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Introduction Psychosocial functioning is a key factor determining prognosis, severity, impairment and quality of life in people who have a mental disorder. The mini-ICF-APP was developed to provide a standardised classification of functioning and disability. However, despite its gaining popularity little is known about its structure and performance. This paper examines the structure of the mini-ICF-APP using factor analysis techniques. Materials and methods In a clinical sample of 3178 patients, with psychiatric diagnoses from several ICD-10 categories, we analysed internal consistency, item inter-correlations and the factorial structure of the data, with reference to ICD-10 diagnostic categories; Neurocognitive Disorders; Alcohol Use Disorders; Substance Use Disorders; Schizophrenia and Psychotic Disorders; Bipolar Disorder; Major Depressive Disorder; Anxiety Disorders; Personality Disorders; and Neurodevelopmental Disorders. Results We found good internal consistency and item inter-correlations (Cronbach alpha = 0.92) for the mini-ICF-APP. We were able to identify pivotal domains (flexibility, assertiveness and intimate relationships), which demonstrate sub-threshold influences on other domains. The factor analysis yielded a one-factor model as ideal for the whole sample and for all diagnostic categories. For some diagnostic categories the data suggested a two or three-factor model, however, with poorer fit indices. Conclusions The factor structure of the mini-ICF-APP appears to modify according to the main diagnosis. However, a one-factor model demonstrates better fit regardless of diagnostic category. Consequently, we consider the mini-ICF-APP to be a trans-diagnostic measurement instrument for the assessment and grading of psychosocial functioning. The use of the mini-ICF-APP sum score seems to best reflect the degree of impairment in an individual, even taking into account that affected domains may lead to sub-threshold effects on other domains.

BackgroundThe assessment of functioning and impairment due to psychiatric illness has been acknowledged to be crucial for research and practice. This led to the development of the mini-ICF-APP, which provides a reliable and time-efficient measure of functioning and impairment. Although its use is increasing, it remains unclear how it reflects severity and how change might be interpreted from a clinical perspective.MethodsIn a clinical sample of 3067 individuals hospitalized for mental health treatment, we used an equipercentile approach to link the mini-ICF-APP with the Clinical Global Impression scale (CGI) at admission and discharge. We linked the mini-ICF-APP sum score to the CGI-S scale and the mini-ICF-APP proportional change between admission and discharge to the CGI-I scale.ResultsThe mini-ICF-APP and CGI scales showed a Spearman correlation of 0.50 (p p > .000); “no-change” in the CGI-I corresponded to an increase or decrease of 2%; “minimally-improved” to a mini-ICF-APP reduction of 3–30%; “much-improved” to a reduction of 31–63%; “very-much-improved” to a reduction of ≥64% “minimally-worse” to an increase of 3–34% “much-worse” to an increase of 35–67%; and finally “very-much-worse” with an increase of ≥68%.ConclusionsOur findings improve understanding of the clinical meaning of the mini-ICF-APP sum score and percentage change in patients hospitalized for treatment.

Rationale, aims and objectives The aim of this study was to examine the validity of the Health of the Nation Outcome Scales (HoNOS) in terms of change in relation to sex, clinical characteristics and level of clinical change as assessed using other measures. Methods The sample consisted of N = 690 admissions from one Swiss psychiatric hospital who were assessed at admission and discharge using the HoNOS and the clinical global impression (CGI) scale. Repeated measures analyses of variance were conducted to compare changes in HoNOS scores over time stratified by sex, diagnostic category and CGI level of change, controlled for age and previous hospitalizations. Two-way interactions between time and these factors were calculated and post hoc t-tests were conducted to compare changes in HoNOS scores between admission and discharge at factor levels. Results HoNOS scores significantly decreased from admission to discharge in bivariate analyses although no main effect of time was found in multivariate models. Sex was found to moderate change in HoNOS behavioural subscale scores; primary diagnosis at admission moderated change in HoNOS total scores, the behavioural subscale and the social subscale; and CGI level of change moderated the change in all HoNOS scales. Conclusions Our findings confirmed the sensitivity to change of the HoNOS in psychiatric settings from admission to discharge. Furthermore, we found that this change reflected similar changes in the CGI, a well-established measure for the evaluation of clinical outcomes, which, in turn supports the validity of the HoNOS.

Nachdem in den Neurowissenschaften die Untersuchung der neuronalen Grundlagen emotionaler Prozesse lange Zeit vernachlässigt wurde, setzte mit dem Aufkommen neuer Methoden der funktionellen Bildgebung ein zunehmendes Interesse an der neuronalen Repräsentation emotionaler Prozesse ein. Gemäss neueren Forschungsergebnissen werden emotionale Prozesse durch überlappende neuronale Netzwerke prozessiert, wobei der Interaktion des limbisches Systems mit heteromodalen Assoziationskortices eine hohe Relevanz für die Verarbeitung emotionaler Informationen zukommt.

Present neuroimaging findings suggest two subtypes of trauma response, one characterized predominantly by hyperarousal and intrusions, and the other primarily by dissociative symptoms. The neural underpinnings of these two subtypes need to be better defined. Fourteen women with childhood abuse and the current diagnosis of dissociative amnesia or dissociative identity disorder but without posttraumatic stress disorder (PTSD) and 14 matched healthy comparison subjects underwent functional magnetic resonance imaging (fMRI) while finding their way in a virtual maze. The virtual maze presented a first-person view (egocentric), lacked any topographical landmarks and could be learned only by using egocentric navigation strategies. Participants with dissociative disorders (DD) were not impaired in learning the virtual maze when compared with controls, and showed a similar, although weaker, pattern of activity changes during egocentric learning when compared with controls. Stronger dissociative disorder severity of participants with DD was related to better virtual maze performance, and to stronger activity increase within the cingulate gyrus and the precuneus. Our results add to the present knowledge of preserved attentional and visuospatial mnemonic functioning in individuals with DD.

Background: Schizophrenia is a severe mental disorder that is characterized by symptomatic severity but also by high levels of functional impairment. An evaluation of clinical outcome in treatment of schizophrenia should therefore target not only assessing symptom change but also alterations in functioning. This study aimed to investigate whether there is an agreement between functional and symptom-based outcomes in a clinical sample of admissions with chronic forms of schizophrenia. Methods: A full 3-year cohort of consecutive inpatient admissions for schizophrenia (N=205) was clinically rated with the Positive And Negative Symptom Scale (PANSS) and the Health of the Nation Outcome Scales (HoNOS) as measures of functioning at the time of admission and discharge. The sample was stratified twofold: First, according to the degree of PANSS symptom improvement during treatment with the sample being divided into three treatment response groups: Non-response (NR), low-response (LR) and high-response (HR). Second, achievement of remission was defined using the Remission in Schizophrenia Working Group criteria (RSWGcr) based on selected PANSS symptoms. Repeated measures analyses were used to compare the change of HoNOS-scores over time across groups. Results: More than a half of all admissions achieved a symptom reduction of at least 20% during treatment and around one quarter achieved remission at discharge. Similarly, HoNOS-scores improved significantly between admission and discharge. Interaction analyses indicated higher functional improvements to be associated with increasing levels of treatment response. Conclusion: Functional improvement in individuals treated for schizophrenia was linked to a better clinical outcome, which implies a functional association. Thus, improvement of functioning represents an important therapeutic target in the treatment of schizophrenia.

Recent research indicates that longstanding temporal lobe epilepsy (TLE) is associated with extratemporal, i.e. parietal cortex damage. We investigated egocentric and allocentric memory by use of first-person large-scale virtual reality environments in patients with TLE. We expected that TLE patients with parietal cortex damage were impaired in the egocentric memory task. Twenty-two TLE patients with hippocampal sclerosis (HS) and 22 TLE patients without HS were compared with 42 healthy matched controls on two virtual reality tasks affording to learn a virtual park (allocentric memory) and a virtual maze (egocentric memory). Participants further received a neuropsychological investigation and MRI volumetry at the time of the assessment. When compared with controls, TLE patients with HS had significantly reduced size of the ipsilateral and contralateral somatosensory cortex (postcentral gyrus). When compared with controls or TLE patients without HS, TLE patients with HS were severely impaired learning the virtual maze. Considering all participants, smaller volumes of the left-sided postcentral gyrus were related to worse performance on the virtual maze. It is concluded that the paradigm of egocentric navigation and learning in first-person large-scale virtual environments may be a suitable tool to indicate significant extratemporal damage in individuals with TLE.

Psychotic symptoms in schizophrenia are related to disturbed self-recognition and to disturbed experience of agency. Possibly, these impairments contribute to first-person large-scale egocentric learning deficits. Sixteen inpatients with schizophrenia and 16 matched healthy comparison subjects underwent functional magnetic resonance imaging (fMRI) while finding their way in a virtual maze. The virtual maze presented a first-person view, lacked any topographical landmarks and afforded egocentric navigation strategies. The participants with schizophrenia showed impaired performance in the virtual maze when compared with controls, and showed a similar but weaker pattern of activity changes during egocentric learning when compared with controls. Especially the activity of task-relevant brain regions (precuneus and posterior cingulate and retrosplenial cortex) differed from that of controls across all trials of the task. Activity increase within the right-sided precuneus was related to worse virtual maze performance and to stronger positive symptoms in participants with schizophrenia. We suggest that psychotic symptoms in schizophrenia are related to aberrant neural activity within the precuneus. Possibly, first-person large-scale egocentric navigation and learning designs may be a feasible tool for the assessment and treatment of cognitive deficits related to self-recognition in patients with schizophrenia., Highlights ► Schizophrenia has been related to disturbed self-recognition and experience of agency. ► Schizophrenia patients show relative hypoactivation during egocentric maze learning. ► Positive symptoms are related to aberrant precuneus activity. ► Positive symptoms are related to impaired egocentric maze learning. ► Egocentric learning deficits may be indicative of disturbed experience of agency.

Present evidence suggests that medial temporal cortices subserve allocentric representation and memory, whereas egocentric representation and memory also depends on parietal association cortices and the striatum. Virtual reality environments have a major advantage for the assessment of spatial navigation and memory formation, as computer-simulated first-person environments can simulate navigation in a large-scale space. Twenty-nine patients with amnestic MCI (aMCI) were compared with 29 healthy matched controls on two virtual reality tasks affording to learn a virtual park (allocentric memory) and a virtual maze (egocentric memory). Participants further received a neuropsychological investigation and MRI volumetry at the time of the assessment. Results indicate that aMCI patients had significantly reduced size of the hippocampus bilaterally and the right-sided precuneus and inferior parietal cortex. aMCI patients were severely impaired learning the virtual park and the virtual maze. Smaller volumes of the right-sided precuneus were related to worse performance on the virtual maze. Participants with striatal lacunar lesions committed more errors than participants without such lesions on the virtual maze but not on the virtual park. aMCI patients later converting to dementia (n=15) had significantly smaller hippocampal size when compared with non-converters (n=14). However, both groups did not differ on virtual reality task performance. Our study clearly demonstrates the feasibility of virtual reality technology to study spatial memory deficits of persons with aMCI. Future studies should try to design spatial virtual reality tasks being specific enough to predict conversion from MCI to dementia and conversion from normal to MCI.

Background Present evidence suggests that the hippocampus (HC) and the parahippocampal cortex (PHC) are involved in allocentric (world-centered) spatial memory. However, the putative role of the PHC in egocentric (body-centered) spatial learning has received only limited systematic investigation. Methods To examine the role of the PHC in egocentric learning, 19 healthy volunteers learned to find their way in a virtual maze during functional magnetic resonance imaging (fMRI). The virtual maze presented a first-person view, lacked any topographical landmarks and could be learned only using egocentric navigation strategies. Results During learning, increased medial temporal lobe activity was observed in the PHC bilaterally. Activity was also observed in cortical areas known to project to the PHC and proposed to contribute to egocentric spatial navigation and memory. Conclusions Our results point to a role of the PHC for the representation and storage of egocentric information. It seems possible that the PHC contributes to egocentric memory by its feedback projections to the posterior parietal cortex. Moreover, access to allocentric and egocentric streams of spatial information may enable the PHC to construct a global and comprehensive representation of spatial environments and to promote the construction of stable cognitive maps by translating between egocentric and allocentric frames of memory.

This paper presents the Social Phobia Psychotherapy Research Network (SOPHO-NET). SOPHO-NET is among the five research networks on psychotherapy funded by "Bundesministerium fur Bildung und Forschung". The research program encompasses a coordinated group of studies of social phobia. In the central project (Study A), a multi-center randomized controlled trial, refined models of manualized cognitive-behavioral therapy (CBT) and manualized short-term psychodynamic psychotherapy (STPP) are compared in the treatment of social phobia. A sample of n=512 outpatients will be randomized to either CBT, STPP or wait list. For quality assurance and treatment integrity, a specific project has been established (Project Q). Study A is complemented by four interrelated projects focusing on attachment style (Study B1), cost-effectiveness (Study B2), polymorphisms in the serotonin transporter gene (Study C1) and on structural and functional deviations of hippocampus and amygdala (Study C2). Thus, the SOPHO-NET program allows for a highly interdisciplinary research of psychotherapy in social phobia.

This paper presents the Social Phobia Psychotherapy Research Network. The research program encompasses a coordinated group of studies adopting a standard protocol and an agreed-on set of standardized measures for the assessment and treatment of social phobia (SP). In the central project (study A), a multicenter randomized controlled trial, refined models of manualized cognitive-behavioral therapy and manualized short-term psychodynamic psychotherapy are compared in the treatment of SP. A sample of 512 outpatients will be randomized to either cognitive-behavioral therapy, short-term psychodynamic psychotherapy or waiting list. Assessments will be made at baseline, at the end of treatment and 6 and 12 months after the end of treatment. For quality assurance and treatment integrity, a specific project using highly elaborated measures has been established (project Q). Study A is complemented by 4 interrelated add-on projects focusing on attachment style (study B1), on cost-effectiveness (study B2), on variation in the serotonin transporter gene in SP (study C1) and on structural and functional deviations of the hippocampus and amygdala (study C2). Thus, the Social Phobia Psychotherapy Research Network program enables a highly interdisciplinary research into SP. The unique sample size achieved by the multicenter approach allows for studies of subgroups (e.g. comorbid disorders, isolated vs. generalized SP), of responders and nonresponders of each treatment approach, for generalization of results and for a sufficient power to detect differences between treatments. Psychological and biological parameters will be related to treatment outcome, and variables for differential treatment indication will be gained. Thus, the results provided by the network may have an important impact on the treatment of SP and on the development of treatment guidelines for SP.

Present evidence suggests that schizophrenia is associated with explicit memory deficits, whereas implicit memory seems to be largely preserved. Virtual reality studies on declarative allocentric memory in schizophrenia are rare, and studies on implicit egocentric memory in schizophrenia are lacking. However, virtual realities have a major advantage for the assessment of spatial navigation and memory formation, as computer-simulated first-person environments can simulate navigation in a large-scale space. Twenty-five subjects with recent-onset schizophrenia were compared with 25 healthy matched control subjects on two virtual reality tasks affording the navigation and learning of a virtual park (allocentric memory) and a virtual maze (egocentric memory). Compared with control subjects, schizophrenia subjects were significantly impaired in learning the virtual park. However, schizophrenia subjects were as able as control subjects to learn the virtual maze. Stronger disorganized symptoms of schizophrenia subjects were significantly related to more errors on the virtual maze. It is concluded that egocentric spatial learning adds to the many other implicit cognitive skills being largely preserved in schizophrenia. Possibly, the more global neural network supporting egocentric spatial learning is less affected than the declarative hippocampal memory system in early stages of schizophrenia and may offer opportunities for compensation in the presence of focal deficits.

As the amygdala is involved in various aspects of emotional processing, its characterization using neuroimaging modalities, such as functional magnetic resonance imaging (fMRI), is of great interest. However, in fMRI, the amygdala region suffers from susceptibility artifacts that are composed of signal dropouts and image distortions. Various technically demanding approaches to reduce these artifacts have been proposed, and most require alterations beyond a mere change of the acquisition parameters and cannot be easily implemented by the user without changing the MR sequence code. In the present study, we therefore evaluated the impact of simple alterations of the acquisition parameters of a standard gradient-echo echo-planar imaging technique at 3 T composed of echo times (TEs) of 27 and 36 ms as well as section thicknesses of 2 and 4 mm while retaining a section orientation parallel to the intercommissural plane and an in-plane resolution of 2x2 mm(2). In contrast to previous studies, we based our evaluation on the resulting activation maps using an emotional stimulation paradigm rather than on MR raw image quality only. Furthermore, we tested the effects of spatial smoothing of the functional raw data in the course of postprocessing using spatial filters of 4 and 8 mm. Regarding MR raw image quality, a TE of 27 ms and 2-mm sections resulted in the least susceptibility artifacts in the anteromedial aspect of the temporal lobe. The emotional stimulation paradigm resulted in robust bilateral amygdala activation for the approaches with 2-mm sections only -- but with larger activation volumes for a TE of 36 ms as compared with that of 27 ms. Moderate smoothing with a 4-mm spatial filter represented a good compromise between increased sensitivity and preserved specificity. In summary, we showed that rather than applying advanced modifications of the MR sequence, a simple increase in spatial resolution (i.e., the reduction of section thickness) is sufficient to improve the detectability of amygdala activation.

Blood-based tests for the differential diagnosis of Alzheimer’s disease (AD) are under intensive investigation and have shown promising results with regard to Aβ40 and Aβ42 peptide species in incipient AD. Moreover, plasma Aβ40 was suggested as an independent cerebrovascular risk factor candidate. These considerations prompted us to analyse a total of 72 plasma samples in vascular dementias (VAD, n = 15), AD with cerebrovascular disease (AD with CVD, n = 7), AD (n = 15), Parkinson’s disease and Parkinson’s disease dementia (PD/PDD, n = 20) and 15 patients with depression that served as controls (DC) for distinct plasma amyloid-beta (Aβ) peptide patterns. For the analysis of plasma we used immunoprecipitation followed by the quantitative Aβ-SDS-PAGE/immunoblot. For comparison, CSF tau and Aβ1–42 analyses were performed. The major outcome was an increase in Aβ1–40 in plasma of VAD paralleled by a decrease in the ratio of Aβ1–38/Aβ1–40. The ratio Aβ1–38/Aβ1–40 in plasma enabled contrasts of beyond 85% and 80% for discriminating VAD from DC and all other patients, respectively. In CSF, we confirmed the typical CSF biomarker constellation of increased tau and diminished Aβ1–42 levels for AD. The diagnostic accuracy of plasma Aβ1–38/Aβ1–40 for VAD resembled the accuracy of CSF biomarkers for AD. From the presented results, we consider the ratio of plasma Aβ1–38/Aβ1–40 peptides to be a blood-based biomarker candidate for VAD.

Functional imaging studies have shown that the posterior parahippocampal gyrus (PHG) is involved in allocentric (world-centered) object and scene recognition. However, the putative role of the posterior PHG in egocentric (body-centered) spatial memory has received only limited systematic investigation. Thirty-one subjects with pharmacoresistant medial temporal lobe epilepsy (TLE) and temporal lobe removal were compared with 19 matched healthy control subjects on a virtual reality task affording the navigation in a virtual maze (egocentric memory). Lesions of the hippocampus and PHG of TLE subjects were determined by three-dimensional magnetic resonance imaging volumetric assessment. The results indicate that TLE subjects with right-sided posterior PHG lesions were impaired on virtual maze acquisition when compared with controls and TLE subjects with anterior PHG lesions. Larger posterior PHG lesions were significantly related to stronger impairments in virtual maze performance. Our results point to a role of the right-sided posterior PHG for the representation and storage of egocentric information. Moreover, access to both allocentric and egocentric streams of spatial information may enable the posterior PHG to construct a global and comprehensive representation of spatial environments.

Increasing evidence suggests that schizophrenia is associated with various morphological and functional abnormalities of the frontal cortex. So far research has concentrated on the dorsolateral and orbitofrontal cortex. Behavioral evidence suggests however that regions responsible for higher motor control are compromised in schizophrenia as well. The current study assessed volumes of the anterior supplementary motor area (pre-SMA) and implicit motor sequence learning in 15 subjects with first-episode schizophrenia and 15 healthy matched controls. Pre-SMA volumes were assessed by three-dimensional structural magnetic resonance imaging (3D-MRI) and manual parcellation according to an established protocol. Implicit motor sequence learning was assessed using the Serial Reaction-Time Task (SRTT). Compared with control subjects, schizophrenia subjects had significantly smaller volumes of the left pre-SMA (16%). Subjects with schizophrenia were severely impaired on sequence-specific implicit motor learning. Size of the left pre-SMA of schizophrenia subjects was significantly related to impaired implicit learning. We conclude that subjects with first-episode schizophrenia have a morphological abnormality of the left pre-SMA that might predispose them to develop disturbances of higher motor control during acute episodes of psychosis. These structural and behavioral abnormalities might be conceptualized within a broader model that views schizophrenia as a disorder of disturbed coordination of thought and action.

The authors sought to clarify whether lesions in different parts of the cerebellum result in differential cognitive and affective impairment. Six subjects with cerebellar lesions due to posterior inferior cerebellar artery (PICA) infarction, five subjects with lesions in the SCA vascular territory, and 11 matched controls were administered a battery of standard neuropsychological tests. PICA lesions but not SCA lesions resulted in cognitive and affective deficits pointing to a dominant role of posterior cerebellar regions in cognitive and affective processing.

Individuals with schizophrenia have difficulties in emotional information processing. A relationship between behavioral variables of emotional processing and structural amygdala alterations in schizophrenia has been proposed but not shown, yet. Morphological studies of amygdala size in schizophrenia have yielded inconsistent results. The current study assessed paired associates learning of emotional and neutral faces in 16 subjects with schizophrenia during acute episode and in relative remission after 3 months. Sixteen matched controls were studied for comparison. Subjects also underwent structural magnetic resonance imaging (3D-MRI) at the first time of assessment. Subjects with schizophrenia showed a significant decrease (by 13%) in total size of the amygdala compared to controls, which was more pronounced on the right side. Subjects with schizophrenia improved associative learning of facial identities but not of emotional facial expressions after relative remission of psychotic symptoms. Volume of the right amygdala in subjects with schizophrenia and in controls was significantly related to emotional learning, indicating better learning in subjects with larger amygdala size. Our results indicate that subjects with schizophrenia have a deficit to form associations when emotionally loaded material is used. This deficit seems to be trait-like and independent of disease state. It seems to be linked to size reduction of the right amygdala in schizophrenia.

The goal of this study was to assess facial affect recognition abilities in subjects with various schizophrenia subtypes and subjects with major depression. A total of six disorganized, 21 paranoid and 18 residual subjects with schizophrenia (DSM-IV criteria) were compared with 21 subjects with major depression (DSM-IV criteria) and 30 matched healthy control subjects. Two experimental tasks requiring the sorting and rating of emotional facial expressions were applied. Disorganized and paranoid subjects showed strong impairments in the sorting of emotional facial expressions. Depressive subjects displayed only minor deficits, and residual subjects were unimpaired. Subjects with disorganized schizophrenia rated emotional facial expressions as more aroused, and depressive subjects rated them as less aroused, than the other study groups. Our study demonstrates strong deficits in facial affect recognition in subjects with schizophrenia and pronounced disorganized or psychotic symptoms. Deficits in facial affect recognition are specific to schizophrenia. They may be considered as a state marker of schizophrenia.

Background. The symptom domain of inattention in attention deficit/hyperactivity disorder (ADHD) suggests that there are neuropsychological fields of attention in which subjects with ADHD express deficits. However, studies using differentiated neuropsychological attentional tests in ADHD are lacking.Method. A consecutive series of 35 subjects with ADHD aged 9–12 years were assessed on a computer-driven neuropsychological test battery for attentional functions. Their performance was classified according to the data of a normative sample of 187 healthy subjects aged 9–12 years, and compared with the performance of 35 matched healthy control subjects.Results. According to normative data, most ADHD subjects performed on all attentional measures within the normal range. Comparisons with the control group revealed that ADHD subjects reacted faster on all attentional tests, yielding statistical significance for the Go/No go test and the Divided Attention test. They also performed with significantly fewer errors on the Divided Attention test. On the Go/No go test, Visual Scanning test and Attentional Shift test ADHD subjects committed significantly more errors than control subjects.Conclusions. Our results suggest a differential pattern rather than a deficit pattern of attentional functions in ADHD. It is suggested that the more rapid response style of ADHD subjects leads to a more erroneous performance in self-paced attentional tasks and to a better performance in externally paced attentional tasks. However, neuropsychological tests of attention do not contribute to the clinical diagnosis of ADHD.

The aim of this study was to examine the performance of the Health of the Nation Outcome Scales (HoNOS) against other measures of functioning and mental health in a full three-year cohort of admissions to a psychiatric hospital. A sample of N=1719 patients (35.3% females, aged 17-78 years) was assessed using observer-rated measures and self-reports of psychopathology at admission. Self-reports were available from 51.7% of the sample (34.4% females, aged 17-76 years). Functioning and psychopathology were compared across five ICD-10 diagnostic groups: substance use disorders, schizophrenia and psychotic disorders, affective disorders, anxiety/somatoform disorders and personality disorders. Associations between the measures were examined, stratifying by diagnostic subgroup. The HoNOS were strongly linked to other measures primarily in psychotic disorders (except for the behavioral subscale), while those with substance use disorders showed rather poor links. Those with anxiety/somatoform disorders showed null or only small associations. This study raises questions about the overall validity of the HoNOS. It seems to entail different levels of validity when applied to different diagnostic groups. In clinical practice the HoNOS should not be used as a stand-alone instrument to assess outcome but rather as part of a more comprehensive battery including diagnosis-specific measures.

The aim of this study was to examine the validity of the Health of the Nation Outcome Scales (HoNOS) in terms of change in relation to sex, clinical characteristics and level of clinical change as assessed using other measures.The sample consisted of N = 690 admissions from one Swiss psychiatric hospital who were assessed at admission and discharge using the HoNOS and the clinical global impression (CGI) scale. Repeated measures analyses of variance were conducted to compare changes in HoNOS scores over time stratified by sex, diagnostic category and CGI level of change, controlled for age and previous hospitalizations. Two-way interactions between time and these factors were calculated and post hoc t-tests were conducted to compare changes in HoNOS scores between admission and discharge at factor levels.HoNOS scores significantly decreased from admission to discharge in bivariate analyses although no main effect of time was found in multivariate models. Sex was found to moderate change in HoNOS behavioural subscale scores; primary diagnosis at admission moderated change in HoNOS total scores, the behavioural subscale and the social subscale; and CGI level of change moderated the change in all HoNOS scales.Our findings confirmed the sensitivity to change of the HoNOS in psychiatric settings from admission to discharge. Furthermore, we found that this change reflected similar changes in the CGI, a well-established measure for the evaluation of clinical outcomes, which, in turn supports the validity of the HoNOS.

To investigate the role of unilateral amygdala lesions on processing emotions, 22 drug-resistant temporal lobe epilepsy (TLE) subjects (12 with left-sided and ten with right-sided focus) were tested, after anterior temporal lobectomy or selective amygdalo-hippocampectomy on two associative learning tasks containing emotional and neutral facial expressions, respectively. Volumetric lesion analysis was performed on the basis of 3-D MR images. No effects of lesion side were found in TLE subjects. Taken the extent of amygdala damage into account, an interaction effect could be shown between task (learning of neutral facial expressions versus emotional facial expressions) and group (subjects with little versus considerable amygdala damage), indicating worse performance of subjects with considerable amygdala damage in learning emotional facial expressions. Subjects with considerable amygdala damage were also significantly impaired in learning emotional facial expressions when compared with control subjects.

The authors sought to determine the long-term outcome of subjects with severe and refractory obsessive-compulsive disorder (OCD) who had undergone ventromedial frontal leukotomy during the 1970s. Special emphasis was given to the analysis of specific lesion sites.Sixteen OCD subjects who had undergone ventromedial frontal leukotomy were evaluated clinically and neuropsychologically and compared to seven well comparison OCD subjects without leukotomy. The 16 leukotomized subjects were divided into three groups according to the main lesion sites as determined by current magnetic resonance imaging scans.The leukotomized OCD subjects showed significant improvement of obsessive-compulsive symptoms; subjects with frontostriatal lesions tended to have improved most. The subjects with combined diagnoses of OCD and obsessive personality disorder (N = 3) had improved significantly less. Of 11 subjects with lesions of the ventral striatum, eight had developed substance dependence postoperatively. Intellectual functions were largely preserved in subjects with ventromedial frontal lesions only or frontostriatal lesions. However, all subjects showed subnormal performance on the Wisconsin Card Sorting Test. Subjects with lesions of the dorsolateral frontal convexity also showed memory problems, attentional slowing, and lower performance IQ.Restricted ventromedial frontal leukotomy should be discussed as a last-resort treatment for severe and refractory OCD but not obsessive personality disorder. Lesions of the ventral striatum were significantly related to the occurrence of substance dependence, suggesting a role of this area in human addictive behavior.

The investigation of emotional processes has been neglected for a long time. But with the appearance of new imaging methods, a growing interest in the neural representation of emotional processes emerged. According to recent findings, emotional information were proceed by overlapping neural networks, especially the interaction between the limbic system and heteromodal association cortices.Nachdem in den Neurowissenschaften die Untersuchung der neuronalen Grundlagen emotionaler Prozesse lange Zeit vernachlässigt wurde, setzte mit dem Aufkommen neuer Methoden der funktionellen Bildgebung ein zunehmendes Interesse an der neuronalen Repräsentation emotionaler Prozesse ein. Gemäss neueren Forschungsergebnissen werden emotionale Prozesse durch überlappende neuronale Netzwerke prozessiert, wobei der Interaktion des limbisches Systems mit heteromodalen Assoziationskortices eine hohe Relevanz für die Verarbeitung emotionaler Informationen zukommt.L'investigation des processus émotionnels a été négligée pendant longtemps. Avec la disponibilité des nouvelles méthodes d'imagerie, cependant, la représentation neuronale des processus émotionnels a émergé. Selon les données récentes, ces processus impliquent l'interaction de réseaux, le système limbique jouant le rôle d'unité centrale. Les malades souffrant de troubles psychiatriques ont souvent des symptômes affectifs qui sont corrélés avec des anomalies de l'interaction entre les aires limbiques et hétéromodales.

A 35-year-old right-handed woman (CK) showed deficits in sorting and rating emotional facial expressions and experienced temporary emotional hyperarousal with panic attacks during a T2-signal enhancement of the reglon of the right amygdala. In a sorting task CK was able to match positive, but not negative, basic emotions. Furthermore CK rated most facial emotions as unpleasant and unaroused. In the further course, the neuroradiologically demonstrated lesion dlsappeared, as well as the Impaired Identification and judgement of emotional faclal expressions. The results suggest that a lesion of the right amygdala is sufficient to disturb the processing of emotional facial expressions.

A 51-year-old male patient (BL) was investigated three years after an intracerebral haemorrhage in the region of the left basal ganglia, resulting in unilateral damage of neostrlatum, ventral striatum, globus pallidus, and basal forebrain. BL manifested average Intelligence, somewhat sub-average attention and working memory, severe anterograde amnesia, and time-limited deficits in autobiographical memory (past decade) and Impaired recall of famous events (especially earller decades). The results are interpreted as supportive of a network of memory-associated regions in which the basal ganglia may take part. They are also considered to be lndicative of a hemispheric-specific recall of old episodic and semantic memories.

Longitudinal studies have failed to find progressive hippocampal size reduction in schizophrenia. However, negative results may have been due to follow-up intervals at disease stages where no significant progressive brain changes occur. Furthermore, only male or mixed gender samples have been studied. Forty-six patients with schizophrenia (23 females) and 46 healthy controls (23 females) underwent three-dimensional structural magnetic resonance imaging of the hippocampus and a clinical investigation. Compared with controls, male but not female participants with schizophrenia displayed hippocampal size reduction. Hippocampal size of female but not male schizophrenia patients was related to disorder duration, indicating smaller hippocampal size in female patients with longer disorder duration. Female schizophrenia patients displayed normal hippocampal size at the onset of disorder, but similarly reduced hippocampal size as male schizophrenia patients after some years of illness had passed. Our results suggest preserved hippocampal size in women with schizophrenia during the first years of illness.

Background: Structural and functional brain imaging studies suggest abnormalities of the amygdala and hippocampus in posttraumatic stress disorder and major depressive disorder. However, structural brain imaging studies in social phobia are lacking. Methods: In total, 24 patients with generalized social phobia (GSP) and 24 healthy controls underwent 3-dimensional structural magnetic resonance imaging of the amygdala and hippocampus and a clinical investigation. Results: Compared with controls, GSP patients had significantly reduced amygdalar (13%) and hippocampal (8%) size. The reduction in the size of the amygdala was statistically significant for men but not women. Smaller right-sided hippocampal volumes of GSP patients were significantly related to stronger disorder severity. Limitations: Our sample included only patients with the generalized subtype of social phobia. Because we excluded patients with comorbid depression, our sample may not be representative. Conclusion: We report for the first time volumetric results in patients with GSP. Future assessment of these patients will clarify whether these changes are reversed after successful treatment and whether they predict treatment response.

This paper presents the Social Phobia Psychotherapy Research Network (SOPHO-NET). SOPHO-NET is among the five research networks on psychotherapy funded by "Bundesministerium für Bildung und Forschung". The research program encompasses a coordinated group of studies of social phobia. In the central project (Study A), a multi-center randomized controlled trial, refined models of manualized cognitive-behavioral therapy (CBT) and manualized short-term psychodynamic psychotherapy (STPP) are compared in the treatment of social phobia. A sample of n=512 outpatients will be randomized to either CBT, STPP or wait list. For quality assurance and treatment integrity, a specific project has been established (Project Q). Study A is complemented by four interrelated projects focusing on attachment style (Study B1), cost-effectiveness (Study B2), polymorphisms in the serotonin transporter gene (Study C1) and on structural and functional deviations of hippocampus and amygdala (Study C2). Thus, the SOPHO-NET program allows for a highly interdisciplinary research of psychotherapy in social phobia.

Present evidence suggests that medial temporal cortices subserve allocentric representation and memory, whereas egocentric representation and memory mainly depends on inferior and superior parietal cortices. Virtual reality environments have a major advantage for the assessment of spatial navigation and memory formation, as computer-simulated first-person environments can simulate navigation in a large-scale space. However, virtual reality studies on allocentric memory in subjects with cortical lesions are rare, and studies on egocentric memory are lacking. Twenty-four subjects with unilateral parietal cortex lesions due to infarction or intracerebral haemorrhage (14 left-sided, 10 right-sided) were compared with 36 healthy matched control subjects on two virtual reality tasks affording to learn a virtual park (allocentric memory) and a virtual maze (egocentric memory). Subjects further received a comprehensive clinical and neuropsychological investigation, and MRI lesion assessment using T(1), T(2) and FLAIR sequences as well as 3D MRI volumetry at the time of the assessment. Results indicate that left- and right-sided lesioned subjects did not differ on task performance. Compared with control subjects, subjects with parietal cortex lesions were strongly impaired learning the virtual maze. On the other hand, performance of subjects with parietal cortex lesions on the virtual park was entirely normal. Volumes of the right-sided precuneus of lesioned subjects were significantly related to performance on the virtual maze, indicating better performance of subjects with larger volumes. It is concluded that parietal cortices support egocentric navigation and imagination during spatial learning in large-scale environments.

OBJECTIVE: Trauma-exposed individuals with post-traumatic stress disorder (PTSD) display reduced amygdala and hippocampal size and impaired cognition. However, studies on trauma-exposed individuals with dissociative amnesia (DA) or dissociative identity disorder (DID) are lacking. METHOD: Twenty-three young women who had experienced severe childhood sexual/physical abuse, diagnosed with DA/DID or PTSD, and 25 healthy control subjects were subjected to 3D structural magnetic resonance imaging of amygdala and hippocampus and a clinical and neuropsychological investigation. RESULTS: Compared with controls, trauma-exposed subjects with PTSD (n = 10) displayed significantly reduced amygdala and hippocampal size and significantly impaired cognition. By contrast, trauma-exposed subjects with DA or DID (n = 13) displayed normal amygdala and hippocampal size and normal cognition. CONCLUSION: We report for the first time volumetric results in subjects with DA/DID without PTSD as comorbid diagnosis. Our results indicate preserved amygdala and hippocampal size and preserved cognition in subjects with these disorders.

Individuals with posttraumatic stress disorder (PTSD) display reduced hippocampus size and impaired cognition. However, studies on individuals with borderline personality disorder (BPD) are rare, and studies on trauma-exposed patients with BPD but without PTSD are lacking.Twenty-four trauma-exposed women with BPD (10 with PTSD and 14 without) and 25 healthy controls underwent 3-dimensional structural magnetic resonance imaging of the amygdala and hippocampus and a clinical and neuropsychological investigation.Compared with controls, patients with BPD and PTSD displayed significantly reduced amygdala (34%) and hippocampus (12%) size and significantly impaired cognition. Trauma-exposed patients with BPD but without PTSD also showed significantly reduced amygdala (22%) and hippocampus (11%) size but normal cognition. Amygdala and hippocampus size did not differ significantly between patients with and without PTSD.The sample sizes of trauma-exposed groups are relatively small. A larger sample size may have revealed statistically significant differences in amygdala size between those with and without PTSD.Our results demonstrate strong amygdala size reduction in trauma-exposed patients with BPD with or without PTSD, much exceeding that reported for trauma-exposed individuals without BPD. Our data suggest that BPD is associated with small amygdala size. Furthermore, evidence is increasing that amygdala and hippocampus size reduction is not only due to PTSD, but also to traumatic exposure.

Blood-based tests for the differential diagnosis of Alzheimer's disease (AD) are under intensive investigation and have shown promising results with regard to Abeta40 and Abeta42 peptide species in incipient AD. Moreover, plasma Abeta40 was suggested as an independent cerebrovascular risk factor candidate. These considerations prompted us to analyse a total of 72 plasma samples in vascular dementias (VAD, n = 15), AD with cerebrovascular disease (AD with CVD, n = 7), AD (n = 15), Parkinson's disease and Parkinson's disease dementia (PD/PDD, n = 20) and 15 patients with depression that served as controls (DC) for distinct plasma amyloid-beta (Abeta) peptide patterns. For the analysis of plasma we used immunoprecipitation followed by the quantitative Abeta-SDS-PAGE/immunoblot. For comparison, CSF tau and Abeta1-42 analyses were performed. The major outcome was an increase in Abeta1-40 in plasma of VAD paralleled by a decrease in the ratio of Abeta1-38/Abeta1-40. The ratio Abeta1-38/Abeta1-40 in plasma enabled contrasts of beyond 85% and 80% for discriminating VAD from DC and all other patients, respectively. In CSF, we confirmed the typical CSF biomarker constellation of increased tau and diminished Abeta1-42 levels for AD. The diagnostic accuracy of plasma Abeta1-38/Abeta1-40 for VAD resembled the accuracy of CSF biomarkers for AD. From the presented results, we consider the ratio of plasma Abeta1-38/Abeta1-40 peptides to be a blood-based biomarker candidate for VAD.

Recent evidence suggests that borderline personality disorder (BPD) is related to reduced size of the parietal lobe. Dissociative symptoms occur in the majority of individuals with BPD. Structural magnetic resonance imaging (3D-MRI) was used to assess volumes of the superior (precuneus, postcentral gyrus) and inferior parietal cortices in 30 young women with BPD who had been exposed to severe childhood sexual and physical abuse and 25 healthy control subjects. Compared with control subjects, BPD subjects had significantly smaller right-sided precuneus (-9%) volumes. The left postcentral gyrus of BPD subjects with the comorbid diagnosis of dissociative amnesia (DA) or dissociative identity disorder (DID) was significantly increased compared with controls (+13%) and compared with BPD subjects without these disorders (+11%). In BPD subjects, stronger depersonalization was significantly related to larger right precuneus size. Possibly, larger precuneus size in BPD is related to symptoms of depersonalization. Increased postcentral gyrus size in BPD may be related to the development of DA or DID in the presence of severe childhood abuse.

Background Amygdala and hippocampus show significant structural abnormalities in major depressive disorder (MDD). Individuals with MDD have difficulties in emotional memory. A relationship between emotional memory deficits and structural abnormalities of amygdala and hippocampus in MDD has been proposed but not shown, yet. Methods The current study assessed memory for emotional faces in 21 young women with recent-onset MDD and 23 matched control subjects. All subjects underwent structural magnetic resonance imaging (3D-MRI) and a clinical and neuropsychological assessment. Results Depressive subjects had significantly enlarged amygdala size and significantly reduced hippocampal size compared with controls. Depressive subjects were significantly impaired in learning emotional facial expressions, with deficits being most pronounced for fearful, surprised and disgusted faces. Depressive subjects with amygdala volumes 1 SD or more above the mean of control subjects showed the strongest impairments. Correlation analyses revealed that larger left amygdala volumes were significantly related to worse memory performance and to higher anxiety scores of depressive subjects. Smaller left hippocampal volumes of depressive subjects were related to higher anxiety scores as well. Limitations All MDD subjects were taking antidepressant medication at the time of the study. Longitudinal studies are needed to clarify whether the behavioral and/or volumetric abnormalities of MDD subjects can be attributed to medication or MDD or both. Conclusions It might be speculated that amygdala enlargement in young MDD subjects is correlated with amygdalar over-activation and resolves with antidepressant treatment, as was shown for amygdalar over-activation.

There has been growing interest in the differential role of medial temporal lobe structures in learning and memory. The goal of the present study was to clarify how lesions of hippocampus, parahippocampal gyrus, and amygdala interfere with associative learning and memory. Thirty subjects with pharmacoresistant medial temporal lobe epilepsy (TLE) and temporal lobe removal were compared with 30 matched healthy control subjects. A set of neuropsychological test measures and an associative learning task requiring the learning and recall of objects and faces were administered. The lesions of hippocampus, parahippocampal gyrus, amygdala, and fusiform gyrus of TLE subjects were determined by three-dimensional magnetic resonance imaging (3-D MRI) volumetric assessment. The results indicate that TLE subjects with combined large hippocampal lesions, large parahippocampal gyrus (i.e., perirhinal/entorhinal) lesions, and large amygdala lesions learned and recalled the associative task significantly worse than control subjects or subjects with small lesions of the hippocampus, parahippocampal gyrus, and amygdala. Regression analysis revealed that larger lesions of the parahippocampal gyrus (i.e., perirhinal/entorhinal cortices) were significantly related to increasing deficits on the task, and that hippocampal and amygdala lesion size did not significantly improve the prediction. Our results suggest that perirhinal and entorhinal cortices may contribute predominantly to the associative learning and recall of objects and faces. © 2004 Wiley-Liss, Inc.

The search for a special neuropsychological profile of frontal lobe epilepsy subjects (FLE) has so far led to inconclusive results. In this paper we compared the preoperative neuropsychological performance of FLE and temporal lobe epilepsy (TLE) subjects. We further investigated whether frontal lobe lesions of epileptogenic cause produce the same type of cognitive dysfunction as do tumours of the frontal lobe. Sixteen FLE subjects were compared to 16 TLE subjects as well as to a group of 10 subjects after the removal of frontal lobe tumors (TUM) and a healthy control group. A set of neuropsychological test measures routinely used for presurgical evaluation, an emotional conceptualization task and two associative learning tasks were administered. We found that subjects with frontal lobe damage were significantly impaired relative to controls on a wide range of cognitive functions independent of neurological cause. FLE subjects could hardly be discriminated from TLE subjects as both groups showed a similarly reduced level of neuropsychological performance. Our results demonstrate the devastating effect that frontal lobe epilepsy can have on cognitive functioning. Routinely used neuropsychological test measures lack the specificity to distinguish between frontal and temporal lobe epilepsy. Highly specialized measures are necessary to reveal differences.

Background: Lesions of the thalamus interfere with cognitive functions mainly in the area of declarative learning and memory. Little is known about the role the thalamus plays in implicit learning. Objective: To study explicit and implicit learning and memory in subjects with thalamic lesions and to analyze the influence of lesion characteristics on cognitive performance. Methods: The authors studied the performance of 15 subjects with focal thalamic infarction or hemorrhage on a comprehensive neuropsychological test battery focusing on tests of explicit memory and learning of a nondeclarative motor skill. Subjects with thalamic lesions were compared to 15 healthy matched control subjects and to a clinical control group of 22 subjects who had sustained basal ganglia lesions. Results: Subjects with thalamic lesions showed well-preserved intellectual and executive functions but demonstrated deficits on measures of attention and psychomotor speed, explicit memory, and implicit visuomotor sequence learning. Lesion size in the thalamus was clearly related to subjects’ long-term explicit memory performance. However, few of the neuropsychological deficits found seemed specific to the long-term neuropsychological outcome of focal thalamic infarctions. Subjects with lesions in the basal ganglia demonstrated similar deficits. Conclusions: Focal subcortical lesions in the thalamus and the basal ganglia lead to a similar profile of neuropsychological deficits. Lesions in the thalamus not only affect declarative memory but also interfere with nondeclarative motor skill learning.

An initial sample of 120 healthy young men was screened by a personality questionnaire and 15 subjects each with highest and lowest scores respectively on emotionality (emotionally labile, EL subjects and emotionally stable, ES subjects) were recruited for a study on the relationship between the degree of emotionality and the basal secretion of stress-sensitive hormones during night-time. The nocturnal urinary excretion of cortisol, testosterone, adrenaline, noradrenaline and melatonin was measured over a period of 5 consecutive nights. The average amounts of each hormone excreted per night were not different between the two extreme groups. The variability of the excretion during the 5 nights of cortisol and testosterone, but not of adrenaline, noradrenaline and melatonin, was significantly higher in EL compared to ES subjects. The larger fluctuations in the nocturnal secretion of these two (and no other) hormones in EL subjects indicate that emotional lability is associated with a more labile regulation of cortisol and testosterone secretion. The observed intraindividual variability of basal stress hormone secretion may contribute to the vast interindividual variability noticed in psychoneuroendocrine stress research, especially in emotionally labile subjects.