EEG: a helpful tool in the prediction of psychosis

Objective: EEG investigation in patients with an at risk mental state (ARMS) for psychosis and patients with a first episode of psychosis (FE) in comparison to healthy controls (HC) in a clinical follow up study of Early Detection of Psychosis. Method: Seventy-three patients (42 ARMS, 31 FE) and 35 HC were investigated. ARMS patients were followed up in order to monitor transition to psychosis. Psychopathology was assessed with respect to positive and negative symptoms. At study baseline EEG was recorded using the 10/20 system. Two blinded neurologists analyzed the EEGs visually for presence of generalized or focal slowing and epileptiform discharges. EEG data were controlled for medication and substance abuse. For statistical analyses we used χ2-tests, logistic regression, ANOVA, and receiver operating characteristics. Results: Patients showed significantly more pathological EEG abnormalities than HC (P<0.05), located more frequently in temporal or fronto-temporal regions (P<0.01) of the brain, with twice as many pathologies in ARMS than in FE patients. The specificity of the prediction of psychosis could be increased from 59 to 73% by considering EEG pathology in addition to psychopathology alone. In contrast, sensitivity of prediction remained unchanged. Conclusions: These results show that EEG investigation in patients at risk for psychosis can add to the identification of those patients who will not develop psychosis later o

Housing situation and healthcare for patients in a psychiatric centre in Berlin, Germany: a cross-sectional patient survey

OBJECTIVE: To determine the housing situation among people seeking psychiatric treatment in relation to morbidity and service utilisation. DESIGN: Cross-sectional patient survey. SETTING: Psychiatric centre with a defined catchment area in Berlin, Germany, March-September 2016. PARTICIPANTS: 540 psychiatric inpatients including day clinics (43.2% of all admitted patients in the study period (n=1251)). MAIN OUTCOME MEASURES: Housing status 30 days prior the interview as well as influencing variables including service use, psychiatric morbidity and sociodemographic variables. RESULTS: In our survey, 327 participants (68.7%) currently rented or owned an own apartment; 62 (13.0%) reported to be homeless (living on the street or in shelters for homeless or refugees); 87 (18.3%) were accommodated in sociotherapeutic facilities. Participants without an own apartment were more likely to be male and younger and to have a lower level of education. Homeless participants were diagnosed with a substance use disorder significantly more often (74.2%). Psychotic disorders were the highest among homeless participants (29.0%). Concerning service use, we did neither find a lower utilisation of ambulatory services nor a higher utilisation of hospital-based care among homeless participants. CONCLUSIONS: Our findings underline the need for effective housing for people with mental illness. Despite many sociotherapeutic facilities, a concerning number of people with mental illness is living in homelessness. Especially early interventions addressing substance use might prevent future homelessness

Aberrant Current Source-Density and Lagged Phase Synchronization of Neural Oscillations as Markers for Emerging Psychosis

Background: Converging evidence indicates that neural oscillations coordinate activity across brain areas, a process which is seemingly perturbed in schizophrenia. In particular, beta (13-30 Hz) and gamma (30-50 Hz) oscillations were repeatedly found to be disturbed in schizophrenia and linked to clinical symptoms. However, it remains unknown whether abnormalities in current source density (CSD) and lagged phase synchronization of oscillations across distributed regions of the brain already occur in patients with an at-risk mental state (ARMS) for psychosis. Methods: To further elucidate this issue, we assessed resting-state EEG data of 63 ARMS patients and 29 healthy controls (HC). Twenty-three ARMS patients later made a transition to psychosis (ARMS-T) and 40 did not (ARMS-NT). CSD and lagged phase synchronization of neural oscillations across brain areas were assessed using eLORETA and their relationships to neurocognitive deficits and clinical symptoms were analyzed using linear mixed-effects models. Results: ARMS-T patients showed higher gamma activity in the medial prefrontal cortex compared to HC, which was associated with abstract reasoning abilities in ARMS-T. Furthermore, in ARMS-T patients lagged phase synchronization of beta oscillations decreased more over Euclidian distance compared to ARMS-NT and HC. Finally, this steep spatial decrease of phase synchronicity was most pronounced in ARMS-T patients with high positive and negative symptoms scores. Conclusions: These results indicate that patients who will later make the transition to psychosis are characterized by impairments in localized and synchronized neural oscillations providing new insights into the pathophysiological mechanisms of schizophrenic psychoses and may be used to improve the prediction of psychosi

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 3.4years, of untreated psychosis 12months. 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 develope

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 25.1 months. 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

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

Differences in DNA repair capacity, cell death and transcriptional response after irradiation between a radiosensitive and a radioresistant cell line

Normal tissue toxicity after radiotherapy shows variability between patients, indicating inter-individual differences in radiosensitivity. Genetic variation probably contributes to these differences. The aim of the present study was to determine if two cell lines, one radiosensitive (RS) and another radioresistant (RR), showed differences in DNA repair capacity, cell viability, cell cycle progression and, in turn, if this response could be characterised by a differential gene expression profile at different post-irradiation times. After irradiation, the RS cell line showed a slower rate of γ-H2AX foci disappearance, a higher frequency of incomplete chromosomal aberrations, a reduced cell viability and a longer disturbance of the cell cycle when compared to the RR cell line. Moreover, a greater and prolonged transcriptional response after irradiation was induced in the RS cell line. Functional analysis showed that 24h after irradiation genes involved in "DNA damage response", "direct p53 effectors" and apoptosis were still differentially up-regulated in the RS cell line but not in the RR cell line. The two cell lines showed different response to IR and can be distinguished with cell-based assays and differential gene expression analysis. The results emphasise the importance to identify biomarkers of radiosensitivity for tailoring individualized radiotherapy protocols

First self-perceived signs and symptoms in emerging psychosis compared with depression

Aim: To investigate differences between the early symptoms of schizophrenia and depressive disorders. Methods: Sixty-one individuals with an at-risk mental state (ARMS), 17 of whom later made the transition to psychosis, 37 patients with a first episode of psychosis and 16 controls with depressive disorders were interviewed about first self-perceived signs and symptoms. Results: In ARMS and first episode of psychosis, on average, first self-perceived signs or symptoms had occurred about 5-6 years before the interview. In ARMS, including transition to psychosis, 'loss of energy' and 'difficulties concentrating' were the most frequently recalled first signs. There was much overlap for the four most frequently mentioned symptoms in the three groups. As compared with ARMS, controls with depressive disorders significantly more often recalled 'depression' and 'social isolation' as the very first signs of disease. Conclusions: Clinicians should consider the development of self-recalled first signs over time carefully when assessing suspected early prodromal stages of schizophrenia and beginning depressive disorder

Can cognitive deficits facilitate differential diagnosis between at-risk mental state for psychosis and depressive disorders?

AIM: Many studies have provided evidence of cognitive deficits in individuals in an 'At Risk Mental State' (ARMS) for psychosis, which makes neuropsychology potentially useful in the early detection of psychosis. As depression is an important differential diagnosis in prodromal states of psychosis, the specificity of neurocognitive deficits in ARMS individuals as compared with non-psychotic depressive disorders is investigated. METHODS: Neurocognitive performance of four groups was analysed: 22 ARMS individuals with later transition to psychosis (ARMS-T), 25 ARMS individuals without later transition to psychosis (ARMS-NT), 34 controls with depressive disorders and 76 healthy controls. The subjects were assessed with a neurocognitive test battery covering the domains' intelligence, executive function and attention/ working memory. MANOVAs, ANOVAs and Tukey's tests were applied after adjustment for confounding factors. RESULTS: ARMS-T showed significant cognitive deficits in working memory and in certain executive function tasks compared with healthy controls as well as with controls with depression. Controls with depression were only impaired in time per move in the tower of Hanoi test when compared with healthy controls. CONCLUSIONS: The psychosis prodrome seems to be associated with cognitive deficits in the domains of working memory and executive function. In contrast, depressive patients showed no cognitive deficits, but slowing in one executive function task. Neurocognitive testing might therefore contribute to the differential diagnosis between prodromal psychosis and depressive disorders