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.

'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.

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.

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.

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.

[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.

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.

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.

Competing definitions of schizophrenia: what can be learned from polydiagnostic studies?

The contemporary diagnoses of schizophrenia (sz)-Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition(DSM-IV) and International Classification of Diseases, 10th Revision(ICD-10)-are widely considered as important scientific achievements. However, these algorithms were not a product of explicit conceptual analyses and empirical studies but defined through consensus with the purpose of improving reliability. The validity status of current definitions and of their predecessors remains unclear. The so-called "polydiagnostic approach" applies different definitions of a disorder to the same patient sample in order to compare these definitions on potential validity indicators. We reviewed 92 polydiagnostic sz studies published since the early 1970s. Different sz definitions show a considerable variation concerning frequency, concordance, reliability, outcome, and other validity measures. The DSM-IV and the ICD-10 show moderate reliability but both definitions appear weak in terms of concurrent validity, eg, with respect to an aggregation of a priori important features. The first-rank symptoms of Schneider are not associated with family history of sz or with prediction of poor outcome. The introduction of long duration criteria and exclusion of affective syndromes tend to restrict the diagnosis to chronic stable patients. Patients fulfilling the majority of definitions (core sz patients) do not seem to constitute a strongly valid subgroup but rather a severely ill subgroup. Paradoxically, it seems that a century after the introduction of the sz concept, research is still badly needed, concerning conceptual and construct validity of sz, its essential psychopathological features, and phenotypic boundaries.

Traumatic impact of a fire disaster on survivors--a 25-year follow-up of the 1978 hotel fire in Borås, Sweden.

The objective of this study was to investigate the long-term psychological and mental health outcomes among survivors of a disastrous hotel fire. A 25-year follow-up investigation among adolescent and young adult survivors of a fire disaster was conducted in Borås, Sweden. A self-evaluation questionnaire and four self-rating scales - the IES-22, PTSS-10, GHQ-28 and SoC - were sent by mail to the participants. The results from the self-reported data showed low levels of psychiatric illness. Moreover, the respondents reported a low level of traumatic stress symptoms. More than 50% of the participants stated that the fire had a determining effect on their lives. Sixteen (21.3%) respondents indicated that the fire still had an impact on their daily lives. Differences between men and women were reported in most of the self-rating scales. The results indicate that a traumatizing experience (such as a fire disaster) still had a small effect on psychological health in a long-term perspective.

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.

Up-regulation of Toll-like receptors 2, 3 and 4 in allergic rhinitis.

BACKGROUND: Toll-like receptors enable the host to recognize a large number of pathogen-associated molecular patterns such as bacterial lipopolysaccharide, viral RNA, CpG-containing DNA and flagellin. Toll-like receptors have also been shown to play a pivotal role in both innate and adaptive immune responses. The role of Toll-like receptors as a primary part of our microbe defense system has been shown in several studies, but their possible function as mediators in allergy and asthma remains to be established. The present study was designed to examine the expression of Toll-like receptors 2, 3 and 4 in the nasal mucosa of patients with intermittent allergic rhinitis, focusing on changes induced by exposure to pollen. METHODS: 27 healthy controls and 42 patients with seasonal allergic rhinitis volunteered for the study. Nasal biopsies were obtained before and during pollen season as well as before and after allergen challenge. The seasonal material was used for mRNA quantification of Toll-like receptors 2, 3 and 4 with real-time polymerase chain reaction, whereas specimens achieved in conjunction with allergen challenge were used for immunohistochemical localization and quantification of corresponding proteins. RESULTS: mRNA and protein representing Toll-like receptors 2, 3 and 4 could be demonstrated in all specimens. An increase in protein expression for all three receptors could be seen following allergen challenge, whereas a significant increase of mRNA only could be obtained for Toll-like receptor 3 during pollen season. CONCLUSION: The up-regulation of Toll-like receptors 2, 3 and 4 in the nasal mucosa of patients with symptomatic allergic rhinitis supports the idea of a role for Toll-like receptors in allergic airway inflammation.

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.

Concentration-dependent effects of native and polymerised alpha1-antitrypsin on primary human monocytes, in vitro.

BACKGROUND: Alpha1-antitrypsin (AAT) is one of the major serine proteinase inhibitors controlling proteinases in many biological pathways. There is increasing evidence that AAT is able to exert other than antiproteolytic effects. To further examine this question we compared how various doses of the native (inhibitory) and the polymerised (non-inhibitory) molecular form of AAT affect pro-inflammatory responses in human monocytes, in vitro. Human monocytes isolated from different donors were exposed to the native or polymerised form of AAT at concentrations of 0.01, 0.02, 0.05, 0.1, 0.5 and 1 mg/ml for 18 h, and analysed to determine the release of cytokines and to detect the activity of NF-kappaB. RESULTS: We found that native and polymerised AAT at lower concentrations, such as 0.1 mg/ml, enhance expression of TNFalpha (10.9- and 4.8-fold, p < 0.001), IL-6 (22.8- and 23.4-fold, p < 0.001), IL-8 (2.4- and 5.5-fold, p < 0.001) and MCP-1 (8.3- and 7.7-fold, p < 0.001), respectively, compared to buffer exposed cells or cells treated with higher doses of AAT (0.5 and 1 mg/ml). In parallel to increased cytokine levels, low concentrations of either conformation of AAT (0.02-0.1 mg/ml) induced NF-kappaB p50 activation, while 1 mg/ml of either conformation of AAT suppressed the activity of NF-kappaB, compared to controls. CONCLUSIONS: The observations reported here provide further support for a central role of AAT in inflammation, both as a regulator of proteinase activity, and as a signalling molecule for the expression of pro-inflammatory molecules. This latter role is dependent on the concentration of AAT, rather than on its proteinase inhibitory activity.

Circulating monocytes from healthy individuals and COPD patients.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by incompletely reversible airflow obstruction associated with inflammation in which monocytes/macrophages are the predominant inflammatory cells. The only known genetic factor related to COPD is inherited PiZZ deficiency of alpha1-antitrypsin (AAT), an inhibitor of serine proteases. METHODS: We investigated the basal and LPS-stimulated release of pro-inflammatory molecules from blood monocytes isolated from age and gender matched healthy (n = 30) and COPD (n = 20) individuals with and without AAT deficiency. RESULTS: After 18 h of cell culture the basal release of MMP-9 was 2.5-fold, p < 0.02 greater, whereas IL-8 was 1.8-fold (p < 0.01) lower from COPD patient monocytes than from controls. LPS-stimulated release of IL-6 and MCP-1 was greater from COPD patient's monocytes relative to controls, while activation of control cells resulted in enhanced secretion of ICAM-1 and MMP-9 compared to COPD patients. Independent of disease status, monocytes from PiZZ AAT carriers released less TNFalpha (by 2.3-fold, p < 0.03). CONCLUSIONS: The basal and LPS-stimulated secretion of specific pro-inflammatory molecules from circulating monocytes differs between healthy and COPD subjects. These findings may be valuable for further studies on the mechanisms involved in recruitment and activation of inflammatory cells in COPD.

Clients with long-term mental disabilities in a Swedish county--conditions of life, needs of support and unmet needs of service provided by the public health and social service sectors.

OBJECTIVE: The purpose of the study was to identify and describe conditions of life and needs of support and public service for clients with a mental disability in a Swedish county population. METHODS: Public health care and social service providers identified clients and completed a questionnaire concerning the clients' conditions of life and their special needs. A consecutively recruited sample of clients completed a similar questionnaire. RESULTS: Totally, 1261 clients were identified. The prevalence of clients with mental disabilities was in the urban and rural areas, 6.4/1000 inhabitants and 4.5/1000 inhabitants, respectively. The most prevalent unmet need (42.9%) was to participate in social and scheduled activities. Almost half of the group was reported to need support in activities of daily living. Clients living in urban settings more often needed support with activities of daily living (P < 0.001), whereas clients living in rural settings more often needed support with job training (P < 0.001) or finding work (P < 0.01). Clients and psychiatric care providers reported the needs of the clients in the same areas; however, clients reported a fewer number of needs than did the care providers. CONCLUSIONS: By using both psychiatric care and social service providers, effective case findings of clients with a mental disability were possible to achieve. In general, there was high agreement between psychiatric care providers and clients regarding the clients' number of needs of support and their unmet needs of service. However, at the individual level, the agreement between client and psychiatric care providers was lower.