Associations between genetic liabilities to smoking behavior and schizophrenia symptoms in patients with a psychotic disorder, their siblings and healthy controls.

It is unknown how smoking behavior polygenic scores (PRS) relate to psychosis and psychotic symptoms. To elucidate this, genotype and phenotype data were collected from patients with schizophrenia, their unaffected siblings, and healthy controls in a six-year follow-up prospective cohort study. Associations between smoking behaviors, PRS and schizophrenia symptoms were explored using linear mixed-effect models. The mean number of cigarettes smoked per day were 18 for patients, 13 for siblings and 12 for controls. In the overall sample, PRSs-smoking initiation (i.e., ever smoking as a binary phenotype, PRS-SI) were positively associated with positive symptoms, negative symptoms, and depressive symptoms, whereas PRSs-AI (age at regular smoking initiation) were negatively associated with all symptom dimensions, with similar effect sizes. When considering groups separately, PRS were only associated with psychotic symptoms in siblings and controls. In conclusion, unaffected siblings show smoking behaviors at an intermediate level between patients and healthy controls. Additionally, PRS-SI and PRS-AI are associated with all symptom dimensions only in unaffected siblings and healthy controls, possibly owing to the dominant role of other (genetic) risk factors in patients. Future studies may examine mechanisms via which genetic risk for smoking affects mental health symptoms.

[The development of a rational national MDMA policy and its relevance for psychiatry]. / Voorstel voor rationeel MDMA-beleid.

BACKGROUND: MDMA (ecstasy) is a relatively safe drug and induces little dependence, but is nevertheless scheduled as a hard drug (Dutch Opium Act, List 1). Concerns about MDMA-related crime, health incidents and possible inappropriate listing of MDMA on List I have led to an ongoing debate about current Dutch ecstasy policy. AIM: To develop a rational MDMA policy that takes into account all aspects related to production, sale and use of MDMA. METHOD: An interdisciplinary group of 18 experts formulates a science-based MDMA policy by assessing the expected effects of 95 policy options on 25 outcomes, including health, crime, law enforcement and finance. The optimal policy model consists of the combination of the 22 policy options with the highest total score on all 25 outcomes. RESULTS: The optimal policy model consisted of a form of regulated production and sale of MDMA, better quality management of ecstasy tablets and more intensive fight against MDMA-related organized crime. Such a policy would lead to a small increase in the prevalence of ecstasy use, but with less health damage, less MDMA-related crime, and less environmental damage. To increase practicality and political feasibility, the optimal model was slightly modified. CONCLUSION: The developed optimal model offers a politically and socially feasible set of policy instrument options, with which the placement of MDMA on List I can be revised, thereby reducing the damage of MDMA to users and society. For psychiatry, it means promoting therapeutic research and less nuisance from unnecessary stigmatization in the treatment of patients.

[Adolescents with concurrent ADHD and substance use disorder; international consensus]. / Jongeren met een stoornis in het gebruik van middelen en ADHD: internationale consensus.

BACKGROUND: Substance use disorder (SUD) is common among youths with attention-deficit/hyperactivity disorder (ADHD). Co-morbid ADHD and SUD in youths complicates screening, diagnosis, and treatment of both disorders and is associated with worse treatment prognosis. Limited research in youths with SUD and co-morbid ADHD provides insufficient basis for firm recommendations. To offer clinicians some guidance on this topic, we present the results of an international consensus procedure. AIM: To summarize an international consensus on diagnosis and treatment of young people with comorbid ADHD and SUD. METHOD: In a modified Delphi-study, a multidisciplinary, international group of 55 experts strived to reach consensus on 37 recommendations. RESULTS: Consensus was reached on 36 recommendations. Routine screening of ADHD and/or SUD is important. For the treatment of co-morbid SUD and ADHD in youths, both psychosocial and pharmacological treatment should be considered. Psychosocial treatment should preferably consist of psychoeducation, motivational interviewing (MI), and cognitive behavioral therapy (CBT) focused on SUD or both disorders. Long-acting stimulants are recommended as first choice pharmacotherapy, preferably embedded in psychosocial treatment. Experts did not agree on the precondition that patients need to be abstinent before starting stimulant treatment. CONCLUSION: Clinicians and youths with co-morbid SUD and ADHD can use this international consensus to choose the best possible treatment.

[Ketamine self-medication in a patient with autism spectrum disorder and comorbid treatment-resistant depression]. / Ketamine als zelfmedicatie bij patiënt met autismespectrumstoornis en therapieresistente depressie.

We saw a 60-year-old male veterinarian with a history of autism spectrum disorder, major depressive disorder, and suicidality. He had been treated with more than 15 psychotropic medications, was admitted to inpatient care several times, and attempted suicide once. His current complaints included a decline in social functioning, repetitive behaviour, sensory hypersensitivity, anxiety, low mood, anhedonia, lack of energy, and chronic suicidality. His last medication consisted of risperidone and valproic acid. Despite intensive treatment, he remained impaired by his complaints and could not return to work. After self-medication with ketamine, he reported that his depressive and suicidal complaints disappeared and that his autism-related complaints diminished. This case - together with previous clinical research - suggests that ketamine is likely to be effective against depression and suicidality, that ketamine is potentially effective against autism-related symptoms, and that increasing awareness of the beneficial effects of ketamine can lead to unsupervised, and therefore risky, use of ketamine as a form of self-medication.

[Psychedelics in the treatment of depression, anxiety, and obsessive-compulsive disorder]. / Psychedelica bij de behandeling van depressie, angst en obsessieve-compulsieve stoornis.

BACKGROUND: There is a need for new, effective treatments for patients with (treatment-resistant) depressive disorders, anxiety disorders and obsessive-compulsive disorder (ocd). At the same time, there is renewed interest in psychedelics for the treatment of psychiatric disorders.
AIM: To provide an overview of results from past and current research into psychedelics in the treatment of depression, anxiety disorders and ocd.
METHOD: Literature search in Medline and PubMed databases, supplemented with cross-references and results from recent studies.
RESULTS: There is a considerable evidence base for the atypical psychedelic ketamine. Ketamine has a rapid, beneficial effect on depression and suicidality; longer-term effects are less clear. Research into classical psychedelics for the treatment of depression and anxiety disorders is currently limited to a few small (open label) studies, although positive outcomes are reported even after a single administration, with potentially longer lasting benefits. Studies must be repeated in larger and more diverse groups of patients.
CONCLUSION: Further research into efficacy, therapeutic mechanisms and intervention models is very worthwhile; for the benefit of patients, but also to provide a deeper insight into the psychotherapeutic and neurobiological mechanisms that play a role in (the treatment of) common mental disorders.

[Ketamine as an anesthetic, analgesic and anti-depressant]. / Ketamine als anestheticum, analgeticum en als antidepressivum.

BACKGROUND: Treatment-resistance occurs in about 30% of patients with depression. Therefore, there is an urgent need to identify new treatment strategies. Ketamine, originally developed as an anesthetic, is studied and applied as treatment for patients with treatment-resistant depression.
AIM: A critical review of the current use of ketamine as an antidepressant.
METHOD: Literature study.
RESULTS: Ketamine is a proven effective acute antidepressant. However, limited information is available about maintenance of effect of ketamine, potential risks of repeated administration, and different routes of administration and treatment schedules.
CONCLUSION: Additional research on ketamine as an antidepressant is needed. Meanwhile, (off-label) treatment should only be applied after careful patient selection and under close monitoring.

[Psychedelics in the treatment of PTSD]. / Psychedelica bij de behandeling van PTSS.

BACKGROUND: Posttraumatic stress disorder (PTSD) is often a chronic condition, despite the availability of various evidence-based treatment options. Psychedelics offer new treatment opportunities.
AIM: An overview of the current evidence, therapeutic context, and possible mechanisms of action of different types of psychedelics in the treatment of PTSD.
METHOD: A scoping review of the available literature.
RESULTS: MDMA-assisted psychotherapy has shown to produce lasting reductions in PTSD symptoms in multiple RCTs. Based on a small number of studies, ketamine administration appears to lead to temporary symptom relief. Current studies are investigating whether the use of ketamine in combination with psychotherapy can lead to lasting reductions in PTSD symptoms. Classical psychedelics (such as psilocybin and LSD) induce psychoactive effects (on behavior or experience) that could contribute to the psychotherapeutic treatment of PTSD but have not yet been investigated in controlled studies. Reported positive effects extend beyond PTSD symptoms only.
CONCLUSION: Psychedelics may have potential to serve as a catalyst for the psychotherapeutic treatment of PTSD. Most evidence exists for MDMA-supported psychotherapy; relatively little research is available on ketamine and classical psychedelics. Future research needs to show whether the use of psychedelics can be integrated into available treatment options for PTSD.

[Psychedelics in the treatment of substance use disorders and psychosis]. / Psychedelica bij de behandeling van verslaving en psychose.

BACKGROUND: After psychedelics were banned in 1968, the flourishing research on the use of psychedelics in patients with a mental disorder stopped abruptly. Recently, we see a renaissance of this research.
AIM: To present an overview of what is known about the treatment of addiction and psychosis with psychedelics.
METHOD: Literature study based on Medline en PubMed publications till December 2019.
RESULTS: Studies on the effectiveness of psychedelics in the treatment of addiction and psychosis is still very limited in size and methodological quality. Nevertheless, most studies show positive effects of both classical and atypical psychedelics in a variety of addictions on motivation, craving, reduced consumption, and abstinence often following a single dose and with long-lasting benefits (3-24 months). Use of ketamine in patients with a psychosis stabilized on an antipsychotic might reduce negative symptoms.
CONCLUSION: Before psychedelics can be used in standard clinical practice for the treatment of patients with an addiction or a psychosis, larger and methodologically better studies are needed. The use of psychedelics also creates an opportunity to better understand the shared underlying pathology of many different mental disorders.

[Psychedelics for existential distress in terminally ill patients]. / Psychedelica bij existentieel lijden bij patiënten met een terminale ziekte.

BACKGROUND: Existential distress in patients with a terminal illness is often associated with (symptoms of) anxiety and depression. Psychotherapeutic interventions seem effective but effects are short-lived. There are no proven effective pharmacological interventions.
AIM: To present an overview of literature on psychedelic treatment of existential distress in patients with terminal illness.
METHOD: Literature research in PubMed/Medline databases, supplemented with cross-references.
RESULTS: 14 clinical studies have been conducted: 6 with classic psychedelics between 1960 and 1980, and 8 with classic psychedelics and ketamine after 2000. Results of early pre-post studies are promising but have serious methodological limitations. Recent clinical research with LSD, psilocybin and ketamine are also promising although limited in terms of research design and generalizability. Overall, studies show a positive effect on existential and spiritual well-being, quality of life, acceptance and (symptoms of) anxiety and depression. Mystical experiences are correlated with positive outcomes. Few adverse effects are reported.
CONCLUSION: Treatment of existential distress using classical psychedelics or ketamine in patients with terminal illness seems auspicious. Larger clinical studies in a more diverse patient population with fewer methodological limitations are needed to draw conclusions about efficacy and generalizability.

[Recreative ecstasy use in the Netherlands: use characteristics, health risks and criminality]. / Recreatief ecstasygebruik in Nederland: gebruikskenmerken, gezondheidsschade en criminaliteit.

BACKGROUND: Ecstasy (MDMA) is used by approximately 370,000 Dutch people yearly, mainly young adults with a good education.
AIM: To describe ecstasy-related negative health effects, health risks, use profiles and crime based on data from scientific literature and other publicly available sources.
RESULTS: Ecstasy appears to cause little health damage during recreational use. Adverse health incidents, particularly hyperthermia, are observed, but are probably partly due to the use of ecstasy under (a combination of) unfavourable circumstances, such as: a warm environment, too little drinking, and considerable physical exertion (dancing). The estimated risk of serious ecstasy-related non-fatal accidents was 1 in 3,400 pills and 1 per 700 users. The number of fatal ecstasy-related incidents is estimated to be a maximum of 35 per year. Crime associated with the production and trade of ecstasy is worrying and, according to some authors, disruptive to society.
CONCLUSION: On the basis of these results, we conclude that the use of ecstasy does involve health risks, but given the widespread use of ecstasy, the number of (fatal) incidents is relatively low. Better information about the conditions under which ecstasy can be used more safely will contribute to fewer incidents.

[Implementation of a stop-smoking support program for patients and employees in a psychiatric hospital: First results]. / Implementatie van een stoppen-met-rokenprogramma in een psychiatrisch ziekenhuis: eerste resultaten.

BACKGROUND: In contrast to several other countries, smoking is not an integral part of treatment during admission to a psychiatric hospital in The Netherlands.
AIM: Implementation of a smoking cessation program for patients and employees of a psychiatric ward of an academic medical center in The Netherlands.
METHOD: Prospective, mixed-method study of implementation of a smoking cessation program for patients and employees of a psychiatric academic hospital in Amsterdam. The program consisted of 7 weekly group meetings by certified smoking cessation coaches. Nicotine replacement therapy was provided for free, if necessary.
RESULTS: During 14 months, 65 individuals were seeking help to stop smoking: 39 patients and 26 employees. Of these, 29 patients and 16 employees participated in group meetings with an average of 2.6 times per person. There were 20 individuals who visited the group meetings or received individual coaching at least 3 times (6 patients and 14 employees). Fifty-five percent of these individuals reported to be smoke-free at 3 months after joining the first meeting. Employees were much more likely to quit than patients. From interviews with 20 participants, it was noticed that combining patients and employees in one group was perceived as a barrier due to a gap in processing speed.
CONCLUSION: On the psychiatric ward of an academic hospital in The Netherlands, there was a positive experience with providing smoking cessation treatment. A small number of employees and patients participated in a smoking cessation program and quitting smoking was reached by only a few patients. Supporting smoking cessation in a psychiatric hospital asks for intensive screening, diagnosing, treatment and smoke-free policies.

Intoxicated aggression: Do alcohol and stimulants cause dose-related aggression? A review.

RATIONALE: Violence and drug use are significant public health challenges that are strongly linked. It is known that alcohol plays a major role in the causation of unnatural deaths and that stimulants like cocaine and amphetamine are often implicated in aggressive acts or violence. However, a clear causal relationship between these substances and aggression, and more specifically a blood concentration threshold at which intoxicated aggression emerges is lacking. In case of a crime and subsequent law enforcement, knowledge about dose-response relationships could be of pivotal importance when evaluating the role of alcohol and drugs in aggressive offences. AIMS: The present review aimed to determine whether there is a causal relation between intoxication with these psychoactive substances and aggression, and to define blood concentration thresholds above which these substances elicit aggression. METHODS: Empirical articles published between 2013 and 2017 and review papers containing the predefined search strings were identified through searches in the PubMed and Embase databases and additional reference list searches. The complete search query yielded 1578 publications. Initially all articles were manually screened by title and abstract. Articles with irrelevant titles, given the selected search terms and review aims were discarded. Remaining articles were carefully studied and those that did not comply with the main objectives of this review were discarded. At the end of this process, 167 titles were found eligible for review. FINDINGS AND CONCLUSION: While placebo-controlled experimental studies clearly showed a causal link between alcohol and aggression, it is evident that such a link has not yet been established for cocaine and amphetamines. In case of alcohol, it is clear that there are various individual and contextual factors that may contribute to the occurrence of an aggressive act during intoxication. A clear threshold blood alcohol concentration has not been defined yet for alcohol, but a statistically significant increase of aggression has been demonstrated at a dose of 0.75 g/kg and higher. Future studies into intoxicated aggression should include multiple doses of alcohol and stimulants and take into account individual and contextual factors.

[International consensus for the screening, diagnosis and treatment of adult patients with substance use disorder and ADHD]. / Internationale consensus voor de screening, diagnose en behandeling van volwassen patiënten met een stoornis in het gebruik van een middel en ADHD.

BACKGROUND: Substance use disorders (SUD) and attention-deficit/hyperactivity disorder (ADHD) often co-occur in adults. Together, they complicate diagnosis and can negatively influence treatment outcome.
AIM: To develop a practical guide to assist professionals with the screening, diagnosis and treatment of adult patients with SUD and ADHD.
METHOD: A literature search and a consensus procedure between several international scientific and clinical experts. This manuscript is an adapted and summarized Dutch version of the International consensus statement on screening, diagnosis and treatment of patients with SUD and comorbid ADHD.
RESULTS: The routine use of adequate screening tools enables ADHD to be detected earlier in adults with SUD. The diagnostic process for ADHD should be initiated as soon as possible in patients with SUD. Integrated treatment, involving a combination of pharmacotherapy and psychotherapy, is preferred. Long-acting stimulants with up-titration to higher dosages may be considered.
CONCLUSION: Early detection of ADHD in patients with SUD is essential for adequate diagnosis and more effective treatment and follow-up for these patients.

Executive Dysfunction in Patients With Korsakoff's Syndrome: A Theory-Driven Approach.

AIMS: In addition to amnesia, executive deficits are prominent in Korsakoff's syndrome (KS), yet poorly studied. This study investigates the degree of executive dysfunction in patients with KS for the three main executive subcomponents shifting, updating and inhibition using novel, theory-driven paradigms. SHORT SUMMARY: Compared to healthy controls, patients with KS show impairments on the executive subcomponents shifting and updating, but not on inhibition. METHODS: Executive functions were measured with six carefully designed tasks in 36 abstinent patients with KS (mean age 62.3; 28% woman) and compared with 30 healthy non-alcoholic controls (mean age 61.8; 40% woman). ANOVAs were conducted to examine group differences and effect sizes were calculated. RESULTS: Compared to healthy controls, patients with KS were impaired on the executive subcomponents shifting and updating. No statistically significant group difference was found on the factor inhibition. CONCLUSIONS: Executive dysfunction in long-abstinent patients with alcoholic KS shows a profile in which shifting and updating ability are affected most. It also highlights that executive dysfunction is an important feature of KS and requires more attention in scientific and clinical practice, as these deficits may also affect daily functioning.

The relation between gray matter volume and the use of alcohol, tobacco, cocaine and cannabis in male polysubstance users.

BACKGROUND: Neuroimaging studies have demonstrated gray matter (GM) volume abnormalities in substance users. While the majority of substance users are polysubstance users, very little is known about the relation between GM volume abnormalities and polysubstance use. METHODS: In this study we assessed the relation between GM volume, and the use of alcohol, tobacco, cocaine and cannabis as well as the total number of substances used, in a sample of 169 males: 15 non-substance users, 89 moderate drinkers, 27 moderate drinkers who also smoke tobacco, 13 moderate drinkers who also smoke tobacco and use cocaine, 10 heavy drinkers who smoke tobacco and use cocaine and 15 heavy drinkers who smoke tobacco, cannabis and use cocaine. RESULTS: Regression analyses showed that there was a negative relation between the number of substances used and volume of the dorsal medial prefrontal cortex (mPFC) and the ventral mPFC. Without controlling for the use of other substances, the volume of the dorsal mPFC was negatively associated with the use of alcohol, tobacco, and cocaine. After controlling for the use of other substances, a negative relation was found between tobacco and cocaine and volume of the thalami and ventrolateral PFC, respectively. CONCLUSION: These findings indicate that mPFC alterations may not be substance-specific, but rather related to the number of substances used, whereas, thalamic and ventrolateral PFC pathology is specifically associated with tobacco and cocaine use, respectively. These findings are important, as the differential alterations in GM volume may underlie different cognitive deficits associated with substance use disorders.

[Personalised treatment of disorders in the use of alcohol and nicotine]. / Gepersonaliseerde behandeling bij stoornissen in het gebruik van alcohol en tabak.

BACKGROUND: There is an increasing interest in personalised treatment based on the individual characteristics of the patient in the field of addiction care. AIM: To summarise the present state of staging and profiling possibilities within addiction care. METHOD: A literature review highlighting the current scientific findings and proposing a theoretical model. RESULTS: There are currently an insufficient number of studies to allow for a fully data driven model. However, research identifying biomarkers is growing and some clinically implementable findings can be put forward. CONCLUSION: a personalised approach in addiction care holds promise. There is an urgent need for better and larger datasets to empirically support models aimed for clinical use.