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To examine the association between advancing pubertal status and the emergence of depressive symptoms in boys and girls from a UK cohort.
Self-reported depressive symptoms were assessed using the Short Mood and Feelings Questionnaire at three time-points (10.5, 13 and 14 years). We derived trait measures of depressive symptom level at each time-point using confirmatory factor analysis and compared the 3 depressive symptom factors with pubertal status (using regular self-reported Tanner assessments from 8-14 years) separately in boys (n=2902) and girls (n=2886). Main effects were estimated, adjusted for time lag between assessment of pubertal status and depressive symptoms, and then further adjusted for confounders (social class, maternal education, parental separation, financial problems, housing tenure).
For girls at age 10.5 years, there was little evidence of a relationship between pubertal status and depressive symptoms, with an increase in symptoms of 0.025 SD's for each additional pubertal stage (indicated by Tanner stages 1 through 5) for breast development and 0.023 SD's for each additional stage for pubic-hair development. With increasing age, the association between pubertal stage and depressive symptoms in girls strengthened. At age 14 years, advancement of each pubertal stage represented an increase in 0.13 SD's of depressive symptoms for breast development and 0.10 SD's for pubic hair development. For boys, there was no clear relationship between pubertal development and depressive symptoms at any time-point.
More advanced pubertal status was associated with an increased level of depressive symptoms in girls in early/mid adolescence but not boys.
The epidemiology of panic disorder has not been investigated in the past in the UK using a nationally representative sample of the population. The aim of the present paper was to examine the epidemiology, comorbidity and functional impairment of subthreshold panic and panic disorder with or without agoraphobia.
We used data from the 2000 Office for National Statistics Psychiatric Morbidity survey (N = 8580). Panic disorder and agoraphobia were assessed with the Revised Clinical Interview Schedule (CIS-R).
The prevalence of panic disorder with or without agoraphobia was 1.70% (95% confidence interval: 1.41–2.03%). Subthreshold panic was more common. Economic inactivity was consistently associated with all syndromes. The comorbidity pattern of the panic syndromes and the associated functional impairment show that panic-related conditions are important public health problems, even in subthreshold status.
The findings show that efforts to reduce the disability associated with psychiatric disorders should include detection and management of panic disorder.
Research on at-risk states of psychosis has mainly aimed to predict conversion. Yet as a considerable number of patients does not to progress to this outcome during the investigated observation periods, the course of these non-converters (NC) is of major interest, particularly with regard to preventive interventions and treatment.
To analyze the psychopathological and functional in 18-month non-converters.
Data were derived from the prospective multicenter European Prediction of Psychosis Study with an 18-month follow-up period. Participants had to fulfill ultra-high risk criteria and/or the COGDIS criterion, which is based on a set of cognitive basic symptoms. Psychopathology was assessed with the Structure Interview for Prodromal Syndromes (SIPS), including the Global Assessment of Functioning Scale (GAF) and a short version of the Schizophrenia Proneness Instrument (SPI-A).
All total and subscale scores improved significantly during follow-up. However, a more detailed analysis revealed that a considerable part of the patients showed no improvement or even a worsening of psychopathology and function.
Our first analysis of course on non-converters shows that a high proportion of patients improved. In the light of results from retrospective studies, however, this improvement has to be interpreted with caution, as the observation period does not allow to determine the proportion of outpost syndromes, i.e. precursors of a later prodrome. Furthermore, a considerable portion of our sample worsened functionally and/or symptomatically. With regard to retrospective schizophrenia related results, very long observation periods may be needed to characterize the patterns of course in subpsychotic syndromes.
Early detection and indicated early intervention in the initial prodromal phase should considerably improve the course of psychoses. Yet, the benefits of such programmes still require an evidence-based evaluation on the basis of a sufficient sample-size.
This report presents an overview on the concept and design of the European Prediction of Psychosis Study (EPOS) an European 4-country naturalistic field-study of the initial Prodrome.
Materials and Methods
Across six participating centres (Germany: Cologne, Berlin; Finland: Turku; The Netherlands: Amsterdam; United Kingdom: Birmingham, Manchester), 16 to 40 year old putatively prodromal persons attending specialized services or general psychiatric services underwent multi-level baseline, 9-months follow-up, and 18-months follow-up examinations. Inclusion criteria were the presence of APS, BLIPS, at least 2 of 9 Basic Symptoms (BS), and Familial Risk or Schizotypal Personality Disorder plus Reduced Functioning (FR+RF). In addition, psychopathological, neurocognitive, neurobiological, psychosocial, and service and treatment-related assessments were carried out.
A substantial part of more than 250 subjects included into the study participated in their respective baseline, 1st follow-up, and 2nd follow-up examinations. A high percentage presented themselves with BS and/or APS, a smaller percentage with BLIPS or FR+RF. The rates of transition into psychosis and the levels of psychopathology, distress and functional decline found among this patient group underline the need for indicated early recognition and intervention.
EPOS provides for the first time a sound data base allowing an evaluation of the applicability and cost-benefit ratio of early detection and intervention programmes in Europe.
A main objective of EPOS is to provide a valid multifactorial model for the prediction of psychosis. One major element of such a model should be the clinical state.
In a European multicentre study, persons fulfilling clinical criteria thought to indicate an increased risk for psychosis (PAR) were assessed amongst others with different psychopathological instruments covering the whole spectrum from basic symptoms to frank psychotic symptoms. Inclusion criteria comprised attenuated positive symptoms (APS), brief limited intermittent psychotic symptoms (BLIPS), cognitive basic symptoms (CogDis) and a combination of family risk and reduced functioning (S&T).
246 PAR were included into the study, mostly by APS or CogDis. Analysis of demographical data showed a high amount of functional impairment, resulting e.g. in low mean GAF scores (51.0 ± 11.8 SD), and of non-psychotic axis-I disorders. In September 2006, the hazard rate for a conversion to psychosis was 15.3 at 12 and 20.0 at 18 months after baseline assessment. According to the inclusion criteria, the highest rate of conversion was observed among PAR with BLIPS. On a dimensional level, a low GAF score was among the best predictors of conversion.
The transition rates of EPOS were in line with recent studies. A first analysis of clinical data supports the notion that the functional state should be an inherent part of any set of clinical risk criteria. Further analysis will consider the contribution of single symptoms or symptom combinations and the impact of symptom duration.
The utility of questionnaire based self-report measures for non-clinical psychotic symptoms is unclear and there are few reliable data about the nature and prevalence of these phenomena in children. The study aimed to investigate psychosis-like symptoms (PLIKS) in children utilizing both self-report measures and semi-structured observer rated assessments.
The study was cross-sectional; the setting being an assessment clinic for members of the ALSPAC birth cohort in Bristol, UK. 6455 respondents were assessed over 21 months, mean age 12.9 years. The main outcome measure was: 12 self-report screening questions for psychotic symptoms followed by semi-structured observer rated assessments by trained psychology graduates. The assessment instrument utilised stem questions, glossary definitions, and rating rules adapted from DISC-IV and SCAN items.
The 6-month period prevalence for one or more PLIKS rated by self-report questions was 38.9 % (95% CI = 37.7-40.1). Prevalence using observer rated assessments was 13.7% (95% CI = 12.8-14.5). Positive Predictive Values for the screen questions versus observer rated scores were low, except for auditory hallucinations (PPV=70%; 95% CI = 67.1-74.2). The most frequent observer rated symptom was auditory hallucinations (7.3%); in 18.8% of these cases symptoms occurred weekly or more. The prevalence of DSM-IV ‘core’ schizophrenia symptoms was 3.62%. Rates were significantly higher in children with low socio-economic status.
With the exception of auditory hallucinations, self-rated questionnaires are likely to substantially over-estimate the frequency of PLIKS in 12-year-old children. However, more reliable observer rated assessments reveal that PLIKS occur in a significant proportion of children.
Craving in negative emotional situations (negative craving) is commonly associated with relapse and heavy alcohol use. Elevated dynorphin levels were associated with negative emotions, while variations in the OPRK1 and PDYN genes encoding OPRK1 receptor and dynorphins were associated with alcohol dependence.
To investigate potential overlap in the genetic factors underlying, negative craving and alcohol dependence.
Examine the association of the negative craving and genetic variation in the OPRK1 and PDYN genes.
13 PDYN and 10 OPRK1 Single Nucleotide Polymorphisms (SNPs), including those previously reported to be associated with alcohol dependence were genotyped in 196 alcohol dependent subjects. The raw scores of the negative subscale of Inventory of Drug Taking Situations (IDTS) were utilized as a quantitative measure of negative craving. Logistic regression models were used to test for associations after controlling for age and gender.
Gene-level haplotype testing demonstrated significant association of negative craving with variation in PDYN (p < 0.05) but not OPRK1 gene. The rs2281285 - rs199794 haplotype showed significant association (p = 0.0236) with negative craving, while rs2235749 - rs10485703 haplotype showed marginally significant association (p = 0.055). This replicates previous findings of association between these haplotypes and alcohol dependence. Negative craving was also associated with PDYN rs2281285 variant (p = 0.012) with estimated effect size of 6.95 (SE = 2.75). This new association finding was not significant after correction for multiple testing (p = 0.18).
Our findings support association of PDYN sequence variation with negative craving in alcohol dependent subjects. Future studies should investigate functional mechanisms of this association.
Ultra-high risk (UHR) criteria are defined by attenuated and/or transient full-blown psychotic symptoms and/or a combination of genetic risk factor and deterioration of functioning. To achieve a higher predictive specificity and a clear threshold of clinical importance, functional impairment has been considered as an obligate part of all UHR criteria.
In the European Prediction of Psychosis Study (EPOS)N = 37 participants converted to psychosis, n = 146 completed the whole 18-month follow-up period without conversion. Assessed by the Global Assessment of Functioning Scale, modified version (GAF-M), the following functional states were considered: Considered GAF-M: ≤30%/≤10% reduction of baseline scores related to highest scores in the previous year; scores ≤70/≤60.
The GAF reduction criteria led to a very unfavorable loss of sensitivity, even, if only 10% were demanded. This was accompanied by correspondingly unfavorable accuracy measures. Introducing functional impairment criteria defined by the current state reported to be predictive for psychiatric caseness (score ≤ 70) or to define serious impairment (score ≤ 60) (Kessler et al., 2002, 2003) kept sensitivity at a perfectly high level, yet did not produce any gain of specificity.
These results were certainly be caused by the fact that the whole group showed already low GAF-M scores in the previous year. Thus, a functional impairment criterion proved not to be useful to improve prediction. However, a combination of APS or BLIPS with a ‘clinical status’ criterion of GAF-M ≤ 70 may be considerable to demonstrate a strong need for intervention.
Quality of life (QoL) is increasingly considered an important outcome in health research. We wished to explore the determinants of change in QoL in patients with schizophrenia over the course of a one-year RCT.
Predictors of change in observer-rated QoL (Quality of Life Scale: QLS) were assessed in 363 patients with schizophrenia during the CUtLASS clinical trial.
Change in QLS score over the course of a year correlated with change in psychotic and depressive symptoms and treatment adherence. Linear regression showed that improvement in QoL was predicted by reduction in negative and depressive symptoms and improvement in adherence rating. These three change scores together explained 38% of the variance in QLS change. Exploration of the direction of any possible causal effect, using TETRAD, indicated that improved adherence leads to improved QoL, and that change in depression also leads to QoL change. The relationship between QoL and negative symptoms suggests that greater social activity (reflected as better QoL scores) improves negative symptoms. Such a direct relationship between treatment adherence and QoL has not been reported before.
Improving adherence to medication would appear to be a key approach to improving measured quality of life in people with schizophrenia.
Depression and obesity are highly prevalent major public health problems that frequently co-occur. Shared aetiological factors have been found between depression and obesity. The role of the fat mass and obesity associated (FTO) gene in body mass index (BMI) and obesity has been confirmed in many independent studies. Recently, we reported the first study implicating FTO in the association between depression and obesity.
We aimed to confirm these findings by investigating the FTO rs9939609 polymorphism in a meta-analysis of 13,701 individuals.
The sample consists of 6,902 depressed cases and 6,799 controls from five studies (Radiant, PsyCoLaus, GSK, MARS and NESDA/NTR). Common inclusion criteria were information available on a lifetime DSM-IV diagnosis of major depressive disorder (MDD), BMI and genotype data. Linear regression models for quantitative traits assuming an additive genetic model were performed to test for association and interaction between rs9939609, BMI and depression. Fixed and random-effects meta-analyses were performed.
Fixed-effects meta-analyses support a significant association between rs9939609 polymorphism and BMI (whole-sample: ß=0.07, p=1.29×10-12, depressive-cases: ß=0.12, p=6.92×10-12). No association was found in controls (ß=0.02, p=0.15). Meta-analyses further support a significant interaction between FTO, BMI and depression (fixed-effects: ß=0.13, p=3.087×10-7; random-effects: ß=0.12, p=0.027), wherein depressed carriers of the risk allele have an additional increase of 2.2% in BMI.
This meta-analysis demonstrates a significant interaction between FTO, depression and BMI, indicating that depression increases the effect of FTO on BMI. Depression-related alterations in key biological processes may interact with the rs9939609 FTO risk allele to increase obesity risk.
The aim of this presentation is to summarize the results of the published systematic reviews / meta-analyses of the randomized controlled trials that have investigated the effectiveness of medications for the treatment of obsessive compulsive disorder (OCD) in children/adolescents and adults and to present preliminary results from a new review study using network meta-analytical techniques
Medline, Cochrane database, and the register of controlled trials maintained by the Cochrane Collaboration Depression, Anxiety & Neurosis Group (CCDAN) were searched for relevant trials, systematic reviews and/or meta-analyses.
Regarding the new review study we were able to extract 103 pharmacological arms (preliminary results: 9 for Fluoxetine, 16 for Fluvoxamine, 11 for Paroxetine, 10 for Sertraline, 16 for Clomipramine, 7 for Citalopram / escitalopram, 2 for Venlafaxine, and 32 for Placebo) with a total number of 6572 patients randomized. The previous meta-analyses have confirmed the efficacy for all SSRIs and Clomipramine in all age groups while for other drugs further evidence is required. In the context of this presentation preliminary results of the relative efficacy of each drug, using network meta-analysis techniques will also be reported.
Several antidepressants have established their efficacy and acceptability for the management of non-resistant OCD. The major weakness of the literature so far is that head to head comparisons between antidepressants are few and therefore it is difficult to establish a clear hierarchy of the efficacy and acceptability of the various agents. This gap in the present literature will be filled by the present review.
A considerable part of clinical high-risk samples does not convert to psychosis within the studies' limited observation periods. A part of these ‘non-converters’ shows a remission of symptoms (with unknown future course). Another part, however, maintains the risk state during follow-up.
Persistence of indicators for an increased risk of psychosis.
To investigate, if persistence of attenuated (APS) or brief limited intermittent psychotic symptoms (BLIPS), the core syndromes of ultra-high risk (UHR) criteria, can be predicted clinically.
N = 129 participants of the European Prediction of Psychosis (EPOS) Study were included into the current analysis. Persistent Risk Symptoms (pRS) were defined as an at-least ‘moderate’ level (SIPS) of at least one positive symptom at all visits (symptom had to remain the same). Functional significance was defined by a GAF-M score ≤60 at 18-month follow-up (T2).
23.3% displayed persistent risk symptoms throughout follow-up. Most frequent pRS were ‘unusual thought contents’, ‘ideas of persecution’ and ‘perceptual disturbances’. In 90% of the pRS subjects, but only in 25.3% of the non-pRS subjects, GAF scores at T2 were below 60 points (p < 0.01).
Logistic regression analysis revealed that the presence of the pRS syndrome at T2 was predictable by the early course of attenuated positive symptoms with maximum accuracy when the number of at least ‘moderate’ symptoms was considered.
A considerable number of subjects at risk showed persistent attenuated positive symptoms associated with long-lasting functional impairments, irrespective of conversion within the foreseeable future.
The ultra-high risk state of developing a psychosis is mainly characterized by attenuated or transient full-blown psychotic symptoms. It can be assessed with the structured interview for prodromal symptoms (SIPS), comprising four domains: positive, negative, disorganization and general symptoms. As the scores of the SOPS sub-domains are regularly used to perform domain-related analyses the stability of the suggested domain structure and item composition is of major interest.
SIPS (version 3.0) data from n = 243 participants of the European Prediction of Psychosis Study (EPOS) were used for the current analysis. Inclusion criteria comprised ultra-high risk criteria and the basic symptom criterion COGDIS. The EPOS investigators received extensive training by one of the scale's authors (Tandy J. Miller, PhD). Pairwise interrater concordance for SIPS was 77%, which was determined acceptable by the training team. A principal component analysis was performed (Eigenvalues > 1, varimax rotation).
A five factor solution emerged. Factor 1 was primarily defined by a loss of intentionality, functioning and stress tolerance, factor 2 by anhedonia and affective blunting, factor 3 by cognitive and behavioural disorganization, factor 4 by delusions. Sleep disturbances and perceptual abnormalities/hallucinations have both been associated with dopaminergic disturbances, this may explain their common appearance on factor 5.
The originally suggested structure of the SIPS proofed not to be stable and was replaced by a five-factor solution. Our results suggest considering a different item and factor structure in future SIPS based data analyses.
This study investigated metabolic, endocrine, appetite and mood responses to a maximal eating occasion in fourteen men (mean: age 28 (sd 5) years, body mass 77·2 (sd 6·6) kg and BMI 24·2 (sd 2·2) kg/m2) who completed two trials in a randomised crossover design. On each occasion, participants ate a homogenous mixed-macronutrient meal (pizza). On one occasion, they ate until ‘comfortably full’ (ad libitum) and on the other, until they ‘could not eat another bite’ (maximal). Mean energy intake was double in the maximal (13 024 (95 % CI 10 964, 15 084) kJ; 3113 (95 % CI 2620, 3605) kcal) compared with the ad libitum trial (6627 (95 % CI 5708, 7547) kJ; 1584 (95 % CI 1364, 1804) kcal). Serum insulin incremental AUC (iAUC) increased approximately 1·5-fold in the maximal compared with ad libitum trial (mean: ad libitum 43·8 (95 % CI 28·3, 59·3) nmol/l × 240 min and maximal 67·7 (95 % CI 47·0, 88·5) nmol/l × 240 min, P < 0·01), but glucose iAUC did not differ between trials (ad libitum 94·3 (95 % CI 30·3, 158·2) mmol/l × 240 min and maximal 126·5 (95 % CI 76·9, 176·0) mmol/l × 240 min, P = 0·19). TAG iAUC was approximately 1·5-fold greater in the maximal v. ad libitum trial (ad libitum 98·6 (95 % CI 69·9, 127·2) mmol/l × 240 min and maximal 146·4 (95 % CI 88·6, 204·1) mmol/l × 240 min, P < 0·01). Total glucagon-like peptide-1, glucose-dependent insulinotropic peptide and peptide tyrosine–tyrosine iAUC were greater in the maximal compared with ad libitum trial (P < 0·05). Total ghrelin concentrations decreased to a similar extent, but AUC was slightly lower in the maximal v. ad libitum trial (P = 0·02). There were marked differences on appetite and mood between trials, most notably maximal eating caused a prolonged increase in lethargy. Healthy men have the capacity to eat twice the energy content required to achieve comfortable fullness at a single meal. Postprandial glycaemia is well regulated following initial overeating, with elevated postprandial insulinaemia probably contributing.