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Schizophrenia has a prodromal phase of several years in most patients, making it possible to identify patients at clinical high risk (CHR) for developing the disorder. So far, these individuals are identified based on clinical criteria alone, and there is no reliable biomarker for predicting the transition to psychosis. It is well-established that reductions in brain volume, especially in the hippocampus, are associated with schizophrenia. Therefore, hippocampal volume may serve as a biomarker for psychosis. Several studies have already investigated hippocampal volume in CHR groups. Based on these studies, the present meta-analysis compares the baseline left and right hippocampal volume of CHR patients who developed a psychosis with that of CHR patients without such a transition. Our results show no statistically significant effect of the hippocampal volume on the transition risk for psychosis.

Evaluation of the efficacy and safety of chemical renal denervation by image-guided periarterial ethanol injection in pigs with emphasis on histopathological characteristics. Unilateral renal periarterial ethanol injection under general anesthesia was performed in 16 animals with the contralateral kidney serving as the control. All interventions were performed in an open MRI system under real-time multiplanar guidance. In 10 pigs an ethanol-carbostesin contrast agent mixture was injected with amounts of 5 ml (6 animals, group I) and 10 ml (4 animals, group II). 6 pigs (group III) were treated with 10 ml of an ethanol-polyacrylic (2 %) mixture. Four weeks after treatment, all animals underwent MRI including MRA. After euthanasia, macroscopic and histologic examination of the kidneys, renal arteries and periarterial tissue was performed to assess nerve injury and potential side effects. Furthermore, the norepinephrine concentration (RTNEC) in the renal tissue was determined as a surrogate parameter of efficacy. Histologic signs of nerval degeneration with various degrees of severity and circumferential distribution were found in all groups. Injury depths ranged up to 7.6 mm. In groups II and III the nerve count was significantly lower on the treated side. Renal artery stenosis was not observed in any pig. In all pigs of group II treatment resulted in neural degeneration with a mean RTNEC reduction of 53 % (p 0.02). In groups I and III significant changes in RTNEC were not observed. Image-guided percutaneous periarterial ethanol injection was efficient and safe for renal denervation. The detected variations in histologic outcome underlined the importance of the preclinical optimization of the technique in order to maximize treatment effects in humans.· Renal denervation by percutaneous periarterial ethanol injection is an effective and potentially safe procedure.. · The percutaneous approach is less prone to anatomical and procedural limitations compared to catheter-based procedures.. · The achievable nerve injury depth lies beyond those of current RFA-probes.. · Efficacy depends on amount, concentration, viscosity and periarterial distribution of the ethanol-mixture.. · Establishing an optimal balance between these parameters is mandatory for a maximum treatment effect at minimum risk for sensitive adjacent structures..· Freyhardt P, Haage P, Walter A et al. Renal Sympathetic Denervation by Image-Guided Percutaneous Ethanol Injection - Histopathologic Characteristics, Efficacy and Safety. Fortschr Röntgenstr 2020; 192: 549 - 560. Evaluation von Wirksamkeit und Sicherheit der chemischen renalen Denervation mittels bildgestützter periarterieller Ethanol-Injektion in Schweinen mit Schwerpunkt auf histopathologische Charakteristiken. In 16 narkotisierten Schweinen erfolgte eine 1-seitige periarterielle Ethanol-Injektion um eine Nierenarterie. Die unbehandelte Niere diente als Kontrolle. Alle Interventionen erfolgten in einem offenen MRT mit multiplanaren Echtzeit-Sequenzen zur Navigation. 10 Schweinen wurden 5 ml (6 Tiere, Gruppe I), respektive 10 ml (4 Tiere, Gruppe II) eines Ethanol-Carbostesin-Kontrastmittelgemisches injiziert. 6 Tiere (Gruppe III) wurden mit 10 ml eines Ethanol-Polyacryl (2 %) -Gemisches behandelt. 4 Wochen nach der Intervention wurde bei allen Tieren eine MRT-Untersuchung mit MRA durchgeführt. Nach erfolgter Euthanasie wurden eine makroskopische und histologische Untersuchung der Nieren, der Nierenarterien sowie des angrenzenden Bindegewebes zum Nachweis induzierter Nervendegenerationen und potenzieller Nebeneffekte durchgeführt. Als Surrogatparameter für die Wirksamkeit wurde die Noradrenalin-Konzentration des Nierengewebes (RTNEC) bestimmt. In den Präparaten aller Gruppen fanden sich histologische Zeichen einer periarteriellen Nervenschädigung unterschiedlicher Ausprägung und zirkumferentieller Verteilung. Die maximale Distanz geschädigter Nerven zur Gefäßintima betrug 7,6 mm. In den Gruppen II und III zeigte sich die Nervenanzahl auf der behandelten Seite signifikant reduziert im Vergleich zur Gegenseite. Nierenarterienstenosen fanden sich bei keinem Versuchstier. In Gruppe II wiesen alle Tiere einen signifikanten RTNEC-Abfall mit einer mittleren Reduktion von 53 % (p 0,02) auf der behandelten Seite auf. In den Gruppen I und III wurde keine signifikante Veränderung der RTNEC beobachtet. Die bildgestützte, perkutane periarterielle Ethanol-Injektion zur renalen Denervation erwies sich als wirksam und sicher. Die beobachteten Variationen in der Ausprägung der induzierten histopathologischen Veränderungen unterstreichen die Notwendigkeit einer Optimierung der Technik mit dem Ziel eines maximalen Behandlungseffekts im Menschen.· Die renale Denervation durch perkutane periarterielle Ethanolinjektion ist eine effektive und potenziell sichere Prozedur.. · Der perkutane Zugang hat weniger anatomische und prozedurale Limitationen als endovaskuläre Verfahren.. · Die erzielbare Tiefe der Nervenschädigung ist größer als bei gängigen RFA-Elektroden.. · Die Wirksamkeit ist abhängig von Menge, Konzentration, Viskosität und periarterieller Verteilung des Ethanolgemischs.. · Eine optimale Balance zwischen diesen Parametern ist entscheidend für eine maximale Effektivität bei minimalem Risiko..

Several magnetic resonance imaging studies have reported reductions in hippocampal volume in patients with psychosis. It is unclear whether structural abnormalities predate illness onset. We conducted a detailed, systematic literature search for studies reporting hippocampal volume in subjects with clinical high-risk, compared to healthy controls. The overall sample size comprised 1429 subjects. Meta-analysis revealed no difference for left, but a small, albeit significant, difference for right hippocampal volume, such that clinical high-risk patients had slightly smaller hippocampal volume than healthy controls (g=0.24, p=0.0418). Meta-regression indicated a moderating effect of manual tracing approach, due to one outlying site. The small difference on the right side did not remain significant (g=0.14, 95%CI=[-0.03-0.32], p=0.11) after removal of this outlier. This meta-analysis suggests that there is no reduction in hippocampal volume before transition to psychosis and hippocampal volume cannot be used as a biomarker in clinical high-risk individuals.

Objectives Impairment in working memory (WM) is a core symptom in schizophrenia. However, little is known about how clinical features influence functional brain activity specific to WM processing during the development of first-episode psychosis (FEP) to schizophrenia (SZ). We compared functional WM-specific brain activity in FEP and SZ patients, including the effects of the duration of illness, psychopathological factors and antipsychotic medication. Methods Cross-sectional study of male FEP (n = 22) and SZ (n = 20) patients performing an n-back task when undergoing functional magnetic resonance imaging (fMRI). Clinical features were collected by semi-structured interviews and medical records. Results The SZ group performed significantly worse than the FEP group in the 2-back condition. The SZ group also showed significantly higher activation in the left superior frontal gyrus in the 2-back versus 0-back condition (2-back > 0-back). This frontal activation correlated positively with negative symptoms and with cumulative antipsychotic medication during the year before the fMRI examination. There were no significant correlations between activation and duration of illness. Conclusion There was greater frontal neural activation in SZ than in FEP. This indicated differences in WM processing, and was significantly related to cumulative antipsychotic exposure and negative symptoms, but not to the duration of illness.

Background Deficits in motivational salience processing have been related to psychotic symptoms and disturbances in dopaminergic neurotransmission. We aimed at exploring changes in salience processing and brain activity during different stages of psychosis and antipsychotic medication effect. Methods We used fMRI during the Salience Attribution Task to investigate hemodynamic differences between 19 healthy controls (HCs), 34 at-risk mental state (ARMS) individuals and 29 individuals with first-episode psychosis (FEP), including a subgroup of 17 FEP without antipsychotic medication (FEP-UM) and 12 FEP with antipsychotic medication (FEP-M). Motivational salience processing was operationalized by brain activity in response to high-probability rewarding cues (adaptive salience) and in response to low-probability rewarding cues (aberrant salience). Results Behaviorally, adaptive salience response was not accelerated in FEP, although they correctly distinguished between trials with low and high reward probability. In comparison to HC, ARMS exhibited a lower hemodynamic response during adaptive salience in the right inferior parietal lobule and FEP-UM in the left dorsal cingulate gyrus. The FEP-M group exhibited a lower adaptive salience response than HC in the right insula and than ARMS in the anterior cingulate gyrus. In unmedicated individuals, the severity of hallucinations and delusions correlated negatively with the insular- and anterior cingulate hemodynamic response during adaptive salience. We found no differences in aberrant salience processing associated with behavior or medication. Conclusion The changes in adaptive motivational salience processing during psychosis development reveal neurofunctional abnormalities in the somatosensory and premotor cortex. Antipsychotic medication seems to modify hemodynamic responses in the anterior cingulate and insula.

Background Brain-derived neurotrophic factor (BDNF) is a neurotrophin involved in neurogenesis and synaptic plasticity in the central nervous system, especially in the hippocampus, and has been implicated in the pathophysiology of several neuropsychiatric disorders. Its Val66Met polymorphism (refSNP Cluster Report: rs6265) is a functionally relevant single nucleotide polymorphism affecting the secretion of BDNF and is implicated in differences in hippocampal volumes. Methods This is a systematic meta-analytical review of findings from imaging genetic studies on the impact of the rs6265 SNP on hippocampal volumes in neuropsychiatric patients with major depressive disorder, anxiety, bipolar disorder or schizophrenia. Results The overall sample size of 18 independent clinical cohorts comprised 1695 patients. Our results indicated no significant association of left (Hedge's g = 0.08, p = 0.12), right (g = 0.07, p = 0.22) or bilateral (g = 0.07, p = 0.16) hippocampal volumes with BDNF rs6265 in neuropsychiatric patients. There was no evidence for a publication bias or any demographic, clinical, or methodological moderating effects. Both Val/Val homozygotes (g = 0.32, p = 0.004) and Met-carriers (g = 0.20, p = 0.004) from the patient sample had significantly smaller hippocampal volumes than the healthy control sample with the same allele. The magnitude of these effects did not differ between the two genotypes. Conclusion This meta-analysis suggests that there is no association between this BDNF polymorphism and hippocampal volumes. For each BDNF genotype, the hippocampal volumes were significantly lower in neuropsychiatric patients than in healthy controls.

Background Individuals with at-risk mental state for psychosis (ARMS) often suffer from depressive and anxiety symptoms, which are clinically similar to the negative symptomatology described for psychosis. Thus, many ARMS individuals are already being treated with antidepressant medication. Objectives To investigate clinical and structural differences between psychosis high-risk individuals with or without antidepressants. Methods We compared ARMS individuals currently receiving antidepressants (ARMS-AD; n = 18), ARMS individuals not receiving antidepressants (ARMS-nonAD; n = 31) and healthy subjects (HC; n = 24), in terms of brain structure abnormalities, using voxel-based morphometry. We also performed region of interest analysis for the hippocampus, anterior cingulate cortex, amygdala and precuneus. Results The ARMS-AD had higher ‘depression’ and lower ‘motor hyperactivity’ scores than the ARMS-nonAD. Compared to HC, there was significantly less GMV in the middle frontal gyrus in the whole ARMS cohort and in the superior frontal gyrus in the ARMS-AD subgroup. Compared to ARMS-nonAD, the ARMS-AD group showed more gray matter volume (GMV) in the left superior parietal lobe, but less GMV in the left hippocampus and the right precuneus. We found a significant negative correlation between attenuated negative symptoms and hippocampal volume in the whole ARMS cohort. Conclusion Reduced GMV in the hippocampus and precuneus is associated with short-term antidepressant medication and more severe depressive symptoms. Hippocampal volume is further negatively correlated with attenuated negative psychotic symptoms. Longitudinal studies are needed to distinguish whether hippocampal volume deficits in the ARMS are related to attenuated negative psychotic symptoms or to antidepressant action., Highlights • We compared brain structure in high-risk patients with/without antidepressants (AD). • We found attenuated negative psychotic symptoms (ANS) irrespective of AD. • We found a significant correlation between ANS and hippocampal volume. • Results indicate relevance of ANS for clinical high-risk studies.

Background: There is only limited agreement with respect to location, directionality and functional implications of brain structural alterations observed in patients with schizophrenia. Additionally, their link to occurrence of psychotic symptoms remains unclear. A viable way of addressing these questions is to examine populations in an at-risk mental state (ARMS) before the transition to psychosis. Methods: We tested for structural brain alterations in individuals in an ARMS compared with healthy controls and patients with first-episode psychosis (FEP) using voxel-based morphometry and measures of cortical thickness. Furthermore, we evaluated if these alterations were modified by age and whether they were linked to the observed clinical symptoms. Results: Our sample included 59 individuals with ARMS, 26 healthy controls and 59 patients with FEP. We found increased grey matter volume and cortical thickness in individuals with ARMS and a similar pattern of structural alterations in patients with FEP. We further found stronger age-related reductions in grey matter volume and cortical thickness in both patients with FEP and individuals with ARMS, linking these alterations to observed clinical symptoms. Limitations: The ARMS group comprised subgroups with heterogeneous levels of psychosis risk and medication status. Furthermore, the cross-sectional nature of our study and the reduced number of older patients limit conclusions with respect to observed interactions with age. Conclusion: Our findings on consistent structural alterations in individuals with ARMS and patients with FEP and their link to clinical symptoms have major implications for understanding their time of occurrence and relevance to psychotic symptoms. Interactions with age found for these alterations may explain the heterogeneity of findings reported in the literature.

IntroductionPituitary enlargement has been reported in individuals with schizophrenic psychosis or an at-risk mental state for psychosis (ARMS). In a previous study, our group could show pituitary volume increase in first episode and ARMS patients with later transition to psychosis (ARMS-T). However, there are no longitudinal studies on this issue so far. We therefore examined longitudinally whether transition to psychosis would be accompanied by a further increase of pituitary volume in antipsychotic-naïve ARMS patients.MethodsMagnetic resonance imaging (MRI) data were acquired from 23 antipsychotic-naïve individuals with an ARMS. Ten subjects developed psychosis (ARMS-T) and 13 did not (ARMS-NT). ARMS-T were re-scanned after the onset of psychosis, and ARMS-NT were re-scanned at the end of the study period.ResultsThere was no significant difference of the pituitary volume between ARMS-T and ARMS-NT in our sample, and there were no significant pituitary volume changes over time.DiscussionLongitudinally, we could not detect any further volumetric changes in the pituitary volume with transition to psychosis.ConclusionsThis, together with the result of our previous study, could indicate that the perceived level of stress in ARMS patients is constantly high from very early onward.

We conducted a systematic review to assess the evidence for specific effects of cannabis on impulsivity, disinhibition and motor control. The review had a specific focus on neuroimaging findings associated with acute and chronic use of the drug and covers literature published up until May 2012. Seventeen studies were identified, of which 13 met the inclusion criteria; three studies investigated acute effects of cannabis (1 fMRI, 2 PET), while six studies investigated non-acute functional effects (4 fMRI, 2 PET), and four studies investigated structural alterations. Functional imaging studies of impulsivity studies suggest that prefrontal blood flow is lower in chronic cannabis users than in controls. Studies of acute administration of THC or marijuana report increased brain metabolism in several brain regions during impulsivity tasks. Structural imaging studies of cannabis users found differences in reduced prefrontal volumes and white matter integrity that might mediate the abnormal impulsivity and mood observed in marijuana users. To address the question whether impulsivity as a trait precedes cannabis consumption or whether cannabis aggravates impulsivity and discontinuation of usage more longitudinal study designs are warranted.

Hintergrund: In Basel haben wir verschiedene Studien zur Verbesserung der Methodik zur Fruherkennung von Psychosen (FePsy) durchgefuhrt. Methodik: Vom 01.03.2000 bis 29.02.2004 wurden 234 Individuen mithilfe des Basler Screening Instruments fur Psychosen (BSIP) gescreent. Bei 10 6 Patienten konnte ein Risikostatus fur Psychosen diagnostiziert werden, 53 davon konnten bis zu 7 Jahre (Mittel 5. 4 Jahre) nachuntersucht werden. Die weiteren Untersuchungen erfolgten u.a. mit einem spezifisch entwickelten Anamnese - Instrument, verschiedenen Skalen zur Psychopathologie, Untersuchungen der Neuropsychologie u n d Feinmotorik , klinische m und quantitative m EEG, MRI des Gehirns, Labor. Ergebnisse: Allein auf der Basis des BSIP konnte eine relativ zuverlassige Vorher sage getroffen werden: 21 (39.6 % ) der als „ Risikopatienten “Identifizierten entwickelten innerhalb der Beobachtungszeit tatsachlich eine Psychose. Post hoc konnte durch spezifischere Gewichtung der Psychopathologie und Einbezug neuropsychologischer Untersuchungen die Vorhersagegenauigkeit auf 81 % gesteigert werden. Die anderen oben genannten Verfahren konnen offensichtlich zur weiteren Verbesserung der Pradiktion beitragen. Schlussfolgerungen: Die Risikoabklarung fur Psychose sollte stufenweise und unter Einbezug verschiedener Untersuchungsebenen erfolgen. Background: We have conducted various studies in Basel with the aim of improving the methods for the early detection of psychosis (Fruherkennung von Psychosen, FePsy).Methods: From 1.3.2000 to 29.2.2004 234 individuals were screened using the Basel Screening Instrument for Psychosis (BSIP). 106 patients were identified as at risk for psychosis; out of these 53 remained in follow-up for up to 7 years (mean 5.4 years). The assessments were done with a specifically developed instrument for history taking, various scales for the psychopathology, assessments of neuropsychology and fine motor functioning, clinical and quantitative EEG, MRI of the brain, laboratory etc.Results: Based on the BSIP alone, a relatively reliable prediction was possible: 21 (39.6 %) of the individuals identified as at risk developed psychosis within the follow-up time. Post-hoc prediction could be improved to 81 % by weighting psychopathology and including neuropsychology. Including the other domains obviously allows further improvements of prediction.Conclusions: The risk for psychosis should be assessed in a stepwise procedure. In a first step, a clinically oriented screening should be conducted. If an at-risk status is found, further assessments in various domains should be done in a specialised centre.

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.

There is strong evidence for abnormal salience processing in patients with psychotic experiences. In particular, there are indications that the degree of aberrant salience processing increases with the severity of positive symptoms. The aim of the present study was to elucidate this relationship by means of brain imaging.Functional magnetic resonance imaging was acquired to assess haemodynamic responses during the Salience Attribution Test, a paradigm for reaction time that measures aberrant salience to irrelevant stimulus features. We included 42 patients who were diagnosed as having a psychotic disorder and divided them into two groups according to the severity of their positive symptoms. Whole brain analysis was performed using Statistical Parametric Mapping.We found no significant behavioural differences with respect to task performance. Patients with more positive symptoms showed increased haemodynamic responses in the left insula corresponding to aberrant salience than in patients with less positive symptoms. In addition, left insula activation correlated negatively with cumulative antipsychotic medication. Aberrant salience processing in the insula may be increased in psychosis, depending on the severity of positive symptoms. This study indicates that clinically similar psychosis manifestations share the same functional characteristics. In addition, our results suggest that antipsychotic medication can modulate insular function.

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-naive 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

The psychosis high-risk state is accompanied by alterations in functional brain activity during working memory processing. We used binary automatic pattern-classification to discriminate between the at-risk mental state (ARMS), first episode psychosis (FEP) and healthy controls (HCs) based on n-back WM-induced brain activity. Linear support vector machines and leave-one-out-cross-validation were applied to fMRI data of matched ARMS, FEP and HC (19 subjects/group). The HC and ARMS were correctly classified, with an accuracy of 76.2% (sensitivity 89.5%, specificity 63.2%, p = 0.01) using a verbal working memory network mask. Only 50% and 47.4% of individuals were classified correctly for HC vs. FEP (p = 0.46) or ARMS vs. FEP (p = 0.62), respectively. Without mask, accuracy was 65.8% for HC vs. ARMS (p = 0.03) and 65.8% for HC vs. FEP (p = 0.0047), and 57.9% for ARMS vs. FEP (p = 0.18). Regions in the medial frontal, paracingulate, cingulate, inferior frontal and superior frontal gyri, inferior and superior parietal lobules, and precuneus were particularly important for group separation. These results suggest that FEP and HC or FEP and ARMS cannot be accurately separated in small samples under these conditions. However, ARMS can be identified with very high sensitivity in comparison to HC. This might aid classification and help to predict transition in the ARMS., Highlights • The ARMS was accurately identified based on an individual patient's response within a WM network. • Regional cortical activations were particularly important for group separation. • Based on WM alterations, FEP and HC or FEP and ARMS could not be accurately separated in small samples.

Background/Aims: Previous diffusion tensor imaging (DTI) studies have shown microstructural changes in the brain white matter of at-risk mental state (ARMS) subjects for psychosis and patients with first-episode psychosis (FEP). However, only a few studies have been conducted in clinical high-risk samples and findings in both groups are inconsistent, in particular along the superior longitudinal fasciculus (SLF). Methods: This DTI study used tract-based spatial statistics (TBSS) to compare fractional anisotropy (FA) and mean diffusivity (MD) between ARMS subjects, untreated and antipsychotic-treated FEP patients and healthy controls (HC) across the whole brain and the SLF. Results: Compared to HC, ARMS and FEP patients showed increased FA and decreased MD in diverse regions across the whole brain including the SLF. FA in the SLF was positively correlated with positive psychotic symptoms in ARMS and FEP individuals. Furthermore, untreated but not treated FEP patients showed increased FA in the left inferior longitudinal fasciculus and right SLF. Conclusion: This study revealed increased FA and decreased MD in early stages of psychosis in widespread white matter tracts including the SLF. Our findings further suggest that microstructural changes in the SLF are probably related to state-dependent psychopathology.

article i nfo Background: Aggression and suicidality prior to the initiation of treatment are frequent phenomena in psychosis patients.IncreasedscoresintheBriefPsychiatric Rating Scale ExcitedComponent(BPRS-EC)have beenshownto 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 b .001), and post- hoc analyses showed significantly higher BPRS-EC scores for ARMS (p = .001) and for FEP patients (p b .001) compared to HC. Differences remained significant after controlling for gender, years of education, and intelli- gence. 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 b .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.

BackgroundThe brain-derived neurotrophic factor (BDNF) Val66Met polymorphism (refSNP Cluster Report: rs6265) is a common and functionally relevant single nucleotide polymorphism (SNP). The gene itself, as well as the SNP rs6265, have been implicated in hippocampal learning and memory. However, imaging genetic studies have produced controversial results about the impact of this SNP on hippocampal volumes in healthy subjects.MethodsWe examined the association between the rs6265 polymorphism and hippocampal volume in 643 healthy young subjects using automatic segmentation and subsequently included these data in a meta-analysis based on published studies with 5298 healthy subjects in total.ResultsWe found no significant association between SNP rs6265 and hippocampal volumes in our sample (g=0.05, p=0.58). The meta-analysis revealed a small, albeit significant difference in hippocampal volumes between genotype groups, such that Met-carriers had slightly smaller hippocampal volumes than Val/Val homozygotes (g=0.09, p=0.04), an association that was only evident when manual (g=0.22, p=0.01) but not automatic tracing approaches (g=0.04, p=0.38) were used. Studies using manual tracing showed evidence for publication bias and a significant decrease in effect size over the years with increasing sample sizes.ConclusionsThis study does not support the association between SNP rs6265 and hippocampal volume in healthy individuals. The weakly significant effect observed in the meta-analysis is mainly driven by studies with small sample sizes. In contrast, our original data and the meta-analysis of automatically segmented hippocampal volumes, which was based on studies with large samples sizes, revealed no significant genotype effect. Thus, meta-analyses of the association between rs6265 and hippocampal volumes should consider possible biases related to measuring technique and sample size.

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.

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.

Experimental and clinical studies give evidence for breakdown of membrane phospholipids during neurodegeneration. In the present study, we measured the levels of glycerophosphocholine (GPCh), phosphocholine (PCh), and choline, that is, water-soluble metabolites of phosphatidylcholine (PtdCho), in human cerebrospinal fluid (CSF). Among 30 cognitively normal patients the average CSF levels of GPCh, phosphocholine and choline were 3.64, 1.28, and 1.93 microM, respectively; metabolite levels did not change with increasing age. When compared with age-matched controls, patients with Alzheimer's disease had elevated levels of all choline metabolites: GPCh was significantly increased by 76% (P