Potential gray matter unpruned in adolescents and young adults dependent on dextromethorphan-containing cough syrups: evidence from cortical and subcortical study

Abstract

Adolescence is a unique period in neurodevelopment. Dextromethorphan (DXM)-containing cough syrups are new addictive drugs used by adolescents and young adults. The effects of chronic DXM abuse on neurodevelopment in adolescents and young adults are still unknown. The aim of this study was to investigate the differences in cortical thickness and subcortical gray matter volumes between DXM-dependent adolescents and young adults and healthy controls, and to explore relationships between alternations in cortical thickness/subcortical volume and DXM duration, initial age of DXM use, as well as impulsive behavior in DXM-dependent adolescents and young adults. Thirty-eight DXM-dependent adolescents and young adults and 18 healthy controls underwent magnetic resonance imaging scanning, and cortical thickness across the continuous cortical surface was compared between the groups. Subcortical volumes were compared on a structure-by-structure basis. DXM-dependent adolescents and young adults exhibited significantly increased cortical thickness in the bilateral precuneus (PreC), left dorsal lateral prefrontal cortex (DLPFC. L), left inferior parietal lobe (IPL. L), right precentral gyrus (PreCG. R), right lateral occipital cortex (LOC. R), right inferior temporal cortex (ITC. R), right lateral orbitofrontal cortex (lOFC. R) and right transverse temporal gyrus (TTG. R) (all p < 0.05, multiple comparison corrected) and increased subcortical volumes of the right thalamus and right pallidum. There was a significant correlation between initial age of DXM use and cortical thickness of the DLPFC. L and PreCG. R. A significant correlation was also found between cortical thickness of the DLPFC. L and impulsive behavior in patients. This was the first study to explore relationships between cortical thickness/subcortical volume and impulsive behavior in adolescents dependent on DXM. These structural changes might explain the neurobiological mechanism of impulsive behavior in adolescent DXM users.

Brain gray matter structures associated with trait impulsivity: A systematic review and voxel‐based meta‐analysis

“…From the identified studies in the systematic review, 16 studies were unable to be included in the meta‐analysis. The reasons are as follows: SBM ( n = 11) (Churchwell & Yurgelun‐todd, 2013; Depping et al, 2018; Grodin et al, 2017; Hirjak et al, 2017; Holmes et al, 2016; Kubera et al, 2018; Merz et al, 2018; Miglin et al, 2019; Qiu et al, 2017; Schilling et al, 2012; Tu et al, 2017), manual drawings ( n = 4) (Caravaggio et al, 2018; Dang et al, 2016; Mei et al, 2015; Sala et al, 2011), and not whole‐brain results ( n = 1) (Wang et al, 2017) (see Table 1). Finally, a total of 14 whole‐brain VBM studies were included in the meta‐analysis incorporating 1977 healthy subjects and 65 peak coordinates.…”

Focus on Over-the-Counter Drugs' Misuse: A Systematic Review on Antihistamines, Cough Medicines, and Decongestants

“…Their misuse potential may be particularly significant in adolescents and young adults (10,12,113). OTC recreational intake appeared to be associated with high/very high dosages (17,27,30,31,35,36,40,42 (27,36,63,90,93), illegal online pharmacies/shops (36,42,70,77), and theft/burglary from hospitals, residences, and pharmacies (27,105,110). DXM pills named "Snurf " were also reported to have been acquired online and in having been marketed as a legal high (70).…”

“…Out of a total of n = 185 OTC misusers described in case reports/series surveys (24,25,77,78,(99)(100)(101)(102)(103), male subjects were the most represented (F/M = 51/134), with an SUD history having been recorded in 53 of them (53/185 = 28.6%). A range of psychiatric diagnoses were reported (45/185 misusers, 24.3%), including mood disorders (e.g., bipolar disorder, depression, dysthymia; N = 26), anxiety disorders (e.g., adjustment disorder, anxiety; N = 5), psychotic disorders (e.g., schizoaffective disorder, schizophrenia, psychosis, delusional disorder; N = 11), attention deficit and hyperactivity disorder (ADHD, N = 1), eating disorders (e.g., bulimia; N = 1), and personality disorders (e.g., dependent disorder; N = 1).…”

Adolescent brain cognitive development (ABCD) study: Overview of substance use assessment methods

“…Finally, prescription stimulant medications have been linked with cognitive enhancement ( Bagot and Kaminer, 2014 ; Coghill et al, 2014 ; Tamminga et al, 2016 ), while prescription anxiolytics/sedatives ( Meador et al, 2011 ; Loring et al, 2012 ; Reissig et al, 2015 ; Ghoneim et al, 1984 ) and opiates ( Allen et al, 2003 ; Schoedel et al, 2010 ) negatively impact memory, processing speed and attention. Over the counter (OTC) cough medication containing dextromethorphan has been linked with cortical thickness in adolescents in one study ( Qiu et al, 2016 ), although this outcome has yet been replicated. It is notable that the majority of these aforementioned studies have numerous methodological weaknesses in that they are primarily cross-sectional, have relatively small sample sizes, lack female participants, have low power to disentangle polydrug effects, or have not been validated in younger adolescents.…”