Effects of one single-dose methylphenidate compared to one single-dose placebo on QbTest performance in adults with untreated ADHD: a randomized controlled trial.

BACKGROUND: Treatment of adults with attention-deficit/hyperactivity disorder (ADHD) primary involves methylphenidate (MPH). Earlier studies have identified placebo responders to increase toward the end of the treatment periods. However, little is known about the immediate effects of placebo on the core symptoms of ADHD in adults. The present study aimed to examine the effects of one single-dose MPH compared to one single-dose placebo during clinical assessments with continuous performance tests (CPT). METHODS: In a randomized study with cross-over design, 40 adults between 19 and 64 years (72.5% women) with untreated ADHD were consecutively enrolled. The study comprised two trial days with four days in between. The QbTest was performed twice on the same day, before and 80 min after intake of one single-dose 20 mg immediate release methylphenidate (IR-MPH) and with one single-dose placebo, in randomized order. RESULTS: Performance improved in QbInattention, F (3, 117) = 38.25, p < 0.001, after given IR-MPH (mean diff = 1.14) and after placebo (mean diff = 0.60) with the effect sizes 1.17 and 0.63 respectively. IR-MPH improved performance in QbActivity (mean diff = 0.81, p < 0.001) and QbImpulsivity (mean diff = 0.46, p < 0.04). The proportion of improvements (a decrease by ≥ 0.5 Qb-score) in the parameters QbInattention, QbActivity and QbImpulsivity were 90%, 60% and 52.5%, respectively. After given placebo, corresponding proportions were 60%, 30% and 35%, respectively. CONCLUSIONS: There seems to be an immediate placebo response in the core symptom inattention. The effect of placebo cannot be ruled out and must be taken in consideration during drug trials with continuous performance tests (CPTs). TRIAL REGISTRATION: ClinicalTrials.gov; Identifier: NCT02473185.

Contrasting expectancy effects with objective measures in adults with untreated ADHD during QbTest.

Expectancy has been associated with neuropsychological assessments and cognitive performance. However, little is known about the effects of expectations in clinical assessments during drug trials with continuous performance tests (CPTs). In a randomized, double-blind study with cross-over design, we examined if the participants' self-reported expectations changed after one-single dose immediate release methylphenidate (MPH) and after one-single dose placebo during the QbTest. Forty adults between 19 and 64 years (72.5% women) with un treated ADHD were consecutively enrolled in the study and their assessments of expected performance, mental effort, perceived performance and help from the pill were analyzed. The study comprised two trial days with four days in between. The QbTest was performed twice on the same day, before and 80 minutes after a pill. Our study demonstrates that there were expectancy effects during CPTs. Participants reported lower mental effort and improved their performance in the coronary parameter QbInattention both after MPH and after placebo. No significant differences in expected performance were reported. The participants seemed to show some uncertainty when assessing their expected performance, however, they could evaluate their performance afterwards. In clinical practice, the focus should be on reinforcing patients' expectations in order to increase treatment effects.

Disordered Selfhood in Schizophrenia and the Examination of Anomalous Self-Experience: Accumulated Evidence and Experience.

Disordered selfhood in schizophrenia was rediscovered at the turn of the millennium. In 2005, Psychopathology published the psychometric instrument, the Examination of Anomalous Self-Experience (EASE). In this article, we summarize the historical background of the creation of the EASE, explicate the notion of the disorder of basic or minimal self with the help of phenomenological philosophy, and provide a brief description of clinical manifestations targeted by the EASE. We also present our personal experience using and teaching the EASE and summarize the empirical evidence obtained so far. We conclude that the basic self-disorder represents a crucial phenotype of schizophrenia spectrum disorders and that this phenotype offers a potential avenue to empirical pathogenetic research and psychotherapeutic treatment.

[Differential diagnosis in obsessive-compulsive disorder].

Obsessive-compulsive-like symptomatology may be present in various psychiatric disorders including schizophrenia. This has been described since Kraepelin and Bleuler. In this review, we draw attention to the often ignored notion of pseudo-obsession. The concept can add to the distinction between true obsession in OCD and related psychopathological phenomena in the schizophrenia spectrum disorders and improve diagnostic practice. The recent changes in the diagnostic manuals have made this distinction more difficult by allowing a lack of insight and delusional beliefs in the diagnostic criteria for OCD.

'The schizophrenic basic mood (self-disorder)', by Hans W Gruhle (1929).

During the first half of the twentieth century, German psychiatry came to consider 'Ich-Störungen', best translated as self-disorders, to be important features of schizophrenia. The present text is a translation of a chapter by the German psychiatrist Hans Gruhle, which is extraordinarily clear and emblematic for this research line. Published in 1929, it was part of a book co-written with Josef Berze, The Psychology of Schizophrenia (concerning its subjectivity). Gruhle claims that the essential core of schizophrenia is of an affective nature, a 'mood' manifesting itself as self-disorder, an unstable, incomplete pre-reflective self-awareness. His impact on contemporary psychiatry was probably limited due to his confrontational style, but this text has great significance for the modern revival of phenomenological research in schizophrenia.

Genetics of Schizophrenia: Overview of Methods, Findings and Limitations.

Genetics constitute a crucial risk factor to schizophrenia. In the last decade, molecular genetic research has produced novel findings, infusing optimism about discovering the biological roots of schizophrenia. However, the complexity of the object of inquiry makes it almost impossible for non-specialists in genetics (e.g., many clinicians and researchers) to get a proper understanding and appreciation of the genetic findings and their limitations. This study aims at facilitating such an understanding by providing a brief overview of some of the central methods and findings in schizophrenia genetics, from its historical origins to its current status, and also by addressing some limitations and challenges that confront this field of research. In short, the genetic architecture of schizophrenia has proven to be highly complex, heterogeneous and polygenic. The disease risk is constituted by numerous common genetic variants of only very small individual effect and by rare, highly penetrant genetic variants of larger effects. In spite of recent advances in molecular genetics, our knowledge of the etiopathogenesis of schizophrenia and the genotype-environment interactions remain limited.

Self-Disorders: Clinical and Conceptual Implications for the Diagnostic Concept of Schizophrenia.

The release of DSM-5 and the preparations for the launch of the ICD-11 provoked a series of critiques of psychiatric classification, which continues to depend largely on clinical description. Among the immediate problems are those of arbitrary diagnostic thresholds, tendency to reification, rigid category boundaries, comorbidity, diagnostic 'epidemics' and differential diagnostic dilemmas. We argue that many of those problems stem from the polythetic-operational definitions of psychiatric categories, which thereby come to lack an organizing prototype-directed or gestaltic intelligibility principle. We illustrate these issues by briefly examining the current operational diagnosis of schizophrenia, its demarcation from affective illness and the status of the spectrum concept and the prodrome of schizophrenia. We point out that European research on schizophrenia always allocated an important diagnostic weight to a certain prototypical trait core of the illness, phenomenologically indispensable for its demarcation from other, nonschizophrenic psychotic conditions. We believe that the notion of self-disorder (reflective of the structural alterations of subjectivity), itemized into its various aspects in the Examination of Anomalous Self-Experience scale, is an important step forward in a more precise psychopathological articulation of that core, strengthening its clinical and research utility.

Exploring rationality in schizophrenia.

BACKGROUND: Empirical studies of rationality (syllogisms) in patients with schizophrenia have obtained different results. One study found that patients reason more logically if the syllogism is presented through an unusual content. AIMS: To explore syllogism-based rationality in schizophrenia. METHOD: Thirty-eight first-admitted patients with schizophrenia and 38 healthy controls solved 29 syllogisms that varied in presentation content (ordinary v. unusual) and validity (valid v. invalid). Statistical tests were made of unadjusted and adjusted group differences in models adjusting for intelligence and neuropsychological test performance. RESULTS: Controls outperformed patients on all syllogism types, but the difference between the two groups was only significant for valid syllogisms presented with unusual content. However, when adjusting for intelligence and neuropsychological test performance, all group differences became non-significant. CONCLUSIONS: When taking intelligence and neuropsychological performance into account, patients with schizophrenia and controls perform similarly on syllogism tests of rationality. DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: © The Royal College of Psychiatrists 2015. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

Alcohol and drug use, smoking, and gambling among psychiatric outpatients: a 1-year prevalence study.

BACKGROUND AND AIMS: Studies of alcohol habits in general psychiatric populations are scarce. The objective was to investigate alcohol and drug use, smoking, and gambling in a clinical sample of psychiatric outpatients. A further aim was to study age and gender differences in the rates of these habits. METHODS: Data were collected among psychiatric outpatients with mainly mood (47%) and anxiety (35%) disorders. A questionnaire package was distributed, including AUDIT (Alcohol Use Disorders Identification Test), DUDIT (Drug Use Disorders Identification Test), tobacco items, and gambling items. Two major drinking categories were formed: "Nonhazardous alcohol use" (NH) and "Alcohol use above hazardous levels" (AH). RESULTS: In total, 2160 patients (65% females) responded to the questionnaire package. The AH rate was high among psychiatric outpatients (28.4%), particularly among young females (46.6%). Young female patients also reported a high prevalence of problematic drug use (13.8%). Problematic drug use, daily smoking, and problematic gambling were frequent. The unhealthy habits were linked to AH. CONCLUSIONS: Alcohol and drug use, smoking, and gambling are all highly prevalent among psychiatric outpatients. Young females are in particular need of attention. Interventions should be tailored for co-occurring psychiatric disorders and applied within routine psychiatric care.

Brief alcohol intervention in a psychiatric outpatient setting: a randomized controlled study.

BACKGROUND: Although brief alcohol intervention (BI) is widely studied, studies from psychiatric outpatient settings are rare. The aim of this study was to investigate the effects of two variants of BI in psychiatric outpatients. By using clinical psychiatric staff to perform the interventions, we sought to collect information of the usefulness of BI in the clinical setting. METHODS: Psychiatric outpatients with Alcohol Use Disorders Identification Test (AUDIT) scores indicating hazardous or harmful drinking were invited to participate in the study. The outpatients were randomized to minimal (assessment, feedback, and an informational leaflet) or BI (personalized advice added). Measurements were performed at baseline and at six and 12 months after the intervention. The primary outcome was change in AUDIT score at the 12-month follow-up. RESULTS: In all, 150 patients were enrolled and received either a minimal intervention (n = 68) or BI (n = 82). At 12 months, there was a small reduction in AUDIT score in both groups, with no significant differences in outcome between groups. At 12-month follow-up, 21% of participants had improved from a hazardous AUDIT score level to a nonhazardous level, and 8% had improved from a harmful level to a hazardous level (8%). CONCLUSIONS: Brief alcohol interventions may result in a reduction of AUDIT score to a small extent in psychiatric patients with hazardous or harmful alcohol use. Results suggest that BI may be of some value in the psychiatric outpatient setting. Still, more profound forms of alcohol interventions with risky-drinking psychiatric patients need elaboration.

Brief alcohol screening in a clinical psychiatric population: special attention needed.

INTRODUCTION AND AIMS: Abbreviated versions of the Alcohol Use Disorders Identification Test (AUDIT) and single-item screeners show promising results but have not previously been investigated in a clinical psychiatric setting. The aim of the present study was to investigate the capacity of three brief screening methods to detect hazardous drinking in a psychiatric treatment-seeking population. DESIGN AND METHODS: Data were collected from consecutive patients (n = 1811) visiting a general psychiatric clinic. The screening capacity of the heavy episodic drinking (HED) screener, AUDIT item # 3 (AUDIT-3) and the three consumption items of AUDIT (AUDIT-C) was compared to the result of the full 10-item AUDIT with cut-off points 6 for women and 8 for men. RESULTS: The HED screener and AUDIT-3 with recommended cut-offs captured low rates of hazardous drinkers when compared to the full AUDIT. Lowering the cut-offs created rates far above those of the full AUDIT. AUDIT-C with recommended cut-off limits categorised nearly the same rates of men as the full AUDIT but much higher rates of women. Raising the cut-off for women approached the detection rate of AUDIT-C closely to that of the full AUDIT. DISCUSSION AND CONCLUSIONS: The findings of this study suggest that the HED screener is not sensitive enough in the clinical psychiatric setting. When designing alcohol screening measures to be used all over health-care organisations, special attention should be paid to psychiatric patients. If a somewhat more extensive screening tool is used, the full AUDIT is recommended.

Three hours of training improve psychiatric staff's self-perceived knowledge and attitudes toward problem-drinking patients.

INTRODUCTION AND AIMS: Staff attitudes are an important factor in the successful implementation of systematic alcohol strategies and policies. The forms and extent of training needed to improve therapeutic attitude among psychiatric staff to problem drinking are unclear. The aim of the investigation was to study the knowledge and attitudes of psychiatric staff toward problem-drinking patients. A further aim was to investigate whether a short 3 h training is sufficient to improve knowledge and therapeutic attitude toward problem drinking. DESIGN AND METHODS: A tailored training model for psychiatric staff (non-physicians) was carried out at a medium size university clinic. Participants were medical (nurses and psychiatric aides) and non-medical staff (psychologists and social workers). The training consisted of a 2 h workshop and a 1 h follow-up session. Knowledge and attitudes were measured at baseline and follow up by a questionnaire including vignettes assessment and the Short Alcohol and Alcohol Problems Perception Questionnaire. RESULTS: In total, 115 persons completed the questionnaire (follow-up rate 83.5%). The distribution was even (50% for the medical and 50% for the non-medical staff). After training, the non-medical staff estimated vignette case severity higher than before. Both staff groups estimated their capacity to help a patient with complex problems higher after training. Role adequacy was higher in both subgroups after training. Medical staff scored work satisfaction higher after the training. DISCUSSION AND CONCLUSIONS: Three hours of tailored training for psychiatric staff improve their knowledge and therapeutic attitude to problem-drinking patients.

Self-experience in the early phases of schizophrenia: 5-year follow-up of the Copenhagen Prodromal Study.

Despite the avalanche of empirical data on prodromal/"at risk" conditions, the essential aspects of the vulnerability to the schizophrenia spectrum remain largely unaddressed. We report here the results of the Copenhagen Schizophrenia Prodromal Study, a prospective, observational study of first admission patients in putative state of beginning psychosis (N=151) with a follow-up length of 60 months. At follow-up, the rate of conversion to schizophrenia spectrum diagnosis was 37%, whereas the conversion rate from schizotypal disorder to schizophrenia was 25%. High levels of perplexity and self-disorders baseline scores yielded the best prediction of the subsequent development of schizophrenia spectrum disorders. Escalating transitions within the spectrum (i.e., from schizotypal disorder to schizophrenia) were not associated to any candidate psychopathological predictor.

Allergen-induced accumulation of CD68-,CD123+ dendritic cells in the nasal mucosa.

BACKGROUND: Dendritic cells are antigen-presenting cells central to the immune system. They activate and orchestrate the innate and the adaptive immune systems. This phenotypically diverse group can be further divided into 2 subsets, the CD11c+ myeloid dendritic cells (mDCs) and the CD123+ plasmacytoid dendritic cells (pDCs). The aim of the study was to investigate the effect of allergen exposure on dendritic cells in subjects with allergic rhinitis. METHODS: Atopic and non-atopic subjects were challenged intranasally with birch or timothy allergen. Nasal biopsies were taken before and 24 h after challenge, and were, after CD68 exclusion, stained for expression of CD11c and CD123 to identify dendritic cell subsets. The effect of allergic mediators on CD68⁻,CD123+ cells was studied with flow cytometry analysis in peripheral blood. RESULTS: The amount of CD68⁻,CD123+ cells increased in the nasal sub-epithelium upon allergen challenge, whereas the number of CD68⁻,CD11c+ cells was unaffected. In vitro study of the effect of inflammatory mediators on pDC phenotype showed an increased activation in response TNF-α, IL-4 and CpG. Furthermore, TNF-α caused a higher activation among atopic than non-atopic subjects. CONCLUSIONS: An increased number of CD68⁻,CD123+ dendritic cells along with the positive pDC response following stimulation with inflammatory mediators suggest that the increased pDCs may be of an activated phenotype. It also suggests that the inflammatory response by pDCs to mediators such as TNF-α may be markedly higher in atopic subjects. These data support the notion of pDCs as important participants in allergic rhinitis.

Attenuation of beta and gamma oscillations in schizophrenia spectrum patients following hand posture perturbation.

Several electroencephalographic (EEG) studies in schizophrenia report that the patients have reduced evoked gamma activity following visual and auditory stimulation. Somatosensory gamma activity has not previously been examined. It has been suggested that a dysfunction basic to schizophrenia spectrum traits would involve proprioceptive information processing and this has recently been supported by the finding of diminished latency of early proprioceptive evoked potentials in a sample of chronic schizophrenia patients. The proprioceptive stimulus used previously, and presently, consisted of an abrupt increase of weight on a hand-held load. Eighteen first-time admitted schizophrenia spectrum patients and 18 healthy matched comparison subjects were included. Proprioceptive evoked potentials were recorded as 64-channels EEG for 120 trials in two runs differing in sequence. Contra-lateral evoked beta (latency 90 ms, frequency 21 Hz) and gamma (latency 70 ms, frequency 32 Hz) oscillations were attenuated in the patient group. The healthy comparison subjects had increased gamma amplitude in the left hemisphere in the regular sequence, a phenomenon not seen in the patients. The deviant findings were unexpectedly more circumscribed in the schizophrenia than in the schizotypal personality disorder (SPD) patients. Future studies should include several concurrent psychophysiological measures.

Support in housing: a comparison between people with psychiatric disabilities and people with intellectual disabilities.

The primary objective of this study was to compare type of housing and support in housing in two groups (people with psychiatric disabilities and people with intellectual disabilities) typically dependent on support in everyday life. A second objective was to examine whether type of housing and support in housing were related to gender within the two groups. Information was obtained by available questionnaire reports provided by staff members. The results indicate unequal accessibility of support in housing in relation to the two groups. Moreover, the findings suggest that type of disability is a more determining factor than gender regarding support in housing.

Exhaled breath condensate-site and mechanisms of formation.

Exhaled breath condensate (EBC) analysis is a promising tool for diagnosis and management of pulmonary diseases. Its clinical usefulness is still limited however due to unresolved issues around e.g. reproducibility, anatomical site of origin of EBC solutes and mechanisms of EBC formation. To gain some knowledge on these issues, three different airway deposition patterns of an aqueous aerosol containing technetium-99m were studied in eight healthy non-smoking subjects. EBC was collected 20 min after each radioaerosol administration and analyzed for gamma radiation and electrolytes. Radioaerosol deposition in preferentially central lung compared with preferentially peripheral lung resulted in 3.8 times higher EBC radioactivity. EBC concentrations of Na(+) and K(+) correlated significantly indicating dilution by water vapor to be a major source of variability. Since Na(+)/K(+)- and Na(+)/S(2-)-concentration ratios, but not Na(+)/Cl(-)- or Na(+)/Ca(2+)-, were comparable to those previously reported for alveolar lining fluid (ALF), some mechanisms other than dilution are likely also to be involved. In conclusion, our findings indicate that EBC derives mainly from the central airways, that the electrolyte composition of EBC does not consistently reflect that of ALF, and that EBC concentrations of electrolytes are determined not only by ALF dilution with water vapor but also by other mechanisms.

Premorbid IQ varies across different definitions of schizophrenia.

The nature of the association between IQ and schizophrenia is still unclear. So far no study addressed this issue in relation to the breadth or scope of the very concept of schizophrenia. We examined the premorbid IQ in a polydiagnostic study with four classifications of schizophrenia: ICD-8/9, ICD-10, St. Louis and Flexible System-Wide. Only the ICD-10 schizophrenia patients exhibited a significantly lower premorbid IQ. There were suggestive differences between the four examined systems as well as between the ICD-10 paranoid and non-paranoid subtypes. Exploration of crucial diagnostic features of schizophrenia in relation to IQ revealed associations between low premorbid IQ and hallucinations as well as negative symptoms. It is concluded that premorbid IQ varies across different definitions of schizophrenia.

Expression of Toll-like receptor 9 in nose, peripheral blood and bone marrow during symptomatic allergic rhinitis.

BACKGROUND: Allergic rhinitis is an inflammatory disease of the upper airway mucosa that also affects leukocytes in bone marrow and peripheral blood. Toll-like receptor 9 (TLR9) is a receptor for unmethylated CpG dinucleotides found in bacterial and viral DNA. The present study was designed to examine the expression of TLR9 in the nasal mucosa and in leukocytes derived from different cellular compartments during symptomatic allergic rhinitis. METHODS: The study was based on 32 patients with seasonal allergic rhinitis and 18 healthy subjects, serving as controls. Nasal biopsies were obtained before and after allergen challenge. Bone marrow, peripheral blood and nasal lavage fluid were sampled outside and during pollen season. The expression of TLR9 in tissues and cells was analyzed using immunohistochemistry and flow cytometry, respectively. RESULTS: TLR9 was found in several cell types in the nasal mucosa and in different leukocyte subpopulations derived from bone marrow, peripheral blood and nasal lavage fluid. The leukocyte expression was generally higher in bone marrow than in peripheral blood, and not affected by symptomatic allergic rhinitis. CONCLUSION: The widespread expression of TLR9 in the nasal mucosa along with its rich representation in leukocytes in different compartments, demonstrate the possibility for cells involved in allergic airway inflammation to directly interact with bacterial and viral DNA.