Abnormal effective connectivity and psychopathological symptoms in the psychosis high-risk state.

BACKGROUND: Recent evidence has revealed abnormal functional connectivity between the frontal and parietal brain regions during working memory processing in patients with schizophrenia and first-episode psychosis. However, it still remains unclear whether abnormal frontoparietal connectivity during working memory processing is already evident in the psychosis high-risk state and whether the connection strengths are related to psychopathological outcomes. METHODS: Healthy controls and antipsychotic-naive individuals with an at-risk mental state (ARMS) performed an n-back working memory task while undergoing functional magnetic resonance imaging. Effective connectivity between frontal and parietal brain regions during working memory processing were characterized using dynamic causal modelling. RESULTS: Our study included 19 controls and 27 individuals with an ARMS. In individuals with an ARMS, we found significantly lower task performances and reduced activity in the right superior parietal lobule and middle frontal gyrus than in controls. Furthermore, the working memory-induced modulation of the connectivity from the right middle frontal gyrus to the right superior parietal lobule was significantly reduced in individuals with an ARMS, while the extent of this connectivity was negatively related to the Brief Psychiatric Rating Scale total score. LIMITATIONS: The modest sample size precludes a meaningful subgroup analysis for participants with a later transition to psychosis. CONCLUSION: This study demonstrates that abnormal frontoparietal connectivity during working memory processing is already evident in individuals with an ARMS and is related to psychiatric symptoms. Thus, our results provide further insight into the pathophysiological mechanisms of the psychosis high-risk state by linking functional brain imaging, computational modelling and psychopathology.

Help-seeking and pathways to care in the early stages of psychosis.

PURPOSE: Delay in the treatment of a first psychotic episode can have a negative influence on the future course of the disease. In this context, it is important to examine pathways to care to understand factors contributing to delay in access to adequate care. METHODS: Using the Basel Interview for Psychosis, we examined the help-seeking behaviour of 61 individuals with an at-risk mental state for psychosis and 37 patients with a first episode of psychosis in a low threshold health care system as part of the Basel early detection of psychosis study. RESULTS: The median duration of untreated illness was 3.4 years, of untreated psychosis 12 months. Eighty-six percent of all individuals sought help of some kind before reaching our specialised early detection outpatient clinic, with a mean number of help-seeking contacts of 1.5 prior to referral. The most frequent first help-seeking contacts were family members or relatives n = 24 (26.7 %), close friends n = 17 (17.9 %), psychiatrists in private practice n = 13 (14.4 %) or general practitioners n = 11 (12.2 %). Most patients consulted other health professionals in the early course of the illness before reaching our specialised service; help-seeking with non-medical institutions was rare. Women had more help-seeking contacts than men before contact with our early detection clinic. CONCLUSIONS: Family, close friends and medical professionals play an important role in help-seeking leading to specialised psychiatric care. Men seek help less often; specific strategies for encouraging young, at-risk men to seek help should be developed.

Different duration of at-risk mental state associated with neurofunctional abnormalities. A multimodal imaging study.

OBJECTIVES: Neurofunctional alterations are correlates of vulnerability to psychosis, as well as of the disorder itself. How these abnormalities relate to different probabilities for later transition to psychosis is unclear. We investigated vulnerability- versus disease-related versus resilience biomarkers of psychosis during working memory (WM) processing in individuals with an at-risk mental state (ARMS). EXPERIMENTAL DESIGN: Patients with "first-episode psychosis" (FEP, n = 21), short-term ARMS (ARMS-ST, n = 17), long-term ARMS (ARMS-LT, n = 16), and healthy controls (HC, n = 20) were investigated with an n-back WM task. We examined functional magnetic resonance imaging (fMRI) and structural magnetic resonance imaging (sMRI) data in conjunction using biological parametric mapping (BPM) toolbox. PRINCIPAL OBSERVATIONS: There were no differences in accuracy, but the FEP and the ARMS-ST group had longer reaction times compared with the HC and the ARMS-LT group. With the 2-back > 0-back contrast, we found reduced functional activation in ARMS-ST and FEP compared with the HC group in parietal and middle frontal regions. Relative to ARMS-LT individuals, FEP patients showed decreased activation in the bilateral inferior frontal gyrus and insula, and in the left prefrontal cortex. Compared with the ARMS-LT, the ARMS-ST subjects showed reduced activation in the right inferior frontal gyrus and insula. Reduced insular and prefrontal activation was associated with gray matter volume reduction in the same area in the ARMS-LT group. CONCLUSIONS: These findings suggest that vulnerability to psychosis was associated with neurofunctional alterations in fronto-temporo-parietal networks in a WM task. Neurofunctional differences within the ARMS were related to different duration of the prodromal state and resilience factors.

Can cortical thickness asymmetry analysis contribute to detection of at-risk mental state and first-episode psychosis? A pilot study.

PURPOSE: To investigate whether cortical thickness analysis in individuals with an at-risk mental state (ARMS) might contribute to early detection of psychosis. MATERIALS AND METHODS: Ethics committee approval and written informed consent were obtained. Cortical thickness was analyzed because early disease-related morphometric changes were expected to be most pronounced in the cerebral cortex. With the assumption of progressive change in cortical thickness from control subjects, to those with an ARMS, and then to those who have had a first episode (FE) of psychosis, the brain regions that substantially differ between those with FE psychosis and control subjects were identified. Whether these regions help discriminate between the ARMS group and control subjects was tested. Because normal interindividual variation of cortical thickness, even for control subjects, may exceed that expected with early disease-related changes, intraindividual cortical thickness asymmetry was analyzed. Twenty age- and sex-matched individuals for each group (ARMS group, FE group, and control subjects) were recruited within a prospective early-detection study. High-spatial-resolution magnetization-prepared rapid gradient-echo magnetic resonance (MR) brain images were acquired with a 1.5-T MR imager. Cortical thickness asymmetry was analyzed in 41 anatomic regions corresponding to the Talairach standard brain atlas. RESULTS: Direct cortical thickness analysis did not help distinguish between groups. Cortical thickness asymmetry analysis helped distinguish between groups (P = .007); variability increased from control subjects, to the ARMS group, and then to the FE group in seven anatomic regions (P < .0001). Cortical thickness asymmetry in these regions helped distinguish the FE group from control subjects (P = .0006; sensitivity, 70.0%; specificity, 85.0%) and showed a trend toward helping to distinguish the ARMS group from control subjects (P = .06; sensitivity, 75.0%; specificity, 65.0%). CONCLUSION: Cortical thickness asymmetry analysis is more accurate than direct cortical thickness measurement in distinguishing the control from the FE group and might contribute to early detection of an ARMS.

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.

Outcome of individuals "not at risk of psychosis" and prognostic accuracy of the Basel Screening Instrument for Psychosis (BSIP).

BACKGROUND: We aimed to determine the prognostic accuracy of the Basel Screening Instrument for Psychosis (BSIP) in terms of specificity, sensitivity, positive and negative predictive value by following up individuals that were initially not considered to be at increased risk of psychosis based on the BSIP. Moreover, clinical characteristics of these individuals were examined given the relative lack of such information in the literature. METHODS: As part of the "Früherkennung von Psychosen" (FePsy) study, 87 individuals were screened with the BSIP. Of these, 64 were classified at baseline as being in an at-risk mental state (ARMS+) for psychosis using the BSIP and followed up at regular time intervals for at least 2 years to determine a putative transition to psychosis. Twenty-three individuals were classified at baseline as not being in an at-risk mental state (ARMS-) using the BSIP and re-assessed after 4 years. Sensitivity, specificity, positive and negative predictive value of the BSIP were computed. Clinical characteristics of the ARMS- group were analysed descriptively. RESULTS: During the follow-up period, none of the ARMS- individuals, but 21 of ARMS+ had developed psychosis. Sensitivity of the BSIP was 1.0, specificity was 0.35. The majority of ARMS- individuals showed depressive disorders or anxiety disorders and varying levels of functioning. CONCLUSIONS: The BSIP has good prognostic accuracy for detecting the prodromal phase of psychosis with an excellent sensitivity and a specificity similar to other risk instruments and the advantage of a relatively short duration. Depressive and anxiety symptoms commonly develop in ARMS- individuals.

The neuropsychology of emerging psychosis and the role of working memory in episodic memory encoding.

BACKGROUND: Episodic memory encoding and working memory (WM) deficits are among the first cognitive signs and symptoms in the course of schizophrenia spectrum disorders. However, it is not clear whether the deficit pattern is generalized or specific in nature. We hypothesized that encoding deficits at an early stage of the disease might be due to the more fundamental WM deficits. METHODS: We examined episodic memory encoding and WM by administering the California Verbal Learning Test, a 2-back task, and the Wisconsin Card Sorting Test in 90 first-episode psychosis (FE) patients and 116 individuals with an at-risk mental state for psychosis (ARMS) compared to 57 healthy subjects. RESULTS: Learning progress, but not span of apprehension, was diminished to a similar extent in both the ARMS and the FE. We showed that this was due to WM impairment by applying a structural equation approach. CONCLUSION: Thus, we conclude that verbal memory encoding deficits are secondary to primary WM impairment in emerging psychosis.

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.

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.

Duration of untreated psychosis/illness and brain volume changes in early psychosis.

The time period during which patients manifest psychotic or unspecific symptoms prior to treatment (duration of untreated psychosis, DUP, and the duration of untreated illness, DUI) has been found to be moderately associated with poor clinical and social outcome. Equivocal evidence exists of an association between DUP/DUI and structural brain abnormalities, such as reduced hippocampus volume (HV), pituitary volume (PV) and grey matter volume (GMV). Thus, the goal of the present work was to examine if DUP and DUI are associated with abnormalities in HV, PV and GMV. Using a region of interest (ROI) based approach, we present data of 39 patients from the Basel FePsy (Früherkennung von Psychosen, early detection of psychosis) study for which information about DUP, DUI and HV, PV and GMV data could be obtained. Twenty-three of them were first episode psychosis (FEP) and 16 at-risk mental state (ARMS) patients who later made the transition to frank psychosis. In unadjusted analyses, we found a significant positive correlation between DUP and PV in FEP patients. However, when adjusted for covariates, we found no significant correlation between DUP or DUI and HV, PV or GMV anymore. There only was a trend for decreasing GMV with increasing DUI in FEP. Our results do not comprehensively support the hypothesis of a "toxic" effect of the pathogenic mechanism underlying untreated psychosis on brain structure. If there is any effect, it might rather occur very early in the disease process, during which patients experience only unspecific symptoms.

Gender differences in the psychopathology of emerging psychosis.

BACKGROUND: Gender differences have often been found in psychopathological symptoms among chronic schizophrenia and first-episode psychosis (FEP) patients. However, many of these studies suffer from methodological problems and show inconsistent results. Furthermore, very few studies have investigated gender differences in individuals with an at-risk mental state (ARMS) for psychosis. METHODS: Psychopathological symptoms were assessed in 117 ARMS and 87 FEP patients by two observer-rated scales, namely, the expanded version of the Brief Psychiatric Rating Scale (BPRS) and the Scale for the Assessment of Negative Symptoms (SANS), and by one self-report scale, the Frankfurt Complaint Questionnaire (FCQ). Gender differences were investigated by applying Analyses of Variance using the BPRS, SANS and FCQ subscales as dependent variables, and group and sex as between-subject factors - in a second step by including age, antipsychotic, antidepressant and cannabis use as covariates. RESULTS: There were no significant gender × patient group interactions, suggesting that gender effects did not differ between patient groups. Women had higher scores in positive psychotic symptoms (BPRS Psychosis/ Thought Disturbance) while men had higher scores in negative symptoms (BPRS negative symptoms, SANS total score, as well as subscales Affective Flattening, Avolition-Apathy and Asociality-Anhedonia). However, the differences did not withstand correction for multiple testing. The results did not change when corrected for potential confounders. CONCLUSIONS: There do not seem to be any gender differences in psychopathology, neither in ARMS nor in FEP patients, as regards self-reported or observerrated symptoms, when corrected for multiple testing and potential confounders.

Evidence for an agitated-aggressive syndrome predating the onset of psychosis.

BACKGROUND: Aggression and suicidality prior to the initiation of treatment are frequent phenomena in psychosis patients. Increased scores in the Brief Psychiatric Rating Scale Excited Component (BPRS-EC) have been shown to predict involuntary treatment, aggression, and suicide in first-episode psychosis (FEP) patients. However, it is unclear if an agitated-aggressive syndrome as measured with the BPRS-EC is already present in at-risk mental state (ARMS). METHODS: BPRS-EC scores from 43 ARMS patients, 50 FEP patients, and 25 healthy controls (HC) were analyzed. Multivariate analyses were performed to review if group differences were mediated by potential confounders. In addition, the association of BPRS-EC scores with clinical variables was examined. RESULTS: BPRS-EC scores were significantly different across diagnostic groups (H(2)=22.1; p<.001), and post-hoc analyses showed significantly higher BPRS-EC scores for ARMS (p=.001) and for FEP patients (p<.001) compared to HC. Differences remained significant after controlling for gender, years of education, and intelligence. No significant differences emerged between ARMS and FEP patients. BPRS-EC was significantly correlated with lower intelligence (r=-.27; p=.008), reduced level of functioning (r=-.44; p<.001), and with smoking behavior (r=.22; p=.019). CONCLUSIONS: ARMS and FEP patients in our sample had significantly higher BPRS-EC scores compared to HC. This may constitute a correlate of an agitated-aggressive syndrome and an increased risk for aggression and suicidality.

Are neurological soft signs pre-existing markers in individuals with an at-risk mental state for psychosis?

Neurological soft signs (NSS) are more common in schizophrenic psychoses and in genetically high-risk individuals than in healthy controls. But nothing is known so far regarding individuals with a clinical at-risk mental state (ARMS). The goals of our study therefore were (a) to compare the NSS frequency in ARMS individuals to that of first-episode psychosis (FEP) patients and (b) to test whether NSS could predict the transition to psychosis. Neurological soft signs were assessed using a shortened version of the Neurological Evaluation Scale (NES). Fifty-three ARMS individuals (16 with later transition to psychosis=ARMS-T, and 37 without transition=ARMS-NT) and 27 FEP patients were recruited through the Basel Early Detection Clinic FePsy. Of the FEP patients 37% showed NSS. We found no significant differences between FEP and ARMS-T patients or between ARMS-NT and ARMS-T. Our findings of NSS being present already before transition to psychosis to the same extent as after transition provide further support to the neurodevelopmental hypothesis of schizophrenic psychoses. Furthermore, our findings might indicate that ARMS-NT individuals also suffer from some sort of neurodevelopmental abnormalities.

Distinguishing prodromal from first-episode psychosis using neuroanatomical single-subject pattern recognition.

BACKGROUND: The at-risk mental state for psychosis (ARMS) and the first episode of psychosis have been associated with structural brain abnormalities that could aid in the individualized early recognition of psychosis. However, it is unknown whether the development of these brain alterations predates the clinical deterioration of at-risk individuals, or alternatively, whether it parallels the transition to psychosis at the single-subject level. METHODS: We evaluated the performance of an magnetic resonance imaging (MRI)-based classification system in classifying disease stages from at-risk individuals with subsequent transition to psychosis (ARMS-T) and patients with first-episode psychosis (FE). Pairwise and multigroup biomarkers were constructed using the structural MRI data of 22 healthy controls (HC), 16 ARMS-T and 23 FE subjects. The performance of these biomarkers was measured in unseen test cases using repeated nested cross-validation. RESULTS: The classification accuracies in the HC vs FE, HC vs ARMS-T, and ARMS-T vs FE analyses were 86.7%, 80.7%, and 80.0%, respectively. The neuroanatomical decision functions underlying these discriminative results particularly involved the frontotemporal, cingulate, cerebellar, and subcortical brain structures. CONCLUSIONS: Our findings suggest that structural brain alterations accumulate at the onset of psychosis and occur even before transition to psychosis allowing for the single-subject differentiation of the prodromal and first-episode stages of the disease. Pattern regression techniques facilitate an accurate prediction of these structural brain dynamics at the early stage of psychosis, potentially allowing for the early recognition of individuals at risk of developing psychosis.

Duration of untreated psychosis and cognitive functioning.

BACKGROUND: Studies examining the influence of duration of untreated psychosis (DUP) or duration of untreated illness (DUI) on cognition vary with regard to results and methods. This study is the first in this field to include an at risk mental state with later transition to psychosis (ARMS-T) sample and to analyse how the DUI relates to their cognitive functioning. Because methodological operationalization of cognitive functioning in previous studies is highly heterogeneous, we aimed to compare different approaches. METHOD: 60 first episode psychosis (FEP) patients and 24 ARMS-T patients were examined. Associations between DUP, DUI and neurocognitive performance were tested by three different operationalizations of cognition: as the raw outcome measure of different neuropsychological tests, as outcome scores which were normed on a sample of 75 healthy participants, and as the deterioration index (DI). RESULTS: There were no significant correlations between DUP or DUI and outcome of neuropsychological tests in both normed and raw scores. When adjusted for covariates, DUP and DUI also did not significantly predict any cognitive performance. There was no significant relationship between DUP or DUI and the DI index. However, longer DUP and DUI were significantly associated with stronger negative symptoms. CONCLUSIONS: This study could not confirm an association between duration of untreated psychosis or duration of untreated illness and neurocognitive performance in the ARMS-T and FEP samples. This could be because schizophrenic psychoses are neurodevelopmental disorders in which most cognitive deficits exist long before the onset of psychiatric symptoms.

Cannabis use and brain structural alterations of the cingulate cortex in early psychosis.

As cannabis use is more frequent in patients with psychosis than in the general population and is known to be a risk factor for psychosis, the question arises whether cannabis contributes to recently detected brain volume reductions in schizophrenic psychoses. This study is the first to investigate how cannabis use is related to the cingulum volume, a brain region involved in the pathogenesis of schizophrenia, in a sample of both at-risk mental state (ARMS) and first episode psychosis (FEP) subjects. A cross-sectional magnetic resonance imaging (MRI) study of manually traced cingulum in 23 FEP and 37 ARMS subjects was performed. Cannabis use was assessed with the Basel Interview for Psychosis. By using repeated measures analyses of covariance, we investigated whether current cannabis use is associated with the cingulum volume, correcting for age, gender, alcohol consumption, whole brain volume and antipsychotic medication. There was a significant three-way interaction between region (anterior/posterior cingulum), hemisphere (left/right cingulum) and cannabis use (yes/no). Post-hoc analyses revealed that this was due to a significant negative effect of cannabis use on the volume of the posterior cingulum which was independent of the hemisphere and diagnostic group and all other covariates we controlled for. In the anterior cingulum, we found a significant negative effect only for the left hemisphere, which was again independent of the diagnostic group. Overall, we found negative associations of current cannabis use with grey matter volume of the cingulate cortex, a region rich in cannabinoid CB1 receptors. As this finding has not been consistently found in healthy controls, it might suggest that both ARMS and FEP subjects are particularly sensitive to exogenous activation of these receptors.

Brain connectivity abnormalities predating the onset of psychosis: correlation with the effect of medication.

IMPORTANCE: Brain imaging studies have identified robust changes in brain structure and function during the development of psychosis, but the contribution of abnormal brain connectivity to the onset of psychosis is unclear. Furthermore, antipsychotic treatment can modulate brain activity and functional connectivity during cognitive tasks. OBJECTIVES: To investigate whether dysfunctional brain connectivity during working memory (WM) predates the onset of psychosis and whether connectivity parameters are related to antipsychotic treatment. DESIGN: Dynamic causal modeling study of functional magnetic resonance imaging data. SETTING: Participants were recruited from the specialized clinic for the early detection of psychosis at the Department of Psychiatry, University of Basel, Basel, Switzerland. PARTICIPANTS: Seventeen participants with an at-risk mental state (mean [SD] age, 25.24 [6.3] years), 21 individuals with first-episode psychosis (mean [SD] age, 28.57 [7.2] years), and 20 healthy controls (mean [SD] age, 26.5 [4] years). MAIN OUTCOME AND MEASURE: Functional magnetic resonance imaging data were recorded while participants performed an N-back WM task. Functional interactions among brain regions involved in WM, in particular between frontal and parietal brain regions, were characterized using dynamic causal modeling. Bayesian model selection was performed to evaluate the likelihood of alternative WM network architectures across groups, whereas bayesian model averaging was used to examine group differences in connection strengths. RESULTS: We observed a progressive reduction in WM-induced modulation of connectivity from the middle frontal gyrus to the superior parietal lobule in the right hemisphere in healthy controls, at-risk mental state participants, and first-episode psychosis patients. Notably, the abnormal modulation of connectivity in first-episode psychosis patients was normalized by treatment with antipsychotics. CONCLUSIONS AND RELEVANCE: Our findings suggest that the vulnerability to psychosis is associated with a progressive failure of functional integration of brain regions involved in WM processes, including visual encoding and rule updating, and that treatment with antipsychotics may have the potential to counteract this.

Hippocampal volume in subjects at high risk of psychosis: a longitudinal MRI study.

INTRODUCTION: The hippocampal formation has been studied extensively in schizophrenic psychoses and alterations in hippocampal anatomy have been consistently reported. Chronic schizophrenia seems to be associated with bilateral hippocampal volume (HV) reduction, while in patients with an at-risk mental state (ARMS) there are contradictory results. This is the first region of interest (ROI) based follow-up MRI study of hippocampal volume comparing ARMS individuals with and without transition to psychosis. The aim was to investigate the timing of HV changes in ARMS in the early phase of psychosis. METHODS: Magnetic resonance imaging data from 18 antipsychotic-naïve individuals with an ARMS were collected within the FePsy-clinic for early detection of psychoses. During follow-up 8 subjects transitioned to psychosis (ARMS-T) and 10 did not (ARMS-NT). Subjects were re-scanned after the onset of psychosis or at the end of the follow-up if they did not develop psychosis. RESULTS: Across both groups there was a significant decrease in HV over time (p<0.05). There was no significant difference in progression between ARMS-T and ARMS-NT. Antipsychotic medication at follow up was associated with increased HV (p<0.05). CONCLUSIONS: We found a decrease of HV over time in subjects with an ARMS, independently of clinical outcome. We may speculate that the decrease of HV over time might reflect brain degeneration processes.

Cingulate volume abnormalities in emerging psychosis.

BACKGROUND: Neuroanatomical abnormalities, including cingulate cortex volume abnormalities, are a common feature in psychosis. However, the extent to which these are related to a vulnerability to psychosis, as opposed to the disorder per se, is less certain. AIM UND HYPOTHESES: The aim of the present study is to compare cingulate gray matter volumes in different stages of psychosis. We reviewed previous studies of subjects in a prodromal stage of psychosis and tested cingulate volume changes during the transition to psychosis. METHODS: A cross-sectional MRI study of manually traced cingulate gray-matter volumes in 37 individuals with an at risk mental state (ARMS) for psychosis, 23 individuals with a first-episode psychosis (FEP), and 22 healthy controls (HC) was performed using a 1.5 T MRI-scanner. 16 of 37 ARMS individuals (43 %) developed psychosis during follow up (ARMS-T), whereas 21 did not (ARMS-NT). The mean duration of follow up in ARMS was 25.1 months. 8 cingulate subregions were analysed in a region-of-interest analysis. RESULTS: Compared to HC, subjects with an ARMS had significantly reduced left caudal anterior cingulate cortex volume (p < 0.027). This finding was also evident at a trend level (p: 0.069) in FEP patients. Within ARMS, the ARMS-T group showed a significantly reduced whole right cingulate cortex (p: 0.036), right subgenual cingulate cortex (p: 0.036) and right posterior cingulate cortex (p: 0.012) compared to ARMS-NT. DISCUSSION: These results suggest that the at risk mental state is associated with cingulate volume reductions, in particular in the left caudal anterior cingulate cortex (CACC). These abnormalities do not only seem to occur with transition to psychosis, but may be a correlate of an increased vulnerability to psychosis.