Effects of acute tryptophan depletion on central processing of CT-targeted and discriminatory touch in humans

C‐tactile afferents (CTs) are slowly conducting nerve fibres, present only in hairy skin. They are optimally activated by slow, gentle stroking touch, such as those experienced during a caress. CT stimulation activates affective processing brain regions, alluding to their role in affective touch perception. We tested a theory that CT‐activating touch engages the pro‐social functions of serotonin, by determining whether reducing serotonin, through acute tryptophan depletion, diminishes subjective pleasantness and affective brain responses to gentle touch. A tryptophan depleting amino acid drink was administered to 16 healthy females, with a further 14 receiving a control drink. After 4 h, participants underwent an fMRI scan, during which time CT‐innervated forearm skin and CT non‐innervated finger skin was stroked with three brushes of differing texture, at CT‐optimal force and velocity. Pleasantness ratings were obtained post scanning. The control group showed a greater response in ipsilateral orbitofrontal cortex to CT‐activating forearm touch compared to touch to the finger where CTs are absent. This differential response was not present in the tryptophan depleted group. This interaction effect was significant. In addition, control participants showed a differential primary somatosensory cortex response to brush texture applied to the finger, a purely discriminatory touch response, which was not observed in the tryptophan depleted group. This interaction effect was also significant. Pleasantness ratings were similar across treatment groups. These results implicate serotonin in the differentiation between CT‐activating and purely discriminatory touch responses. Such effects could contribute to some of the social abnormalities seen in psychiatric disorders associated with abnormal serotonin function. C‐tactile afferents (CTs) are present in hairy skin, responding to caress‐like touch and hypothesized to provide the neural substrate for affective touch. Acute tryptophan depletion (TRP‐) and fMRI were used to investigate the role of serotonin in central responses to CT vs. non‐CT touch. Findings implicate a role for serotonin in differentiating between CT/non‐CT touch, providing a potential mechanism underlying altered touch responses in psychiatric disorders such as depression and autism.