Pitt Psychiatry Research Published in Molecular Psychiatry
Multiple Pitt Psychiatry investigators have recently published studies in Molecular Psychiatry. Below is a roundup of recent original research on adolescent neurodevelopment, aging and cognition, and the association between sleep and psychosis.
Pitt Psychiatry investigators used a novel, non-invasive, neuroimaging marker that is sensitive to developmental changes in dopamine to examine how it contributed to plastic changes in excitation and inhibition in the prefrontal cortex, as well as cognitive function, throughout adolescence. They demonstrate that dopamine function supports adolescent changes in prefrontal glutamate, and the relative balance between glutamate and GABA, as well as age-related improvements in cognition. Together, these results provide support for a model whereby dopamine plays an important role in sculpting prefrontal cortex physiology and higher-order cognition during the critical transition from adolescence to adulthood.
Ashely Parr, PhD (Research Assistant Professor of Psychiatry), serves as first and corresponding author, with Beatriz Luna, PhD (Distinguished Professor of Psychiatry and Professor of Psychology, Bioengineering and Radiology, and Staunton Professor of Pediatrics and Psychiatry), as senior author.
Parr AC, Perica MI, Calabro FJ, Foran W, Moon CH, Hetherington H, Luna B.
Molecular Psychiatry. 2024 Dec 9. doi: 10.1038/s41380-024-02860-7. Epub ahead of print. PMID: 39653761.
A team of scientists published a study identifying age-related changes in the density of large dendritic spines within the precuneus, an area selectively vulnerable to early accumulation of Alzheimer disease-related pathology. In addition, they identified 203 proteins that statistically mediate the effect of age on large dendritic spine density. Using computational pharmacology, the team identified ten drugs that are predicted to therapeutically target these mediators, informing future studies designed to test their effects on age-related dendritic spine loss and cognitive decline.
Joshua Krivinko, MD (postdoctoral scholar) serves as first author, with Robert Sweet, MD (UPMC Endowed Professor in Psychiatric Neuroscience and Professor of Neurology) and Matthew MacDonald, PhD (Associate Professor of Psychiatry), as senior authors.
Krivinko JM, Fan P, Sui Z, Happe C, Hensler C, Gilardi J, Ikonomovic MD, McKinney BC, Newman J, Ding Y, Wang L, Sweet RA, MacDonald ML.
Molecular Psychiatry (2024). https://doi.org/10.1038/s41380-024-02817-w
Aging disrupts the coordination between mRNA and protein expression in mouse and human midbrain
A team of investigators examined whether age-related dopamine neuron loss—a primary feature of Parkinson’s disease—also occurs during healthy aging, but to a lesser degree. They demonstrated loss of coordination between mRNA and protein expression during aging that is highly conserved between mouse and human midbrain. These results also suggest age-associated homeostatic mechanisms that maintain protein expression by maintaining expression of ribosomal genes. Ultimately, these findings highlight an important set of biological changes associated with aging within both mouse and human dopamine and glutamate systems.
Silas Buck, PhD (postdoctoral associate, Duke University), and Sam Mabry, PhD (postdoctoral associate, University of Pittsburgh), serve as co-first authors, with Zachary Freyberg, MD, PhD (Associate Professor of Psychiatry and Cell Biology), as senior author.
Buck SA, Mabry SJ, Glausier JR, Banks-Tibbs T, Ward C, Kozel J, Fu C, Fish KN, Lewis DA, Logan RW, Freyberg Z.
Molecular Psychiatry (2025). https://doi.org/10.1038/s41380-025-02909-1
Pitt Psychiatry scientists employed a multimodal imaging approach to investigate mediodorsal thalamus-dorsolateral prefrontal cortex dysfunctions in the at-risk for psychosis state. In the current study, they demonstrated thalamocortical connectivity and sleep spindle deficits in clinical high-risk for psychosis vs. unaffected comparison subjects, which were associated with glutamate/creatine levels and pointed to distinct alterations in the mediodorsal thalamus-dorsolateral prefrontal cortex circuit. Furthermore, using thalamocortical connectivity and sleep spindle parameters to identify clinical high-risk for psychosis and unaffected comparison subgroups and predict their working memory performance, the authors found that those with intact connectivity and spindle duration were almost all unaffected comparison subjects, while individuals with both measures altered were virtually all clinical high-risk for psychosis and showed worse working memory performances. Building on these findings, future work utilizing multimodal imaging combined with computational psychiatry may help establish the mediodorsal thalamus-dorsolateral prefrontal cortex circuit and related functional measures as a putative biological target for early, personalized interventions in at-risk individuals aimed at improving their cognitive functioning.
Ahmadreza Keihani, PhD (postdoctoral associate), and Francesco Donati, MD (Research Instructor in Psychiatry), serve as co-first authors, with Ahmad Mayeli, PhD (Research Assistant Professor of Psychiatry), and Fabio Ferrarelli, MD, PhD (Associate Professor of Psychiatry), as senior authors.
Keihani A, Donati FL, Janssen SA, Huston CA, Moon CH, Hetherington HP, Wilson JD, Mayeli A, Ferrarelli F.
Molecular Psychiatry (2025). https://doi.org/10.1038/s41380-025-02924-2