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Aggression on psychiatric wards develops under influence of patient, staff and ward factors. Assessment of naturalistic derived staff and ward factors might increase better understanding of how aggressive incidents develop on psychiatric wards.ObjectiveStudying staff and ward factors including interactions between patients and nurses prior and after development of aggression, within a naturalistic closed ward setting.DesignA prospective naturalistic experience sampling method (ESM) study.Setting and participantsA high intensive care unit of a mental health institution in The Netherlands where 29 nurses answered beeps generated by an app during approximately 7 consecutive days with questions regarding their subjective feelings, ward atmosphere, location, interaction they had with patients and their colleagues and whether an incident took place.Main outcome measuresAssociations were established between different staff and ward factors and the occurrence of aggressive incidents on the ward.ResultsRisk for aggression was associated with the nurse being with a patient (OR=2.26, 95% CI 0.99 to 5.15, p=0.05). No significant association was found between discussing with the patient and setting a limit or physical absence of the nurse on the one hand and aggression on the other. More experienced nurses encountered more aggression (OR=3.5, 95% CI 1.32 to 8.26, p=0.01). Age and gender of the nurse were not associated with aggression development. Exceeding the maximum bed capacity was associated with a greater risk for aggression (OR=5.36, 95% CI 1.69 to 16.99, p=0.004). There was no significant association when analysing a more positive atmosphere on the ward or positive affect of the nurse, but negative affect of the nurses showed a trend for an association with less aggression.ConclusionAggression is a problem that should be managed from a multidimensional perspective. The quality of interaction between nurses and patients is crucial. Exceeding the maximum bed capacity is likely associated with more aggression.

Introduction:Mental disorders are increasingly common among adults in both the developed and developing world and are predicted by the WHO to be the leading cause of disease burden by 2030. Many common physical conditions are more common among people who also have a common mental disorder. This scoping review aims to examine the current literature about the prevention, identification and treatment of physical problems among people with pre-existing mental health disorders in primary care in Europe.Methods:The scoping review framework comprised a five-stage process developed by Arksey & O’Malley (2005). The search process was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Both quantitative and qualitative studies were included, with no restriction on study design.Results:The initial search identified 299 studies, with a further 28 added from the hand-search (total n = 327) of which 19 were considered relevant to the review research question and included for full analysis. Depression was the mental health condition most commonly studied (nine studies), followed by depression and anxiety (seven studies), with three studies examining any mental disorder. Eleven studies examined the effects of various interventions to address physical and mental comorbidity, with the most commonly studied intervention being collaborative care.Conclusions:With just 19 studies meeting our criteria for inclusion, there is clearly a paucity of research in this area. Further research is essential in order to understand the pathophysiological mechanisms underlying the association between mental disorders and chronic conditions.

BackgroundIndividuals with autism spectrum disorder (ASD) appear to be at increased risk of non-affective psychotic disorder (NAPD) and bipolar disorder (BD). However, most previous studies examined the co-occurrence of ASD and NAPD or BD, ignoring possible diagnostic bias and selection bias. We used longitudinal data from Dutch psychiatric case registers to assess the risk of NAPD or BD among individuals with ASD, and compared the results to those obtained for the Dutch population in earlier studies.MethodsIndividuals with ASD (n = 17 234) were followed up between 16 and 35 years of age. Kaplan–Meier estimates were used to calculate the risk of NAPD or BD. We conducted separate analyses to reduce possible bias, including an analysis among individuals diagnosed with ASD before age 16 years (n = 8337).ResultsOf the individuals with ASD, 23.50% (95% confidence interval 21.87–25.22) were diagnosed with NAPD and 3.79% (3.06–4.69) with BD before age 35 years. The corresponding figures for the general population were 0.91% (0.63–1.28) and 0.13% (0.08–0.20). Risk estimates were substantially lower, but still higher than general population estimates, when we restricted our analyses to individuals diagnosed with ASD before age 16, with 1.87% (1.33–2.61) being diagnosed with NAPD and 0.57% (0.21–1.53) with BD before age 25 years. The corresponding figures for the general population were 0.63% (0.44–0.86) and 0.08% (0.05–0.12).ConclusionsIndividuals with ASD are at increased risk of NAPD or BD. This is likely not the result of diagnostic or selection bias.

Psychotic experiences, social functioning and general psychopathology are important targets for early intervention in individuals with Ultra-High-Risk state (UHR) and a first-episode psychosis (FEP). Acceptance and Commitment Therapy (ACT) is a promising, next-generation Cognitive Behavioural Therapy (CBT) that aims to modify these targets, but evidence on sustainable change and its underlying mechanisms in individuals' daily lives remains limited. The aim of the INTERACT study is to investigate the efficacy of a novel ecological momentary intervention, Acceptance and Commitment Therapy in Daily Life (ACT-DL) in a multi-centre randomised controlled trial of individuals with UHR or FEP.In a multi-centre randomised controlled trial, individuals aged 16-65 years with UHR or FEP will be randomly allocated to ACT-DL in addition to treatment as usual (TAU) as the experimental condition or a control condition of TAU only, which will include - for the entire study period - access to routine mental health care and, where applicable, CBT for psychosis (CBTp). Outcomes will be assessed at baseline (i.e. before randomisation), post-intervention (i.e. after the 8-week intervention period), and 6-month and 12-month follow-ups (i.e. 6 and 12 months after completing the intervention period) by blinded assessors. The primary outcome will be distress associated with psychotic experiences, while secondary outcomes will include (momentary) psychotic experiences, social functioning and psychopathology. Process measures to assess putative mechanisms of change will include psychological flexibility, stress sensitivity and reward experiences. In addition, acceptability, treatment adherence and treatment fidelity of ACT-DL will be assessed.The current study is the first to test the efficacy of ACT-DL in individuals with UHR and FEP. If this trial demonstrates the efficacy of ACT-DL, it has the potential to significantly advance the treatment of people with UHR and FEP and, more generally, provides initial support for implementing mHealth interventions in mental health services.Netherlands Trial Register, ID: NTR4252. Registered on 26 September 2013.

Background The onset of mental disorders typically occurs between the ages of 12 and 25, and the burden of mental health problems is the most consequential for this group. Indicated prevention interventions to target individuals with subclinical symptoms to prevent the transition to clinical levels of disorders, even leading to suicide, have shown to be effective. However, the threshold to seek help appears to be high. Digital interventions could offer a solution, especially during the Covid-19 pandemic. This implementation study will investigate the digital indicated prevention intervention ENgage YOung people Early (ENYOY), the Dutch version of the original Moderated Online Social Therapy Platform (MOST+) from Australia. In addition, the relationship between stress biomarkers, symptoms and outcome measures of youth using the platform will be investigated in this study. Methods The MOST+ platform will be adapted, translated and developed for the situation in the Netherlands in collaboration with a Youth Panel. A prospective cohort of 125 young people (16–25 years) with beginning mental health complaints will be on the platform and followed for a year, of which 10 participants will have an additional smart watch and 10 participants will be asked to provide feedback about the platform. Data will be collected at baseline and after 3, 6 and 12 months. Outcome measures are Psychological Distress assessed with the Kessler Psychological Distress Scale (K10), Social and occupational functioning (measures by the SOFAS), positive mental health indicators measured by the Positive Health Instrument, stress biomarkers with a smart-watch, website journeys of visitors, and feedback of youth about the platform. It will be a mixed-method study design, containing qualitative and quantitative measures. Discussion This trial will specifically address young people with emerging mental health complaints, and offers a new approach for treatment in the Netherlands. Considering the waiting lists in (child and adolescent)-psychiatry and the increase in suicides among youth, early low-threshold and non-stigmatizing help to support young people with emerging psychiatric symptoms is of crucial importance. Moreover, this project aims to bridge the gap between child and adolescent and adult psychiatry. Trial registration Netherlands Trial Register ID NL8966, retrospectively registered on the 19th of October 2020.

background Psychiatric disorders in adults often result from psychiatric problems during childhood and adolescence. aim In the light of prevention of psychiatric disorders in adults, we focus on adolescence. method Based on the working method of the transitional psychiatry unit, we describe the characteristics of the patient group and the necessities of adequate treatment and care for young people who are suffering from a stagnation in development due to psychiatric problems. results Family therapy, new authority/non-violent resistance and our own RAISING skills are tools for treating these young people. Here we focus on the adolescent's development. This early treatment prevents the development of irreversible symptoms and serious psychiatric illness during adulthood. conclusion Transitional psychiatry forms part of the answer in the search of pro-active medicine. Tijdschrift voor Psychiatrie 63(2021)2, 115-119.

Background: Little is known about the burden of (sub-threshold) mental health problems in youth. Aim: To examine the burden of mental health problems in terms of health-related quality of life (HRQoL) and cost-of-illness, for first visitors of the Dutch youth walk-in centres (@ease). Method: A bottom-up, prevalence-based burden of disease study from a societal perspective. HRQoL was assessed through the EuroQoL (EQ-5D-5L), and cost-of-illness via items about truancy and health care utilization. Results: Participants (N = 80) showed a decreased HRQoL compared to the general population of Dutch youth. In the three months prior to their 1st attendance, participants skipped on average 4.11 days of school and had 1.03 health care visits, leading to total costs of €512.64 per person. Females had significantly higher health care costs and lower HRQoL. Health care use was lower in those not speaking the Dutch language. Living alone was a significant predictor of truancy (costs), and therefore total costs. Conclusions: Mental health problems in youth consulting @ease have a considerable impact on the individual’s HRQoL, and an economic impact on society, yet almost 75% is not receiving care. A lack of interventions in this critical period in life may have major lifelong consequences.

Alzheimer's disease constitutes a growing cause of cognitive impairment in aging population. Given that current treatments do not produce the desired therapeutic effects, the need for finding alternative biological and pharmacological approaches is critical. Accumulating evidence suggests inflammatory and oxidative stress responses as potential causal factors of cognitive impairments in Alzheimer's disease and healthy aging. Curcumin has received increased interest due to its unique molecular structure that targets inflammatory and antioxidant pathways as well as (directly) amyloid aggregation; one of the major hallmarks of Alzheimer's disease. Therefore, this review summarizes preclinical and clinical findings on curcumin as a potential cognitive enhancer in Alzheimer's disease and normal aging. Databases used for literature searches include PubMed, EMBASE and Web of Science; in addition, clinicaltrials.gov was used to search for clinical studies. Overall, animal research has shown very promising results in potentiating cognition, both physiologically and behaviourally. However, human studies are limited and results are less consistent, complicating their interpretation. These inconsistencies may be related to differences in methodology and the included population. Taking into account measurements of important inflammatory and antioxidant biomarkers, optimal dosages of curcumin, food interactions, and duration of treatment would increase our understanding on curcumin's promising effects on cognition. In addition, increasing curcumin's bioavailability could benefit future research.

BackgroundPatients with a deletion at chromosome 22q11.2 (22q11DS) have 30% lifetime risk of developing a psychosis. People fulfilling clinical criteria for ultra-high risk (UHR) for psychosis have 30% risk of developing a psychosis within 2 years. Both high-risk groups show white-matter (WM) abnormalities in microstructure and volume compared to healthy controls (HC), which have been related to psychotic symptoms. Comparisons of WM pathology between these two groups may specify WM markers related to genetic and clinical risk factors.MethodFractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD) were assessed using diffusion tensor magnetic resonance imaging (MRI), and WM volume with structural MRI, in 23 UHR patients, 21 22q11DS patients, and 33 HC.ResultsCompared to UHR patients 22q11DS patients had (1) lower AD and RD in corpus callosum (CC), cortical fasciculi, and anterior thalamic radiation (ATR), (2) higher FA in CC and ATR, and (3) lower occipital and superior temporal gyrus WM volume. Compared to HC, 22q11DS patients had (1) lower AD and RD throughout cortical fasciculi and (2) higher FA in ATR, CC and inferior fronto-occipital fasciculus. Compared to HC, UHR patients had (1) higher mean MD, RD, and AD in CC, ATR and cortical fasciculi, (2) no differences in FA.ConclusionsUHR and 22q11DS patients share a susceptibility for developing psychosis yet were characterized by distinct patterns of WM alterations relative to HC. While UHR patients were typified by signs suggestive of aberrant myelination, 22q11DS subjects showed signs suggestive of lower axonal integrity.

BackgroundPhenylketonuria (PKU), a genetic metabolic disorder that is characterized by the inability to convert phenylalanine to tyrosine, leads to severe intellectual disability and other cerebral complications if left untreated. Dietary treatment, initiated soon after birth, prevents most brain-related complications. A leading hypothesis postulates that a shortage of brain monoamines may be associated with neurocognitive deficits that are observable even in early-treated PKU. However, there is a paucity of evidence as yet for this hypothesis.MethodsWe therefore assessedin vivostriatal dopamine D2/3receptor (D2/3R) availability and plasma monoamine metabolite levels together with measures of impulsivity and executive functioning in 18 adults with PKU and average intellect (31.2 ± 7.4 years, nine females), most of whom were early and continuously treated. Comparison data from 12 healthy controls that did not differ in gender and age were available.ResultsMean D2/3R availability was significantly higher (13%;p= 0.032) in the PKU group (n= 15) than in the controls, which may reflect reduced synaptic brain dopamine levels in PKU. The PKU group had lower plasma levels of homovanillic acid (p< 0.001) and 3-methoxy-4-hydroxy-phenylglycol (p< 0.0001), the predominant metabolites of dopamine and norepinephrine, respectively. Self-reported impulsivity levels were significantly higher in the PKU group compared with healthy controls (p= 0.033). Within the PKU group, D2/3R availability showed a positive correlation with both impulsivity (r= 0.72,p= 0.003) and the error rate during a cognitive flexibility task (r= 0.59,p= 0.020).ConclusionsThese findings provide further support for the hypothesis that executive functioning deficits in treated adult PKU may be associated with cerebral dopamine deficiency.

BackgroundThe majority of people with psychosis suffer from cognitive problems. These cognitive problems are among the most disabling features of the illness and have a negative effect on clinical outcome. Research has demonstrated that acetylcholine including muscarinic receptors play an important role in cognitive function. A post-mortem study in chronic patients with schizophrenia demonstrated a decrease of 75% of muscarinic M1 receptors.AimThe aim of this study was to investigate the role of M1 receptors in-vivo in brain and cognitive function in psychosis.MethodsThirty medication free patients with psychosis and 30 healthy controls matched for age, gender and IQ were included for 1) 1x IDEX Spect scan to determine M1 binding potential; 2) 2x fMRI scan using a visual memory task; 3) 2x MRS to determine choline concentrations; 2x CANTAB cognitive battery. Except for SPECT all subjects were tested twice, once with placebo and once with biperiden M1 antagonist.ResultatenPatients demonstrated a significant negative correlation between M1 binding potential and cognitive impairments and negative symptom scores on PANSS. Following biperiden challenge, performance on verbal learning and memory was worse. Hippocampal activity was larger during a visual memory task in patients.ConclusieThese results support a role for the M1 receptor in cognitive function in psychosis.Disclosure of interestThe author has not supplied his/her declaration of competing interest.

Background 22q11 deletion syndrome (22q11DS) is associated with mild or borderline intellectual disability (ID). There are hardly any reports on subjects with 22q11DS with moderate or severe ID, and therefore its behavioural and psychiatric characteristics are unknown. Method We describe behavioural and psychiatric characteristics of 33 adults with 22q11DS and a Full-Scale IQ (FSIQ) below 55. Participants were divided into two groups: one group having a FSIQ ≤ 55 caused by intellectual decline (n = 21) and one group with a FSIQ ≤ 55 who had always functioned at this level (n = 12). Results High scores on psychopathology sub-scales were found for both subgroups. 22q11DS patients with intellectual decline showed higher rates of co-morbid psychopathology, particularly psychosis. Furthermore, psychosis and intellectual decline were positive correlated. Conclusion This is the first report addressing adult patients with 22q11DS and moderate to severe ID. Overall we found high levels of psychopathology with higher scores of psychopathology in the intellectual decline group. Life time psychosis seems to be related to deterioration.

22q11.2 deletion syndrome (22q11DS) is one of the most common recurrent copy-number variant disorder, caused by a microdeletion in chromosome band 22q11.2 and occurring with a population prevalence of 1 in 2000. Until today there has been no evidence that the size of the deletion has an influence on the clinical phenotype. Most studies report that 22q11DS is associated with mild or borderline intellectual disability. There are a limited number of reports on 22q11DS subjects with moderate or severe intellectual disability. In this study we describe 63 adult patients with 22q11DS, including 22q11DS patients functioning at a moderate to severe intellectual disabled level. Deletion size was established with an experimental Multiplex ligation-dependent probe amplification (MLPA) mixture (P324) in addition to the commonly used MLPA kit (P250). We compared deletion size with intellectual functioning and presence of psychotic symptoms during life. The use of the experimental MLPA kit gives extra information on deletion size, only when combined with the common MLPA kit. We were able to detect eleven atypical deletions and in two cases the deletion size was shorter than all other "typical ones". We conclude that the use of the experimental kit P324 gives extra information about the deletion size, but only when used together with the standard P250 kit. We did not found any relation of deletion size with intelligence or presence of psychosis.

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.

Background22q11.2 deletion syndrome (22q11DS) is a genetic disorder caused by a microdeletion on chromosome 22q11.2 and associated with an increased risk for psychosis. A dysfunctional motivational reward system is thought to be one of the salient features in psychosis caused by abnormal dopamine functioning. It is unknown whether patients with 22q11DS have a dysfunctional reward system.MethodsThis study aims to investigate reward learning in 22q11DS. The study included 10 adults with 22q11DS (age: 33.1 years, 60% female) and 10 age-gender-matched healthy controls (HC, age: 39.7 years, 60% female). A single infusion 18F-fallypride PET scan was acquired during which all subjects performed a version of the learning phase of the Probabilistic Stimulus Selection Task for reward learning (RL), modified to deliver social feedback.ResultsIQ-scores were significantly lower in the 22q11DS group (P < .001) compared to HC. The 22q11DS group both earned significantly less money (P < .05) and performed worse during the RL-task (P < .05) than HC. However, the learning curve for the RL-task was the same for both groups. IQ-scores were a significant positive predictor for earnings (P < .05) and performance (P < .05), but not for the learning curve.ConclusionsThese preliminary results indicate that people with 22q11DS are capable of learning at the same speed as HC, however they are less susceptible for reward than HC because their overall performance during RL is worse than HC. This lower reward sensitivity could be a result of haplo-insufficiency of COMT in 22q11DS and consequently abnormal prefrontal dopamine functioning.Disclosure of interestThe authors have not supplied their declaration of competing interest.

It has been hypothesised that in subjects with 22q11 deletion syndrome (22q11DS) disturbances of the dopamine (DA) system contribute to their increased risk for cognitive deficits and psychiatric problems. However, central DAergic neurotransmission in 22q11DS has not been investigated. We measured striatal D2 receptor binding potential (D2R BPND) using (S)-(-)-3-iodo-2-hydroxy-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl)methyl] benzamide-single photon emission computed tomography ([123I]IBZM SPECT) in 12 adults with 22q11DS and 12 matched controls. Correlations between D2R BPND and plasma prolactin (pPRL) levels were also determined. 22q11DS subjects and controls had similar D2R BP ND. There was a positive correlation between D2R BP ND and pPRL values in controls, but no such relation was found in 22q11DS subjects. This study suggests that a 22q11 deletion does not affect striatal DAergic neurotransmission in the living human brain. However, the disturbed relationship between D2R BPND and pPRL values suggests DAergic dysfunction at a different level. Further studies on DAergic function in extra-striatal brain regions and under challenged conditions are needed.

Purpose To study striatal dopamine D-2 receptor availability in DYT11 mutation carriers of the autosomal dominantly inherited disorder myoclonus-dystonia (M-D).Methods Fifteen DYT11 mutation carriers ( 11 clinically affected) and 15 age- and sex-matched controls were studied using I-123-IBZM SPECT. Specific striatal binding ratios were calculated using standard templates for striatum and occipital areas.Results Multivariate analysis with corrections for ageing and smoking showed significantly lower specific striatal to occipital IBZM uptake ratios (SORs) both in the left and right striatum in clinically affected patients and also in all DYT11 mutation carriers compared to control subjects.Conclusions Our findings are consistent with the theory of reduced dopamine D-2 receptor (D2R) availability in dystonia, although the possibility of increased endogenous dopamine, and consequently, competitive D2R occupancy cannot be ruled out.

Alpha-methyl-para-tyrosine (AMPT) temporarily inhibits tyrosine hydroxylase, the rate limiting step in the dopamine biosynthesis cascade. AMPT has been approved for clinical use in phaeochromocytoma in 1979. Recently however, AMPT has been increasingly employed as a pharmacological challenge in acute dopamine depletion studies including neuroimaging studies. The use of this exciting challenge technique allows us to increase our understanding of dopaminergic neurotransmission in the brain. In addition, there have been clinical reports that AMPT may be useful to treat movement disorders like dystonia, dyskinesia and Huntingtons chorea, psychiatric disorders like mania, psychosis, obsessive compulsive disorder and substance abuse as well as behavioral problems in 22q11 deletion syndrome. In this review we will discuss the effects of AMPT in challenge studies that have been reported in humans. Furthermore we will review all studies reporting therapeutic effects of AMPT in neuropsychiatric disorders and adverse effects associated with AMPT use reported in both challenge and therapeutic research.

Introduction: The aim of this prospective study was to compare the predictive validity of early improvement of subjective experience and early improvement of rater assessed symptoms on enduring symptomatic remission (ESR) status during 5 years follow. Methods: 110 consecutively admitted patients suffering from a first episode of schizophrenia or related disorders were investigated. We defined early improvement of subjective well-being as a delta-score of the total Subjective Well-being under Neuroleptics scale-20 item version (SWN-K) at admission and after 6 weeks treatment. The severity of psychopathology was assessed with the Positive and Negative Syndrome Scale (PANSS) at admission, 6 weeks, 6 months, 3 and 5 years after admission. Enduring symptomatic remission (ESR) was defined as complying to the symptomatic remission criteria at PANSS assessment at 6 months and 5 years and continuing this state between 6 months and 5 years follow-up. Paired-samples and independent t-test were used to compare means. Results: Patients with ESR (n=30) had a higher mean improvement of subjective well-being during early treatment as assessed with the SWN-K than those without ESR (n=74) (p=0.004). Early symptomatic improvement as assessed with the PANSS was not related to ESR (p=0.95). Discussion: Early improvement of subjective well-being is related to ESR in first episode schizophrenia or related disorders.

Changes that occur in the behaviour of voltage-gated ion channels and ligand-gated receptor channels due to gene mutations or auto-immune attack are the cause of channelopathies in the central and peripheral nervous system. Although the relation between molecular channel defects and clinical symptoms has been explained in the case of many neuromuscular channelopathies, the pathophysiology of auto-immunity in neuropsychiatric syndromes is still unclear.To review recent findings regarding neuronal auto-immune reactions in severe neuropsychiatric syndromes.Using PubMed, we consulted the literature published between 1990 and August 2014 relating to the occurrence of auto-immune antibodies in severe and persistent neuropsychiatric syndromes.Auto-antibodies have only limited access to the central nervous system, but if they do enter the system they can, in some cases, cause disease. We discuss recent findings regarding the occurrence of auto-antibodies against ligand-activated receptor channels and potassium channels in neuropsychiatric and neurological syndromes, including schizophrenia and limbic encephalitis.Although the occurrence of several auto-antibodies in schizophrenia has been confirmed, there is still no proof of a causal relationship in the syndrome. We still have no evidence of the prevalence of auto-immunity in neuropsychiatric syndromes. The discovery that an antibody against an ion channel is associated with some neuropsychiatric disorders may mean that in future it will be possible to treat patients by means of immunosuppression, which could lead to an improvement in a patient's cognitive abilities.

Stress is an important risk factor in the etiology of psychotic disorder. Preclinical work has shown that stress primarily increases dopamine (DA) transmission in the frontal cortex. Given that DA-mediated hypofrontality is hypothesized to be a cardinal feature of psychotic disorder, stress-related extrastriatal DA release may be altered in psychotic disorder. Here we quantified for the first time stress-induced extrastriatal DA release and the spatial extent of extrastriatal DA release in individuals with non-affective psychotic disorder (NAPD). Twelve healthy volunteers (HV) and 12 matched drug-free NAPD patients underwent a single infusion [18F]fallypride positron emission tomography scan during which they completed the control and stress condition of the Montreal Imaging Stress Task. HV and NAPD did not differ in stress-induced [18F]fallypride displacement and the spatial extent of stress-induced [18F]fallypride displacement in medial prefrontal cortex (mPFC) and temporal cortex (TC). In the whole sample, the spatial extent of stress-induced radioligand displacement in right ventro-mPFC, but not dorso-mPFC or TC, was positively associated with task-induced subjective stress. Psychotic symptoms during the scan or negative, positive and general subscales of the Positive and Negative Syndrome Scale were not associated with stress-induced [18F]fallypride displacement nor the spatial extent of stress-induced [18F]fallypride displacement in NAPD. Our results do not offer evidence for altered stress-induced extrastriatal DA signaling in NAPD, nor altered functional relevance. The implications of these findings for the role of the DA system in NAPD and stress processing are discussed.

Objective: There is growing evidence that estrogen may protect against age-related cognitive decline and reduce the risk of developing Alzheimer's disease (AD) in healthy, postmenopausal women. The underlying biological basis for this is not known but may include preservation of cholinergic systems. Cholinergic dysfunction has been implicated in the aetiology of age-related memory impairment and AD. We studied the effect of prolonged use of estrogen replacement therapy (ERT) on central cholinergic tone in healthy postmenopausal women. Method: Growth hormone (GH) responses to oral pyridostigmine (120 mg) were measured over a 3 h period in thirty healthy postmenopausal women, 15 on long-term ERT and 15 ERT naive. Results: GH release following pyridostigmine was significantly larger in ERT treated women than in ERT naive women. In addition within the ERT treated group there was a significant positive correlation between duration of estrogen treatment and GH response. Conclusions: Long-term ERT can enhance cholinergic function in postmenopausal women and this may be related to duration of estrogen treatment. Modulation of central cholinergic function may be one mechanism by which long-term ERT could preserve cognitive function in healthy, postmenopausal women. (C) 2002 Elsevier Science Ltd. All rights reserved

Velo-cardio-facial syndrome (VCFS) is associated with deletions on the long arm of chromosome 22, mild intellectual disability, poor social interaction and a high prevalence of psychosis. However, to date there have been no studies investigating the neuropsychological functioning of adults with VCFS. We compared 19 adults with VCFS with 19 age, gender and IQ matched controls using a comprehensive neuropsychological battery. Compared to controls, adults with VCFS had significant impairments in visuoperceptual ability (Visual Object and Space Perception Battery), problem solving and planning (Tower of London) and abstract and social thinking (Comprehension WAIS-R). It is likely that haploinsufficiency (reduced gene dosage) of a neurodevelopmental gene or genes mapping to chromosome 22q11 underlies the cognitive deficits observed in individuals with VCFS.

This presentation reports on the outcomes of a practice-based and science-based enterprise in the Netherlands to develop a comprehensive national prevention program focused on children of parents with a mental illness. An outline of the multicomponent program is presented which includes a wide set of interventions that address evidence-based risk factors and protective factors in multiple domains, including children in different age groups, parents and families, social networks, professionals and the community as a whole.The 20-year history of this program illustrates the importance of long-term collaborative investments that are required of practitioners, policymakers and scientists to develop and implement a nationwide, comprehensive approach for addressing the prevalent transmission of psychiatric problems from parent to child. The results of recently undertaken controlled efficacy studies of various preventive interventions are presented, as well as findings from process evaluations. Also, strengths and weaknesses of the current program are discussed and recommendations will be offered for the main challenges ahead in terms of program innovation, implementation and research.Disclosure of interestThe author has not supplied his declaration of competing interest.

Estrogen replacement therapy (ERT) may preserve cognitive function in postmenopausal women, but the mechanism is unknown. Thus, the authors studied aging of parietal lobe and hippocampus using proton MR spectroscopy. ERT naïve postmenopausal women had a significant increase in choline-containing compounds (Cho) compared to long-term ERT users and young women. Cho reflects increased neuronal/glial membrane turnover. Thus, ERT's "neuroprotective" effect may include modulating the effects of age on neural integrity in brain regions involved in cognitive function.

BackgroundVelo-cardio-facial syndrome (VCFS) is associated with deletions in the q11 band of chromosome 22, learning disability and psychosis, but the neurobiological basis is poorly understood.AimsTo investigate brain anatomy in adults with VCFS.MethodMagnetic resonance imaging was used to study 10 patients with VCFS and 13 matched controls. We carried out three analyses: qualitative; traced regional brain volume; and measurement of grey and white matter volume.ResultsThe subjects with VCFS had: a high prevalence of white matter hyperintensities and abnormalities of the septum pellucidum; a significantly smaller volume of cerebellum; and widespread differences in white matter bilaterally and regional specific differences in grey matter in the left cerebellum, insula, and frontal and right temporal lobes.ConclusionsDeletion at chromosome 22q11 is associated with brain abnormalities that are most likely neurodevelopmental and may partially explain the high prevalence of learning disability and psychiatric disorder in VCFS.

The processing of changing nonverbal social signals such as facial expressions is poorly understood, and it is unknown if different pathways are activated during effortful (explicit), compared to implicit, processing of facial expressions. Thus we used fMRI to determine which brain areas subserve processing of high‐valence expressions and if distinct brain areas are activated when facial expressions are processed explicitly or implicitly. Nine healthy volunteers were scanned (1.5T GE Signa with ANMR, TE/TR 40/3,000 ms) during two similar experiments in which blocks of mixed happy and angry facial expressions (“on” condition) were alternated with blocks of neutral faces (control “off” condition). Experiment 1 examined explicit processing of expressions by requiring subjects to attend to, and judge, facial expression. Experiment 2 examined implicit processing of expressions by requiring subjects to attend to, and judge, facial gender, which was counterbalanced in both experimental conditions. Processing of facial expressions significantly increased regional blood oxygenation level‐dependent (BOLD) activity in fusiform and middle temporal gyri, hippocampus, amygdalohippocampal junction, and pulvinar nucleus. Explicit processing evoked significantly more activity in temporal lobe cortex than implicit processing, whereas implicit processing evoked significantly greater activity in amygdala region. Mixed high‐valence facial expressions are processed within temporal lobe visual cortex, thalamus, and amygdalohippocampal complex. Also, neural substrates for explicit and implicit processing of facial expressions are dissociable: explicit processing activates temporal lobe cortex, whereas implicit processing activates amygdala region. Our findings confirm a neuroanatomical dissociation between conscious and unconscious processing of emotional information. Hum. Brain Mapping 9:93–105, 2000. © 2000 Wiley‐Liss, Inc.

BackgroundCognitive impairment is considered to be a core characteristic of schizophrenia. The relationship between psychosis and cognitive deterioration, however, remains unclear. This longitudinal study investigated the neuropsychological functioning of patients before and after their first psychotic episode. Cognitive functioning of participants who later developed a psychosis was compared to that of people at ultra-high risk (UHR) for psychosis who did not develop psychosis at follow-up and healthy controls.MethodParticipants were 41 persons at UHR for psychosis (the UHR group), of whom 17 developed psychosis between the first and second assessment. Seventeen healthy controls were included in the study. Cognitive performance was assessed at intake (T0) and again after 18 months (T1). The areas of cognitive functioning assessed include verbal memory and learning, visuospatial working memory, executive function, sustained attention and motor speed.ResultsThe transition group did not perform significantly worse at the second assessment than at the first on any of the outcome measures. The UHR group performed better on a verbal learning and memory test at T1 compared to T0. At T0, the control group scored significantly better than the UHR group and the transition group on the verbal learning and memory test and the verbal fluency test.ConclusionsThe results indicate that no cognitive deterioration occurs during the first psychotic episode. Problems in verbal memory may be present before the first episode of psychosis.

This study examines the effects of angiotensin II on hypertrophy and proliferation of aortic smooth muscle cells from spontaneously hypertensive and Wistar-Kyoto rats and the receptor subtypes mediating these effects. In quiescent confluent cells, angiotensin II induced a dose-dependent increase in thymidine and leucine incorporation without stimulating cell proliferation. In nonconfluent cells, angiotensin II stimulated cell proliferation only in combination with a submaximal concentration of fetal calf serum. These effects were enhanced in cells from spontaneously hypertensive rats compared with Wistar-Kyoto rats. The effects of angiotensin II could be blocked by the AT1 receptor antagonist DuP 753 but not by the AT2 receptor ligand PD 123177. In receptor binding studies with cells derived from both rat strains, AT1-typical binding was observed. These data show that the angiotensin II receptors present in vascular smooth muscle cells in culture from both rat strains are of the AT1 receptor subtype. This receptor subtype appears to mediate vascular smooth muscle cell hypertrophy and proliferation as well as vasoconstriction. Although no difference in the receptor profile was detectable between the two rat strains, the affinity for the ligands to the receptor and the receptor density tended to be greater in cells from spontaneously hypertensive rats than in cells from Wistar-Kyoto rats. These results may partly explain the greater hypotensive response to angiotensin II receptor blockade in spontaneously hypertensive rats than in Wistar-Kyoto rats, although both rat strains have the same plasma concentrations of angiotensin II.

Objective: Prediction of transition to psychosis in the prodromal phase of schizophrenia has raised interest in intervention prior to the onset of frank psychosis. The aim of this review was to examine whether interventions in the prodromal phase have a favourable benefit/risk ratio. Method: A literature search in PubMed, EMBASE and PsycINFO was performed. Results: Three randomized clinical trials with antipsychotic medication and/or cognitive behavioural therapy as clinical intervention suggested a positive effect at the end of treatment, but no significant differences were found at the end of follow-up periods from 1 to 4 years. Naturalistic studies present a hypothesis about a possible preventive effect of antidepressive medication. The results of eight other studies are more difficult to interpret. Side-effects of antipsychotic medication and non-adherence with medication are essential problems. Conclusion: At the present time, the data concerning the benefits and risks do not justify prodromal intervention as standard clinical practice. © 2009 John Wiley & Sons A/S.

Variation in estrogen level is reported by some to affect brain maturation and memory. The neurobiological basis for this may include modulation of the serotonergic system. No neuroimaging studies have directly examined the effect of extended estrogen therapy (ET), on the 5-HT(2A) receptor in human brain. We investigated the effect of long-term ET on cortical 5-HT(2A) receptor availability in postmenopausal women. In a cross-sectional study, we compared cortical 5-HT(2A) receptor availability in 17 postmenopausal ERT-naive women and 17 long-term oophorectomised estrogen-users, age- and IQ-matched using single photon emission tomography and the selective 5-HT(2A) receptor ligand (123)I-5-I-R91150. Also, we used the Revised Wechsler Memory Scale to relate memory function to 5-HT(2A) receptor availability. Never-users had significantly higher 5-HT(2A) receptor availability than estrogen-users in hippocampus (1.17 vs. 1.11, respectively, p=0.02), although this did not remain significant after correction for multiple comparisons. Hippocampal 5-HT(2A) receptor availability correlated negatively with verbal and general memory and delayed recall (r=-0.45, p=0.01; r=-0.40, p=0.02; r=-0.36, p=0.04). Right superior temporal 5-HT(2A) receptor availability correlated negatively with verbal memory (r=-0.36, p=0.04). In estrogen-users, receptor availability correlated negatively with verbal and general memory (r=-0.70, p=0.002; r=-0.69, p=0.002); and in never-users, receptor availability negatively correlated with attention and concentration (r=-0.54, p=0.02). Long-term ET may be associated with lower 5-HT(2A) receptor availability in hippocampus. This may reflect increased activity within the serotonergic pathway leading to down-regulation of post-synaptic receptor. Also, increased availability of the 5-HT(2A) receptor in hippocampus is associated with poorer memory function.

Haploinsufficiency of 22q11 genes including catechol-O-methyltransferase (COMT) and proline dehydrogenase (PRODH) may result in structural and functional brain abnormalities and increased vulnerability to schizophrenia as observed in patients with microdeletions of 22q11. Thus, COMT and PRODH could be modifier genes for schizophrenia. We examined association of polymorphisms in COMT and PRODH with brain anatomy in young patients with schizophrenia and schizoaffective disorder. We acquired structural magnetic resonance imaging data from 51 male patients and genotyped two single nucleotide polymorphisms (SNPs) in the COMT gene and three in the PRODH gene. Statistical Parametric Mapping software and optimized voxel-based morphometry were used to determine regional gray matter (GM) and white matter (WM) density differences, and total GM and WM volume differences between genotype groups. Two nonsynonymous SNPs in the PRODH gene were associated with bilateral frontal WM density reductions and an SNP in the P2 promoter region of COMT (rs2097603) was associated with GM increase in the right superior temporal gyrus. Furthermore, we found evidence for COMT and PRODH epistasis: in patients with a COMT Val allele (rs4680) and with one or two mutated PRODH alleles, we observed increased WM density in the left inferior frontal lobe. Our results suggest that genetic variation in COMT and PRODH has significant effects on brain regions known to be affected in schizophrenia. Further research is needed to investigate the role of 22q11 genes on brain structure and function and their role in vulnerability for schizophrenia.

BackgroundVelo-cardio-facial syndrome (VCFS) is associated with deletions at chromosome 22q11, abnormalities in brain anatomy and function, and schizophrenia-like psychosis. Thus it is assumed that one or more genes within the deleted region are crucial to brain development. However, relatively little is known about how genetic variation at 22q11 affects brain structure and function. One gene on 22q11 is catechol-O-methyltransferase (COMT): an enzyme that degrades dopamine and contains a functional polymorphism (Val158Met) affecting enzyme activity. Here, we investigated the effect of COMT Val158Met polymorphism on brain anatomy and cognition in adults with VCFS.MethodThe COMT Val158Met polymorphism was genotyped for 26 adults with VCFS on whom DNA was available. We explored its effects on regional brain volumes using hand tracing approaches; on regional grey- and white-matter density using computerized voxel-based analyses; and measures of attention, IQ, memory, executive and visuospatial function using a comprehensive neuropsychological test battery.ResultsAfter corrections for multiple comparisons Val-hemizygous subjects, compared with Met-hemizygotes, had a significantly larger volume of frontal lobes. Also, Val-hemizygotes had significantly increased grey matter density in cerebellum, brainstem, and parahippocampal gyrus, and decreased white matter density in the cerebellum. No significant effects of COMT genotype on neurocognitive performance were found.ConclusionsCOMT genotype effects on brain anatomy in VCFS are not limited to frontal regions but also involve other structures previously implicated in VCFS. This suggests variation in COMT activity is implicated in brain development in VCFS.