General distress, hopelessness—suicidal ideation and worrying in adolescence: Concurrent and predictive validity of a symptom-level bifactor model for clinical diagnoses

BACKGROUND: Clinical disorders often share common symptoms and aetiological factors. Bifactor models acknowledge the role of an underlying general distress component and more specific sub-domains of psychopathology which specify the unique components of disorders over and above a general factor. METHODS: A bifactor model jointly calibrated data on subjective distress from The Mood and Feelings Questionnaire and the Revised Children's Manifest Anxiety Scale. The bifactor model encompassed a general distress factor, and specific factors for (a) hopelessness-suicidal ideation, (b) generalised worrying and (c) restlessness-fatigue at age 14 which were related to lifetime clinical diagnoses established by interviews at ages 14 (concurrent validity) and current diagnoses at 17 years (predictive validity) in a British population sample of 1159 adolescents. RESULTS: Diagnostic interviews confirmed the validity of a symptom-level bifactor model. The underlying general distress factor was a powerful but non-specific predictor of affective, anxiety and behaviour disorders. The specific factors for hopelessness-suicidal ideation and generalised worrying contributed to predictive specificity. Hopelessness-suicidal ideation predicted concurrent and future affective disorder; generalised worrying predicted concurrent and future anxiety, specifically concurrent generalised anxiety disorders. Generalised worrying was negatively associated with behaviour disorders. LIMITATIONS: The analyses of gender differences and the prediction of specific disorders was limited due to a low frequency of disorders other than depression. CONCLUSIONS: The bifactor model was able to differentiate concurrent and predict future clinical diagnoses. This can inform the development of targeted as well as non-specific interventions for prevention and treatment of different disorders.

LUPA: a European initiative taking advantage of the canine genome architecture for unravelling complex disorders in both human and dogs

The domestic dog offers a unique opportunity to explore the genetic basis of disease, morphology and behaviour. Humans share many diseases with our canine companions, making dogs an ideal model organism for comparative disease genetics. Using newly developed resources, genome-wide association studies in dog breeds are proving to be exceptionally powerful. Towards this aim, veterinarians and geneticists from 12 European countries are collaborating to collect and analyse the DNA from large cohorts of dogs suffering from a range of carefully defined diseases of relevance to human health. This project, named LUPA, has already delivered considerable results. The consortium has collaborated to develop a new high density single nucleotide polymorphism (SNP) array. Mutations for four monogenic diseases have been identified and the information has been utilised to find mutations in human patients. Several complex diseases have been mapped and fine mapping is underway. These findings should ultimately lead to a better understanding of the molecular mechanisms underlying complex diseases in both humans and their best friend.

A 600 kb deletion syndrome at 16p11.2 leads to energy imbalance and neuropsychiatric disorders

BACKGROUND: The recurrent ~600 kb 16p11.2 BP4-BP5 deletion is among the most frequent known genetic aetiologies of autism spectrum disorder (ASD) and related neurodevelopmental disorders. OBJECTIVE: To define the medical, neuropsychological, and behavioural phenotypes in carriers of this deletion. METHODS: We collected clinical data on 285 deletion carriers and performed detailed evaluations on 72 carriers and 68 intrafamilial non-carrier controls. RESULTS: When compared to intrafamilial controls, full scale intelligence quotient (FSIQ) is two standard deviations lower in carriers, and there is no difference between carriers referred for neurodevelopmental disorders and carriers identified through cascade family testing. Verbal IQ (mean 74) is lower than non-verbal IQ (mean 83) and a majority of carriers require speech therapy. Over 80% of individuals exhibit psychiatric disorders including ASD, which is present in 15% of the paediatric carriers. Increase in head circumference (HC) during infancy is similar to the HC and brain growth patterns observed in idiopathic ASD. Obesity, a major comorbidity present in 50% of the carriers by the age of 7 years, does not correlate with FSIQ or any behavioural trait. Seizures are present in 24% of carriers and occur independently of other symptoms. Malformations are infrequently found, confirming only a few of the previously reported associations. CONCLUSIONS: The 16p11.2 deletion impacts in a quantitative and independent manner FSIQ, behaviour and body mass index, possibly through direct influences on neural circuitry. Although non-specific, these features are clinically significant and reproducible. Lastly, this study demonstrates the necessity of studying large patient cohorts ascertained through multiple methods to characterise the clinical consequences of rare variants involved in common diseases.

Interactional behaviour as a marker for screening patients with environment-related complaints

BACKGROUND: Adequate assessment of symptoms of patients suffering from environmental illnesses requires appropriate procedures such as psychological and psychiatric diagnostics, medical screening and a thorough analysis of noxious environmental factors. The Basel pilot research project established a multi-methodological assessment procedure that meets these criteria. However, an exhaustive three-fold analysis is very costly in terms of both equipment and personnel, and hence the need for a heuristic approach and pre-screening persists. METHOD: The three-fold diagnostic approach was preceded by a structured psychodynamic interview; the findings were used to construct a new profile of the patient's interactional behaviour (IB) in conjunction with the interviewer's countertransference. The extent to which this new profile could predict the results of the multi-method assessment was then assessed. RESULTS: A low level of IB on the part of the patient significantly predicted the degree of stress and the extent of the psychiatric diagnosis, including personality disorders. A negative IB was associated with negative personality traits. Furthermore, a high level of IB implied more medical, but not more environmental, findings which could plausibly be related to the patient's complaints. CONCLUSIONS: Assessment of patients' IB in conjunction with one's own countertransference is very helpful as a preliminary heuristic approach and may lead to consequences for treatment and therapy. Therefore, the training provided for experts who deal with patients suffering from environment-related complaints should place more specific emphasis on assessing patients' behaviour and on incorporating information gathered from countertransference. Nevertheless, an interdisciplinary assessment including medical, psychological/psychiatric, and environmental expertise remains mandatory for adequate and satisfactory diagnosis of patients with environment-related complaints.

Isolated mediotegmental lesion causing narcolepsy and rapid eye movement sleep behaviour disorder: a case evidencing a common pathway in narcolepsy and rapid eye movement sleep behaviour disorder

Narcolepsy is usually an idiopathic disorder, often with a genetic predisposition. Symptomatic cases have been described repeatedly, often as a consequence of hypothalamic lesions. Conversely, REM (rapid eye movement) sleep behaviour disorder (RBD) is usually a secondary disorder, often due to degenerative brain stem disorders or narcolepsy. The case of a hitherto healthy man is presented, who simultaneously developed narcolepsy and RBD as the result of an acute focal inflammatory lesion in the dorsomedial pontine tegmentum in the presence of normal cerebrospinal fluid hypocretin-1 levels and in the absence of human lymphocyte antigen haplotypes typically associated with narcolepsy and RBD (DQB1*0602, DQB1*05). This first observation of symptomatic narcolepsy with RBD underlines the importance of the mediotegmental pontine area in the pathophysiology of both disorders, even in the absence of a detectable hypocretin deficiency and a genetic predisposition.

[Therapy of disorders with central pain sensitization.]

Previous somatic pain experience (priming), psychobiographic imprinting (pain proneness), and stress (action proneness) are key to an enhanced centralised pain response. This centralised pain response clinically manifests itself in pain sensitization and chronification. The therapeutic approach to chronic centralised pain disorders is multimodal. The overarching aim of the various interventions of a multimodal treatment program is to activate anti-nociceptive areas of the cerebral matrix involved in pain processing. The lists of medications targeting neuropathic and somatoform pain disorder show considerable overlap. Psychotherapy helps patients with central pain sensitization to improve pain control, emotional regulation and pain behaviour.

Who stays, who benefits? Predicting dropout and change in cognitive behaviour therapy for psychosis

This study investigates predictors of outcome in a secondary analysis of dropout and completer data from a randomized controlled effectiveness trial comparing CBTp to a wait-list group (Lincoln et al., 2012). Eighty patients with DSM-IV psychotic disorders seeking outpatient treatment were included. Predictors were assessed at baseline. Symptom outcome was assessed at post-treatment and at one-year follow-up. The predictor x group interactions indicate that a longer duration of disorder predicted less improvement in negative symptoms in the CBTp but not in the wait-list group whereas jumping-to-conclusions was associated with poorer outcome only in the wait-list group. There were no CBTp specific predictors of improvement in positive symptoms. However, in the combined sample (immediate CBTp+the delayed CBTp group) baseline variables predicted significant amounts of positive and negative symptom variance at post-therapy and one-year follow-up after controlling for pre-treatment symptoms. Lack of insight and low social functioning were the main predictors of drop-out, contributing to a prediction accuracy of 87%. The findings indicate that higher baseline symptom severity, poorer functioning, neurocognitive deficits, reasoning biases and comorbidity pose no barrier to improvement during CBTp. However, in line with previous predictor-research, the findings imply that patients need to receive treatment earlier.

Factor structure of the Bern Psychopathology Scale in a sample of patients with schizophrenia spectrum disorders.

BACKGROUND The Bern Psychopathology Scale (BPS) is based on a system-specific approach to classifying the psychopathological symptom pattern of schizophrenia. It consists of subscales for three domains (language, affect and motor behaviour) that are hypothesized to be related to specific brain circuits. The aim of the study was to examine the factor structure of the BPS in patients with schizophrenia spectrum disorders. METHODS One hundred and forty-nine inpatients with schizophrenia spectrum disorders were recruited at the Department of Psychiatry II, Ulm University, Germany (n=100) and at the University Hospital of Psychiatry, Bern, Switzerland (n=49). Psychopathology was assessed with the BPS. The VARCLUS procedure of SAS(®) (a type of oblique component analysis) was used for statistical analysis. RESULTS Six clusters were identified (inhibited language, inhibited motor behaviour, inhibited affect, disinhibited affect, disinhibited language/motor behaviour, inhibited language/motor behaviour) which explained 40.13% of the total variance of the data. A binary division of attributes into an inhibited and disinhibited cluster was appropriate, although an overlap was found between the language and motor behaviour domains. There was a clear distinction between qualitative and quantitative symptoms. CONCLUSIONS The results argue for the validity of the BPS in identifying subsyndromes of schizophrenia spectrum disorders according to a dimensional approach. Future research should address the longitudinal assessment of dimensional psychopathological symptoms and elucidate the underlying neurobiological processes.