The disruption of brain energy metabolism, leading to alterations in synaptic signaling, neural circuitry, and neuroplasticity, has been implicated in severe mental illnesses such as schizophrenia, bipolar disorder, and major depressive disorder. The therapeutic potential of ketogenic interventions in these disorders suggests a link between metabolic disturbances and disease pathology; however, the precise mechanisms underlying these metabolic disturbances, and the therapeutic effects of metabolic ketogenic therapy, remain poorly understood. In this study, we conducted an in silico analysis of transcriptomic data to investigate perturbations in metabolic pathways in the brain across severe mental illnesses via gene expression profiling. We also examined dysregulation of the same pathways in rodent or cell culture models of ketosis, comparing these expression profiles to those observed in the disease states. Our analysis revealed significant perturbations across all metabolic pathways, with the greatest perturbations in glycolysis, the tricarboxylic acid (TCA) cycle, and the electron transport chain (ETC) across all three disorders. Additionally, we observed some discordant gene expression patterns between disease states and ketogenic intervention studies, suggesting a potential role for ketone bodies in modulating pathogenic metabolic changes. Our findings highlight the importance of understanding metabolic dysregulation in severe mental illnesses and the potential therapeutic benefits of ketogenic interventions in restoring metabolic homeostasis. This study provides insights into the complex relationship between metabolism and neuropsychiatric disorders and lays the foundation for further experimental investigations aimed at appreciating the implications of the present transcriptomic findings as well as developing targeted therapeutic strategies.

The relationship between paraquat exposure and Parkinson's disease (PD) has been extensively studied. Numerous paraquat-induced rodent models of PD have been developed, however, substantial variability in dosing regimens and study design complicates interpretation. Improving the translational relevance of these models is critical. The aim of this systematic review and meta-analysis was to evaluate the face validity of paraquat-induced rodent models of PD. Studies which quantitatively evaluated substantia nigra pars compacta (SNpc) neuronal loss and behavioral motor deficits were included. An electronic search in three databases was performed. A systematic review and meta-analysis was performed of 54 studies (84 experimental groups). Random-effects meta-analyses of continuous data showed a significant effect of SNpc neuronal loss (SMD=3.07, 95% CI 2.48, 3.65; I²=78.1%; p < 0.0001) and motor deficit in studies using the rotarod test, open field test, rearing, and gait analysis, but not the pole test. Subgroup analyses and meta-regression for varying studying characteristics did not account for all heterogeneity. A random-effects meta-analysis of binary data for the event that a significant motor deficit was observed according to the percent SNpc neuron loss revealed a pooled odds ratio (OR=5.08, 95% CI 0.96, 26.83; I²=71.4%; p = 0.0009) and favored a motor deficit in experimental groups that had 26% or greater SNpc neuronal loss. We discuss here how varying study characteristics contribute to the heterogeneity in results across studies. Our findings support the continued use of paraquat-induced rodent models of PD as translationally relevant models, and we highlight the importance of applying appropriate study characteristics in future studies.

Ventriculoperitoneal (VP) shunts are a common use for the treatment of hydrocephalus, which is a condition causing excessive cerebrospinal fluid (CSF) buildup in the brain. The shunt drains the CSF from the brain and into the abdomen, where it can be absorbed by the body. Although a widely used and successful procedure, it is unclear whether neurosurgical placement of this shunt may directly cause psychiatric abnormalities, especially regarding the dopaminergic system. In this paper, we first review relevant literature and discuss the dopamine circuitry in the brain. The literature suggests a shunt-associated clinical syndrome, which may include a reduction in facial and/or verbal expressivity, reduced willful movement, rigidity, and vertical gaze palsy. Typical presentation occurs within three months of a shunt revision. In patients with a VP shunt, these signs may be a strong indicator of mechanical or functional shunt malfunction. We then present two cases of hydrocephalus managed with a VP shunt, where both patients developed symptoms suggestive of psychosis and/or dopamine pathway pathology after shunt placement. We conclude that clinicians should have a suspicion for shunt-associated symptomology in patients with a history of recently treated hydrocephalus who present with psychomotor, personality, or cognitive changes.

Paw preference in rats is widely used to study hemispheric lateralization, but many individual studies are underpowered and employ inconsistent methods, leading to conflicting reports of population-level bias. We conducted a PRISMA-compliant systematic review and meta-analysis to determine whether rats consistently display paw preference at the individual and population levels, and to evaluate the influence of behavioral test type, strain, sex, and age. Studies published between 1930 and 2025 were identified through PubMed, Google Scholar, and ScienceDirect. Data were extracted on strain, age, sex, behavioral paradigm, and paw-preference classification. Random-effects models were used to estimate pooled prevalence, with subgroup analyses for key variables. Forty studies (n = 1,609 rats) met inclusion criteria. At the individual level, 84% of rats displayed consistent paw preference (95% CI: 78–89%, p < 0.0001), demonstrating robust individual-level lateralization. However, population-level analyses showed no universal directional bias, right paw use occurred in 48% of rats (95% CI: 43–54%) and left paw use in 39% (95% CI: 34–44%). Ambidextrous classification thresholds were standardized across studies to ensure comparability. Subgroup analyses indicated modest strain- and test-dependent effects, with Sprague Dawley rats tending toward balanced paw use, while other strains showed slight rightward bias. Skilled-reaching tasks produced slightly stronger asymmetry than the Collins test. Sex- and age-related differences were subtle and inconsistent. Overall, rats exhibit reliable individual-level paw preference without species-wide directional asymmetry, distinguishing them from humans. Standardized testing protocols and balanced cohort designs will enhance reproducibility and translational relevance in lateralization research.

The disruption of brain energy metabolism, leading to alterations in synaptic signaling, neural circuitry, and neuroplasticity, has been implicated in severe mental illnesses such as schizophrenia, bipolar disorder, and major depressive disorder. The therapeutic potential of ketogenic interventions in these disorders suggests a link between metabolic disturbances and disease pathology; however, the precise mechanisms underlying these metabolic disturbances and the therapeutic effects of metabolic ketogenic therapy remain poorly understood. In this study, we conducted an in silico analysis of transcriptomic data to investigate perturbations in metabolic pathways in the brain across severe mental illnesses via gene expression profiling. We also examined dysregulation of the same pathways in rodent or cell culture models of ketosis, comparing these expression profiles to those observed in the disease states. Our analysis revealed significant perturbations across all metabolic pathways, with the greatest perturbations in glycolysis, the tricarboxylic acid (TCA) cycle, and the electron transport chain (ETC) across all three disorders. Additionally, we observed some discordant gene expression patterns between disease states and ketogenic intervention studies, suggesting a potential role for ketone bodies in modulating pathogenic metabolic changes. Our findings highlight the importance of understanding metabolic dysregulation in severe mental illnesses and the potential therapeutic benefits of ketogenic interventions in restoring metabolic homeostasis. This study provides insights into the complex relationship between metabolism and neuropsychiatric disorders and lays the foundation for further experimental investigations aimed at appreciating the implications of the present transcriptomic findings as well as developing targeted therapeutic strategies.