Association of Four Medication Classes and Non-suicidal Self-injury in Adolescents with Affective Disorders - A Retrospective Chart Review.

BACKGROUND: Non-suicidal self-injury (NSSI) behaviour is frequently observed in children and adolescents with psychiatric conditions. Affected individuals are regularly treated with psychotropic drugs, although the impact of these agents on NSSI behaviour remains elusive. METHODS: We performed a retrospective chart review from clinical routine data in a large cohort (N=1140) of adolescent inpatients with primary affective and non-affective psychiatric disorders according to ICD-10 (mean age=15.3±1.3 years; 72.6% female). Four separate mixed regression models compared the frequency of NSSI between treatment periods without any medication and four medication categories (benzodiazepines, selective serotonin reuptake inhibitors (SSRIs), high- and low-potency antipsychotics). RESULTS: In those individuals with affective disorders as the primary diagnosis, periods without medication were associated with significantly lower NSSI/day compared to all four other medication conditions (benzodiazepines p<10-8, antidepressants/SSRIs p=0.0004, high-potency antipsychotics p=0.0009, low-potency antipsychotics p<10 -4). In individuals with a primary diagnosis other than an affective disorder, NSSI was significantly lower during the period without medication compared to the treatment periods with benzodiazepines (p=0.005) and antidepressants/SSRIs (p=0.01). However, NSSI rates in the no-medication condition were comparable to NSSI rates under high-potency (p=0.89) and low-potency antipsychotics (p=0.53). CONCLUSIONS: The occurrence of NSSI correlates with the treatment with a psychotropic drug in children and adolescents with psychiatric disorders. Due to the retrospective design, it remains elusive to what extent psychotropic drugs might alter the frequency of NSSI in adolescents or if NSSI might indicate a transdiagnostic feature of more pronounced disease severity.

Psychotropic drugs for the treatment of non-suicidal self-injury in children and adolescents: a systematic review and meta-analysis.

Non-suicidal self-injury (NSSI) in children and adolescents is a frequent phenomenon. NSSI at any time is a significant predictor of future NSSI but also, and more importantly, for suicide attempts. Less evidence is available for the impact, or more specifically, the therapeutic effect of psychotropic drugs on the emergence of NSSI in this population. The phenomenon is clinically highly relevant since adolescent psychiatric inpatients are often affected by NSSI and most of them are treated with psychotropic drugs. While previous reviews on NSSI comprised suicidal self-injury (SSI), this review aims at elucidating the potential impact of psychotropic drugs on the emergence of specifically NSSI in children and adolescents. Systematic searches of articles indexed electronically in PubMed, Embase and PsycInfo were conducted (PROSPERO CRD42020209505). Studies included in the quantitative synthesis were evaluated using the SIGN level of evidence rating. Meta-analyses were performed using RevMan (Version 5.4). 2227 records were identified through database searches. Two additional records were identified manually. In total, seven studies were included in qualitative and four studies in quantitative analyses. In a meta-analysis, selective serotonin reuptake inhibitors (SSRIs) were compared vs. control medication (placebo or serotonin-norepinephrine reuptake inhibitor) and here, no statistically significant difference between the groups could be observed regarding the frequency of NSSI events (Risk Ratio (RR) = 1.07, 95% confidence interval (CI) 0.60-1.91, p = 0.82, I2 = 12%). Evidence regarding the association of SSRI use and NSSI among children and adolescents is sparse and the impact of psychotropic drugs in general on NSSI rates in this population should be addressed in future clinical and observational studies.

Conditioned place preference for social interaction in rats: contribution of sensory components.

A main challenge in the therapy of drug dependent individuals is to help them reactivate interest in non-drug-associated activities. We previously developed a rat experimental model based on the conditioned place preference (CPP) paradigm in which only four 15-min episodes of social interaction with a gender- and weight-matched male Sprague Dawley rat (1) reversed CPP from cocaine to social interaction despite continuing cocaine training and (2) prevented the reinstatement of cocaine CPP. In the present study, we investigated which of the sensory modalities of the composite stimulus "social interaction" contributes most to the rats' preference for it. If touch was limited by steel bars spaced at a distance of 2 cm and running across the whole length of a partitioning, CPP was still acquired, albeit to a lesser degree. If both rats were placed on the same side of a partitioning, rats did not develop CPP for social interaction. Thus, decreasing the available area for social interaction from 750 to 375 cm(2) prevented the acquisition of CPP to social interaction despite the fact that animals could touch each other more intensely than through the bars of the partitioning. When touch was fully restricted by a glass screen dividing the conditioning chambers, and the only sensory modalities left were visual and olfactory cues, place preference shifted to place aversion. Overall, our findings indicate that the major rewarding sensory component of the composite stimulus "social interaction" is touch (taction).

Differential effects of accumbens core vs. shell lesions in a rat concurrent conditioned place preference paradigm for cocaine vs. social interaction.

BACKGROUND: A main challenge in the therapy of drug dependent individuals is to help them reactivate interest in non-drug-associated activities. Among these activities, social interaction is doubly important because treatment adherence itself depends on it. We previously developed a rat experimental model based on the conditioned place preference (CPP) paradigm in which only four 15-min episodes of social interaction with a gender- and weight-matched male conspecific (i) reversed CPP from cocaine to social interaction despite continuing cocaine training and (ii) prevented the reinstatement of cocaine CPP. In the present study, we investigated if the two subregions of the nucleus accumbens (Acb), i.e., the core (AcbC) and the shell (AcbSh), would differentially affect CPP for cocaine vs social interaction. METHODOLOGY/PRINCIPAL FINDINGS: Animals were concurrently trained for CPP pairing cocaine with one compartment and social interaction with the other (i.e., mutually exclusive stimulus presentation during training). Excitotoxic lesioning of the AcbC or the BLA shifted CPP toward social interaction, whereas AcbSh inactivation shifted CPP toward cocaine. CONCLUSIONS: Overall, our findings suggest that inactivation of the AcbC or the BLA is sufficient to shift CPP away from a drug of abuse toward social interaction. Lesioning the AcbSh produced the opposite effect.