Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.64898/2026.06.24.734301

A Meta-Analysis of the Converging Effects of Different Classes of Antipsychotics on the Frontal Cortex Transcriptome in Laboratory Rodents and Non-Human Primates

Bhuiyan, M. R.·Hagenauer, M. H.·Geoghegan, E. M.·Flandreau, E. I.·Watson, S. J.·Akil, H.
View original source ↗Export metadata ↓

Abstract

BackgroundPsychotic illnesses are among the most debilitating classes of psychiatric disorders, requiring targeted and effective treatment strategies. Although antipsychotics are the primary pharmacological therapy for psychosis, their full range of effects remain unclear, including effects within the frontal cortex, a brain region linked structurally and functionally to psychotic disorders. MethodsTo examine the effects of antipsychotic treatment on the frontal cortex, we conducted a meta-analysis of publicly available rodent (rat, mice) transcriptional profiling datasets (microarray, RNA-Seq). Five datasets (GSE45229, GSE93918, GSE2547, GSE4031.1, GSE66275) were identified within the Gemma database using pre-specified search terms and inclusion/exclusion criteria (date: 7/7/2024), yielding differential expression results for eight drug vs. control comparisons (collective n=68). A random-effects meta-analysis model was fit to the log2 fold changes for each gene, and p-values adjusted for false discovery rate (FDR), with follow-up analyses exploring robustness, heterogeneity, and publication bias. To increase the power and generalizability of our findings, an exploratory meta-analysis was also run incorporating antipsychotic effects from both rodents and nonhuman primates (collective n=101), and compared to findings from individuals with schizophrenia. ResultsOur meta-analysis yielded stable estimates for 12,190 genes, identifying 63 genes that were differentially expressed following antipsychotic treatment ("DEGs", FDR<0.05). Differential expression included genes important for serotonergic and cholinergic signalling, and was enriched within pathways linked to oligodendrocyte development and myelination, physiological and cellular stress responses, and cardiovascular function. An exploratory meta-analysis combining rodent and nonhuman primate results confirmed these observations and yielded additional findings (117 DEGs total). Comparisons with human post-mortem findings suggested that some schizophrenia-related gene expression may instead reflect antipsychotic treatment. ConclusionFurther validation is necessary, but our findings suggest that antipsychotics may assist in the regulation of specific structural and functional changes within the frontal cortex linked to psychotic disorders. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=104 SRC="FIGDIR/small/734301v1_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@1aaa2ecorg.highwire.dtl.DTLVardef@1ae6819org.highwire.dtl.DTLVardef@13454a2org.highwire.dtl.DTLVardef@a0877c_HPS_FORMAT_FIGEXP M_FIG C_FIG Key PointsO_LIPsychosis is treated using two broad types of antipsychotic medication: first-generation (typical) and second-generation (atypical). C_LIO_LIUnderstanding the congruent effects of different types of antipsychotics on regions important for psychosis, such as the frontal cortex, can highlight essential mechanisms. C_LIO_LIA meta-analysis of public transcriptional profiling datasets identified genes and functional gene sets that are differentially expressed across antipsychotic categories. C_LI

Explore related subjects

neurosciencePreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Bhuiyan, M. R., Hagenauer, M. H., Geoghegan, E. M., Flandreau, E. I., Watson, S. J., Akil, H.. 2026-06-29. A Meta-Analysis of the Converging Effects of Different Classes of Antipsychotics on the Frontal Cortex Transcriptome in Laboratory Rodents and Non-Human Primates. https://doi.org/10.64898/2026.06.24.734301

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Same Movements, Different Skills: How Context Shapes Learning in Humans and Neural Networks

What determines whether experiences are integrated into shared representations or split? Motor skill learning offers a revealing test: when two tasks require an identical sequence of movements, both intuition and theory suggest that practice in one should generalize to the other. Yet we find that changing context can make identical movements different skills. In simple recurrent networks trained on the same sequence across contexts, splitting was greatest when strong contextual inputs coincided with a high initial weight scale; neither alone sufficed. Greater representational separation coincided with separate context-specific learning curves. Humans practicing the same finger sequence while alternating between two performance-irrelevant contexts likewise exhibited context-specific curves, rather than the single continuous trajectory observed when practicing in a single context. State-space modeling favored split learning states in humans and very weakly coupled states in the most context-dependent networks. These findings have broader implications for understanding how learning generalizes across contexts.

neuroscience↗
bioRxiv2026

Postpartum resource scarcity reshapes maternal care, offspring prioritization, and the steroid-sensitive medial preoptic area

Parental care requires balancing offspring needs with environmental constraints, yet how resource scarcity alters the organization of maternal responses remains poorly understood. Here, we examined maternal behavior, offspring prioritization, and steroid receptor-associated extracellular matrix organization in postpartum rats exposed to limited bedding and nesting (LBN) or control conditions with ample nesting materials. LBN increased pup-directed and reduced self-directed behaviors but also increased behavioral entropy, a measure of behavioral fragmentation, indicating less predictable caregiving sequences. LBN dams preferentially retrieved male pups first, whereas control dams preferentially retrieved females first. LBN also increased the proportion of pup-investigation time directed toward males compared with controls. In offspring on postnatal day 10, corticosterone was elevated in female but not male LBN pups, a pattern that paralleled the maternal male bias. To identify associated neurobiological changes, we assessed steroid receptors and extracellular matrix organization in the medial preoptic area (mPOA), a key region for maternal behavior. LBN increased numbers of estrogen receptor (ER)- and androgen receptor (AR)-immunoreactive cells, reduced perineuronal net (PNN) abundance, and decreased receptor-positive cell enwrapment. Because PNNs constrain structural plasticity, these findings suggest that the postpartum environment alters the organization of steroid receptor-associated extracellular matrix, potentially modulating experience-dependent plasticity in neurosteroid-sensitive circuits. In sum, LBN increases the levels of maternal engagement while reshaping its temporal organization and allocation, accompanied by selective remodeling of steroid-sensitive preoptic architecture. Therefore, maternal adaptation to adversity may be better understood as changes in caregiving allocation strategies rather than a simple gain or loss of maternal care.

neuroscience↗
bioRxiv2026

The Computational Grammar of Human Behaviour in a Biological Environment

Human behaviour unfolds as an extended stream of spontaneous actions shaped by environmental demands and the agent's goals. The organisation of these actions, situated between setting abstract goals and concrete movement execution, remains poorly characterised. Here, we introduce DynaClade, an unsupervised temporal action segmentation algorithm for human full-body motion capture data, and apply it to freely moving participants navigating ecologically realistic risky foraging environments in virtual reality. DynaClade identifies discrete actions whose kinematic characteristics and spatial distributions correspond to environmental affordances, supporting the validity of the approach. Among these actions, we discovered a hitherto undescribed movement pattern defined by increased body sway without locomotion. Action sequences were highly non-random and showed clear history dependence beyond first-order Markov structure, most of which was explained by a second-order prediction. This higher-order structure was well captured in a hidden Markov model, in which some of the observed actions were associated with more than one latent state. Each of these latent states corresponded to the same action in a distinct action context. These findings suggest that spontaneous human actions are predominantly selected based on the current action and context, rather than following pre-planned or habitually assembled sequences.

neuroscience↗