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AimThis study aimed to explore the effect of intermittent theta burst stimulation (iTBS) of the right and left dorsolateral prefrontal cortex (DLPFC) in people with self-reported dysregulated eating behaviors but without a diagnosis of eating disorders (EDs).MethodsParticipants were randomly divided into two equivalent groups according to the side (right or left) of the hemisphere to be stimulated and they were tested before and after a single iTBS session. Outcome measurements were scores on self-report questionnaires assessing psychological dimensions related to eating behaviors (EDI-3), anxiety (STAI-Y), and tonic electrodermal activity.ResultsThe iTBS interfered with both psychological and neurophysiological measures. Significant variations of physiological arousal after iTBS of both the right and left DLPFC were witnessed by increased mean amplitude of non-specific skin conductance responses. With regard to the psychological measures, the iTBS on the left DLPFC significantly reduced the scores of the EDI-3 subscales drive for thinness and body dissatisfaction. Interestingly, these two scales are two of the three EDI-3 clinic scales (drive for thinness, body dissatisfaction, and bulimia) used as specific markers to assess the onset and/or maintenance of eating disorders.ConclusionOur results show that the left DLPFC iTBS has an impact on the psychological dimensions that are risk factors for the onset of eating disorders, suggesting that an altered hemispheric asymmetry similar to that encountered in clinical populations is present in normal subjects even in the absence of clinical symptoms.

Very preterm (VPT) infants need long-lasting hospitalization in the Neonatal Intensive Care Unit (NICU) during which they are daily exposed to pain-related stress. Alterations of DNA methylation at the promoter region of the SLC6A4 have been associated with early adverse experiences in infants. The main aim of the present work was to investigate the association between level of exposure to pain-related stress during hospitalization and changes in SLC6A4 DNA methylation at NICU discharge in VPT infants. In order to exclude the potential effect of birth status (i.e., preterm vs. full-term birth) on SLC6A4 methylation, we preliminarily assessed SLC6A4 epigenetic differences between VPT and full-term (FT) infants at birth. Fifty-six VPT and thirty-two FT infants participated in the study. The level of exposure to pain-related stress was quantified on the basis of the amount of skin-breaking procedures to which they were exposed. VPT infants were divided in two sub-groups: low-pain exposure (LPE, N = 25) and high-pain exposure (HPE, N = 31). DNA methylation was evaluated at birth for both VPT and FT infants, assessing 20 CpG sites within the SLC6A4 promoter region. The same CpG sites were re-evaluated for variations in DNA methylation at NICU discharge in LPE and HPE VPT infants. No differences in SLC6A4 CpG sites’ methylation emerged between FT and VPT infants at birth. Methylation at CpG sites 5 and 6 significantly increased from birth to NICU discharge only for HPE VPT infants. Findings show that preterm birth per se is not associated with epigenetic alterations of the SLC6A4, whereas higher levels of pain-related stress exposure during NICU stay might alter the transcriptional functionality of the serotonin transporter gene.

Parkinson’s disease is a common neurodegenerative disorder caused by the degeneration of midbrain substantia nigra dopaminergic neurons that project to the striatum. Despite extensive investigation aimed at finding new therapeutic approaches, the dopamine precursor molecule, 3,4-dihydroxyphenyl-L-alanine (L-DOPA), remains the most effective and commonly used treatment. However, chronic treatment and disease progression lead to changes in the brain’s response to L-DOPA, resulting in decreased therapeutic effect and the appearance of dyskinesias. L-DOPA-induced dyskinesia (LID) interferes significantly with normal motor activity and persists unless L-DOPA dosages are reduced to below therapeutic levels. Thus, controlling LID is one of the major challenges in Parkinson’s disease therapy. LID is the result of intermittent stimulation of supersensitive D1 dopamine receptors located in the very severely denervated striatal neurons. Through increased coupling to Gαolf, resulting in greater stimulation of adenylyl-cyclase, D1 receptors phosphorylate DARPP-32 and other protein kinase A targets. Moreover, D1 receptor stimulation activates ERK and triggers a signaling pathway involving mTOR and modifications of histones that results in changes in translation, chromatin modification and gene transcription. In turn, sensitization of D1 receptor signaling causes a widespread increase in the metabolic response to D1 agonists and changes in the activity of basal ganglia neurons that correlate with the severity of LID. Importantly, different studies suggest that dyskinesias may share mechanisms with drug abuse and long term memory involving D1 receptor activation. Here we review evidence implicating D1 receptor signaling in the genesis of LID, analyze mechanisms that may translate enhanced D1 signaling into dyskinetic movements, and discuss the possibility that the mechanisms underlying LID are not unique to the Parkinson’s disease brain.