A naturalistic cohort study of first-episode schizophrenia spectrum disorder: A description of the early phase of illness in the PSYSCAN cohort.

BACKGROUND: We examined the course of illness over a 12-month period in a large, international multi-center cohort of people with a first-episode schizophrenia spectrum disorder (FES) in a naturalistic, prospective study (PSYSCAN). METHOD: Patients with a first episode of schizophrenia, schizoaffective disorder (depressive type) or schizophreniform disorder were recruited at 16 institutions in Europe, Israel and Australia. Participants (N = 304) received clinical treatment as usual throughout the study. RESULTS: The mean age of the cohort was 24.3 years (SD = 5.6), and 67 % were male. At baseline, participants presented with a range of intensities of psychotic symptoms, 80 % were taking antipsychotic medication, 68 % were receiving psychological treatment, with 46.5 % in symptomatic remission. The mean duration of untreated psychosis was 6.2 months (SD = 17.0). After one year, 67 % were in symptomatic remission and 61 % were in functional remission, but 31 % had been readmitted to hospital at some time after baseline. In the cohort as a whole, depressive symptoms remained stable over the follow-up period. In patients with a current depressive episode at baseline, depressive symptoms slightly improved. Alcohol, tobacco and cannabis were the most commonly used substances, with daily users of cannabis ranging between 9 and 11 % throughout the follow-up period. CONCLUSIONS: This study provides valuable insight into the early course of a broad range of clinical and functional aspects of illness in FES patients in routine clinical practice.

The association between childhood trauma and tobacco smoking in patients with psychosis, unaffected siblings, and healthy controls.

In patients with psychosis, rates of tobacco smoking and childhood trauma are significantly higher compared to the general population. Childhood trauma has been proposed as a risk factor for tobacco smoking. However, little is known about the relationship between childhood trauma and smoking in psychosis. In a subsample of the Genetic Risk and Outcome of Psychosis study (760 patients with psychosis, 991 unaffected siblings, and 491 healthy controls), tobacco smoking was assessed using the Composite International Diagnostic Interview and childhood trauma was measured with the Childhood Trauma Questionnaire. Logistic regression models were used to assess associations between trauma and smoking, while correcting for confounders. Positive associations were found between total trauma, abuse, and neglect, and an increased risk for smoking in patients, while correcting for age and gender (ORtrauma 1.77, 95% CI 1.30-2.42, p < 0.001; ORabuse 1.69, 95% CI 1.23-2.31, p = 0.001; ORneglect 1.48, 95% CI 1.08-2.02, p = 0.014). In controls, total trauma and abuse were positively associated with smoking, while correcting for age and gender (ORtrauma 2.40, 95% CI 1.49-3.88, p < 0.001; ORabuse 2.02, 96% CI 1.23-3.32, p = 0.006). All associations lost their significance after controlling for additional covariates and multiple testing. Findings suggest that the association between childhood trauma and tobacco smoking can be mainly explained by confounders (gender, cannabis use, and education) in patients with psychosis. These identified aspects should be acknowledged in tobacco cessation programs.

Exploring pathway interactions to detect molecular mechanisms of disease: 22q11.2 deletion syndrome.

BACKGROUND: 22q11.2 Deletion Syndrome (22q11DS) is a genetic disorder characterized by the deletion of adjacent genes at a location specified as q11.2 of chromosome 22, resulting in an array of clinical phenotypes including autistic spectrum disorder, schizophrenia, congenital heart defects, and immune deficiency. Many characteristics of the disorder are known, such as the phenotypic variability of the disease and the biological processes associated with it; however, the exact and systemic molecular mechanisms between the deleted area and its resulting clinical phenotypic expression, for example that of neuropsychiatric diseases, are not yet fully understood. RESULTS: Using previously published transcriptomics data (GEO:GSE59216), we constructed two datasets: one set compares 22q11DS patients experiencing neuropsychiatric diseases versus healthy controls, and the other set 22q11DS patients without neuropsychiatric diseases versus healthy controls. We modified and applied the pathway interaction method, originally proposed by Kelder et al. (2011), on a network created using the WikiPathways pathway repository and the STRING protein-protein interaction database. We identified genes and biological processes that were exclusively associated with the development of neuropsychiatric diseases among the 22q11DS patients. Compared with the 22q11DS patients without neuropsychiatric diseases, patients experiencing neuropsychiatric diseases showed significant overrepresentation of regulated genes involving the natural killer cell function and the PI3K/Akt signalling pathway, with affected genes being closely associated with downregulation of CRK like proto-oncogene adaptor protein. Both the pathway interaction and the pathway overrepresentation analysis observed the disruption of the same biological processes, even though the exact lists of genes collected by the two methods were different. CONCLUSIONS: Using the pathway interaction method, we were able to detect a molecular network that could possibly explain the development of neuropsychiatric diseases among the 22q11DS patients. This way, our method was able to complement the pathway overrepresentation analysis, by filling the knowledge gaps on how the affected pathways are linked to the original deletion on chromosome 22. We expect our pathway interaction method could be used for problems with similar contexts, where complex genetic mechanisms need to be identified to explain the resulting phenotypic plasticity.

Parkinsonism in Genetic Neurodevelopmental Disorders: A Systematic Review.

Background: With advances in clinical genetic testing, associations between genetic neurodevelopmental disorders and parkinsonism are increasingly recognized. In this review, we aimed to provide a comprehensive overview of reports on parkinsonism in genetic neurodevelopmental disorders and summarize findings related to genetic diagnosis, clinical features and proposed disease mechanisms. Methods: A systematic literature review was conducted in PubMed and Embase on June 15, 2021. Search terms for parkinsonism and genetic neurodevelopmental disorders, using generic terms and the Human Phenotype Ontology, were combined. Study characteristics and descriptive data were extracted from the articles using a modified version of the Cochrane Consumers and Communication Review Group's data extraction template. The protocol was registered in PROSPERO (CRD42020191035). Results: The literature search yielded 208 reports for data-extraction, describing 69 genetic disorders in 422 patients. The five most reported from most to least frequent were: 22q11.2 deletion syndrome, beta-propeller protein-associated neurodegeneration, Down syndrome, cerebrotendinous xanthomatosis, and Rett syndrome. Notable findings were an almost equal male to female ratio, an early median age of motor onset (26 years old) and rigidity being more common than rest tremor. Results of dopaminergic imaging and response to antiparkinsonian medication often supported the neurodegenerative nature of parkinsonism. Moreover, neuropathology results showed neuronal loss in the majority of cases. Proposed disease mechanisms included aberrant mitochondrial function and disruptions in neurotransmitter metabolism, endosomal trafficking, and the autophagic-lysosomal and ubiquitin-proteasome system. Conclusion: Parkinsonism has been reported in many GNDs. Findings from this study may provide clues for further research and improve management of patients with GNDs and/or parkinsonism.

Aggression on the psychiatric ward: Prevalence and risk factors. A systematic review of the literature.

INTRODUCTION: On psychiatric wards, aggressive behaviour displayed by patients is common and problematic. Understanding factors associated with the development of aggression offers possibilities for prevention and targeted interventions. This review discusses factors that contribute to the development of aggression on psychiatric wards. METHOD: In Pubmed and Embase, a search was performed aimed at: prevalence data, ward characteristics, patient and staff factors that are associated with aggressive behaviour and from this search 146 studies were included. RESULTS: The prevalence of aggressive behaviour on psychiatric wards varied (8-76%). Explanatory factors of aggressive behaviour were subdivided into patient, staff and ward factors. Patient risk factors were diagnosis of psychotic disorder or bipolar disorder, substance abuse, a history of aggression, younger age. Staff risk factors included male gender, unqualified or temporary staff, job strain, dissatisfaction with the job or management, burn-out and quality of the interaction between patients and staff. Staff protective factors were a good functioning team, good leadership and being involved in treatment decisions. Significant ward risk factors were a higher bed occupancy, busy places on the ward, walking rounds, an unsafe environment, a restrictive environment, lack of structure in the day, smoking and lack of privacy. CONCLUSION: Despite a lack of prospective quantitative data, results did show that aggression arises from a combination of patient factors, staff factors and ward factors. Patient factors were studied most often, however, besides treatment, offering the least possibilities in prevention of aggression development. Future studies should focus more on the earlier stages of aggression such as agitation and on factors that are better suited for preventing aggression such as ward and staff factors. Management and clinicians could adapt staffing and ward in line with these results.

The association between smoking behaviour, social cognition and social functioning in patients with a non-affective psychotic disorder: A prospective follow-up study.

Introduction: In patients with psychotic disorders, both tobacco smoking and deficits in social cognition and social functioning are highly prevalent. However, little is known about their relationship in psychosis. The authors sought to evaluate the multi-cross-sectional and longitudinal associations between tobacco smoking, social cognition and social functioning in a large prospective study. Methods: This study was performed within the Genetic Risk and Outcome of Psychosis (GROUP) Study, a cohort study conducted in patients with non-affective psychosis (N = 1074), their unaffected siblings (N = 1047) and healthy controls (N = 549). At baseline, three years and six years of follow-up, data on tobacco smoking (using the Composite International Diagnostic Review), social cognition (emotion processing and theory of mind) and social functioning were collected. To assess associations between tobacco smoking and social cognition or social functioning, multivariate linear mixed-effects models and multiple linear regression models were used. Bonferroni correction for multiple testing was applied. Results: A significant positive association was found between smoking and emotion processing (as part of social cognition) in the patient group (estimate = 1.96, SE = 0.6, p = 0.003). However, smoking was significantly negatively associated with participating in pro-social activities compared with non-smoking (estimate = −2.55, SE = 0.9, p = 0.004). Change in smoking behaviour was not associated with social cognition or social functioning in the longitudinal analyses. Conclusion: Findings indicate that smoking patients with a non-affective psychotic disorder slightly outperformed their non-smoking peers on a task on social cognition, but participated less in pro-social activities. Commencement or cessation of smoking was not related to social cognition or functioning.

Screening for inborn errors of metabolism in psychotic patients using Next Generation Sequencing.

Inborn errors of metabolism (IEMs) are a group of rare genetic disorders which, when emerging later in life, are often characterized by neuropsychiatric manifestations including psychosis. This study aimed to determine whether it would be useful to screen patients presenting with a psychotic disorder for IEMs by a single blood sample using Next Generation Sequencing (NGS), in order to detect rare, treatable causes of psychotic disorders. Blood was drawn from 60 patients with a psychotic disorder, with a duration of illness of less than 5 years. Blood samples were screened for 67 genes using NGS (Illumina® MiSeq sequencing technique). The results were compared to the human reference genome (GoNL, n = 498). The identified variants were classified according to the ACMG classification. For the psychotic patients, 6 variants of a likely pathogenic (class 4, n = 2) or pathogenic (class 5, n = 4) origin were found. As all variants were heterozygous, no patients were considered to be affected by an IEM. For the GoNL control group, 73 variants of a likely pathogenic (class 4, n = 31) or pathogenic (class 5, n = 42) origin were found. All of these found variants were heterozygous. Therefore, these individuals from the control group were considered to be a carrier only. Thus, no patients were identified to have an IEM as an underlying disease using this approach. However, NGS may be useful to detect variants of genes associated with IEMs in an enriched subgroup of psychotic patients.

Striatal dopamine synthesis capacity in autism spectrum disorder and its relation with social defeat: an [18F]-FDOPA PET/CT study.

Alterations in dopamine signalling have been implied in autism spectrum disorder (ASD), and these could be associated with the risk of developing a psychotic disorder in ASD adults. Negative social experiences and feelings of social defeat might result in an increase in dopamine functioning. However, few studies examined dopamine functioning in vivo in ASD. Here we examine whether striatal dopamine synthesis capacity is increased in ASD and associated with social defeat. Forty-four unmedicated, non-psychotic adults diagnosed with ASD and 22 matched controls, aged 18-30 years, completed a dynamic 3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine positron emission tomography/computed tomography ([18F]-FDOPA PET/CT) scan to measure presynaptic dopamine synthesis capacity in the striatum. We considered unwanted loneliness, ascertained using the UCLA Loneliness Scale, as primary measure of social defeat. We found no statistically significant difference in striatal dopamine synthesis capacity between ASD and controls (F1,60 = 0.026, p = 0.87). In ASD, striatal dopamine synthesis capacity was not significantly associated with loneliness (ß = 0.01, p = 0.96). Secondary analyses showed comparable results when examining the associative, limbic, and sensorimotor sub-regions of the striatum (all p-values > 0.05). Results were similar before and after adjusting for age, sex, smoking-status, and PET/CT-scanner-type. In conclusion, in unmedicated, non-psychotic adults with ASD, striatal dopamine synthesis capacity is not increased and not associated with social defeat.

Prevention of Psychosis: Advances in Detection, Prognosis, and Intervention.

Importance: Detection, prognosis, and indicated interventions in individuals at clinical high risk for psychosis (CHR-P) are key components of preventive psychiatry. Objective: To provide a comprehensive, evidence-based systematic appraisal of the advancements and limitations of detection, prognosis, and interventions for CHR-P individuals and to formulate updated recommendations. Evidence Review: Web of Science, Cochrane Central Register of Reviews, and Ovid/PsychINFO were searched for articles published from January 1, 2013, to June 30, 2019, to identify meta-analyses conducted in CHR-P individuals. MEDLINE was used to search the reference lists of retrieved articles. Data obtained from each article included first author, year of publication, topic investigated, type of publication, study design and number, sample size of CHR-P population and comparison group, type of comparison group, age and sex of CHR-P individuals, type of prognostic assessment, interventions, quality assessment (using AMSTAR [Assessing the Methodological Quality of Systematic Reviews]), and key findings with their effect sizes. Findings: In total, 42 meta-analyses published in the past 6 years and encompassing 81 outcomes were included. For the detection component, CHR-P individuals were young (mean [SD] age, 20.6 [3.2] years), were more frequently male (58%), and predominantly presented with attenuated psychotic symptoms lasting for more than 1 year before their presentation at specialized services. CHR-P individuals accumulated several sociodemographic risk factors compared with control participants. Substance use (33% tobacco use and 27% cannabis use), comorbid mental disorders (41% with depressive disorders and 15% with anxiety disorders), suicidal ideation (66%), and self-harm (49%) were also frequently seen in CHR-P individuals. CHR-P individuals showed impairments in work (Cohen d = 0.57) or educational functioning (Cohen d = 0.21), social functioning (Cohen d = 1.25), and quality of life (Cohen d = 1.75). Several neurobiological and neurocognitive alterations were confirmed in this study. For the prognosis component, the prognostic accuracy of CHR-P instruments was good, provided they were used in clinical samples. Overall, risk of psychosis was 22% at 3 years, and the risk was the highest in the brief and limited intermittent psychotic symptoms subgroup (38%). Baseline severity of attenuated psychotic (Cohen d = 0.35) and negative symptoms (Cohen d = 0.39) as well as low functioning (Cohen d = 0.29) were associated with an increased risk of psychosis. Controlling risk enrichment and implementing sequential risk assessments can optimize prognostic accuracy. For the intervention component, no robust evidence yet exists to favor any indicated intervention over another (including needs-based interventions and control conditions) for preventing psychosis or ameliorating any other outcome in CHR-P individuals. However, because the uncertainty of this evidence is high, needs-based and psychological interventions should still be offered. Conclusions and Relevance: This review confirmed recent substantial advancements in the detection and prognosis of CHR-P individuals while suggesting that effective indicated interventions need to be identified. This evidence suggests a need for specialized services to detect CHR-P individuals in primary and secondary care settings, to formulate a prognosis with validated psychometric instruments, and to offer needs-based and psychological interventions.

Complete Sequence of the 22q11.2 Allele in 1,053 Subjects with 22q11.2 Deletion Syndrome Reveals Modifiers of Conotruncal Heart Defects.

The 22q11.2 deletion syndrome (22q11.2DS) results from non-allelic homologous recombination between low-copy repeats termed LCR22. About 60%-70% of individuals with the typical 3 megabase (Mb) deletion from LCR22A-D have congenital heart disease, mostly of the conotruncal type (CTD), whereas others have normal cardiac anatomy. In this study, we tested whether variants in the hemizygous LCR22A-D region are associated with risk for CTDs on the basis of the sequence of the 22q11.2 region from 1,053 22q11.2DS individuals. We found a significant association (FDR p < 0.05) of the CTD subset with 62 common variants in a single linkage disequilibrium (LD) block in a 350 kb interval harboring CRKL. A total of 45 of the 62 variants were associated with increased risk for CTDs (odds ratio [OR) ranges: 1.64-4.75). Associations of four variants were replicated in a meta-analysis of three genome-wide association studies of CTDs in affected individuals without 22q11.2DS. One of the replicated variants, rs178252, is located in an open chromatin region and resides in the double-elite enhancer, GH22J020947, that is predicted to regulate CRKL (CRK-like proto-oncogene, cytoplasmic adaptor) expression. Approximately 23% of patients with nested LCR22C-D deletions have CTDs, and inactivation of Crkl in mice causes CTDs, thus implicating this gene as a modifier. Rs178252 and rs6004160 are expression quantitative trait loci (eQTLs) of CRKL. Furthermore, set-based tests identified an enhancer that is predicted to target CRKL and is significantly associated with CTD risk (GH22J020946, sequence kernal association test (SKAT) p = 7.21 × 10-5) in the 22q11.2DS cohort. These findings suggest that variance in CTD penetrance in the 22q11.2DS population can be explained in part by variants affecting CRKL expression.

Immune aberrations in children with Autism Spectrum Disorder: a case-control study from a tertiary care neuropsychiatric hospital in India.

Multiple studies have identified the presence of peripheral immune aberrations in subjects with Autism Spectrum Disorder (ASD). However, comprehensive assessment of these peripheral immune aberrations, in the cellular and systemic compartments, in a single group of subjects with ASD is lacking. We assessed proportions of various subsets of immune cells in peripheral blood (T helper cells, T regulatory cells, B cells, monocytes, Natural Killer cells, dendritic cells) by multi-parametric flow cytometry in 50 children with ASD and compared it with thirty healthy controls matched for age, gender, socio-economic status and body mass index. There were no significant differences noted in the proportion of T regulatory cells, B cells, monocytes and Natural Killer cells, between ASD subjects and controls. On the contrary, the proportion of activated Th17 and myeloid dendritic cells were significantly higher in children with ASD. Based on these findings, group comparison of serum levels of Th17 cytokines (interleukin-6, interleukin-17A) was performed. Elevated serum levels of interleukin-6 and interleukin-17A in children with ASD corroborated our immunophenotyping findings. We did not find any significant differences among the pro-inflammatory (interleukin-1ß), Th1 (interferon-γ) and Th2 (interleukin-4) cytokines. This is the first evidence with concurrent findings from immunophenotyping and cytokine data demonstrating activation of the Th17 pathway in subjects with ASD. This finding assumes significance in the light of recent maternal immune activation mouse model study that has highlighted the role of Th17 pathway in the pathophysiology of ASD. Future longitudinal studies are needed to clarify the role of this dysregulated immune pathway in the development of ASD.

Effect of Pharmacological Interventions on the Fronto-Cingulo-Parietal Cognitive Control Network in Psychiatric Disorders: A Transdiagnostic Systematic Review of fMRI Studies.

Executive function deficits, such as working memory, decision-making, and attention problems, are a common feature of several psychiatric disorders for which no satisfactory treatment exists. Here, we transdiagnostically investigate the effects of pharmacological interventions (other than methylphenidate) on the fronto-cingulo-parietal cognitive control network, in order to identify functional brain markers for future procognitive pharmacological interventions. Twenty-nine manuscripts investigated the effect of pharmacological treatment on executive function-related brain correlates in psychotic disorders (n = 11), depression (n = 4), bipolar disorder (n = 4), ADHD (n = 4), OCD (n = 2), smoking dependence (n = 2), alcohol dependence (n = 1), and pathological gambling (n = 1). In terms of impact on the fronto-cingulo-parietal network, the preliminary evidence for catechol-O-methyl-transferase inhibitors, nicotinic receptor agonists, and atomoxetine was relatively consistent, the data for atypical antipsychotics and anticonvulsants moderate, and interpretation of the data for antidepressants was hampered by the employed study designs. Increased activity in task-relevant areas and decreased activity in task-irrelevant areas were the most common transdiagnostic effects of pharmacological treatment. These markers showed good positive and moderate negative predictive value. It is concluded that fronto-cingulo-parietal activity changes can serve as a marker for future procognitive interventions. Future recommendations include the use of randomized double-blind designs and selective cholinergic and glutamatergic compounds.

COMT Val(158)Met genotype and cannabis use in people with an At Risk Mental State for psychosis: Exploring Gene x Environment interactions.

BACKGROUND: Epidemiological and retrospective studies suggest a cannabis x catechol-O-methyltransferase (COMT) Val(158)Met interaction effect on development of psychosis. The aim of this study was to examine this interaction and its association with severity of subclinical symptoms in people with an At Risk Mental State (ARMS) for psychosis. METHODS: Severity of symptoms, cannabis use and genotype were assessed at baseline in 147 help-seeking young adults who met the ARMS criteria and agreed to participate in the Dutch Early Detection and Intervention (EDIE-NL) trial. RESULTS: Cannabis use and COMT Val-allele showed an interaction effect in ARMS subjects. Subjects who were weekly cannabis users at some point prior to entering the study showed more severe positive symptoms. This effect increased if they were carriers of the COMT Val-allele and even more so if they were homozygous for the Val-allele. CONCLUSIONS: Our results suggest that the COMT Val(158)Met polymorphism moderates the effect of regular cannabis use on severity of subclinical psychotic symptoms.

Effects of cannabis use on event related potentials in subjects at ultra high risk for psychosis and healthy controls.

Cannabis use has consistently been associated with psychotic symptoms as well as cognitive impairments. Moreover, its use may provoke subclinical psychotic symptoms and is associated with neuropsychological dysfunctions in subjects at ultra high risk (UHR) for developing psychosis. However, to our knowledge, no data are yet available on the relationship between cannabis use, UHR symptoms and information processing as assessed with event related potentials (ERP) in UHR subjects. This cross-sectional study therefore aimed to investigate N100, N200, P200 and P300 ERP components in 48 UHR subjects (19 cannabis users; UHR+C) and 50 healthy controls (21 cannabis users; HC+C). Results showed smaller P300 amplitudes in HC+C and UHR subjects compared to HC-C. Moreover, HC+C showed prolonged P300 and N200 latencies compared to HC-C and UHR-C. No significant ERP differences were found between UHR+C and UHR-C. Regarding the relationship between information processing and psychopathology, we found associations between ERP components and severity of UHR symptoms, findings being most pronounced for N100 latencies and P300 amplitudes and severity of general psychopathology and positive symptoms. We conclude that UHR subjects and healthy cannabis users demonstrate similar P300 amplitude reductions compared to non-using control subjects. In addition, the interrelation of cannabis use with prolonged ERP latencies may signify reduced information processing speed associated with cannabis use. Finally, our findings cautiously support the hypothesis that the clinical phenomena of the UHR state may be associated with abnormalities in stimulus processing.

Unexpected detection of nodular melanoma of the skin on the scalp by I-123 IBZM brain SPECT.

Melanocytes and dopaminergic neurons share the same ectodermal origin and can both produce melanin. Indeed, in vivo studies have shown that the radiopharmaceutical iodine-123-iodobenzamide (I-123 IBZM), which binds in vivo to dopamine D(2/3) receptors, is also able to detect melanoma, and particularly melanotic melanoma. We report a case of intense IBZM uptake in nodular melanoma of the skin on the scalp. The presence of unexpected focal IBZM uptake of the skin justified histologic examination, which revealed nodular melanoma. Melanoma should be considered when one is confronted with atypical focal uptake of benzamide derivatives like IBZM, in or outside the brain.

Sexual dysfunction and hormonal changes in first episode psychosis patients on olanzapine or risperidone.

Atypical antipsychotics interfere with central and peripheral neurotransmitter systems and with hormonal production. In this study we compared the effect of olanzapine and risperidone on hormonal state and sexual function (by using the Questionnaire for Sexual Dysfunction, QSD) in 40 patients with a first episode psychosis. Results were compared to those of 34 healthy controls. Patients using risperidone had significant higher prolactin levels than patients using olanzapine. Patients using olanzapine had significantly higher 17beta-estradiol levels than patients using risperidone. Overall satisfaction with sexuality was less in patients compared to controls, but not different between patients using olanzapine and those using risperidone. Problems with sexual arousal were significantly higher in patients using olanzapine compared to patients using risperidone. A significantly higher frequency of problems with ejaculation and problems with insensibility of genitals were found in patients compared to healthy controls. We found no relation between medication, prolactin and 17beta-estradiol levels, frequency of sexual activity, overall satisfaction with sexuality and any of the 18 sexual dysfunctions we investigated. Our results suggests that sexual dysfunction in patients with first episode psychosis might occur despite normal prolactin levels. Also, sexual dysfunction is highly prevalent in healthy controls. Awareness should be raised of potential sexual problems in young adults.

Occupancy of dopamine D2 receptors by antipsychotic drugs is related to nicotine addiction in young patients with schizophrenia.

RATIONALE: Occupancy of dopamine D2 receptors by antipsychotic drugs depends on the individual availability of D2 receptors and on the dose and type of antipsychotic medication. It has been suggested that a low availability of these receptors may increase the risk for addictive behavior. OBJECTIVE: This study aims to show that patients with relatively high occupancy of D2 receptors by antipsychotic drugs are more prone to nicotine consumption. METHODS: Striatal D2 receptor occupancy by equivalent doses of olanzapine or risperidone was assessed with [123I]iodobenzamide single-photon emission computed tomography (SPECT) in 36 patients with schizophrenia. Smoking status at the time of SPECT imaging was assessed. The number of cigarettes used in the following three consecutive years was estimated with the Life Chart Schedule (LCS). RESULTS: There was a positive and significant relation between D2 receptor occupancy following treatment with olanzapine (n=19) or risperidone (n=12) and the number of cigarettes smoked in three consecutive years (r=0.60, p<0.001) in patients who smoked. There was a significant difference in the percentage of D2 occupancy for smokers (mean 74.3%, SD 12.8, n=31) and nonsmokers (mean 49.8%, SD 9.1, n=5). CONCLUSION: Frequency of cigarette smoking in schizophrenic patients treated with antipsychotic medication is significantly and negatively related to the availability of striatal D2 receptors.