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Individuals at Ultra High Risk (UHR) for psychosis typically present with attenuated psychotic symptoms. However it is difficult to predict which individuals will later develop frank psychosis when their mental state is rated in terms of individual symptoms.
The objective of the study was to examine the phenomenological structure of the UHR mental state and identify symptom profiles that predict later transition to psychosis.
Psychopathological data from a large sample of UHR subjects were analysed using latent class cluster analysis.
A total of 318 individuals with a UHR for psychosis. Data were collected from two specialised community mental health services for people at UHR for psychosis: OASIS in London and PACE, in Melbourne.
Latent class cluster analysis produced 4 classes: Class 1 - Mild was characterized by lower scores on all the CAARMS items. Subjects in Class 2 - Moderate scored moderately on all CAARMS items and was more likely to be in employment. Those in Class 3 - Moderate-Severe scored moderately-severe on negative symptoms, social isolation and impaired role functioning. Class 4 - Severe was the smallest group and was associated with the most impairment: subjects in this class scored highest on all items of the CAARMS, had the lowest GAF score and were more likely to be unemployed. This group was also characterized by the highest transition rate (41%).
Different constellations of symptomatology are associates with varying levels of risk to of transition to psychosis.
To investigate the effect of past depression, past and current eating disorders (ED) on perinatal anxiety and depression in a large general population cohort of pregnant women, the Avon Longitudinal Study of Parents And Children (ALSPAC).
Anxiety and depression were measured during and after pregnancy in 10,887 women, using the Crown-Crisp Experiential Inventory and Edinburgh Postnatal Depression Scale. Women were grouped according to depression and ED history: past ED with (n = 123) and without past depression (n = 50), pregnancy ED symptoms with (n = 77) and without past depression (n = 159), past depression only (n = 818) and controls (n = 9,660). We compared the course of depression and anxiety with linear mixed-effect regression models; and probable depressive and anxiety disorders using logistic regression.
Women with both past depression and past/current ED had high anxiety and depression across time perinatally; this was most marked in the group with pregnancy ED symptoms and past depression (b coefficient:5.1 (95% CI 4.1-6.1), p < 0.0001), especially at 8 months post-partum. At 18 weeks in pregnancy all women (apart from those with past ED only) had a higher risk for a probable depressive and anxiety disorder compared to controls. At 8 months post-partum pregnancy ED symptoms and/or past depression conferred the highest risk for a probable depressive and anxiety disorder.
Pregnancy ED symptoms and past depression have an additive effect in increasing the risk for depression and anxiety perinatally. Screening at risk women for anxiety and depression in the perinatal period might be beneficial.
The increased prevalence of metabolic syndrome in people with severe mental illness (SMI) is well documented. The International Diabetes Federation (IDF) criteria for metabolic syndrome are three or more of the following: waist circumference ( 80 cm (females), (94 cm (males) OR BMI (30, triglycerides >1.7 mmol/l or on treatment, raised blood pressure (systolic >130 mg Hg or diastolic >85 mm Hg, OR on treatment for hypertension), raised fasting blood glucose (.5.6 mmol/l) OR diagnosed type II diabetes) and reduced HDL cholesterol (< 1.03 mmol/l) OR on treatment.
The IMPACT RCT is a Department of Health funded trial of a health promotion intervention (HPI) delivered by care co-ordinators to people with SMI across South London, Kent and Sussex. The intervention is focussed on improving health by addressing modifiable lifestyle factors such as diet, physical activity, obesity, cigarette smoking, alcohol and substance use.
We investigated the prevalence of metabolic syndrome in a sample of 212 patients for whom we had relevant baseline measures.
Data (weight, BMI, waist circumference, blood pressure, fasting HDL cholesterol, triglycerides and glucose levels) were analysed on 212 patients.
45% of the sample met IDF criteria for metabolic syndrome. Mean BMI was 30.6, glucose 6.4 mmol/L, triglycerides 2.0 mmol/L, HDL 1.2 (mmol/L), waist circumference 105.8 cm, and BP 122/82 mm Hg.
Metabolic syndrome was highly prevalent in this sample, significantly increasing the risk of physical morbidity and potentially lowering life expectancy. There is an unmet need for health promotion interventions in order to lower morbidity and mortality risk in these populations.
The long-term clinical validity of the At Risk Mental State (ARMS) for the prediction of non-psychotic mental disorders is unknown.
Clinical register-based cohort study including all non-psychotic individuals assessed by the Outreach And Support in South London (OASIS) service (2002–2015). The primary outcome was risk of developing any mental disorder (psychotic or non-psychotic). Analyses included Cox proportional hazard models, Kaplan–Meier survival/failure function and C statistics.
A total of 710 subjects were included. A total of 411 subjects were at risk (ARMS+) and 299 not at risk (ARMS−). Relative to ARMS−, the ARMS+ was associated with an increased risk (HR = 4.825) of developing psychotic disorders, and a reduced risk (HR = 0.545) of developing non-psychotic disorders (mainly personality disorders). At 6-year, the ARMS designation retained high sensitivity (0.873) but only modest specificity (0.456) for the prediction of psychosis onset (AUC 0.68). The brief and limited intermittent psychotic symptoms (BLIPS) subgroup had a higher risk of developing psychosis, and a lower risk of developing non-psychotic disorders as compared to the attenuated psychotic symptoms (APS) subgroup (P < 0.001).
In the long-term, the ARMS specifically predicts the onset of psychotic disorders, with modest accuracy, but not of non-psychotic disorders. Individuals meeting BLIPS criteria have distinct clinical outcomes.
In the long-term, the ARMS designation is still significantly associated with an increased risk of developing psychotic disorders but its prognostic accuracy is only modest. There is no evidence that the ARMS is associated with an increased risk of developing non-psychotic mental disorders. The BLIPS subgroup at lower risk of developing non-psychotic disorders compared to the APS subgroup.
While incident diagnoses employed in this study are high in ecological validity they have not been subjected to formal validation with research-based criteria.
In recent years the association between sexual dysfunction (SD) and obesity in the general population has drawn major attention. Although sexual dysfunction is common in psychosis, its relationship with weight gain and obesity remains unclear.
To investigate the association between sexual dysfunction and obesity in a cohort of patients with first episode psychosis.
Sexual function was assessed in a cohort of patients with first episode psychosis using the Sexual Function Questionnaire (SFQ). Anthropometric measures, including weight, BMI, waist, waist–hip ratio were investigated. Additionally, leptin and testosterone were investigated in male patients.
A total of 116 patients (61 males and 55 females) were included. Of these 59% of males and 67.3% of females showed sexual dysfunction (SD) according to the SFQ. In males, higher SFQ scores were significantly correlated with higher BMI (Std. β = 0.36, P = 0.01), higher leptin levels (Std. β = 0.34, P = 0.02), higher waist–hip ratio (Std. β = 0.32, P = 0.04) and lower testosterone levels (Std. β = −0.44, P = 0.002). In contrast, in females, SFQ scores were not associated with any of these factors.
While sexual dysfunction is present in both female and male patients with their first episode of psychosis, only in males is sexual dysfunction associated with increased BMI and waist–hip ratio. The association between SD, BMI, low levels of testosterone and high levels of leptin suggest that policies that lead to healthier diets and more active lifestyles can be beneficial at least, to male patients.
During the past two decades, it has been amply documented that neuropsychiatric disorders (NPDs) disproportionately account for burden of illness attributable to chronic non-communicable medical disorders globally. It is also likely that human capital costs attributable to NPDs will disproportionately increase as a consequence of population aging and beneficial risk factor modification of other common and chronic medical disorders (e.g., cardiovascular disease). Notwithstanding the availability of multiple modalities of antidepressant treatment, relatively few studies in psychiatry have primarily sought to determine whether improving cognitive function in MDD improves patient reported outcomes (PROs) and/or is cost effective. The mediational relevance of cognition in MDD potentially extrapolates to all NPDs, indicating that screening for, measuring, preventing, and treating cognitive deficits in psychiatry is not only a primary therapeutic target, but also should be conceptualized as a transdiagnostic domain to be considered regardless of patient age and/or differential diagnosis.
Most studies underline the contribution of heritable factors for psychiatric disorders. However, heritability estimates depend on the population under study, diagnostic instruments, and study designs that each has its inherent assumptions, strengths, and biases. We aim to test the homogeneity in heritability estimates between two powerful, and state of the art study designs for eight psychiatric disorders.
We assessed heritability based on data of Swedish siblings (N = 4 408 646 full and maternal half-siblings), and based on summary data of eight samples with measured genotypes (N = 125 533 cases and 208 215 controls). All data were based on standard diagnostic criteria. Eight psychiatric disorders were studied: (1) alcohol dependence (AD), (2) anorexia nervosa, (3) attention deficit/hyperactivity disorder (ADHD), (4) autism spectrum disorder, (5) bipolar disorder, (6) major depressive disorder, (7) obsessive-compulsive disorder (OCD), and (8) schizophrenia.
Heritability estimates from sibling data varied from 0.30 for Major Depression to 0.80 for ADHD. The estimates based on the measured genotypes were lower, ranging from 0.10 for AD to 0.28 for OCD, but were significant, and correlated positively (0.19) with national sibling-based estimates. When removing OCD from the data the correlation increased to 0.50.
Given the unique character of each study design, the convergent findings for these eight psychiatric conditions suggest that heritability estimates are robust across different methods. The findings also highlight large differences in genetic and environmental influences between psychiatric disorders, providing future directions for etiological psychiatric research.
False positive findings in science are inevitable, but are they particularly common in psychology and psychiatry? The evidence that we review suggests that while not restricted to our field, the problem is acute. We describe the concept of researcher ‘degrees-of-freedom’ to explain how many false-positive findings arise, and how the various strategies of registration, pre-specification, and reporting standards that are being adopted both reduce and make these visible. We review possible benefits and harms of proposed statistical solutions, from tougher requirements for significance, to Bayesian and machine learning approaches to analysis. Finally we consider the organisation and methods for replication and systematic review in psychology and psychiatry.
Recent theories suggest that poor working memory (WM) may be the cognitive underpinning of negative symptoms in people with schizophrenia. In this study, we first explore the effect of cognitive remediation (CR) on two clusters of negative symptoms (i.e. expressive and social amotivation), and then assess the relevance of WM gains as a possible mediator of symptom improvement.
Data were accessed for 309 people with schizophrenia from the NIMH Database of Cognitive Training and Remediation Studies and a separate study. Approximately half the participants received CR and the rest were allocated to a control condition. All participants were assessed before and after therapy and at follow-up. Expressive negative symptoms and social amotivation symptoms scores were calculated from the Positive and Negative Syndrome Scale. WM was assessed with digit span and letter-number span tests.
Participants who received CR had a significant improvement in WM scores (d = 0.27) compared with those in the control condition. Improvements in social amotivation levels approached statistical significance (d = −0.19), but change in expressive negative symptoms did not differ between groups. WM change did not mediate the effect of CR on social amotivation.
The results suggest that a course of CR may benefit behavioural negative symptoms. Despite hypotheses linking memory problems with negative symptoms, the current findings do not support the role of this cognitive domain as a significant mediator. The results indicate that WM improves independently from negative symptoms reduction.
We examined longitudinally the course and predictors of treatment resistance in a large cohort of first-episode psychosis (FEP) patients from initiation of antipsychotic treatment. We hypothesized that antipsychotic treatment resistance is: (a) present at illness onset; and (b) differentially associated with clinical and demographic factors.
The study sample comprised 323 FEP patients who were studied at first contact and at 10-year follow-up. We collated clinical information on severity of symptoms, antipsychotic medication and treatment adherence during the follow-up period to determine the presence, course and predictors of treatment resistance.
From the 23% of the patients, who were treatment resistant, 84% were treatment resistant from illness onset. Multivariable regression analysis revealed that diagnosis of schizophrenia, negative symptoms, younger age at onset, and longer duration of untreated psychosis predicted treatment resistance from illness onset.
The striking majority of treatment-resistant patients do not respond to first-line antipsychotic treatment even at time of FEP. Clinicians must be alert to this subgroup of patients and consider clozapine treatment as early as possible during the first presentation of psychosis.
A significant minority of people presenting with a major depressive episode (MDE) experience co-occurring subsyndromal hypo/manic symptoms. As this presentation may have important prognostic and treatment implications, the DSM–5 codified a new nosological entity, the “mixed features specifier,” referring to individuals meeting threshold criteria for an MDE and subthreshold symptoms of (hypo)mania or to individuals with syndromal mania and subthreshold depressive symptoms. The mixed features specifier adds to a growing list of monikers that have been put forward to describe phenotypes characterized by the admixture of depressive and hypomanic symptoms (e.g., mixed depression, depression with mixed features, or depressive mixed states [DMX]). Current treatment guidelines, regulatory approvals, as well the current evidentiary base provide insufficient decision support to practitioners who provide care to individuals presenting with an MDE with mixed features. In addition, all existing psychotropic agents evaluated in mixed patients have largely been confined to patient populations meeting the DSM–IV definition of “mixed states” wherein the co-occurrence of threshold-level mania and threshold-level MDE was required. Toward the aim of assisting clinicians providing care to adults with MDE and mixed features, we have assembled a panel of experts on mood disorders to develop these guidelines on the recognition and treatment of mixed depression, based on the few studies that have focused specifically on DMX as well as decades of cumulated clinical experience.
Psychiatric research has entered the age of ‘Big Data’. Datasets now routinely involve thousands of heterogeneous variables, including clinical, neuroimaging, genomic, proteomic, transcriptomic and other ‘omic’ measures. The analysis of these datasets is challenging, especially when the number of measurements exceeds the number of individuals, and may be further complicated by missing data for some subjects and variables that are highly correlated. Statistical learning-based models are a natural extension of classical statistical approaches but provide more effective methods to analyse very large datasets. In addition, the predictive capability of such models promises to be useful in developing decision support systems. That is, methods that can be introduced to clinical settings and guide, for example, diagnosis classification or personalized treatment. In this review, we aim to outline the potential benefits of statistical learning methods in clinical research. We first introduce the concept of Big Data in different environments. We then describe how modern statistical learning models can be used in practice on Big Datasets to extract relevant information. Finally, we discuss the strengths of using statistical learning in psychiatric studies, from both research and practical clinical points of view.
Difficulties in set-shifting are commonly reported in both autism spectrum disorder (ASD) and anorexia nervosa (AN) populations. Despite this, it is not known whether this cognitive profile persists across different ages, or whether the profiles seen in ASD and AN are comparable. This systematic review and meta-analyses aimed to compare the set-shifting profiles, as measured by the Wisconsin Card Sorting Test (WCST) in adults and younger people with either ASD or AN, relative to healthy controls (HCs) and to statistically compare performance on the WCST between ASD and AN. In all, 24 studies on ASD and 22 studies on AN were identified. In ASD, there were significant differences between the clinical group and HCs, with the ASD group making significantly more perseverative errors, indicating greater difficulty in set-shifting [pooled effect size of d = 0.67, 95% confidence interval (CI) 0.53–0.81, p ⩽ 0.001]. This effect was consistent across the age span. For AN studies, there was a significant difference between adults with AN and HCs (d = 0.52, 95% CI 0.36–0.68, p ⩽ 0.001) but a non-significant effect in child studies (d = 0.25, 95% CI −0.05 to 0.55, z = 1.66, p = 0.096). Meta-regression indicated no effect of diagnosis (AN or ASD) on performance in adult studies but there was a non-significant trend (p = 0.053) towards children with ASD performing worse than children with AN. While difficulties with set-shifting appear to be stable in ASD, there may be differences between children and adults with AN, which warrant further investigation.
The aims of the study were to determine the prevalence of cardiometabolic risk factors and establish the proportion of people with psychosis meeting criteria for the metabolic syndrome (MetS). The study also aimed to identify the key lifestyle behaviours associated with increased risk of the MetS and to investigate whether the MetS is associated with illness severity and degree of functional impairment.
Baseline data were collected as part of a large randomized controlled trial (IMPaCT RCT). The study took place within community mental health teams in five Mental Health NHS Trusts in urban and rural locations across England. A total of 450 randomly selected out-patients, aged 18–65 years, with an established psychotic illness were recruited. We ascertained the prevalence rates of cardiometabolic risk factors, illness severity and functional impairment and calculated rates of the MetS, using International Diabetes Federation (IDF) and National Cholesterol Education Program Third Adult Treatment Panel criteria.
High rates of cardiometabolic risk factors were found. Nearly all women and most men had waist circumference exceeding the IDF threshold for central obesity. Half the sample was obese (body mass index ≥ 30 kg/m2) and a fifth met the criteria for type 2 diabetes mellitus. Females were more likely to be obese than males (61% v. 42%, p < 0.001). Of the 308 patients with complete laboratory measures, 57% (n = 175) met the IDF criteria for the MetS.
In the UK, the prevalence of cardiometabolic risk factors in individuals with psychotic illnesses is much higher than that observed in national general population studies as well as in most international studies of patients with psychosis.
Almost no literature addresses treatment planning for the forensic psychiatric patient. In the absence of such guidance, recovery-oriented multifocal treatment planning has been imported into forensic mental health systems from community psychiatric settings, despite the fact that conditions of admission and discharge are vastly different for forensic psychiatry inpatients. We propose that instead of focusing on recovery, forensic treatment planning should prioritize forensic outcomes, such as restoration of trial competence or mitigation of violence risk, as the first steps in a continuum of care that eventually leads to the patient’s ability to resolve forensic issues and return to the community for recovery-oriented care. Here we offer a model for treatment planning in the forensic setting.
Recent randomized controlled trials suggest some efficacy for focused interventions in subjects at high risk (HR) for psychosis. However, treating HR subjects within the real-world setting of prodromal services is hindered by several practical problems that can significantly make an impact on the effect of focused interventions.
All subjects referred to Outreach and Support in South London (OASIS) and diagnosed with a HR state in the period 2001–2012 were included (n = 258). Exposure to focused interventions was correlated with sociodemographic and clinical characteristics at baseline. Their association with longitudinal clinical and functional outcomes was addressed at follow-up.
In a mean follow-up time of 6 years (s.d. = 2.5 years) a transition risk of 18% was observed. Of the sample, 33% were treated with cognitive behavioural therapy (CBT) only; 17% of subjects received antipsychotics (APs) in addition to CBT sessions. Another 17% of subjects were prescribed with antidepressants (ADs) in addition to CBT. Of the sample, 20% were exposed to a combination of interventions. Focused interventions had a significant relationship with transition to psychosis. The CBT + AD intervention was associated with a reduced risk of transition to psychosis, as compared with the CBT + AP intervention (hazards ratio = 0.129, 95% confidence interval 0.030–0.565, p = 0.007).
There were differential associations with transition outcome for AD v. AP interventions in addition to CBT in HR subjects. These effects were not secondary to baseline differences in symptom severity.