Search

This is an exciting time for psychedelics and related drugs, with a renewed scientific interest in their potential benefits for a range of mental health disorders and addictions. However, much is yet to be discovered about this group of drugs, including precisely how they work in the brain; how their biological effects interact with psychological support to effect therapeutic change; how long their benefits endure; and how safe they are in the longer term. The nature of the psychedelic experience, its necessity in obtaining therapeutic benefit, and how the psychological component can be safely delivered are outstanding issues. There are also questions to be answered regarding how these drugs can be integrated into mainstream service delivery, how they will be made available and funded, and what training will be required of therapists. Finally, gold-standard trial designs, addressing thorny issues such as blinding and placebo response, as well as expectancy bias, need to be agreed and adopted, as we explore efficacy and safety across a growing range of mental health and addictive disorders.

There is substantial contemporary interest in psychedelic agents as medicines for maladies of the mind. This follows research in the 1950s and 1960s exploring the use of LSD and other psychedelics to treat a range of psychiatric illnesses as well as addictions. This research was shut down after prohibition of these drugs; however, the last decade has seen a major renewal of interest in the therapeutic use of psychedelics and related drugs in psychiatry. Part of the Oxford Psychiatry Library series, this book provides an overview of this hugely exciting field, covering the history of psychedelics, clinical aspects, risks and side effects, precautions, and processes. Psilocybin (found in ‘magic mushrooms’) has been used effectively for amelioration of distress in people with depression and anxiety in the context of potentially life-ending cancers. MDMA (‘ecstasy’) has shown efficacy for severe posttraumatic stress disorder, with enduring benefit. Other psychedelics, both plant-derived (e.g. ayahuasca) and synthetically produced (e.g. LSD) are also being investigated for their potential therapeutic value. These agents not only herald a new neurobiology but also allow an integration of psychotherapy with biological compounds that is truly novel and that challenges established psychiatric practice. Further, the action of these agents on the brain allows an exploration of how the brain works to ‘open up’ to psychotherapeutic healing. This book will appeal to clinicians in mental health and addictions, policy makers and neuroscientists; to pharmacists and pharmacologists; and to the general public.

Background: Music listening is a staple and valued component of psychedelic therapy, and previous work has shown that psychedelics can acutely enhance music-evoked emotion. Aims: The present study sought to examine subjective responses to music before and after psilocybin therapy for treatment-resistant depression, while functional magnetic resonance imaging (fMRI) data was acquired. Methods: Nineteen patients with treatment-resistant depression received a low oral dose (10 mg) of psilocybin, and a high dose (25 mg) 1 week later. fMRI was performed 1 week prior to the first dosing session and 1 day after the second. Two scans were conducted on each day: one with music and one without. Visual analogue scale ratings of music-evoked ‘pleasure’ plus ratings of other evoked emotions (21-item Geneva Emotional Music Scale) were completed after each scan. Given its role in musical reward, the nucleus accumbens (NAc) was chosen as region of interest for functional connectivity (FC) analyses. Effects of drug (vs placebo) and music (vs no music) on subjective and FC outcomes were assessed. Anhedonia symptoms were assessed pre- and post-treatment (Snaith–Hamilton Pleasure Scale). Results: Results revealed a significant increase in music-evoked emotion following treatment with psilocybin that correlated with post-treatment reductions in anhedonia. A post-treatment reduction in NAc FC with areas resembling the default mode network was observed during music listening (vs no music). Conclusion: These results are consistent with current thinking on the role of psychedelics in enhancing music-evoked pleasure and provide some new insight into correlative brain mechanisms.

Microdosing is the practice of regularly using very low doses of psychedelic drugs. Anecdotal reports suggest that it may enhance well-being, creativity and cognition. Here, we use data from a self-blinding microdose trial, a large (n=240) placebo-controlled citizen science trial of microdosing to investigate whether tolerance develops during microdosing. We conceptualized tolerance as the relationship between correct microdose guess probability and the number of previous microdoses taken within the trial’s timeframe: if tolerance develops then, correct microdose guess probability should decrease with more microdoses taken. Mixed linear regression models show that correct microdose guess probability decreases with number of microdoses taken (mean±se: -.017±.007; p=.009**), suggesting that tolerance developed. Secondary post-hoc analysis revealed that this tolerance was present with LSD/LSD-analogue microdoses (mean±se: -.026±.007; p

Psilocybin therapy for depression has started to show promise, yet the underlying causal mechanisms are not currently known. Here we leveraged the differential outcome in responders and non-responders to psilocybin (10mg and 25mg, 7 days apart) therapy for depression - to gain new insights into regions and networks implicated in the restoration of healthy brain dynamics. We used whole-brain modelling to fit the spatiotemporal brain dynamics at rest in both responders and non-responders before treatment. Dynamic sensitivity analysis of systematic perturbation of these models enabled us to identify specific brain regions implicated in a transition from a depressive brain state to a heathy one. Binarizing the sample into treatment responders (> 50% reduction in depressive symptoms) versus non-responders enabled us to identify a subset of regions implicated in this change. Interestingly, these regions correlate with in vivo density maps of serotonin receptors 5-HT2A and 5-HT1A, which psilocin, the active metabolite of psilocybin, has an appreciable affinity for, and where it acts as a full-to-partial agonist. Serotonergic transmission has long been associated with depression and our findings provide causal mechanistic evidence for the role of brain regions in the recovery from depression via psilocybin.

OBJECTIVES: To perform a Bayesian reanalysis of a recent trial of psilocybin (COMP360) versus escitalopram for Major Depressive Disorder (MDD) in order to provide a more informative interpretation of the indeterminate outcome of a previous frequentist analysis. DESIGN: Reanalysis of a two-arm double-blind placebo controlled trial. PARTICIPANTS: Fifty-nine patients with MDD. INTERVENTIONS: Two doses of psilocybin 25mg and daily oral placebo versus daily escitalopram and 2 doses of psilocybin 1mg, with psychological support for both groups. OUTCOME MEASURES: Quick Inventory of Depressive Symptomatology–Self-Report (QIDS SR-16), and three other depression scales as secondary outcomes: HAMD-17, MADRS, and BDI-1A. RESULTS: Using Bayes factors and ‘skeptical priors’ which bias estimates towards zero, for the hypothesis that psilocybin is superior by any margin, we found indeterminate evidence for QIDS SR-16, strong evidence for BDI-1A and MADRS, and extremely strong evidence for HAMD-17. For the stronger hypothesis that psilocybin is superior by a ‘clinically meaningful amount’ (using literature defined values of the minimally clinically important difference), we found moderate evidence against it for QIDS SR-16, indeterminate evidence for BDI-1A and MADRS, and moderate evidence supporting it for HAMD-17. Furthermore, across the board we found extremely strong evidence for psilocybin’s non-inferiority versus escitalopram. These findings were robust to prior sensitivity analysis. CONCLUSIONS: This Bayesian reanalysis supports the following inferences: 1) that psilocybin did indeed outperform escitalopram in this trial, but not to an extent that was clinically meaningful—-and 2) that psilocybin is almost certainly non-inferior to escitalopram. The present results provide a more precise and nuanced interpretation to previously reported results from this trial, and support the need for further research into the relative efficacy of psilocybin therapy for depression with respect to current leading treatments. TRIAL REGISTRATION NUMBER: NCT03429075

Psychedelic therapy (PT) is an emerging paradigm with great transdiagnostic potential for treating a range of psychiatric disorders, including depression, addiction, eating disorders, post-traumatic stress disorder, and others. ‘Classic’ serotonergic psychedelics, such as psilocybin, lysergic acid diethylamide (LSD), N, N-Dimethyltryptamine (DMT) and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), form the main focus of this movement, but other substances including ketamine, 3,4-Methylenedioxymethamphetamine (MDMA) and ibogaine also hold promise. The development of these novel treatment modalities in the early 21st century has occurred concurrently with the wider use of advanced human neuroscientific research methods; principally neuroimaging. This has enabled assessment of drug and therapy brain effects with greater precision and quantification than any previous novel development in psychiatric pharmacology. We outline some of the major trends in existing data and suggest that the modern development of PT has benefitted greatly from the use of neuroimaging. Important gaps in existing knowledge are identified which can be addressed by future neuroimaging work, principally using combined Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI) methods, plus other adjunct techniques. Suggestions for future multimodal imaging studies are discussed, which would resolve some of these questions and provide a firmer foundation for the development of PT.

This document details an authors' response to a critique of their work entitled: Skepticism About Recent Evidence that Psilocybin Opens Depressed Minds.

Psychedelics are a unique class of drug that commonly produce vivid hallucinations as well as profound psychological and mystical experiences. A grouping of interconnected brain regions characterized by increased temporal coherence at rest have been termed the Default Mode Network (DMN). The DMN has been the focus of numerous studies assessing its role in self-referencing, mind wandering, and autobiographical memories. Altered connectivity in the DMN has been associated with a range of neuropsychiatric conditions such as depression, anxiety, post-traumatic stress disorder, attention deficit hyperactive disorder, schizophrenia, and obsessive-compulsive disorder. To date, several studies have investigated how psychedelics modulate this network, but no comprehensive review, to our knowledge, has critically evaluated how major classical psychedelic agents—lysergic acid diethylamide, psilocybin, and ayahuasca—modulate the DMN. Here we present a systematic review of the knowledge base. Across psychedelics there is consistent acute disruption in resting state connectivity within the DMN and increased functional connectivity between canonical resting-state networks. Various models have been proposed to explain the cognitive mechanisms of psychedelics, and in one model DMN modulation is a central axiom. Although the DMN is consistently implicated in psychedelic studies, it is unclear how central the DMN is to the therapeutic potential of classical psychedelic agents. This article aims to provide the field with a comprehensive overview that can propel future research in such a way as to elucidate the neurocognitive mechanisms of psychedelics.

Criteria for treatment-resistant depression (TRD) and partially responsive depression (PRD) as subtypes of major depressive disorder (MDD) are not unequivocally defined. In the present document we used a Delphi-method-based consensus approach to define TRD and PRD and to serve as operational criteria for future clinical studies, especially if conducted for regulatory purposes. We reviewed the literature and brought together a group of international experts (including clinicians, academics, researchers, employees of pharmaceutical companies, regulatory bodies representatives, and one person with lived experience) to evaluate the state-of-the-art and main controversies regarding the current classification. We then provided recommendations on how to design clinical trials, and on how to guide research in unmet needs and knowledge gaps. This report will feed into one of the main objectives of the EUropean Patient-cEntric clinicAl tRial pLatforms, Innovative Medicines Initiative (EU-PEARL, IMI) MDD project, to design a protocol for platform trials of new medications for TRD/PRD.

Psilocybin therapy shows antidepressant potential, but its therapeutic actions are not well understood. We assessed the subacute impact of psilocybin on brain function in two clinical trials of depression. The first was an open-label trial of orally administered psilocybin (10 mg and 25 mg, 7 d apart) in patients with treatment-resistant depression. Functional magnetic resonance imaging (fMRI) was recorded at baseline and 1 d after the 25-mg dose. Beck's depression inventory was the primary outcome measure ( MR/J00460X/1 ). The second trial was a double-blind phase II randomized controlled trial comparing psilocybin therapy with escitalopram. Patients with major depressive disorder received either 2 × 25 mg oral psilocybin, 3 weeks apart, plus 6 weeks of daily placebo ('psilocybin arm') or 2 × 1 mg oral psilocybin, 3 weeks apart, plus 6 weeks of daily escitalopram (10-20 mg) ('escitalopram arm'). fMRI was recorded at baseline and 3 weeks after the second psilocybin dose ( NCT03429075 ). In both trials, the antidepressant response to psilocybin was rapid, sustained and correlated with decreases in fMRI brain network modularity, implying that psilocybin's antidepressant action may depend on a global increase in brain network integration. Network cartography analyses indicated that 5-HT2A receptor-rich higher-order functional networks became more functionally interconnected and flexible after psilocybin treatment. The antidepressant response to escitalopram was milder and no changes in brain network organization were observed. Consistent efficacy-related brain changes, correlating with robust antidepressant effects across two studies, suggest an antidepressant mechanism for psilocybin therapy: global increases in brain network integration.

Psychedelic therapy is perhaps the most exciting new development in psychiatry. Not only does it offer a radical new approach to treatment where mainstream approaches have proven ineffective, but the growing evidence for transdiagnostic efficacy is eliciting a re-think of current diagnostic and symptom-specific approaches to psychiatry. This excitement has led to a massive investment in this field with many tens of new pharmaceutical companies being set up to research the effects of known psychedelics and develop new patentable molecules. Whilst this enthusiasm is to be welcomed, it is important that new research is properly grounded in established facts and reflects current knowledge. In this commentary we lay out the knowledge framework that should be taken into account by all innovative researchers in this field.

Background Internationally, one of the most common conditions for which people seek medicinal cannabis (MC) is chronic pain. However, relatively little is known about the effectiveness of cannabis for reducing pain in Australia. Medicinal cannabis was made legally available in Australia in 2016. Project Twenty21 Australia is an observational study that follows patients prescribed MC for chronic pain, anxiety, PTSD and multiple sclerosis for up to 12 months. It commenced recruitment in February 2022. This paper describes some preliminary findings for a cohort of patients with chronic pain. Method Participants seeking treatment for chronic pain are prescribed MC from within a Project Formulary, and complete questionnaires at baseline then three monthly for up to 12 months. Pain severity and interference are assessed using the Brief Pain Index while standardised measures of quality of life, mood and sleep quality are also applied. Results By 30 November 2022, 55 participants with chronic pain had completed the first three-month follow-up. Patients reported a low quality of life and high levels of co-morbidity. Three-month data indicate that MC use was associated with significant reductions in self-reported pain intensity and pain interference (Effect sizes = 0.66 [95% CI = 0.34–0.98] and 0.56 [0.24–0.88], respectively). Additionally, there were significant improvements in quality of life, general health, mood/depression and sleep (Effect sizes = 0.53–0.63). One adverse reaction was reported which was mild in nature. Conclusions Preliminary evidence suggests that MC may be effective in reducing both pain severity and pain interference while also improving quality of life, general health, mood and sleep in patients with chronic pain. Increasing uptake of MC coupled with growing evidence of both the effectiveness and safety of these medications indicate a need both to make MC more widely available and to reduce financial costs associated with its use.

Background Since medical access to medicinal cannabis (MC) was legalised in Australia in 2016, numbers of people prescribed MC have increased exponentially. There is a need for safety and effectiveness data on the longer-term use of MC in real-world settings. This paper describes the methodology of Project Twenty21 Australia, an observational study that commenced early in 2022 and its preliminary findings. Method This study tests whether medicinal cannabis is effective in four primary conditions: chronic pain, anxiety, posttraumatic stress disorder and multiple sclerosis (MS). Participants are prescribed MC from within a Project Formulary, completing questionnaires at baseline then 3 monthly for up to 12 months. Results Between the start of the study in February and 30 August 2022, 278 participants had been recruited into the study: 50.7% female, 48.2% male and 1.1% non-binary with average age 39.2 years (18–77). Patients reported a low quality of life and high levels of co-morbidity. Three-month data, available for 71 participants, indicate that MC was associated with substantial improvements in self-reported quality of life, general health, mood/depression and sleep with standardised effect size estimates ranging from 0.57 to 0.93. Three adverse reactions were reported. Conclusions This paper describes the protocol used for an observational study conducted in Australia assessing the effectiveness of MC in four main conditions. We have established the feasibility of collecting real-world data on symptoms and quality of life in people receiving treatment with MC. Preliminary evidence suggests that MC may be effective in improving quality of life, general health, mood and sleep.

Rationale A general feeling of disconnection has been associated with mental and emotional suffering. Improvements to a sense of connectedness to self, others and the wider world have been reported by participants in clinical trials of psychedelic therapy. Such accounts have led us to a definition of the psychological construct of ‘connectedness’ as ‘a state of feeling connected to self, others and the wider world’. Existing tools for measuring connectedness have focused on particular aspects of connectedness, such as ‘social connectedness’ or ‘nature connectedness’, which we hypothesise to be different expressions of a common factor of connectedness. Here, we sought to develop a new scale to measure connectedness as a construct with these multiple domains. We hypothesised that (1) our scale would measure three separable subscale factors pertaining to a felt connection to ‘self’, ‘others’ and ‘world’ and (2) improvements in total and subscale WCS scores would correlate with improved mental health outcomes post psychedelic use. Objectives To validate and test the ‘Watts Connectedness Scale’ (WCS). Methods Psychometric validation of the WCS was carried out using data from three independent studies. Firstly, we pooled data from two prospective observational online survey studies. The WCS was completed before and after a planned psychedelic experience. The total sample of completers from the online surveys was N = 1226. Exploratory and confirmatory factor analysis were performed, and construct and criterion validity were tested. A third dataset was derived from a double-blind randomised controlled trial (RCT) comparing psilocybin-assisted therapy (n = 27) with 6 weeks of daily escitalopram (n = 25) for major depressive disorder (MDD), where the WCS was completed at baseline and at a 6-week primary endpoint. Results As hypothesised, factor analysis of all WCS items revealed three main factors with good internal consistency. WCS showed good construct validity. Significant post-psychedelic increases were observed for total connectedness scores (η2 = 0.339, p p r = 0.42, r = 0.38, r = 0.42, respectively, p ηp2 = 0.133, p = 0.009). Conclusions The WCS is a new 3-dimensional index of felt connectedness that may sensitively measure therapeutically relevant psychological changes post-psychedelic use. We believe that the operational definition of connectedness captured by the WCS may have broad relevance in mental health research.

In 2015 and 2016, during the debates that culminated in The Psychoactive Substances Act 2016, both houses of the UK parliament debated the pharmacology of nitric oxide and amyl nitrites, otherwise known as “poppers”. The original draft Psychoactive Substances Bill had recommended that poppers should be made illegal. However, after strong opposition inside the Conservative party, the ruling party at the time, the government found a way to not ban them by claiming they were not psychoactive. Nitrous oxide, another recreational gas, was also a possible target of the Psychoactive Substances Bill but this was never explicitly mentioned in the debates. Once the Psychoactive Substances Act came into force the Crown Prosecution Service stated that nitrous oxide was psychoactive and so illegal to sell for psychoactive purposes. Many sellers of nitrous oxide canisters were arrested and some sent to prison. A series of Crown court prosecutions for nitrous oxide possession followed in which the Crown claim that nitrous oxide was psychoactive was challenged. In some of these the defendant was acquitted so making its current legal status uncertain . Here we delve into the pharmacology of nitric oxide and nitrous oxide and how the effects of these two gasses are related. A clear understanding of the pharmacology of these gasses is essential for the scientific underpinning of legislation which will directly impact on the life of recreational users and people involved in the selling of these substances.

A 49-year-old woman was diagnosed with an ER + , PR-, HER2 + , BRCA- invasive ductal carcinoma which progressed metastatically to include bone, liver, and lymph node involvement. Standardised care included a 26-month treatment period with targeted chemotherapy and a ketogenic diet. The patient also began a course of cannabinoid-based therapy, consisting initially of a titrated high-dose protocol of mixed cannabidiol (CBD) and d9-tetrahydrocannabinol (THC) chemotypes, as well as psilocybin-assisted psychotherapy at macro and intermittent micro-doses. At the end of the five-month treatment period PET/CT investigations revealed no evidence of metastatic disease and chemotherapy was withdrawn. A one year follow up CT investigation concluded no evidence of residual or recurrent disease. A recurrence of disease was noted at 18 months follow up. Over these 18 months the cannabis regimen was titrated down to 60% of the initial protocol. This was subsequently increased to the initial dosing protocol following detection of recurrent disease and this titration occurred over a 10-month period where it remained stable. 16 months following the detection of recurrence of disease, favourable results were observed in the patient with evidence of receding cancer progression. Over the last 15 years there has been a considerable body of in-vitro and in-vivo evidence supporting the anti-neoplastic properties of cannabinoids and more recently psychedelics. Indeed, growing anecdotal and real-world evidence is reported of the therapeutic effect of cannabinoids and psychedelics in reducing both tumour proliferation and aiding as a palliative medicine to treat pain and psychological distress associated with cancer and chemotherapy. The data presented here indicate the potential therapeutic utility of such adjunctive pharmacological interventions in an individual with metastatic breast cancer.

The recent surge in recreational (non-medical) use of nitrous oxide (N2O, also known as ‘laughing gas’) often by inhaling it from balloons, has attracted the attention of some politicians with calls to control its possession under the United Kingdom (UK) Misuse of Drugs Act 1971 (currently selling, but not possession, for recreational use is controlled under the Psychoactive Substances Act 2016). Meanwhile, the recreational use of nitric monoxide (NO) as delivered by alkyl nitrites, also known as ‘poppers’ has also raised concerns, but unlike N2O, its use was not controlled under the 2016 Act. To inform future-decision making processes and ensure that any such decisions are based on the best evidence, Drug Science conducted a Multi-Criteria Decision Analysis (MCDA) about N2O and poppers to compare the overall harms of these two drugs to the harms of 20 drugs previously evaluated and published by Nutt et al. The group assessed harm scores for N2O and poppers on the original 16 harm criteria using the associated 0 to 100 scales, on each of which 100 had been assigned to the most harmful drug and zero to the least harmful, though that often meant no harm. On the overall harm scale, N2O scored 6, just above magic mushrooms (psilocybin) while ‘poppers’ scored 5. Together these are the three lowest drugs on the overall harm scale. Although their overall scores are similar, the reasons behind the ratings differ. Nitrous oxide was considered more harmful than poppers for Dependence, Environmental Damage, Drug Related Relative Impairment of Mental Functioning, and Family Adversities, while poppers are more harmful than N2O for Injury, Drug Related Damage, Economic Cost, and Drug Related Mortality. When assessing the risk different substances may hold when making policy decisions, it is important to acknowledge the relative contribution of these diverse harms within different domains.

Alcohol works on the brain to produce its desired effects, e.g., sociability and intoxication, and hence the brain is an important organ for exploring subsequent harms. These come in many different forms such as the consequences of damage during intoxication, e.g., from falls and fights, damage from withdrawal, damage from the toxicity of alcohol and its metabolites and altered brain structure and function with implications for behavioral processes such as craving and addiction. On top of that are peripheral factors that compound brain damage such as poor diet, vitamin deficiencies leading to Wernicke-Korsakoff syndrome. Prenatal alcohol exposure can also have a profound impact on brain development and lead to irremediable changes of fetal alcohol syndrome. This chapter briefly reviews aspects of these with a particular focus on recent brain imaging results. Cardiovascular effects of alcohol that lead to brain pathology are not covered as they are dealt with elsewhere in the volume.

This article covers the renaissance of classical psychedelic drugs such as psilocybin and LSD plus 3,4-methylene dioxymethamphetamine (MDMA-ecstasy) in psychiatric research. These drugs were used quite extensively before they became prohibited. This ban had little impact on recreational use, but effectively stopped research and clinical treatments, which up to that point had looked very promising in several areas of psychiatry. In the past decade a number of groups have been working to re-evaluate the utility of these substances in medicine. So far highly promising preliminary data have been produced with psilocybin in anxiety, depression, smoking, alcoholism, and with MDMA for post-traumatic stress disorder (PTSD) and alcoholism. These findings have led to the European Medicines Agency approving psilocybin for a phase 3 study in treatment-resistant depression and the Food and Drug Administration for PTSD with MDMA. Both trials should read out in 2020, and if the results are positive we are likely to see these medicines approved for clinical practice soon afterwards. .Mettre la traduction ES.Mettre la traduction FR.

This chapter was inadvertently published with Fig. 1 which do not belong to this chapter and hence Fig. 1 is deleted from this chapter later.

Anxiety disorders are the most common mental health problem in the world and also claim the highest health care cost among various neuropsychiatric disorders. Anxiety disorders have a chronic and recurrent course and cause significantly negative impacts on patients' social, personal, and occupational functioning as well as quality of life. Despite their high prevalence rates, anxiety disorders have often been under-diagnosed or misdiagnosed, and consequently under-treated. Even with the correct diagnosis, anxiety disorders are known to be difficult to treat successfully. In order to implement better strategies in diagnosis, prognosis, treatment decision, and early prevention for anxiety disorders, tremendous efforts have been put into studies using genetic and neuroimaging techniques to advance our understandings of the underlying biological mechanisms. In addition to anxiety disorders including panic disorder, generalised anxiety disorder (GAD), specific phobias, social anxiety disorders (SAD), due to overlapping symptom dimensions, obsessive-compulsive disorder (OCD), and post-traumatic stress disorder (PTSD) (which were removed from the anxiety disorder category in DSM-5 to become separate categories) are also included for review of relevant genetic and neuroimaging findings. Although the number of genetic or neuroimaging studies focusing on anxiety disorders is relatively small compare to other psychiatric disorders such as psychotic disorders or mood disorders, various structural abnormalities in the grey or white matter, functional alterations of activity during resting-state or task conditions, molecular changes of neurotransmitter receptors or transporters, and genetic associations have all been reported. With continuing effort, further genetic and neuroimaging research may potentially lead to clinically useful biomarkers for the prevention, diagnosis, and management of these disorders.