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Human neuropsychiatric disorders are associated with genetic and environmental factors affecting the brain, which has been subjected to strong evolutionary pressures resulting in an enlarged cerebral cortex and improved cognitive performance. Thus, genes involved in human brain evolution may also play a role in neuropsychiatric disorders. We test whether genes associated with 7 neuropsychiatric phenotypes are enriched in genomic regions that have experienced rapid changes in human evolution (HARs) and importantly, whether HAR status interacts with developmental brain expression to predict associated genes. We used the most recent publicly available GWAS and gene expression data to test for enrichment of HARs, brain expression, and their interaction. These revealed significant interactions between HAR status and whole-brain expression across developmental stages, indicating that the relationship between brain expression and association with schizophrenia and intelligence is stronger among HAR than non-HAR genes. Follow-up regional analyses indicated that predicted HAR-expression interaction effects may vary substantially across regions and developmental stages. Although depression indicated significant enrichment of HAR genes, little support was found for HAR enrichment among bipolar, autism, ADHD, or Alzheimer's associated genes. Our results indicate that intelligence, schizophrenia, and depression-associated genes are enriched for those involved in the evolution of the human brain. These findings highlight promising candidates for follow-up study and considerations for novel drug development, but also caution careful assessment of the translational ability of animal models for studying neuropsychiatric traits in the context of HARs, and the importance of using humanized animal models or human-derived tissues when researching these traits.

Neuroscientific research on pleasant touch has focused on the C-tactile pathway for gentle stroking and has successfully explained how these sensory fibers transmit information about affective social touch to the brain and induce sensations of pleasantness. The C-tactile social/affective touch hypothesis even proposes that C-tactile fibers form a privileged pathway underlying social touch. However, deep pressure is a type of touch commonly considered pleasant and calming, occurring in hugs, cuddling, and massage. In this paper we introduce a paradigm for studying pleasant deep pressure and propose that it constitutes another important form of social touch. We describe development of the oscillating compression sleeve (OCS) as one approach to administering deep pressure and demonstrate that this touch is perceived as pleasant and calming. Further, we show that deep pressure can be imaged with functional magnetic resonance imaging (MRI) using the air-pressure-driven OCS and that deep pressure activates brain regions highly similar to those that respond to C-tactile stroking, as well as regions not activated by stroking. We propose that deep pressure constitutes another social touch pathway of evolutionary importance signaling the close proximity of conspecifics.

Both light skin stroking (engaging the C-tactile afferent sensory pathway) and deep pressure touch (as in deep tissue massage) are commonly perceived as pleasant and relaxing. Opioid blockade has been found to increase receipt of grooming in monkeys, suggesting possible opioid modulation of touch pleasantness. Recently, human data [1] suggested that blocking opioid receptors might decrease the perceived intensity of gentle brushing but increase its pleasantness. The current study examined the role of endogenous opioids in the perceived intensity and pleasantness of pleasant touch. Using a double-blind cross-over design, 24 healthy adult participants received intravenous naloxone or saline (control) on separate days. Blocks of gentle brushing and deep pressure compression were administered on the lower left calf. Participants rated the intensity and pleasantness of each stimulus, as well as current mood and anxiety. Naloxone significantly reduced perceived intensity of gentle brushing (p = 0.039), but did not affect brushing pleasantness (p = 0.44) or intensity or pleasantness of deep pressure (p = 0.97; p = 0.85). The naloxone-induced reduction in gentle touch intensity replicates results previously seen in chronic pain patients [1]. The lack of effect on pleasantness in this study versus [1] could relate to differences in the location of touch (arm or leg), sex of the experimenters, or whether the touch followed pain tasks. However, in the current study, naloxone was marginally anxiolytic (p = 0.07), and naloxone-induced changes in touch pleasantness were significantly more correlated with subsequent mood and anxiety ratings than were changes during saline (mood p = 0.04; anxiety p