Distress and sleep quality in young amphetamine-type stimulant users with an affective or psychotic illness
Introduction
Amphetamine-type stimulant (ATS) drugs are synthetic sympathomimetic amines which characteristically exert marked stimulant effects on the central nervous system and represent the second-most used class of illicit substances worldwide, following cannabis (Degenhardt et al., 2013, United Nations Office on Drugs and Crime, 2016). The ATS class comprises the structural analogues of amphetamine, with the commonest forms including methamphetamine (‘ice’), methylenedioxymethamphetamine (MDMA, ‘ecstasy’), and dextroamphetamine (Sulzer et al., 2005). Numerous physical health risks are associated with ATS use, including cardiovascular disease and cardiovascular-related death among methamphetamine users (Darke et al., 2017), and rare MDMA-associated fatalities related to malignant hyperthermia and other factors (Hegadoren et al., 1999). These risks may be particularly pronounced in those already at-risk of cardiovascular complications associated with poor lifestyle factors, several of which are common to psychiatric patients (e.g. cigarette smoking) (Kalman et al., 2005, Kaye et al., 2007). Within Australia, estimates of regular and dependent users has risen since 2010, with the sharpest increase reported in the 15–24- and 25–35- year-old age groups (Degenhardt et al., 2016b). With respect to neurodevelopment and serious physical health risks, ATS use by young people is concerning and warrants timely investigation.
Adolescence and early adulthood are periods of peak brain development, during which multiple age-dependent processes dynamically operate to optimise neural function (Paus, 2005). Brain maturation is however a graded process, with asynchronous development of limbic and related systems involved in sensation-seeking and reward sensitivity, and frontal systems underpinning behavioural inhibition and emotion regulation (Bava and Tapert, 2010, Paus, 2005), inadvertently leaving open a window of vulnerability for the development of substance use and mental health problems. As the peak age of both psychiatric illness onset and substance use initiation typically align with these protracted maturations, it is plausible that substance use may perturb development and amplify risk for psychopathology and associated sequelae (Lubman and Yucel, 2008). Substance use may additionally disrupt sleep-wake cycles and neurocognitive functioning, which may lead to downstream impacts on recovery and socio-occupational engagement (Davidson et al., 2015).
ATS use has in particular been implicated in generating positive psychotic and affective symptoms, disrupting sleep, and compromising neurocognitive function. Early seminal work demonstrated provocation of psychotic experiences in non-psychotic participants following amphetamine administration (Angrist and Gershon, 1970), with later studies observing symptom exacerbation in psychotic patients (Curran et al., 2004) and a dose-response relationship between methamphetamine and psychotic symptoms in non-clinical users (McKetin et al., 2013). Links between affective states (e.g. distress, low mood, irritability, hyper-arousal) and ATS use have additionally been observed, commonly conceptualized as the “come-down”, often thought to be attributable to drug withdrawal (Srisurapanont et al., 1999). With respect to sleep/wake and circadian disturbances, preclinical work has revealed persistent circadian alterations and suprachiasmatic nucleus dysregulation (a key sleep-wake region) following MDMA administration (Colbron et al., 2002), with observational studies in humans revealing poorer sleep quality among current MDMA and methamphetamine users (Allen et al., 1993, Perez et al., 2008).
There is additionally a sizeable literature detailing negative associations between ATS use and neurocognition. Several cross-sectional reports suggest a portion of MDMA users display diminished memory performance (Bhattachary and Powell, 2011, Reneman et al., 2001), with a prospective study observing poorer verbal memory among MDMA-naïve individuals who had later incident use, relative to those who were persistently MDMA-naïve (Schilt et al., 2007). Two meta-analyses provide support for poorer cognition in MDMA users relative to controls across a range of domains such as learning, memory, executive function, among others (Kalechstein et al., 2007, Roberts et al., 2016). Similarly, a number of cross-sectional studies and one meta-analysis have suggested reduced performance in methamphetamine users compared to controls across a number of neurocognitive domains including learning, memory, executive function, among others (Dean et al., 2013, Scott et al., 2007), however with some evidence of recovery following abstinence (Iudicello et al., 2010).
Unfortunately, most studies examining these associations have excluded participants with a co-occurring psychiatric diagnosis, limiting generalisability of findings. Individuals with psychiatric illnesses typically present with poor sleep, psychopathology and compromised neurocognition, and the extent to which comorbid ATS use exacerbates such problems has important clinical implications. Accordingly, we examined cross-sectional associations between comorbid ATS use and neurocognition, sleep, socio-occupational functioning and psychopathology in a sample of young, help-seeking mental health outpatients. A clinical control group with no lifetime ATS use and another group of currently abstinent past users were assessed and matched for age, gender, education and estimated premorbid IQ. We hypothesised that: i) current users would perform worse than never users on measures of learning, memory, executive functioning and psychomotor speed (with small-to-medium effect sizes; Kalechstein et al., 2007; Scott et al., 2007), with past users performing intermediately; ii) current users would exhibit greater psychotic symptomology than both comparison groups; iii) all three groups would report poor subjective sleep quality, with current users reporting the poorest; and iv) current users would score lowest on a clinician-rated socio-occupational functioning scale.
Section snippets
Participants
One-hundred-and-sixty-five outpatients with an affective- or psychosis-spectrum illness were recruited from one of two youth mental health specialist service sites (headspace): Campderdown (inner-western Sydney) or Campbelltown (south-western Sydney) (Rickwood et al., 2007). All patients were receiving case management and relevant psychosocial interventions. It was ensured that current pharmacotherapeutic regimens were stabilized, which included the following: no psychotropic medications
Comparison of demographic, clinical, sleep and socio-occupational variables
Demographic, clinical, sleep and socio-occupational variables for the groups were analysed with one-way ANOVAs. Normality and homogeneity of variance were satisfactory, with Scheffe's post hoc test determining where statistically significant differences were located. As presented in Table 1, there were no significant differences among the groups in distribution of age, gender, educational attainment or estimated premorbid IQ.
Contrary to expectations, there were no statistically significant
Discussion
Two key findings emerged from this study. First, current users were significantly more distressed than their never-using peers, and second, current users reported significantly poorer subjective sleep quality and increased subjective sleep disturbances than never users. Somewhat surprisingly, we observed no significant differences in neurocognition, psychotic symptomology or socio-occupational functioning.
Our finding of heightened distress in current users is consistent with the ATS and
Conflict of interest
D.F.H has received honoraria for educational seminars from JanssenCilag and Eli Lilly. I.B.H is a Commissioner in Australia's new National Mental Health Commission from 2012. He was a director of headspace: the national youth mental health foundation until January 2012. He was previously the chief executive officer (till 2003) and clinical adviser (till 2006) of beyondblue, an Australian National Depression Initiative. He is the Co-Director, Health and Policy at the Brain and Mind Centre that
Role of the funding source
This work was partially supported by a Research Training Program Stipend Scholarship through the University of Sydney awarded to J.J.C. and a National Health and Medical Research Council Australia Fellowship (no. 511921) awarded to I.B.H. These funders had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
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