Reward responsivity and habit formation in the co-occurrence of restrictive eating and nonsuicidal self-injury.

Dysfunctions in reward and/or habit formation have been proposed as factors contributing individually to the maintenance of restrictive eating and nonsuicidal self-injury (NSSI). However, despite the high comorbidity between these behaviors, the associations between reward and habit formation in their co-occurrence remains unclear. This study examined self-reported reward responsivity and habit strength among individuals with co-occurring restrictive eating and NSSI (Comorbid group; n = 108) and those with one behavior only (One-behavior group; n = 113). Hierarchical logistic regression analyses assessed the association between reward and habit features and the co-occurrence of restrictive eating and NSSI, accounting for the effects of impulsivity (a characteristic commonly considered to underlie co-occurring disordered eating and NSSI). Partial correlations examined the relationships between these features and the severity of eating disorder and NSSI symptoms, also controlling for impulsivity. Lower reward responsivity was associated with the co-occurrence of restrictive eating and NSSI, even after accounting for impulsivity (p = 0.017). In exploratory analyses, this relationship was no longer significant after accounting for self-reported depression. No significant associations were found regarding habit formation and restrictive eating and NSSI co-occurrence. Lower reward responsivity was linked to increased NSSI frequency and versatility in both groups and associated with severity of eating pathology in the Comorbid group (ps < 0.05). Our findings suggest that blunted reward responsivity may relate to the co-occurrence of restrictive eating, NSSI, and depressive symptoms, as well as the severity of restrictive eating and NSSI. Reward disturbances may serve as a crucial target in the treatment of multiple self-destructive behaviors.

Decreased gray matter volume in regions associated with affective pain processing in unmedicated individuals with nonsuicidal self-injury.

Nonsuicidal self-injury (NSSI) has been consistently associated with a reduced aversion to physical pain. Yet, little research has been done to investigate the brain structures related to pain in individuals with NSSI. This study examined gray matter volume patterns of pain processing regions in participants engaging in NSSI (n = 63) and age-, sex-, and handedness-matched healthy controls (n = 63). Voxel-based morphometry was performed to explore gray matter volume in regions of interest (ROIs) and partial correlation analyses were conducted to identify their associations with the frequency, versatility, duration, functions, and pain intensity of self-injury. As a result, significant volume decreases were found in the right anterior insula, bilateral secondary somatosensory cortex (SII), and left inferior frontal gyrus. Moreover, individuals with smaller anterior insula and SII volume showed a higher likelihood of endorsing affect-regulation and sensation-seeking functions of NSSI, as well as engaging in self-injury with a greater perceived intensity of pain. Our results provide the first empirical evidence that individuals with NSSI may exhibit distinct characteristics in brain regions associated with the affective component of pain processing. These neurobiological changes may be associated with their maladaptive response to noxious and painful NSSI experiences.

Population pharmacokinetics of palonosetron and model-based assessment of dosing strategies.

PURPOSE: Palonosetron is the most recent 5-hydroxytryptamine-3 receptor antagonist, and its fixed dose of 0.075 mg is indicated for the prevention of postoperative nausea and vomiting. This study aimed to examine whether fixed dosing is more appropriate than body size-based dosing through the development of a population pharmacokinetic model and model-based simulations. METHODS: Fifty-one adult patients undergoing general anesthesia received single intravenous palonosetron administrations 30 min before the end of surgery. Palonosetron concentrations were measured in blood samples collected at various timepoints within 48 h. A population pharmacokinetic analysis was performed by non-linear mixed-effects modeling, and the area under the curves (AUCs) for fixed dosing and body size-based dosing were simulated. RESULTS: The pharmacokinetics of palonosetron were best described by the three-compartment model, and lean body weight (LBW) was the most significant covariate for all pharmacokinetic parameters. In a patient with LBW of 40 kg, typical clearance and central volume of distribution were 0.102 L/min and 6.98 L, respectively. In simulations, the overall interindividual variability in AUC (0, 48 h) of fixed dosing was not much higher than that of body size-based dosing. In subgroup analysis, the AUCs (0, 48 h) of fixed dosing were considerably lower in the high-weight subgroup and higher in the low-weight subgroup than the median-weight subgroup. In contrast, LBW-based dosing showed similar AUC distributions among the three subgroups. CONCLUSION: LBW-based dosing might be suitable for high-weight patients to avoid possible underdosing. Nevertheless, the current fixed dosing of palonosetron is acceptable for adult patients with normal weight.