle the complexity in MDD. Moreover, patient neuroimaging data typically contains normal sources of variance shared with healthy controls, which can obscure disorder-specific variance and complicate the delineation of disease heterogeneity. MethodsWe employed contrastive principal component analysis to extract disorder-specific variations in fMRI-based resting-state functional connectivity (RSFC) by contrasting MDD patients (N=233) with age-matched healthy controls (N=285). We then applied sparse canonical correlation analysis to identify latent dimensions in the disorder variations by linking the extracted contrastive connectivity features to clinical symptoms in MDD patients. ResultsTwo significant and generalizable dimensions linking distinct brain circuits and clinical profiles were discovered. The first dimension, associated with an apparent "internalizing-externalizing" symptom dimension, was characterized by self-connections within the visual network and also associated with choice reaction times of cognitive tasks. The second dimension, associated with personality facets such as extraversion and conscientiousness typically inversely associated with depression symptoms, is primarily driven by self-connections within the dorsal attention network. This "depression-protective personality" dimension is also associated with multiple cognitive task performances related to psychomotor slowing and cognitive control. ConclusionsOur contrastive RSFC-based dimensional approach offers a new avenue to dissect clinical heterogeneity underlying MDD. By identifying two stable, neurophysiology-informed symptom dimensions in MDD patients, our findings may enhance disease mechanism insights and facilitate precision phenotyping, thus advancing the development of targeted therapeutics for precision mental health. Trial RegistrationEstablishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for Depression (EMBARC), NCT#01407094

neuroscience↗

bioRxiv2019

Neuro-transcriptomic signatures for mood disorder morbidity and suicide mortality

Suicidal behaviors are strongly linked with mood disorders, but the specific neurobiological and functional gene-expression correlates for this linkage remain elusive. We performed neuroimaging-guided RNA-sequencing in two studies to test the hypothesis that imaging-localized gray matter volume (GMV) loss in mood disorders, harbors gene-expression changes associated with disease morbidity and related suicide mortality in an independent postmortem cohort. To do so, first, we conducted study 1 using an anatomical likelihood estimation (ALE) MRI meta-analysis including a total of 47 voxel-based morphometry (VBM) publications (i.e. 26 control>major depressive disorder (MDD) studies, and 21 control>bipolar disorder (BD) studies) in 2387 (living) participants. Study 1 meta-analysis identified a selective anterior insula cortex (AIC) GMV loss in mood disorders. We then used this results to guide study 2 postmortem tissue dissection and RNA-Sequencing of 100 independent donor brain samples with a life-time history of MDD (N=30), BD (N=37) and control (N=33). In study 2, exploratory factor-analysis identified a higher-order factor representing number of Axis-1 diagnoses (e.g. substance use disorders/psychosis/anxiety, etc.), referred to here as morbidity and suicide-completion referred to as mortality. Comparisons of case-vs-control, and factor-analysis defined higher-order-factor contrast variables revealed that the imaging-identified AIC GMV loss sub-region harbors differential gene-expression changes in high morbidity-&-mortality versus low morbidity-&-mortality cohorts in immune, inflammasome, and neurodevelopmental pathways. Weighted gene co-expression network analysis further identified co-activated gene modules for psychiatric morbidity and mortality outcomes. These results provide evidence that AIC anatomical signature for mood disorders are possible correlates for gene-expression abnormalities in mood morbidity and suicide mortality.

neuroscience↗