Ute Gschwandtner

Regional Gray Matter Volume Abnormalities in the At Risk Mental State

BACKGROUND Individuals with an At Risk Mental State (ARMS) have a very high risk of developing a psychotic disorder but the basis of this risk is unclear. We addressed this issue by studying gray matter volume in this group with magnetic resonance imaging (MRI). METHODS Thirty-five individuals with an ARMS, 25 patients with first episode schizophrenia, and 22 healthy volunteers were studied using a 1.5T MRI scanner. Twelve (34%) of the ARMS group developed schizophrenia in the 2 years subsequent to scanning. RESULTS There were significant volumetric differences between the three groups in the left insula, superior temporal gyrus, cingulate gyrus and precuneus. In these regions, the volume in the ARMS group was smaller than in volunteers but not significantly different from that in the first episode (FE) group. Direct comparison of the ARMS and control groups revealed additional areas of reduced volume in the left medial temporal cortex. Within the ARMS group, those subjects who later developed psychosis had less gray matter than subjects who did not in the right insula, inferior frontal and superior temporal gyrus. CONCLUSIONS The ARMS was associated with reductions in gray matter volume in areas that are also reduced in schizophrenia, suggesting that these are a correlate of an increased vulnerability to psychosis. Volumetric differences within the ARMS group may be related to the subsequent onset of schizophrenia in a subset of those at high risk.

Efficacy of Using Cognitive Status in Predicting Psychosis: A 7-Year Follow-Up

BACKGROUND Despite extensive early detection research in schizophrenic psychoses, methods for identifying at-risk individuals and predicting their transition to psychosis are still unreliable. Moreover, there are sparse data on long-term prediction. We therefore investigated long-term psychosis transition in individuals with an At Risk Mental State (ARMS) and examined the relative efficacy of clinical and neuropsychological status in optimizing the prediction of transition. METHODS Sixty-four individuals with ARMS for psychosis were identified from all referrals to our early detection clinic between March 1, 2000 and February 29, 2004. Fifty-three (83%) were followed up for up to 7 (mean 5.4) years. RESULTS Twenty-one of the 53 staying in follow-up developed psychosis, corresponding to a transition rate of .34 (Kaplan-Meier estimates). Median time to transition was 10 months (range <1-55). Six of all transitions (29%) occurred only after 12 months from referral. Best transition predictors within this population were selected attenuated psychotic symptoms (suspiciousness), negative symptoms (anhedonia/asociality), and cognitive deficits (reduced speed of information processing). With these predictors in an integrated model for predicting transition to psychosis, the overall predictive accuracy was 80.9% with a sensitivity of 83.3% and a specificity of 79.3%. CONCLUSIONS Follow-up of ARMS subjects should exceed the usual 12 months. Prediction of transitions could be improved by a stronger weighting of certain early symptoms and by introducing neurocognitive tests into a stepwise risk assessment. Confirmatory research will hopefully further improve risk algorithm, including psychopathology and neuropsychological performance, for clinical application in early detection clinics.

Reductions in frontal, temporal and parietal volume associated with the onset of psychosis

BACKGROUND Volumetric MRI abnormalities similar to those evident in schizophrenia are also evident in people at very high risk of psychosis. Which volumetric abnormalities are related to psychotic illness, as opposed to vulnerability to psychosis is unclear. The aim of the study was to compare regional gray matter volume in people before and after the onset of psychosis using a within-subject prospective design. METHODS MRI data were acquired from individuals when they presented with an at-risk mental state (ARMS, n=20). Over the following 3 years, 10 subjects developed psychosis and 10 did not. Subjects were re-scanned after the onset of psychosis or at the end of follow-up if they did not become psychotic. Images were processed and analyzed using voxel-based morphometry (SPM5). RESULTS In subjects who developed psychosis there were longitudinal volume reductions in the orbitofrontal, superior frontal, inferior temporal, medial and superior parietal cortex, and in the cerebellum. There were no longitudinal changes in subjects who did not develop psychosis. CONCLUSIONS The onset of psychosis was associated with a reduction in gray matter volume in frontal, temporal and parietal cortex. These abnormalities may be particularly associated with psychotic illness, as opposed to a vulnerability to psychosis.

The Basel early-detection-of-psychosis (FEPSY)-study - design and preliminary results

Objective:  Early detection and therapy of schizophrenic psychoses have become broadly accepted aims in psychiatry, recently even in very early stages of the disorder when clear diagnostic criteria are not yet fulfilled. However, reliable and widely applicable methods do not yet exist. This study aims at contributing to the improvement of the early assessment of psychosis.

Pathologic gambling in patients with Parkinson's disease.

Patients with Parkinsons disease frequently have depression, anxiety, and obsessive-compulsive disorder. We observed two patients who had episodes of pathologic gambling. At the same time, their Parkinsons disease deteriorated and they initiated self-medication with dopaminergic drugs. In both patients, signs were present of an addiction to dopaminergic medication. Pathologic gambling ceased in these patients after a few months. The significance of an insufficient dopaminergic reward system in patients with stereotypical addictive-like behavior (e.g., pathologic gambling) is discussed in this report. The most likely explanation for this newly recognized behavioral disorder in patients with Parkinsons disease is enhanced novelty seeking as a consequence of overstimulation of mesolimbic dopamine receptors resulting from addiction to dopaminergic drugs.

Structural brain abnormalities in individuals with an at-risk mental state who later develop psychosis

BACKGROUND Neuroanatomical abnormalities are a well-established feature of schizophrenia. However, the timing of their emergence and the extent to which they are related to vulnerability to the disorder as opposed to psychotic illness itself is unclear. AIMS To assess regional grey matter volume in the at-risk individuals who subsequently developed psychosis. METHOD Magnetic resonance imaging data from at-risk individuals who developed psychosis (n=12) within the following 25 months were compared with data from healthy volunteers (n=22) and people with first-episode psychosis (n=25). RESULTS Compared with healthy volunteers, individuals who subsequently developed psychosis had smaller grey matter volume in the posterior cingulate gyrus, precuneus, and paracentral lobule bilaterally and in the left superior parietal lobule, and greater grey matter volume in a left parietal/posterior temporal region. Compared with first-episode patients, they had relatively greater grey matter volume in the temporal gyrus bilaterally and smaller grey matter volume in the right lentiform nucleus. CONCLUSIONS Some of the structural brain abnormalities in individuals with an at-risk mental state may be related to an increased vulnerability to psychosis, while others are associated with the development of a psychotic illness.

Das Basel Screening Instrument für Psychosen (BSIP): Entwicklung, Aufbau, Reliabilität und Validität

BACKGROUND Early detection of psychosis is of growing clinical importance. So far there is, however, no screening instrument for detecting individuals with beginning psychosis in the atypical early stages of the disease with sufficient validity. We have therefore developed the Basel Screening Instrument for Psychosis (BSIP) and tested its feasibility, interrater-reliability and validity. AIM Aim of this paper is to describe the development and structure of the instrument, as well as to report the results of the studies on reliability and validity. METHOD The instrument was developed based on a comprehensive search of literature on the most important risk factors and early signs of schizophrenic psychoses. The interraterreliability study was conducted on 24 psychiatric cases. Validity was tested based on 206 individuals referred to our early detection clinic from 3/1/2000 until 2/28/2003. RESULTS We identified seven categories of relevance for early detection of psychosis and used them to construct a semistructured interview. Interrater-reliability for high risk individuals was high (Kappa .87). Predictive validity was comparable to other, more comprehensive instruments: 16 (32 %) of 50 individuals classified as being at risk for psychosis by the BSIP have in fact developed frank psychosis within an follow-up period of two to five years. CONCLUSIONS The BSIP is the first screening instrument for the early detection of psychosis which has been validated based on transition to psychosis. The BSIP is easy to use by experienced psychiatrists and has a very good interrater-reliability and predictive validity.

Neuropsychological deficits in individuals with an at risk mental state for psychosis — Working memory as a potential trait marker

OBJECTIVE To investigate the neuropsychological profile of individuals with an at risk mental state for psychosis (ARMS, N=60) compared to healthy controls (HC, N=51) and to identify those cognitive domains which discriminate best between groups. METHOD Study subjects and controls were compared using a neuropsychological test battery covering the domains of intelligence (LPS3, MWT-A), executive functions (ToH, WCST, TAP - Go/NoGo), working memory (Tests for Attentional Performance (TAP) - Working Memory), and attention (CPT-OX). A multivariate analysis of variance (MANOVA) comparing ARMS subjects with HC was conducted. A stepwise logit regression procedure was performed in order to determine the subset of measures which best distinguish ARMS subjects from HC. RESULTS ARMS subjects revealed deficiencies in intelligence, executive functions, working memory and attention. Verbal intelligence, executive functions, and, in particular, working memory discriminated best between the groups. CONCLUSION Individuals with an at risk mental state for psychosis already show impairment of neuropsychological functions prior to the onset of the first psychotic episode and can best be distinguished from healthy controls on the basis of working memory.

Early detection and treatment of schizophrenia: how early?

Objective:  Whereas early detection and therapy of schizophrenic psychoses until some time ago concentrated on frank schizophrenia, during the last years some centres have also started to treat patients even before a clear diagnosis could be established. This paper attempts to discuss if and when this is justified in the light of recent research.

Hippocampus abnormalities in at risk mental states for psychosis? A cross-sectional high resolution region of interest magnetic resonance imaging study

BACKGROUND Hippocampal volume (HV) reduction is well documented in schizophrenia. However, it is still unclear whether this change is a pre-existing vulnerability factor, a sign of disease progression, a consequence of environmental factors, such as drug use, antipsychotic medication, or malnutrition. The timing of HV changes is not well established, but a lack of macrostructural hippocampal brain abnormalities before disease onset would rather support a neuroprogressive illness model. AIM To investigate the timing of HV changes in emerging psychosis. METHODS A cross-sectional MRI study of manually traced HVs in 37 individuals with an At Risk Mental State (ARMS) for psychosis, 23 individuals with First-Episode Psychosis (FEP), and 22 Healthy Controls (HC) was performed. We compared left and right HVs corrected for whole brain volume across groups using analysis of covariance (ANCOVA) with gender as a covariate. Sixteen of 37 ARMS individuals developed a psychotic disorder during follow up (ARMS-T). The mean duration of follow up in ARMS was 25.1months. RESULTS The overall ANCOVA model comparing left HVs across FEP, ARMS and HC indicated a significant general group effect (p<.05) with largest volumes in ARMS and smallest in FEP. ARMS-T subjects had significantly larger left HVs compared to FE but no HV differences compared to HC (p<0.05). Over all groups, we found an asymmetry between the left and right mean HVs and a strong effect of sex. DISCUSSION The present study suggests that macrostructural hippocampal abnormalities probably occur in the context of the first psychotic breakdown.