Alcohol use disorder continues to impose a devastating toll on global health, with current pharmacotherapies offering limited efficacy and a high relapse rate. The pursuit of new molecular targets is, therefore, a priority for the field. Histamine receptors, particularly the H3 subtype, have emerged as intriguing candidates due to their modulatory role in neurotransmitter release and neural plasticity. The H3 receptor’s ability to regulate the release of histamine, dopamine, acetylcholine, and other key neurotransmitters establishes it as a nexus point within neural circuits implicated in addiction, reward, and executive control mechanisms distorted by prolonged alcohol exposure.

The research team led by Le Foll, Naassila, and Jeanblanc embarked on an exhaustive exploration of H3 receptors’ pharmacodynamics and behavioral implications across various animal models of AUD. Their methodological rigor extends beyond conventional neurochemical assays, incorporating sophisticated behavioral paradigms designed to mimic the multifaceted nature of alcohol dependence and relapse. Such paradigms included operant self-administration, reinstatement models to simulate relapse, and the evaluation of withdrawal symptoms, thereby providing a layered understanding of how histamine receptor modulation can alter addictive behaviors.

Central to the study’s novelty is its critical lens on the translatability of animal data to human clinical contexts. Although preclinical models have long been the backbone of drug discovery, the authors underscore inconsistencies in predictive validity, particularly when assessing neuropsychiatric conditions like AUD. Their data reveal that while histamine H3 receptor antagonists or inverse agonists exhibit robust efficacy in reducing alcohol consumption and mitigating relapse behaviors in rodents, the magnitude and consistency of these effects are variable. The findings suggest that factors such as species differences, dosing regimens, and the complexity of human AUD heterogeneity may contribute to this translational gap.

Delving deeper into mechanistic insights, the study elucidates how H3 receptor modulation influences neuronal circuits within the mesolimbic dopamine system—a principal pathway underpinning reward and addiction. Histamine H3 receptors act as autoreceptors and heteroreceptors, tuning the release of neurotransmitters in regions such as the nucleus accumbens and prefrontal cortex. By dampening or enhancing the activity of these circuits, H3 receptor-targeted compounds can recalibrate the dysfunctional signaling cascades that sustain craving and compulsive alcohol-seeking behaviors.

The pharmacological profiles of candidate compounds were scrutinized for their receptor affinity, specificity, and capacity to traverse the blood-brain barrier. The researchers employed advanced in vivo imaging and receptor occupancy studies to confirm central engagement, a crucial parameter for CNS-targeted therapies. Concurrently, electrophysiological recordings shed light on synaptic plasticity changes induced by H3 receptor ligands, revealing alterations in long-term potentiation and depression processes that may underlie behavioral adaptations to chronic alcohol use.

However, the translational narrative is layered with complexity. The authors argue that reliance on simplistic behavioral endpoints, such as mere reductions in alcohol consumption, fails to capture the multidimensional nature of AUD in humans. Cognitive deficits, stress response abnormalities, and social factors intricately modulate disease trajectory and treatment response, factors often absent in animal models. This discrepancy emphasizes the need for integrative approaches that combine genetic, epigenetic, and environmental factors influencing histaminergic signaling in human populations.

Furthermore, the study advocates for refinement in animal model design to encompass more clinically relevant variables, including sex differences, poly-substance use scenarios, and prolonged exposure paradigms. Such nuanced modeling could bridge the chasm between animal efficacy signals and clinical outcomes, thereby accelerating the path from bench to bedside. The authors poignantly highlight that without improving model predictability, promising drug candidates may either be prematurely discarded or fail in costly clinical trials, stalling advancement in AUD therapeutics.

In a broader context, this research reinforces a paradigm shift in drug development that transcends target identification to emphasize context-dependent biology. Histamine H3 receptor targeting exemplifies how receptor pharmacology cannot be decoupled from the intricate neural and behavioral milieu in which it operates. The findings propel a call for multidisciplinary collaboration, integrating neurobiology, behavioral science, pharmacology, and computational modeling to develop predictive frameworks capable of forecasting human clinical responses with greater fidelity.

Moreover, the implications extend beyond alcohol use disorder. The H3 receptor’s involvement in cognition, sleep regulation, and other psychiatric conditions suggests that insights gleaned here may inform therapeutic strategies across a spectrum of neuropsychiatric illnesses. This cross-disorder relevance heightens the significance of establishing robust translational models that can faithfully recapitulate human neural and behavioral pathophysiology.

From a clinical translational perspective, the research offers cautious optimism. By pinpointing the nuanced roles of H3 receptor ligands in modifying addiction circuits and highlighting their potential to attenuate relapse-like behaviors, the study lays groundwork for developing next-generation pharmacotherapies. Nonetheless, the authors reiterate the indispensable need for early-phase clinical trials employing biomarkers of receptor engagement and functional imaging to validate preclinical findings and refine dosing strategies.

The article also underscores emerging technological advancements that could enhance translational fidelity. Innovations in gene-editing tools, inducible pluripotent stem cell-derived human neurons, and organoid models present exciting avenues to simulate human-specific histamine receptor dynamics ex vivo. Coupled with machine learning algorithms analyzing behavioral and molecular datasets, these technologies promise to surmount current limitations of animal models and usher in a new era of precision neuropsychopharmacology.

In summary, the study by Le Foll and colleagues charts a reflective and forward-thinking course for AUD drug discovery. By juxtaposing compelling preclinical evidence for histamine H3 receptor targeting with the sobering realities of translational hurdles, it invites the scientific community to recalibrate expectations and methodologies. This balanced perspective enhances the probability that future therapies transitioning from animal models to clinical implementation will realize their full potential in alleviating the global burden of alcohol use disorder.

As the global health community continues to wrestle with the complexities of addiction, this research serves as a clarion call for innovation not just in drug targets but in the very frameworks we employ to study them. It emphasizes that understanding the interplay between neurochemical circuits and behavioral manifestations in a clinically relevant context is paramount to devising effective and sustainable treatment options. The histamine H3 receptor, once a peripheral player in neuropharmacology, now emerges as a promising yet cautionary emblem of this intricate scientific journey.

Subject of Research: Histamine H3 receptor as a therapeutic target for alcohol use disorder and the challenges of translating animal model findings to clinical drug development.

Article Title: Histamine H3 Receptor as a target for alcohol use disorder: challenging the predictability of animal models for clinical translation in drug development.

Article References:
Le Foll, B., Naassila, M., Jeanblanc, J. et al. Histamine H3 Receptor as a target for alcohol use disorder: challenging the predictability of animal models for clinical translation in drug development. Transl Psychiatry (2026). https://doi.org/10.1038/s41398-026-03807-y

Image Credits: AI Generated

DOI: https://doi.org/10.1038/s41398-026-03807-y

Methamphetamine addiction remains a formidable public health challenge globally, characterized by compulsive drug-seeking behaviors and recurrent relapse despite existing treatment modalities. Psychological craving—an intense, often overwhelming desire to use the substance—is a key component of addiction that pathophysiologically involves complex neural circuits, encompassing reward, memory, and executive control pathways. Traditional approaches to craving management, including pharmacotherapies and cognitive-behavioral interventions, have yielded mixed results due to the deep-rooted associative memories triggered by environmental cues linked to past methamphetamine use.

This is where VR-CET positions itself as a revolutionary strategy. By integrating exposure therapy principles with immersive virtual environments, VR-CET immerses patients in carefully designed scenarios that replicate real-life methamphetamine-associated cues such as drug paraphernalia, social contexts, and sensory triggers. This controlled exposure aims to desensitize the conditioned responses to these stimuli, attenuating the emotional and physiological reactions that fuel craving. Unlike conventional cue exposure methods, VR allows a precise, repeatable, and richly interactive simulation of high-risk environments without the ethical and safety concerns of real-world exposure.

The randomized controlled trial spearheaded by Huang, Chen, Wang, and colleagues enrolled male participants diagnosed with methamphetamine use disorder. The study leveraged cutting-edge VR hardware combined with a customized therapeutic software platform to systematically expose participants to a sequence of methamphetamine-related cues. Psychological craving was rigorously assessed using validated scales administered before, during, and after treatment sessions, capturing both immediate and longitudinal effects of the intervention. Control groups received standard therapy without VR exposure, ensuring a robust comparative framework for efficacy evaluation.

Findings revealed a statistically significant reduction in psychological craving among participants undergoing VR-CET as compared to controls. Notably, the diminution in craving was not merely transient; many subjects maintained attenuated craving levels over extended follow-up periods. These results suggest that VR-CET engenders meaningful neurobehavioral changes, potentially by disrupting maladaptive memory reconsolidation mechanisms and recalibrating neural responses to drug-associated stimuli. The immersive nature of VR may amplify these effects by promoting heightened attentional engagement and emotional processing during therapy sessions.

Delving deeper into the neurobiological underpinnings, cue-induced craving activates the mesolimbic dopamine system, particularly the ventral tegmental area and nucleus accumbens, regions integral to reward processing. Concurrently, hippocampal and amygdala circuits encode contextual and emotional aspects of drug memories, reinforcing the power of environmental triggers. VR-CET’s immersive exposure likely facilitates extinction learning—an active process where conditioned associations weaken through repeated, non-reinforced stimulus presentation—thereby recalibrating these interconnected brain regions and reducing pathological craving intensity.

Technologically, the VR system employed in this study incorporated high-fidelity graphical renderings and spatial audio to authentically recreate drug-use contexts. Such multisensory integration is critical for engaging sensorimotor networks and eliciting realistic psychological responses, which are essential for therapeutic efficacy. The adaptability of VR environments permits personalized scenario adjustments tailored to individual cue profiles and craving patterns, enhancing treatment relevance and patient immersion.

In addition to craving attenuation, participants reported improved coping strategies against relapse triggers post-intervention, highlighting VR-CET’s potential to bolster cognitive control and emotional regulation. These psychological benefits may stem from the repeated rehearsal of exposure combined with guided cognitive reframing within the virtual setting, a synergy that standard therapies cannot replicate with equal intensity or safety. Importantly, VR-CET demonstrated good tolerability, with minimal adverse effects, underscoring its clinical viability.

This study marks a paradigm shift in addiction therapy by transcending the limitations of face-to-face exposure and offering a scalable, customizable, and engaging platform. The remote delivery potential inherent to VR technology also aligns with contemporary telemedicine and digital health trends, expanding accessibility for underserved populations and those in resource-limited environments. Future iterations of VR-CET could integrate biometric feedback, neuroimaging data, and machine learning algorithms to optimize personalized treatment trajectories and real-time craving modulation.

Nonetheless, despite these promising outcomes, challenges remain. The study focused exclusively on male individuals, warranting replication across diverse demographic groups, including female patients, to establish generalizability. Furthermore, long-term abstinence rates and functional recovery metrics beyond craving reduction require longitudinal studies to fully ascertain clinical impacts. The financial and infrastructural costs associated with VR systems also pose implementation hurdles, although decreasing technology prices and expanding digital literacy present an optimistic outlook.

Potential synergistic applications of VR-CET extend into other substance use disorders and behavioral addictions, given the shared neurobehavioral mechanisms underpinning craving and relapse. Combining VR-CET with pharmacological agents targeting neuroplasticity, such as NMDA receptor modulators, could potentiate extinction and cognitive restructuring processes. Additionally, integrating VR-CET into comprehensive multidisciplinary programs encompassing psychotherapy, social support, and vocational rehabilitation might enhance holistic recovery outcomes.

Ultimately, the convergence of neuroscience insights, immersive technology, and clinical psychology embodied in VR-CET catalyzes a novel therapeutic frontier. By operationalizing virtual experiences to recalibrate pathological craving circuits safely and effectively, this intervention offers hope for improved recovery trajectories in methamphetamine addiction—a condition that has long eluded consistent therapeutic gains. Stakeholders in addiction medicine, technology development, and policy should closely monitor and support further research and implementation efforts to translate these findings into widespread clinical practice.

This study embodies the transformative potential of digital therapeutics and exemplifies how sophisticated simulation platforms can reshape existing paradigms in mental health treatment. As VR technologies continue to evolve with enhancements in realism, interactivity, and portability, their alignment with neurobehavioral therapies heralds a new era of precision addiction medicine. The evidence provided by Huang and colleagues lays a robust foundation for leveraging immersive VR as a mainstream adjunct in addiction rehabilitation, promising a tangible impact on the lives of millions affected by methamphetamine use disorder worldwide.

Subject of Research:
Methamphetamine use disorder and the efficacy of virtual reality-based cue exposure therapy in reducing psychological craving.

Article Title:
Virtual reality-based cue exposure therapy reduces psychological craving in men with methamphetamine use disorder: a randomized controlled trial.

Article References:
Huang, Q., Chen, X., Wang, X. et al. Virtual reality-based cue exposure therapy reduces psychological craving in men with methamphetamine use disorder: a randomized controlled trial. Transl Psychiatry 15, 318 (2025). https://doi.org/10.1038/s41398-025-03553-7

Image Credits:
AI Generated

DOI:
https://doi.org/10.1038/s41398-025-03553-7

At its core, the nucleus accumbens (NAc) is a key hub in the brain’s reward circuit, functioning as a crossroads where motivational signals are integrated with emotional and cognitive inputs. This region has been extensively studied for its involvement in the pursuit of natural rewards like food and social interaction, as well as in maladaptive behaviors such as drug addiction. The new study conducted by Almeida Rojo, Cai, Barnhardt, and colleagues delves deeper, exploring how fluctuations in sleep patterns modulate the dynamic neural processes within the NAc that drive food reward seeking. Their findings underscore a critical mechanistic link between sleep physiology and motivational states that until now remained poorly understood at the level of circuit dynamics.

Employing cutting-edge neurophysiological recording techniques, the researchers monitored neuronal ensemble activity within the NAc of animal models engaged in food-seeking tasks. By synchronizing these recordings with sleep state analyses, they were able to capture real-time changes in neural firing patterns that correlated with varying sleep stages. Their data revealed that REM sleep—traditionally associated with memory consolidation and emotional processing—exerts a profound regulatory effect on the excitability and plasticity of NAc neurons involved in reward processing. This observation implicates REM sleep as a critical period during which the brain recalibrates motivational signals, fine-tuning the drive to seek out rewarding food stimuli during subsequent wakefulness.

Furthermore, the study elucidates the molecular underpinnings that enable sleep to modulate NAc function. Through molecular assays and pharmacological interventions, the authors identified alterations in dopaminergic signaling pathways within the NAc during different sleep phases. Dopamine, a neurotransmitter intimately tied to reward anticipation and reinforcement learning, displayed variable release patterns governed by sleep architecture. These neurochemical rhythms appear to gate the motivation circuitry, amplifying or dampening reward responsiveness dependent on the quality and quantity of sleep. Such intricate neurochemical interplay provides a mechanistic basis for observed behavioral changes and suggests potential targets for modulating pathological reward-seeking behaviors.

Beyond the immediate neural circuits, the research highlights the systemic nature of sleep’s influence on reward processing. Sleep deprivation or fragmentation, for instance, was shown to disrupt normal NAc dynamics, leading to aberrant food-seeking behavior marked by compulsivity or insensitivity to satiety signals. These behavioral deviations mirror phenotypes observed in eating disorders and obesity, hinting at a potential causal link mediated through disrupted sleep-regulated NAc activity. The implications are profound: improving sleep quality could become a novel therapeutic avenue for correcting maladaptive reward-driven eating and potentially other forms of impulse control disorders.

The methodology embraced by Almeida Rojo and colleagues is notable not only for its technical sophistication but also for its translational relevance. By integrating electrophysiological recordings, sleep scoring, behavioral assays, and neurochemical profiling, the study provides a holistic view of how neural circuits orchestrate food reward seeking within the temporal framework imposed by sleep cycles. This multi-modal approach sets a new standard for dissecting neurobehavioral phenomena, emphasizing the importance of temporal dynamics when investigating brain function.

Critically, the findings challenge conventional perspectives that view reward circuits as relatively static during rest periods. Instead, this work posits that sleep serves as an active modulatory state where neural ensembles involved in reward anticipation and motivation undergo synaptic remodeling and recalibration. This paradigm shift adds nuance to our understanding of sleep’s functional repertoire, extending it beyond passive restoration to encompass complex plasticity mechanisms that shape future behavior. Such insights underscore why chronic sleep disturbances wreak havoc not only on cognition but also on reward-driven behaviors and emotional regulation.

Moreover, the study opens exciting questions for future research. How might different types of rewards—social, monetary, or pharmacological—interact with NAc dynamics during sleep? Could targeted interventions during specific sleep phases enhance or diminish pathological reward seeking? The authors advocate for expanded investigations across species and experimental paradigms, aiming to translate these findings into clinical contexts such as substance use disorders, binge eating, and even depression-related anhedonia, where reward circuits are dysregulated.

Particularly compelling is the potential linkage between circadian rhythms and NAc-mediated reward circuits revealed through this work. The authors hypothesize that the temporal gating of dopamine release by sleep stages aligns with circadian control systems, integrating environmental cues with internal motivational states. This integrative framework posits that optimal reward seeking is achieved through synchronization across multiple neurobiological systems, a balance easily disrupted by modern lifestyle factors such as irregular sleep schedules and artificial light exposure, which are known to impair metabolic and mental health.

From a technological standpoint, the use of in vivo multi-electrode arrays combined with optogenetic manipulation allowed the precise interrogation of circuit components within the NAc. This enabled the team to causally link sleep-dependent changes in neural activity with observable shifts in motivation. By selectively activating or inhibiting specific neuronal subpopulations during defined sleep stages, researchers could mimic or block natural processes, validating the functional relevance of observed neural dynamics. Such experimental rigor strengthens the causal claims of the study and provides a blueprint for dissecting other complex sleep-behavior relationships.

The clinical implications of this research are multiple. Given the prevalent issues of sleep deprivation and disorders in modern societies, understanding how disrupted sleep affects reward-seeking behaviors could inform prevention and treatment strategies for obesity, addiction, and mood disorders. The work suggests that therapeutic approaches aiming to restore normal sleep architecture, possibly augmented by neuromodulatory techniques targeting NAc circuits, might recalibrate maladaptive motivational drives. This represents a promising intersection of neuroscience, sleep medicine, and behavioral therapy.

In conclusion, Almeida Rojo, Cai, Barnhardt, and their team have significantly advanced the field by elucidating how the nucleus accumbens dynamically integrates sleep-related information to regulate food reward seeking. Their research provides compelling evidence that sleep is not a passive backdrop but an active modulator of motivational neurocircuitry. Such insights deepen our understanding of the fundamental brain mechanisms linking sleep, motivation, and behavior and offer hopeful avenues for tackling reward-related disorders through sleep-centered interventions. As sleep science and neuropsychiatry converge, studies like this pave the way for a future where improved sleep hygiene could enhance not only cognitive health but also behavioral resilience.

Subject of Research: Nucleus accumbens dynamics in food reward seeking and how these are regulated by sleep.

Article Title: Nucleus accumbens dynamics in food reward seeking and regulation by sleep.

Article References: Almeida Rojo, A.L., Cai, L., Barnhardt, T.R. et al. Nucleus accumbens dynamics in food reward seeking and regulation by sleep. Transl Psychiatry 15, 219 (2025). https://doi.org/10.1038/s41398-025-03442-z

Image Credits: AI Generated

DOI: https://doi.org/10.1038/s41398-025-03442-z

Dr. Nestler’s scientific journey is characterized by pioneering methodologies that have redefined our understanding of brain adaptations in response to chronic stress and substance abuse. His laboratory has been at the forefront of utilizing viral-mediated gene transfer techniques coupled with inducible genetically engineered mouse models. These innovations allowed unprecedented manipulation of discrete neural circuits within the brain’s reward system, enabling causal investigations into how gene activity modulates behavior. This approach has provided vital mechanistic insights linking molecular changes with the characteristic behavioral phenotypes of addiction, such as compulsive drug seeking and relapse vulnerability.

Beyond dissecting addiction pathways, Dr. Nestler’s research unveiled shared molecular pathways underpinning diverse addiction modalities. His work revealed that common neurobiological mechanisms could govern seemingly distinct addictions, providing a unifying framework for understanding the neuroplasticity involved. Additionally, his laboratory developed one of the most robust mouse models for studying depression and related stress disorders, facilitating exploration of the critical role that reward-related brain circuits play in mood regulation. This animal model has since found resonance in human studies, confirming the translational validity of his findings and paving the way for potential novel therapeutic strategies.

The scope of Dr. Nestler’s research extends to epigenetics, where his team’s gene and chromatin analyses identified key proteins that mediate either susceptibility or resilience to chronic stress exposures. These discoveries have profound implications for psychiatry, as they suggest molecular targets for innovative treatments designed to fortify resilience or reverse maladaptive changes associated with depression and addiction. His work continues to inspire a paradigm shift, emphasizing the plasticity of neural circuits as a foundation for mental health interventions.

Since assuming leadership roles at Mount Sinai in 2016, Dr. Nestler has guided the Icahn School of Medicine’s academic and scientific agenda, advancing institutional research capabilities. As Interim Dean, his strategic focus encompasses fostering interdisciplinary collaborations and translating laboratory discoveries into clinical innovations. Under his stewardship, The Friedman Brain Institute has attracted top-tier scientists worldwide, positioning Mount Sinai as a powerhouse in neuropsychiatric research, with a dynamic emphasis on bridging fundamental neuroscience with patient-centered care.

Before joining Mount Sinai in 2008, Dr. Nestler made impactful contributions at UT Southwestern Medical Center as Chair of Psychiatry and at Yale University as Director of Molecular Psychiatry. His extensive publication record — exceeding 750 articles and five authoritative texts — reflects a career devoted to unraveling the intricacies of brain function and dysfunction. His scholarly influence has been recognized through numerous awards, including the Wilbur Cross Distinguished Alumnus Medal from Yale and the Peter Seeburg Prize in Integrative Neuroscience from the Society for Neuroscience.

Dr. Nestler’s experimental work has significantly advanced the field’s comprehension of how chronic drug exposure induces persistent changes in gene expression within reward-related brain regions such as the nucleus accumbens and ventral tegmental area. By selectively modulating transcription factors and epigenetic regulators, his lab demonstrated that these molecular alterations contribute to long-lasting modifications in synaptic connectivity and neuronal excitability, which manifest behaviorally as drug craving and relapse. These findings underscore the potential of targeting epigenetic mechanisms for developing novel pharmacotherapies.

The translational impact of his research is evident in his laboratory’s exploration of stress-induced plasticity, where they identified molecular signaling pathways mediating vulnerability or resistance to depressive-like behaviors in animal models. These insights inform clinical strategies aiming to identify biomarkers of susceptibility and tailor interventions accordingly. Moreover, the Nestler Laboratory’s work on chromatin remodeling highlights the dynamic nature of the epigenome as both a mediator and potential therapeutic target in neuropsychiatric disorders.

Mount Sinai’s election of Dr. Nestler to the NAS reflects not only his individual achievements but also the institution’s broader commitment to advancing neuroscience. Within the Mount Sinai faculty, six members, including Dr. Nestler, hold NAS memberships, underscoring the system’s prominence in scientific research. This collective expertise contributes to Mount Sinai’s reputation as an epicenter for innovative brain science, integrating basic research with clinical application to address some of the most intractable neurological and psychiatric diseases.

The recognition by leading Mount Sinai leadership captures the transformative role Dr. Nestler plays both scientifically and administratively. Brendan G. Carr, MD, CEO of Mount Sinai Health System, emphasized Dr. Nestler’s stature as a world-class neuroscientist whose research has the potential to impact millions suffering from brain disorders. Dennis S. Charney, Dean Emeritus of the Icahn School of Medicine, praised Dr. Nestler’s visionary leadership in shaping the next chapter of Mount Sinai’s neuroscience enterprise, built on a foundation of translational research and clinical excellence.

Mount Sinai Health System itself is a comprehensive academic medical entity comprising hospitals, outpatient practices, multiple research centers, and educational institutions. It harnesses cutting-edge technologies such as artificial intelligence and informatics to enhance patient care while advancing scientific discovery. This integrated approach ensures that discoveries from laboratories like Dr. Nestler’s are efficiently translated into innovative therapies, shaping the future of personalized neurological and psychiatric care on a global scale.

As Dr. Nestler steps into his role as Interim Dean of the Icahn School of Medicine following Dr. Charney’s retirement, his trajectory highlights a seamless transition of visionary scientific leadership committed to rigorous inquiry and clinical translation. His multifaceted expertise, ranging from molecular neurobiology to institutional stewardship, marks him as a pioneering figure in contemporary neuroscience. The field eagerly anticipates the continued impact of his work, which merges fundamental science with transformative potential for improving human mental health.

Subject of Research: Neuroscience, Molecular Mechanisms of Addiction and Depression
Article Title: [Not provided]
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Image Credits: Mount Sinai Health System
Keywords: Neuroscience, Addiction, Depression, Epigenetics, Brain Circuits, Molecular Psychiatry, Neuroplasticity, Translational Medicine, Icahn School of Medicine, Viral-Mediated Gene Transfer, Chromatin Remodeling, Neuropsychiatric Disorders