PNP-08583; No of Pages 3 Progress in Neuro-Psychopharmacology & Biological Psychiatry xxx (2014) xxx–xxx

Contents lists available at ScienceDirect

Progress in Neuro-Psychopharmacology & Biological Psychiatry journal homepage: www.elsevier.com/locate/pnp

Editorial

Drugs of abuse and psychiatric disorders: Neurobiological and clinical aspects Individuals suffering from psychiatric disorders such as posttraumatic stress disorder, mood disorders, schizophrenia, attention deficit hyperactivity disorder, antisocial and borderline personality disorders are particularly vulnerable to drug abuse and addiction. Compared to the general population, the prevalence of substance use disorders is significantly elevated in these psychiatric populations (Grant et al., 2004; Hasin et al., 2007; Regier et al., 1990; Swendsen et al., 2010). This state, where a psychiatric disorder co-exists with pathological drug seeking and taking behaviour is known as co-morbidity. Co-morbidity has major health implications and represents an important therapeutic challenge. Across psychiatric disorders, addiction is associated with worsening of symptoms, non-compliance, suicidal ideation, violence, legal problems, unemployment, homelessness as well as health problems, such as HIV and hepatitis C (Bornovalova et al., 2005; McCarthy and Petrakis, 2010; Pettinati et al., 2013; Pickard and Fazel, 2013; Willens and Morrison, 2011; Ziedonis et al., 2005). In May of 2013, the Central Nervous System Research Group (Groupe de recherche sur le système nerveux central) of the Université de Montréal, Canada held an international symposium on the issue of addiction and psychiatric disorder co-morbidity. This special issue presents the proceedings from this special symposium. The articles presented here bring forth some of the latest research on the clinical aspects, the neurobiological substrates and the treatment of drug addiction as a disorder and its co-morbidity with other psychiatric disorders. A number of the articles included here review findings derived from studying afflicted individuals. This is complemented by articles reporting on pre-clinical studies where laboratory animals are subjected to environmental, genetic or pharmacological manipulations that model specific aspects of the relationship between drugs and psychiatric disorders. A first series of articles focuses on changes in reward neurocircuitry that are potentially linked to addiction-relevant phenomena. Payer et al. (2013-this issue) present recent findings that might shed new light on the contributions of the dopamine D3 receptor to the addiction process. The D3 receptor is principally found in the subcortical areas that constitute the brain's reward circuitry. Amongst all the dopamine receptor sub-types, the D3 receptor has the highest affinity for endogenous dopamine, suggesting that slight perturbations in dopamine concentration are likely to first affect D3 receptor-mediated behaviours. These behaviours include the operant pursuit of appetitive stimuli, including drugs of abuse. Payer et al. (2013-this issue) review evidence from animal models suggesting that attenuating D3 receptor-mediated decreases addiction-relevant behaviours. The authors then present new human imaging work suggesting that, just as is seen in animal models, D3 receptor upregulation could be a general feature of addiction to psychostimulant drugs like cocaine and methamphetamine. The challenge now is to determine whether D3 receptor upregulation could be

a biomarker for stimulant addiction and whether manipulating D3 receptor function could be a viable treatment strategy in addicts. Dopamine and its receptors play a central role in reward processing, and manipulations that alter dopamine function also alter the response to drugs of abuse. Samaha (2013-this issue) presents work from animal models that could help us better understand how prolonged treatment with antipsychotic medications might impact reward function. Antipsychotic medications are used to manage the symptoms of schizophrenia and related psychiatric disorders. All currently used antipsychotic compounds interact with dopamine D2/3 receptors. Not long after the discovery of antipsychotics, it was also discovered that prolonged treatment with these medications can induce a state of supersensitivity to dopamine stimulation. Until recently, studies on the functional significance of this dopamine supersensitivity were limited to effects on motor behaviour. However, Samaha reviews new work in animals showing that currently used antipsychotic treatment strategies can induce supersensitivity within the brain's dopamine systems, and that this in turn augments the incentive motivational and rewarding properties of drugs and reward cues. At the neurobiological level, these effects are linked to enhanced dopamine-mediated signalling at the post-synaptic level, particularly via the dopamine D2 receptor. These findings suggest that antipsychotic treatment can evoke changes in the brain that contribute to compulsive drug seeking and drug taking behaviours in vulnerable schizophrenia patients. Oleson et al. (2013-this issue) and Lupica and Wang (this issue) draw attention to the close interactions between the dopamine and endocannabinoid systems. They describe how dopamine-endocannabinoid interactions might influence phenomena including conditioned drug withdrawal and drug-evoked changes in reward expectancy. Dopamine neurons within the ventral midbrain fire in bursts when individuals encounter unexpected reward or when reward is expected but not delivered. Under these conditions, the burst firing of dopamine neurons is thought to shape behaviour such that the probability of coming into contact with rewards is optimised. Lupica and Wang discuss new work suggesting that within the ventral midbrain, endocannabinoids modulate the firing activity of local dopamine neurons and that this might modulate behaviour in response to reward, including drug reward. Oleson et al. (2013-this issue) discuss an oftenignored function of dopamine — the regulation of behaviour motivated by aversive stimuli or states. In the addict, cues predictive of aversive withdrawal symptoms can trigger craving and relapse to drug seeking during abstinence. Oleson et al. present findings from animal models suggesting that subsecond phasic dopamine release within the ventral midbrain encode conditioned cues during behaviours driven by negative reinforcement. These dopamine release events could be involved in conditioned withdrawal and its ability to trigger drug-seeking behaviour.

http://dx.doi.org/10.1016/j.pnpbp.2014.03.012 0278-5846/© 2014 Elsevier Inc. All rights reserved.

Please cite this article as: Samaha A-N, Potvin S, Drugs of abuse and psychiatric disorders: Neurobiological and clinical aspects, Prog NeuroPsychopharmacol Biol Psychiatry (2014), http://dx.doi.org/10.1016/j.pnpbp.2014.03.012

2

Editorial

Importantly, the endocannabinoid system modulates subsecond dopamine release events, thus providing new molecular targets to attenuate drug craving and relapse associated with conditioned withdrawal. Ghazzaoui and Abi-Dargham (2013-this issue) bring to attention the fact that interactions between cannabinoids and the dopamine system are complex and deserving of further study. The authors review findings from human imaging studies suggesting that cannabis abuse or dependence does not appear to be linked to dopamine alterations similar to those documented for other drug addictions. While enhanced striatal dopamine neurotransmission might be involved in the acute effects of cannabis, it likely does not contribute in an appreciable way to the neurochemical changes thought to underlie drug addiction. This is a portrait far different from that which has emerged for other drugs of abuse like cocaine, heroin, amphetamine or alcohol. Chronic cannabis use is thought to increase the risk of developing psychosis and psychotic disorders such as schizophrenia. A second series of articles in this issue examines how environmental and genetic variables mediate this effect. O'Tuathaigh et al., (2013-this issue) and Rubino and Parolaro (2013-this issue) examine the contributions of genetic disposition and cannabis use during adolescence to the subsequent development of psychosis and related disorders. O'Tuathaigh et al. review evidence suggesting that genes encoding proteins that regulate dopamine signalling or the development of dopamine neurons such as catechol-O-methyltransferase (COMT), AKT1 and brainderived neurotrophic factor (BDNF) modulate the cannabis-psychosis link, and the authors provide a discussion of the neuronal basis of these relationships. Several lines of evidence suggest that repeated cannabis use during adolescence is linked to an increased risk of later developing psychotic symptoms. Rubino and Parolaro present evidence from animal models suggesting that this might occur in part because cannabis use during adolescence compromises the normal maturation of the endocannabinoid system. This is hypothesised to result in altered connectivity in specific networks of the adult brain (particularly in hippocampal-related circuitry) similar to that seen in patients suffering from schizophrenia. Huizink (2013-this issue) further elaborates on the long-term risks of early exposure to cannabis, with a focus on in utero exposure. Much attention has been paid to the long-lasting effects of in utero exposure to tobacco and alcohol. The effects of in utero cannabis exposure have attracted less attention, in spite of the fact that cannabis is the most commonly used illicit drug during pregnancy. Huizink presents evidence from her own prospective longitudinal human studies as well as from other studies documenting the effects of prenatal cannabis exposure on outcome measures including behaviour and cognitive development at the neonatal, infant and childhood stages. This work suggests that in utero exposure to cannabis likely leads to lower weight at birth, but that longer-lasting deficits in other domains of development are more difficult to establish. Huizing also summarises work on this issue carried out in laboratory animals. Controlled preclinical studies show that in utero exposure to cannabinoids alters foetal development and functional outcomes in the domains of memory, motor activity, short-term learning capacity and emotional reactivity. At the mechanistic level, the long-term effects of prenatal cannabis exposure could result from changes to the normal maturation of the brain, including alterations to dopamine and endocannabinoid networks. Given the established links between cannabis use and the risk of developing schizophrenia, how might the endocannabinoid system be involved in the pathophysiology of schizophrenia? Bossong et al. address this important question in the present issue. The authors present evidence that acute exposure to cannabis or THC alters cognitive processes that are relevant to schizophrenia including memory, emotional processing of fearful stimuli, response inhibition and high level cognitive functions needed for goal-directed behaviour. The authors suggest that these effects of cannabinoids on cognitive brain function could be related to a disruption of endocannabinoid-mediated regulation of synaptic transmission, leading to synaptic inefficiency in key brain regions known to be impaired in schizophrenia.

In addition to cannabis use, tobacco ranks amongst the most abused substances in individuals with psychiatric disorder. Two papers in this special issue focus on the high prevalence of cigarette smoking in attention deficit hyperactivity disorder (ADHD) and in schizophrenia. 'Kollins and Adcock (2014-this issue) discusses the complex relationship between altered dopamine function, reward processing and the vulnerability to tobacco smoking in individuals with attention deficit hyperactivity disorder (ADHD). Although some data in this area are conflicting and additional work is much needed, Kollins reviews findings suggesting that during tasks where rewards are processed, individuals diagnosed with ADHD show lower than normal levels of brain activation in certain dopaminerich regions. The author then presents a framework to link altered dopamine-mediated reinforcement processes and the increased vulnerability to tobacco use and addiction in ADHD. In psychiatric populations, a greater vulnerability to drug abuse and addiction could be related to altered reward processes but also to the ability of drugs to ameliorate some of the psychiatric symptoms. A prominent example of this is cigarette smoking in schizophrenia. The majority of people with schizophrenia smoke cigarettes and also do so more intensely than people without the disorder. In this issue, Mackowick et al. present their own and other work demonstrating that individuals with schizophrenia derive important cognitive benefits from smoking and from other manipulations that increase nicotinic receptor activity. Given this reality, it appears useful to target the nicotine receptor system for the design and exploration of new medications to treat cognitive deficits in schizophrenia. Although cigarette smoking might have some therapeutically useful effects, smoking tobacco increases the liability to several serious conditions including cancer and cardiovascular diseases. Current therapeutic approaches designed to keep abstinent smokers from relapsing are of limited efficacy. For this reason, effective translational research is needed to impel the exploration of new anti-smoking treatments. Strategies to achieve this are reviewed in the present issue by Le Foll et al. The authors highlight the bench-to-bedside strategy that has driven the development and clinical use of inverse agonists at the cannabinoid CB1 receptor as an anti-smoking medication. Le Foll et al. then present an unconventional bedside-to-bench strategy that has led to the discovery that the insula could play an important role in the addictive properties of nicotine. The authors highlight that research that allows close interaction between animal and clinical observations is critical to better understand the neurobiology of tobacco addiction and its treatment. Chronic drug use most often makes mental illness more severe and difficult to treat. At the same time, certain drugs—in particular tobacco—appear to ameliorate at least some psychiatric symptoms. The articles brought together in this special issue aim to spark discussion on several issues related to the co-morbidity problem, from the question of how drugs including cannabis and tobacco can contribute to the aetiology and course of certain psychiatric conditions to what factors can promote or protect from this outcome. The hope is that a reflection on these issues will guide new translational research on the causes and mechanisms of drug use in psychiatric populations. As scientists in this field, our task is to better understand the genetic, neurobiological and environmental processes linking drug abuse and mental illness. Our efforts will bear fruit only if we take every occasion to disseminate our discoveries—this special issue being a vector towards this goal. Thus, we conclude by highlighting the need for increased collaboration between the scientists modelling and researching this co-morbidity, the clinicians treating the afflicted individuals and the members of the government and the public who shape opinion and funding policies on this important issue. References Bornovalova MA, Lejuez CW, Daughters SB, Zachary Rosenthal M, Lynch TR. Impulsivity as a common process across borderline personality and substance use disorders. Clin Psychol Rev 2005;25:790–812. Ghazzaoui R, Abi-Dargham A. Imaging dopamine transmission parameters in cannabis dependence. Prog Neuropsychopharmacol Biol Psychiatry 2013. (this issue).

Please cite this article as: Samaha A-N, Potvin S, Drugs of abuse and psychiatric disorders: Neurobiological and clinical aspects, Prog NeuroPsychopharmacol Biol Psychiatry (2014), http://dx.doi.org/10.1016/j.pnpbp.2014.03.012

Editorial Grant BF, Stinson FS, Dawson DA, Chou SP, Ruan WJ, Pickering RP. Co-occurrence of 12-month alcohol and drug use disorders and personality disorders in the United States: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Arch Gen Psychiatry 2004;61:361–8. Hasin DS, Stinson FS, Ogburn E, Grant BF. Prevalence, correlates, disability, and comorbidity of DSM-IV alcohol abuse and dependence in the United States. Results From the National Epidemiologic Survey on Alcohol and Related Conditions. Arch Gen Psychiatry 2007;64:830–42. Huizink AC. Prenatal cannabis exposure and infant outcomes: Overview of studies. Prog Neuropsychopharmacol Biol Psychiatry 2013. (this issue). Kollins SH, Adcock RA. ADHD, altered dopamine neurotransmission, and disrupted reinforcement processes: Implications for smoking and nicotine dependence. Prog Neuropsychopharmacol Biol Psychiatry. 2014. (this issue). McCarthy E, Petrakis I. Epidemiology and management of alcohol dependence in individuals with post-traumatic stress disorder. CNS Drugs 2010;24:997–1007. Oleson EB, Cachope R, Fitoussi A, Cheer JF. Tales from the dark side: Do neuromodulators of drug withdrawal require changes in endocannabinoid tone? Prog Neuropsychopharmacol Biol Psychiatry 2013. (this issue). O'Tuathaigh CM, Gantois I, Waddington JL. Genetic dissection of the psychotomimetic effects of cannabinoid exposure. Prog Neuropsychopharmacol Biol Psychiatry 2013. (this issue). Payer D, Balasubramaniam G, Boileau I. What is the role of the D receptor in addiction? A mini review of PET studies with [C]-(+)-PHNO. Prog Neuropsychopharmacol Biol Psychiatry 2013. (this issue). Pettinati HM, O'Brien CP, Dundon WD. Current status of co-occurring mood and substance use disorders: a new therapeutic target. Am J Psychiatry 2013;170:23–30. Pickard H, Fazel S. Substance abuse as a risk factor for violence in mental illness: some implications for forensic psychiatric practice and clinical ethics. Curr Opin Psychiatry 2013; 26:349–54. Regier DA, Farmer ME, Rae DS, Locke BZ, Keith BJ, Judd LL, et al. Comorbidity of mental health disorders with alcohol and other drug abuse. JAMA 1990;264:2511–8. Rubino T, Parolaro D. Cannabis abuse in adolescence and the risk of psychosis: A brief review of the preclinical evidence. Prog Neuropsychopharmacol Biol Psychiatry 2013. (this issue). Samaha AN. Can antipsychotic treatment contribute to drug addiction in schizophrenia? Prog Neuropsychopharmacol Biol Psychiatry 2013. (this issue).

3

Swendsen J, Conway KP, Degenhardt L, Glantz M, Jin R, Merikangas KR, et al. Mental disorders as risk factors for substance use, abuse and dependence: results from the 10-year follow-up of the National Comorbidity Survey. Addiction 2010;105: 1117–28. Willens TE, Morrison NR. The intersection of attention-deficit/hyperactivity disorder and substance abuse. Curr Opin Psychiatry 2011;24:280–5. Ziedonis DM, Smelson D, Rosenthal RN, Batki SL, Green AI, Henry RJ, et al. Improving the care of individuals with schizophrenia and substance use disorders: consensus recommendations. J Psychiatr Pract 2005;11:315–39.

Guest Editor Anne-Noël Samaha Department of Pharmacology and CNS Research Group, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada Corresponding author at: Department of Pharmacology, Université de Montréal, C.P. 6128, Succursale Centre-ville, Montreal, Quebec H3C 3J7, Canada. Tel.: +1 514 343 6111x32788; fax: +1 514 343 2291. E-mail address: [email protected]. Guest Editor Stéphane Potvin Department of Psychiatry, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada Available online xxxx

Please cite this article as: Samaha A-N, Potvin S, Drugs of abuse and psychiatric disorders: Neurobiological and clinical aspects, Prog NeuroPsychopharmacol Biol Psychiatry (2014), http://dx.doi.org/10.1016/j.pnpbp.2014.03.012

Drugs of abuse and psychiatric disorders: neurobiological and clinical aspects.

Drugs of abuse and psychiatric disorders: neurobiological and clinical aspects. - PDF Download Free
233KB Sizes 0 Downloads 3 Views