Dimensional approaches to schizophrenia: A comparison of the Bern Psychopathology scale and the five-factor model of the Positive and Negative Syndrome Scale

The aim was to examine to what extent the dimensions of the BPS map the five factors derived from the PANSS in order to explore the level of agreement of these alternative dimensional approaches in patients with schizophrenia. 149 inpatients with schizophrenia spectrum disorders were recruited. Psychopathological symptoms were assessed with the Bern Psychopathology Scale (BPS) and the Positive and Negative Syndrome Scale (PANSS). Linear regression analyses were conducted to explore the association between the factors and the items of the BPS. The robustness of patterns was evaluated. An understandable overlap of both approaches was found for positive and negative symptoms and excitement. The PANSS positive factor was associated with symptoms of the affect domain in terms of both inhibition and disinhibition, the PANSS negative factor with symptoms of all three domains of the BPS as an inhibition and the PANSS excitement factor with an inhibition of the affect domain and a disinhibition of the language and motor domains. The results show that here is only a partial overlap between the system-specific approach of the BPS and the five-factor PANSS model. A longitudinal assessment of psychopathological symptoms would therefore be of interest.

Subtyping schizophrenia: A comparison of positive/negative and system-specific approaches

BACKGROUND Schizophrenia is a heterogeneous disorder. Over the years, different approaches have been proposed to approach this heterogeneity by categorizing symptom patterns. The study aimed to compare positive/negative and system-specific approaches to subtyping. METHODS We used the Positive and Negative Syndrome Scale (PANSS) and Bern Psychopathology Scale (BPS), which consists of subscales for three domains (language, affect and motor behavior) that are hypothesized to be related to specific brain circuits, to assess cross-sectional psychopathological characteristics in a sample of 100 inpatients with schizophrenia spectrum disorders. We then categorized participants into positive/negative and system-specific subgroups to allow comparisons of the two approaches. RESULTS The analyses revealed correlations between the PANSS positive subscore and the BPS affective subscore (r=.446, p<.001) and between the PANSS negative subscore and the BPS motor behavior subscore (r=.227, p=.023). As regards the positive and negative subtype, more participants were classified as positive in the language-dominant subtype (30.3%) and affect-dominant subtype (30.3%), whereas more were classified as negative in the motor behavior-dominant subtype (44.4%). However, most patients met the criteria for the mixed subtype. CONCLUSIONS The results suggest that the positive/negative and system-specific approaches can be regarded as complementary. Future studies should examine both approaches in a longitudinal assessment of psychopathological symptoms and link them with qualitative-phenomenological approaches.

The well-being model: a new drug interaction model for positive and negative effects

BACKGROUND: Drugs are routinely combined in anesthesia and pain management to obtain an enhancement of the desired effects. However, a parallel enhancement of the undesired effects might take place as well, resulting in a limited therapeutic usefulness. Therefore, when addressing the question of optimal drug combinations, side effects must be taken into account. METHODS: By extension of a previously published interaction model, the authors propose a method to study drug interactions considering also their side effects. A general outcome parameter identified as patient's well-being is defined by superposition of positive and negative effects. Well-being response surfaces are computed and analyzed for varying drugs pharmacodynamics and interaction types. In particular, the existence of multiple maxima and of optimal drug combinations is investigated for the combination of two drugs. RESULTS: Both drug pharmacodynamics and interaction type affect the well-being surface and the deriving optimal combinations. The effect of the interaction parameters can be explained in terms of synergy and antagonism and remains unchanged for varying pharmacodynamics. For all simulations performed for the combination of two drugs, the presence of more than one maximum was never observed. CONCLUSIONS: The model is consistent with clinical knowledge and supports previously published experimental results on optimal drug combinations. This new framework improves understanding of the characteristics of drug combinations used in clinical practice and can be used in clinical research to identify optimal drug dosing.

Risks of non-accidental mortality by baseline CD4+ T-cell strata in hepatitis-C-positive and -negative individuals initiating highly active antiretroviral therapy

BACKGROUND: Patients coinfected with hepatitis C virus (HCV) and HIV experience higher mortality rates than patients infected with HIV alone. We designed a study to determine whether risks for later mortality are similar for HCV-positive and HCV-negative individuals when subjects are stratified on the basis of baseline CD4+ T-cell counts. METHODS: Antiretroviral-naive individuals, who initiated highly active antiretroviral therapy (HAART) between 1996 and 2002 were included in the study. HCV-positive and HCV-negative individuals were stratified separately by baseline CD4+ T-cell counts of 50 cell/microl increments. Cox-proportional hazards regression was used to model the effect of these strata with other variables on survival. RESULTS: CD4+ T-cell strata below 200 cells/microl, but not above, imparted an increased relative hazard (RH) of mortality for both HCV-positive and HCV-negative individuals. Among HCV-positive individuals, after adjustment for baseline age, HIV RNA levels, history of injection drug use and adherence to therapy, only CD4+ T-cell strata of <50 cells/microl (RH=4.60; 95% confidence interval [CI] 2.72-7.76) and 50-199 cells/microl (RH=2.49; 95% CI 1.63-3.81) were significantly associated with increased mortality when compared with those initiating therapy at cell counts >500 cells/microl. The same baseline CD4+ T-cell strata were found for HCV-negative individuals. CONCLUSION: In a within-groups analysis, the baseline CD4+ T-cell strata that are associated with increased RHs for mortality are the same for HCV-positive and HCV-negative individuals initiating HAART. However, a between-groups analysis reveals a higher absolute mortality risk for HCV-positive individuals.

Rapid tranquilization of severely agitated patients with schizophrenia spectrum disorders: a naturalistic, rater-blinded, randomized, controlled study with oral haloperidol, risperidone, and olanzapine

INTRODUCTION Agitation is a major problem in acute schizophrenia. Only a few studies have tested antipsychotic agents in severely agitated patients, mainly because of legal issues. Furthermore, most studies were limited to the first 24 hours. We aimed to investigate the efficacy of oral haloperidol, risperidone, and olanzapine in reducing psychotic agitation in severely agitated patients with schizophrenia or schizophreniform or schizoaffective disorder over 96 hours using a prospective, randomized, rater-blinded, controlled design within a naturalistic treatment regimen. METHODS In total, 43 severely agitated patients at acute care psychiatric units were enrolled. Participants were randomly assigned to receive either daily haloperidol 15 mg, olanzapine 20 mg, or risperidone 2 to 6 mg over 5 days. Positive and Negative Syndrome Scale psychotic agitation subscale score was the primary outcome variable. A mixed-model analysis was applied. RESULTS All drugs were effective for rapid tranquilization within 2 hours. Over 5 days, the course differed between agents (P < 0.001), but none was superior. Dropouts occurred only in the risperidone and olanzapine groups. Men responded better to treatment than did women during the initial 2 hours (P = 0.046) as well as over the 5-day course (P < 0.001). No difference between drug groups was observed regarding diazepam or biperiden use. CONCLUSIONS Oral haloperidol, risperidone, and olanzapine seem to be suitable for treating acute severe psychotic agitation in schizophrenia spectrum disorders. Response to oral antipsychotics demonstrated a gender effect with poorer outcome in women throughout the study.

White matter pathway organization of the reward system is related to positive and negative symptoms in schizophrenia

The reward systemin schizophrenia has been linked to the emergence of delusions on the one hand and to negative symptoms such as affective flattening on the other hand. Previous Diffusion Tensor Imaging (DTI) studies reported white matter microstructure alterations of regions related to the reward system. The present study aimed at extending these findings by specifically investigating connection pathways of the reward system in schizophrenia. Therefore, 24 patients with schizophrenia and 22 healthy controls matched for age and gender underwent DTI-scans. Using a probabilistic fiber tracking approachwe bilaterally extracted pathways connecting the ventral tegmental area (VTA) with the nucleus accumbens (NAcc), themedial and lateral orbitofrontal cortices (mOFC, lOFC), the dorsolateral prefrontal cortex (dlPFC) and the amygdala; as well as pathways connecting NAcc with mOFC, lOFC, dlPFC and amygdala resulting in a total of 18 connections. Probability indices forming part of a bundle of interest (PIBI) were compared between groups using independent t-tests. In 6 connection pathways PIBI-valueswere increased in schizophrenia. In 3 of these pathways the spatial extension of connection pathways was decreased. In schizophrenia patients, there was a negative correlation of PIBI-values and PANSS negative scores in the left VTA–amygdala and in the left NAcc–mOFC connection. A sum score of delusions and hallucinations correlated positively with PIBI-values of the left amygdala–NAcc connection. Structural organization of specific segments ofwhite matter pathways of the reward systemin schizophrenia may contribute to the emergence of delusions and negative symptoms in schizophrenia.

An overview of positive and negative effects of gender-fair language use

The basic principle of gender-fair language is symmetric linguistic treatment of women and men. Depending on the structure of the respective language, two principle strategies can be deployed to make a language gender-fair. In languages with few gender-differentiating forms, such as English, there is a tendency towards neutralization. Here, gender-unmarked forms such as police officer or chairperson are used to substitute the male-biased policeman or chairman. The second strategy, feminization, implies that feminine forms of human nouns are used more frequently and systematically to make female referents visible.Since the 1970s, gender-fair language has been suggested, if not prescribed, for both scientific and official texts and its positive effects are widely documented. The use of gender-fair language increases the cognitive availability of feminine exemplars. Also in an applied context women responding to job advertisements formulated in gender-fair language feel more motivated to apply for the position. However, "side effects" of gender-fair language have also been observed: For instance, women referred to with a gender-fair title (e.g. chairperson) were evaluated as lower in status than women referred to with a masculine generic (e.g. chairman). Similarily, social initiatives framed with the use of gender-fair language were evaluated less-favourably than initiatives using traditional language. This presentation presents the gender-fair language use in the framework of a social dilemma. In order to protect themselves (or initiatives they stand for) from being ascribed incompetence or a lower status, women may avoid feminine forms and thus contribute to the perpetuation of gender-unfair language, which may be detrimental for women in general. Raising awareness for this social concern, and framing it both in terms of group and individual interest can direct the discussion about gender-fair language into a broader perspective of gender equality.

Rapid tranquilization of severely agitated patients with schizophrenia spectrum disorders: a naturalistic, rater-blinded, randomized controlled study with oral haloperidol, risperidone, and olanzapine

Agitation is a major problem in acute schizophrenia. Still, only limited evidence exists on antipsychotic efficacy in severely agitated patients after the first 24 hours. We aimed to investigate the efficacy of oral haloperidol, risperidone, and olanzapine in reducing psychotic agitation in severely agitated patients with schizophrenia or schizophreniform or schizoaffective disorder over 96 hours using a prospective, randomized, rater-blinded, controlled design within a naturalistic treatment regimen. We enrolled 43 severely agitated patients at acute care psychiatric units. Participants were randomly assigned to receive either daily haloperidol 15 mg, olanzapine 20 mg, or risperidone 2 – 6 mg over 5 days. Positive and Negative Syndrome Scale psychotic agitation (PANSS-PAS) subscore was the primary outcome variable. A mixed model analyses was applied. All drugs were effective for rapid tranquillization within 2 hours. Over 5 days, the course differed between agents (p < 0.001) but none was superior. Dropouts occurred only in the risperidone and olanzapine groups. Men responded better to treatment than women during the initial 2 hours (p = 0.046) as well as over the 5 day course (p < 0.001). No difference between drug groups was observed regarding diazepam or biperiden use. Oral haloperidol, risperidone, and olanzapine seem to be suitable for treating acute severe psychotic agitation in schizophrenia spectrum disorders. We observed a gender effect with poorer outcome in women.

Static and dynamic characteristics of cerebral blood flow during the resting state in schizophrenia

Background: The cerebral network that is active during rest and is deactivated during goal-oriented activity is called the default mode network (DMN). It appears to be involved in self-referential mental activity. Atypical functional connectivity in the DMN has been observed in schizophrenia. One hypothesis suggests that pathologically increased DMN connectivity in schizophrenia is linked with a main symptom of psychosis, namely, misattribution of thoughts. Methods: A resting-state pseudocontinuous arterial spin labeling (ASL) study was conducted to measure absolute cerebral blood flow (CBF) in 34 schizophrenia patients and 27 healthy controls. Using independent component analysis (ICA), the DMN was extracted from ASL data. Mean CBF and DMN connectivity were compared between groups using a 2-sample t test. Results: Schizophrenia patients showed decreased mean CBF in the frontal and temporal regions (P < .001). ICA demonstrated significantly increased DMN connectivity in the precuneus (x/y/z = -16/-64/38) in patients than in controls (P < .001). CBF was not elevated in the respective regions. DMN connectivity in the precuneus was significantly correlated with the Positive and Negative Syndrome Scale scores (P < .01). Conclusions: In schizophrenia patients, the posterior hub-which is considered the strongest part of the DMN-showed increased DMN connectivity. We hypothesize that this increase hinders the deactivation of the DMN and, thus, the translation of cognitive processes from an internal to an external focus. This might explain symptoms related to defective self-monitoring, such as auditory verbal hallucinations or ego disturbances.