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.

[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.

[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.

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.

The effect of N-acetylcysteine on brain glutamate and gamma-aminobutyric acid concentrations and on smoking cessation: A randomized, double-blind, placebo-controlled trial.

Using data form a 14-day double-blind trial with 48 smokers randomized to either N-acetylcysteine (2400 mg) or placebo, we tested the effect of N-acetylcysteine on glutamate and gamma-aminobutyric acid concentrations in the dorsal anterior cingulate cortex and on smoking cessation. Smoking related behaviors and neurotransmitter concentrations in the dorsal anterior cingulate cortex were assessed before and after treatment. Forty-seven non-smoking males served as baseline controls. Smokers showed higher baseline glutamate but similar gamma-aminobutyric acid concentrations than non-smokers. There were no treatment effects on dorsal anterior cingulate cortex neurotransmitter concentrations, smoking cessation, craving, or withdrawal symptoms. These results confirm glutamate disbalance in smokers, but not efficacy of N-acetylcysteine.

Longitudinal study of hippocampal volumes in heavy cannabis users.

BACKGROUND: Cannabis exposure, particularly heavy cannabis use, has been associated with neuroanatomical alterations in regions rich with cannabinoid receptors such as the hippocampus in some but not in other (mainly cross-sectional) studies. However, it remains unclear whether continued heavy cannabis use alters hippocampal volume, and whether an earlier age of onset and/or a higher dosage exacerbate these changes. METHODS: Twenty heavy cannabis users (mean age 21 years, range 18-24 years) and 23 matched non-cannabis using healthy controls were submitted to a comprehensive psychological assessment and magnetic resonance imaging scan at baseline and at follow-up (average of 39 months post-baseline; standard deviation=2.4). Cannabis users started smoking around 16 years and smoked on average five days per week. A novel aspect of the current study is that hippocampal volume estimates were obtained from manual tracing the hippocampus on T1-weighted anatomical magnetic resonance imaging scans, using a previously validated protocol. RESULTS: Compared to controls, cannabis users did not show hippocampal volume alterations at either baseline or follow-up. Hippocampal volumes increased over time in both cannabis users and controls, following similar trajectories of increase. Cannabis dose and age of onset of cannabis use did not affect hippocampal volumes. CONCLUSIONS: Continued heavy cannabis use did not affect hippocampal neuroanatomical changes in early adulthood. This contrasts with prior evidence on alterations in this region in samples of older adult cannabis users. In young adults using cannabis at this level, cannabis use may not be heavy enough to affect hippocampal neuroanatomy.

Cue-induced striatal activity in frequent cannabis users independently predicts cannabis problem severity three years later.

Cannabis is the most frequently used illicit drug worldwide, but little is known about the mechanisms underlying continued cannabis use. Cue-reactivity (the physical, psychological, behavioural and neural reaction to substance-related cues) might be related to continued cannabis use. In this 3-year prospective neuroimaging study we investigated whether cannabis cue-induced brain activity predicted continued cannabis use and associated problem severity 3 years later. In addition, baseline brain activations were compared between dependent and non-dependent cannabis users at follow-up. Analyses were focussed on brain areas known to be important in cannabis cue-reactivity: anterior cingulate cortex, orbitofrontal cortex, ventral tegmental area, amygdala and striatum. At baseline, 31 treatment-naive frequent cannabis users performed a cue-reactivity functional magnetic resonance imaging task. Of these participants, 23 completed the 3-year follow-up. None of the cue-induced region of interest activations predicted the amount of cannabis use at follow-up. However, cue-induced activation in the left striatum (putamen) significantly and independently predicted problem severity at follow-up (p < 0.001) as assessed with the Cannabis Use Disorder Identification Test. Also, clinically dependent cannabis users at follow-up showed higher baseline activation at trend level in the left striatum compared with non-dependent users. This indicates that neural cue-reactivity in the dorsal striatum is an independent predictor of cannabis use-related problems. Given the relatively small sample size, these results are preliminary and should be replicated in larger samples of cannabis users.

Progress in mind: focus on alcohol use disorders, an elsevier resource centre.

Harmful use of alcohol is one of the top five risks for burden of disease globally and in Europe; in 2012, 3.3 million net deaths (approximately 6% of all global deaths) were attributable to this risk factor. It is also linked to the development of a wide spectrum of alcohol use disorders, ranging from mild manifestations to a severe disease known as alcohol dependence. Alcohol dependence is a progressive, chronic, and relapsing brain disease resulting from the prolonged effects of alcohol on the brain. Alcohol dependence imposes a significant societal burden, with indirect societal costs reaching up to 0.64% of European countries׳ annual gross domestic product. With these facts in mind, it is important to recognize and manage alcohol dependence. Although the biological mechanisms behind the development of alcohol dependence are not fully known, factors that have been shown to influence its development include genetic predisposition, psychological problems, and social interactions. Alcohol use has also been linked to the development of hypertension, liver cirrhosis, chronic pancreatitis, multiple types of cancer, and psychiatric comorbidities such as depression and anxiety disorders. With such severe effects on both individuals and society, it is important to recognize the characteristic signs and symptoms of alcohol dependence and explore new ways to better manage patients with this brain disease. Effective treatment approaches for alcohol dependence include biological, behavioral, and social components addressing the multiple aspects of this disease. Comprehensive, educational platforms in which to explore the many facets of this disease such as the Progress in Mind: Focus on Alcohol Use Disorders Resource Centre, will provide clinicians with the tools necessary for recognizing patients with alcohol dependence and managing their disease along with related comorbidities. Online Access: http://progressinmind.elsevierresource.com.

Psychotic reactions to daily life stress and dopamine function in people with severe hearing impairment.

BACKGROUND: Minor stresses measured in daily life have repeatedly been associated with increased momentary psychotic experiences, both in individuals with psychotic disorders and in persons who are genetically at an increased risk for these disorders. Severe hearing impairment (SHI) is an environmental risk factor for psychotic disorder, possibly due to the experience of social exclusion. The aim of the current study is to investigate whether people with SHI exhibit higher levels of psychotic reactivity to social stressors in daily life than normal-hearing controls and whether this reactivity is associated with decreased baseline dopamine (DA) D2/3 receptor availability and/or elevated DA release following a dexamphetamine challenge. METHOD: We conducted an experience sampling study in 15 young adults with SHI and 19 matched normal-hearing controls who had previously participated in a single photon emission computed tomography study measuring DA D2/3 receptor availability and DA release in response to dexamphetamine. RESULTS: The association between social stress and momentary psychotic experiences in daily life was stronger among SHI participants than among normal-hearing controls. Interactions between social stress and baseline striatal DA D2/3 receptor availability or DA release were not significant in multilevel models of momentary psychotic experiences including age, sex and tobacco use. CONCLUSIONS: While both elevated striatal DA release and elevated psychotic stress reactivity have been found in the same population defined by an environmental risk factor, SHI, their inter-relationship cannot be established. Further research is warranted to clarify the association between biological and psychological endophenotypes and psychosis risk.

[Staging and profiling in addication]. / Stagering en profilering bij verslaving.

BACKGROUND: The existence or non-existence of the formal diagnosis 'substance' or 'dependence' is in fact of little consequence in terms of the severity of the affliction, the course of the disorder and the response to a specific type of treatment. Furthermore, the effective treatments that are currently available seem to work only in a minority of the patients in routine clinical practice. A possible reason for these discrepancies is too much heterogeneity within the diagnostic categories. The planned merging of the diagnoses 'substance abuse' and 'dependence' into a single diagnostic category 'substance use disorder' in DSM-5 is likely to increase the heterogeneity still further. AIM: To provide suggestions for improvement of diagnosis and treatment through staging and profiling of addiction and dependency. METHOD: Study of the relevant literature. RESULTS: A possible solution is to reduce the heterogeneity by the introduction of staging and profiling. Therefore, we present a model for addiction which is based on existing models in oncology and on current knowledge about the neurobiology of addiction. In addition, we demonstrate in what way individual patients with an addiction can be characterised and profiled in more detail through the use of phenotypical, endophenotypical and genetic information. CONCLUSION: The combination of diagnosis, staging and profiling will lead to more effective and efficient treatment for patients suffering from addiction.

Incidental head and neck findings on MRI in young healthy volunteers: prevalence and clinical implications.

We determined the prevalence and clinical relevance of incidental brain and head and neck findings in young healthy volunteers with MR imaging. We retrospectively analyzed the MR images obtained from 203 healthy young adult volunteers (mean age, 21.9 years; range, 18-35 years). The prevalence of the categories of findings (no referral necessary, routine referral, urgent referral, and immediate referral) was scored by a head and neck radiologist or neuroradiologist. We found a high prevalence of incidental brain and head and neck abnormalities (9.4% and 36.7%, respectively); 4.4% of the brain findings and 5.5% of the head and neck findings were classified as in need of referral. Only 1 incidental finding classified as in need of referral (a skull lesion consistent with fibrous dysplasia) was actually referred at the time of the study (5.2%). These findings suggest that a high prevalence of incidental findings is common in healthy young volunteers, though the clinical implications are negligible.

Age at onset of non-affective psychosis in relation to cannabis use, other drug use and gender.

BACKGROUND: Cannabis use is associated with an earlier age at onset of psychotic illness. The aim of the present study was to examine whether this association is confounded by gender or other substance use in a large cohort of patients with a non-affective psychotic disorder. METHOD: In 785 patients with a non-affective psychotic disorder, regression analysis was used to investigate the independent effects of gender, cannabis use and other drug use on age at onset of first psychosis. RESULTS: Age at onset was 1.8 years earlier in cannabis users compared to non-users, controlling for gender and other possible confounders. Use of other drugs did not have an additional effect on age at onset when cannabis use was taken into account. In 63.5% of cannabis-using patients, age at most intense cannabis use preceded the age at onset of first psychosis. In males, the mean age at onset was 1.3 years lower than in females, controlling for cannabis use and other confounders. CONCLUSIONS: Cannabis use and gender are independently associated with an earlier onset of psychotic illness. Our findings also suggest that cannabis use may precipitate psychosis. More research is needed to clarify the neurobiological factors that make people vulnerable to this precipitating effect of cannabis.

Alcohol-use disorder severity predicts first-incidence of depressive disorders.

BACKGROUND: Previous studies suggest that alcohol-use disorder severity, defined by the number of criteria met, provides a more informative phenotype than dichotomized DSM-IV diagnostic measures of alcohol use disorders. Therefore, this study examined whether alcohol-use disorder severity predicted first-incident depressive disorders, an association that has never been found for the presence or absence of an alcohol use disorder in the general population. METHOD: In a national sample of persons who had never experienced a major depressive disorder (MDD), dysthymia, manic or hypomanic episode (n=27 571), we examined whether a version of DSM-5 alcohol-use disorder severity (a count of three abuse and all seven dependence criteria) linearly predicted first-incident depressive disorders (MDD or dysthymia) after 3-year follow-up. Wald tests were used to assess whether more complicated models defined the relationship more accurately. RESULTS: First-incidence of depressive disorders varied across alcohol-use disorder severity and was 4.20% in persons meeting no alcohol-use disorder criteria versus 44.47% in persons meeting all 10 criteria. Alcohol-use disorder severity significantly predicted first-incidence of depressive disorders in a linear fashion (odds ratio 1.14, 95% CI 1.06-1.22), even after adjustment for sociodemographics, smoking status and predisposing factors for depressive disorders, such as general vulnerability factors, psychiatric co-morbidity and subthreshold depressive disorders. This linear model explained the relationship just as well as more complicated models. CONCLUSIONS: Alcohol-use disorder severity was a significant linear predictor of first-incident depressive disorders after 3-year follow-up and may be useful in identifying a high-risk group for depressive disorders that could be targeted by prevention strategies.

Influence of treatment with inhalable heroin on pulmonary function.

This study aims to asses the influence of inhalable heroin on pulmonary function in chronic heroin-dependent patients treated with inhalable heroin. Among 32 patients (all cigarette smokers), a spirometric test was conducted at baseline and after an average period of 10 months of treatment with medically prescribed heroin. Patients showed a high frequency of pulmonary dysfunction at baseline [34%, with percentage of forced expiratory volume in 1 s (%FEV1)<80%]. However, after excluding those who started pulmonary treatment (n=2) or who used heroin intravenously only (n=2), no statistically significant differences in %FEV1 between baseline and follow-up were observed (n=28; mean %FEV1 86% at baseline vs. 91% at follow-up; p=0.09). This small and relatively brief study suggests that 10 months of co-prescribed inhalable heroine base does not seem to (further) deteriorate pulmonary function in chronic, cigarette smoking treatment refractory heroin addicts. Screening for and treatment of pulmonary dysfunction is recommended for methadone patients with and without co-prescribed heroin.

[Spinal epidural abscess as a complication of a finger infection]. / Een spinaal epiduraal abces als complicatie van een ontstoken vinger.

An 81-year-old man was treated with intravenous antibiotics for a soft tissue infection in a finger. Despite adequate antibiotic treatment, he developed signs of spinal cord injury caused by a cervical spinal epidural abscess. An emergency laminectomy was performed. The neurological impairment appeared to be irreversible, and the patient died. Spinal epidural abscess is a rare and serious complication ofa bacteraemia. It is often caused by an infection of the skin or soft tissue with Staphylococcus aureus. Given the risk of rapidly progressive and irreversible neurological damage, this complication must be treated as soon as possible. The treatment of choice is surgery. Conservative management with intravenous antibiotics is an option only under strict conditions.

[Can depressed patients stop smoking? A review]. / Kunnen patiënten met een depressieve stoornis stoppen met roken?

BACKGROUND: Nicotine dependence and depression often occur together in the same patient. It is surprising, therefore, that psychiatry does not do more to persuade these patients to stop smoking. AIM: To ascertain whether a stop-smoking programme should be a standard module of a treatment programme for depression. METHOD: A literature search was conducted with the help of PubMed, Embase and the Cochrane Library and using the search terms: 'major depressive disorder', 'nicotine dependence', 'smoking and smoking cessation'. RESULTS: There is high comorbidity between daily smoking and depression. Genetic factors and acute life-events are risk factors for this comorbidity. Very little research has been done to find out whether depressed patients who quit smoking attain long-lasting abstinence and what the effects of quitting are on their depressive symptoms. Smokers with a history of depression seem to benefit from a stop-smoking programme but it is uncertain whether they also run an increased risk of a new depressive episode. CONCLUSION: There are good reasons for adding a stop-smoking programme to a programme for treating depression in patients who smoke. However, before this plan is implemented we need to find out whether patients who stop smoking are more likely to develop more depressive symptoms and attain long-lasting abstinence.

The ability of YSR scales to predict DSM/DISC-C psychiatric disorders among incarcerated male adolescents.

OBJECTIVE: To investigate whether the empirical or DSM-oriented scales of the Youth Self-Report (YSR) can be used to screen for DSM psychiatric disorders among incarcerated boys. DSM-oriented scales have recently been developed by Achenbach to enhance comparability of YSR results with DSM diagnostic categories. METHOD: A representative sample (N = 196) of incarcerated boys aged 12-18 was assessed with the child version of the Diagnostic Interview Schedule for Children (DISC-C) to diagnose DSM psychiatric disorders, and with the Youth Self-Report (YSR). RESULTS: Only 22% had YSR total problem scores in the clinical range, whereas 90 % met criteria of at least one DSM/DISC-C psychiatric disorder. Weak associations between both empirical and DSM-oriented YSR scale scores and DSM/DISC-C diagnoses were found. CONCLUSIONS: Neither the empirical nor the DSM-oriented YSR scales adequately screen for DSM/DISC-C psychiatric disorders among incarcerated boys. The use of the YSR and the DISC-C to assess DSM constructs results in, at least partially, different diagnostic information.