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Background: This study examined whether mismatch negativity (MMN) responses are impaired in participants at clinical high risk for psychosis (CHR-P) and patients with first-episode psychosis (FEP) and whether MMN deficits predict clinical outcomes in CHR-Ps., Methods: Magnetoencephalography data were collected during a duration-deviant MMN paradigm for a group of 116 CHR-P participants, 33 FEP patients (15 antipsychotic-naïve), clinical high risk negative group (n = 38) with substance abuse and affective disorder, and 49 healthy control participants. Analysis of group differences of source-reconstructed event-related fields as well as time-frequency and intertrial phase coherence focused on the bilateral Heschl's gyri and bilateral superior temporal gyri., Results: Significant magnetic MMN responses were found across participants in the bilateral Heschl's gyri and bilateral superior temporal gyri. However, MMN amplitude as well as time-frequency and intertrial phase coherence responses were intact in CHR-P participants and FEP patients compared with healthy control participants. Furthermore, MMN deficits were not related to persistent attenuated psychotic symptoms or transitions to psychosis in CHR-P participants., Conclusions: Our data suggest that magnetic MMN responses in magnetoencephalography data are not impaired in early-stage psychosis and may not predict clinical outcomes in CHR-P participants., (Copyright © 2023 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Evidence suggests that schizophrenia (ScZ) involves impairments in sensory attenuation. It is currently unclear, however, whether such deficits are present during early-stage psychosis as well as the underlying network and the potential as a biomarker. To address these questions, Magnetoencephalography (MEG) was used in combination with computational modeling to examine M100 responses that involved a "passive" condition during which tones were binaurally presented, while in an "active" condition participants were asked to generate a tone via a button press. MEG data were obtained from 109 clinical high-risk for psychosis (CHR-P) participants, 23 people with a first-episode psychosis (FEP), and 48 healthy controls (HC). M100 responses at sensor and source level in the left and right thalamus (THA), Heschl's gyrus (HES), superior temporal gyrus (STG) and right inferior parietal cortex (IPL) were examined and dynamic causal modeling (DCM) was performed. Furthermore, the relationship between sensory attenuation and persistence of attenuated psychotic symptoms (APS) and transition to psychosis was investigated in CHR-P participants. Sensory attenuation was impaired in left HES, left STG and left THA in FEP patients, while in the CHR-P group deficits were observed only in right HES. DCM results revealed that CHR-P participants showed reduced top-down modulation from the right IPL to the right HES. Importantly, deficits in sensory attenuation did not predict clinical outcomes in the CHR-P group. Our results show that early-stage psychosis involves impaired sensory attenuation in auditory and thalamic regions but may not predict clinical outcomes in CHR-P participants., (© 2023. The Author(s).)

Individuals with a diagnosis of borderline personality disorder (BPD) typically experience discrimination and stigma, resulting in poor identification and delayed care. We conducted a review to examine and synthesize qualitative studies exploring experiences of stigma and discrimination among individuals with BPD. In August 2021, we systematically searched the following databases: Embase, Medline, Cochrane Library, PsycINFO, and Cinhal. We also hand searched reference lists and Google Scholar. We then synthesized studies using meta-ethnography. We included seven articles in the study, all of high or moderate quality. Five themes were identified: (1) resistance from clinicians (withholding information), (2) othering, (3) negative impact on self-image/esteem, (4) hopelessness surrounding the perceived permanency of BPD, and (5) feeling like a burden. This review highlights the need for improved understanding of BPD across health care services. We also discussed the need to introduce a standardized pathway of care across health services following a BPD diagnosis.

Competing Interests: MH leads the RADAR-CNS consortium, a private–public pre-competitive collaboration on mobile health, through which his university receives in-kind and cash contributions from Janssen, Biogen, UCB, Merck, and Lundbeck. All other authors declare no competing interests.

Aim: Language disturbances are a candidate biomarker for the early detection of psychosis. Temporal and prosodic abnormalities have been observed in schizophrenia patients, while there is conflicting evidence whether such deficits are present in participants meeting clinical high-risk for psychosis (CHR-P) criteria., Methods: Clinical interviews from CHR-P participants (n = 50) were examined for temporal and prosodic metrics and compared against a group of healthy controls (n = 17) and participants with affective disorders and substance abuse (n = 23)., Results: There were no deficits in acoustic variables in the CHR-P group, while participants with affective disorders/substance abuse were characterized by slower speech rate, longer pauses and higher unvoiced frames percentage., Conclusion: Our finding suggests that temporal and prosodic aspects of speech are not impaired in early-stage psychosis. Further studies are required to clarify whether such abnormalities are present in sub-groups of CHR-P participants with elevated psychosis-risk., (© 2022 The Authors. Early Intervention in Psychiatry published by John Wiley & Sons Australia, Ltd.)

Introduction: Many gaps exist in our understanding of the developmental pathways to severe mental illness (SMI), including borderline personality disorder (BPD) and psychosis. However, those who have experienced adverse childhood experiences (ACEs) are at an increased risk and there is evidence to suggest that one of the earliest markers is emotional dysregulation. An area which has received relatively less research attention is the role neurodevelopmental disorders (NDDs) play. The aim of this feasibility study was therefore to explore the clinical profiles of young people early in the course of SMI, including their profiles of ACEs, emotional regulation difficulties, borderline personality traits and NDDs., Methods: A cross-sectional study of young people (aged 15-25) at risk of SMI, currently being seen within NHS mental health services, was conducted. This included those with early symptoms of psychosis and/or BPD as assessed by diagnostic interview. Eligible participants self-completed a battery of sociodemographic, clinical, and psychological measures in the company of a researcher. This included assessments of: symptoms of NDDs; borderline pathology traits; ACEs; and difficulties in emotional regulation. Statistical analyses included Mann-Whitney U tests and multiple regression., Results: Of the 118 potentially eligible participants who were referred, 48 were ultimately included in the study. Young people early in the course of SMI reported a high prevalence of ACEs and deficits in emotional regulation. In total, 79% met criteria for attention deficit hyperactivity disorder (ADHD) and/or autism spectrum disorder (ASD). Emotional dysregulation was found to significantly mediate the association between both ACEs and the frequency of NDDs and borderline personality traits, however given the small sample size these results are preliminary in nature., Conclusion: Young people early in the course of SMI are at an increased risk of experiencing multiple childhood adversities and our results indicate a high prevalence of NDDs amongst them. Emotional dysregulation emerged as a potentially significant early marker of future clinical severity. We suggest that the clinical implications of our findings include routine screening for NDDs and ACEs and an increased recognition of the significance of emotional dysregulation. However, larger scale longitudinal studies are needed to investigate these preliminary findings further., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gajwani, Wilson, Nelson, Gumley, Smith and Minnis.)

Introduction: Parental addiction can result in harm to children and removal of children by the Local Authority. Less is known about the impact of removal of children on their parents and whether gender has a role in this process., Methods: Data on 736 service users were obtained from the caseloads of 8 nurses and 12 social care workers from an Alcohol and Drug Recovery Service in Scotland. Gender differences in prevalence/patterns of child removal, associations between child removal and parental factors and the relationship between removal and suicidality were examined., Results: Mothers were more likely to have had one or more children removed compared to fathers (56.6 vs. 17.7%; p < 0.001) and were more likely to have a series of individual child removals (22.5 vs. 4.3%; p = 0.014). In addition to female gender, younger age, drug use, mental health and suicide attempts were also associated with child removal. Mothers who had children removed and women who were not mothers were more likely to have made an attempt to end their lives than women who had children but had not had them removed., Conclusion: Gender differences were apparent in prevalence and patterns of child removal. Mothers were six times more likely to have children removed compared to fathers. Child removal occurred alongside other risk factors suggesting that families need holistic support for their multiple areas of need. Services should be aware of the link between child removal and suicide and provide additional support to mothers during and after removal., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Russell, Gajwani, Turner and Minnis.)

Schizophrenia is characterised by cognitive impairments that are already present during early stages, including in the clinical high-risk for psychosis (CHR-P) state and first-episode psychosis (FEP). Moreover, data suggest the presence of distinct cognitive subtypes during early-stage psychosis, with evidence for spared vs. impaired cognitive profiles that may be differentially associated with symptomatic and functional outcomes. Using cluster analysis, we sought to determine whether cognitive subgroups were associated with clinical and functional outcomes in CHR-P individuals. Data were available for 146 CHR-P participants of whom 122 completed a 6- and/or 12-month follow-up; 15 FEP participants; 47 participants not fulfilling CHR-P criteria (CHR-Ns); and 53 healthy controls (HCs). We performed hierarchical cluster analysis on principal components derived from neurocognitive and social cognitive measures. Within the CHR-P group, clusters were compared on clinical and functional variables and examined for associations with global functioning, persistent attenuated psychotic symptoms and transition to psychosis. Two discrete cognitive subgroups emerged across all participants: 45.9% of CHR-P individuals were cognitively impaired compared to 93.3% of FEP, 29.8% of CHR-N and 30.2% of HC participants. Cognitively impaired CHR-P participants also had significantly poorer functioning at baseline and follow-up than their cognitively spared counterparts. Specifically, cluster membership predicted functional but not clinical outcome. Our findings support the existence of distinct cognitive subgroups in CHR-P individuals that are associated with functional outcomes, with implications for early intervention and the understanding of underlying developmental processes., (© 2021. Crown.)

Psychosis involves changes in GABAergic and glutamatergic neurotransmission in auditory cortex that could be important for understanding sensory deficits and symptoms of psychosis. However, it is currently unclear whether such deficits are present in participants at clinical high-risk for psychosis (CHR-P) and whether they are associated with clinical outcomes. Magnetic Resonance Spectroscopy (MEGAPRESS, 1H-MRS at 3 Tesla) was used to estimate GABA, glutamate, and glutamate-plus-glutamine (Glx) levels in auditory cortex in a large sample of CHR-P ( n = 99), CHR-N (clinical high-risk negative, n = 32), and 45 healthy controls. Examined were group differences in metabolite concentrations as well as relationships with clinical symptoms, general cognition, and 1-year follow-up clinical and general functioning in the CHR-P group. Results showed a marginal ( p = 0.039) main group effect only for Glx, but not for GABA and glutamate concentrations, and only in left, not right, auditory cortex. This effect did not survive multiple comparison correction, however. Exploratory post-hoc tests revealed that there were significantly lower Glx levels ( p = 0.029, uncorrected) in the CHR-P compared to the CHR-N group, but not relative to healthy controls ( p = 0.058, uncorrected). Glx levels correlated with the severity of perceptual abnormalities and disorganized speech scores. However, in the CHR-P group, Glx levels did not predict clinical or functional outcomes. Accordingly, the findings from the present study suggest that MRS-measured GABA, glutamate and Glx levels in auditory cortex of CHR-P individuals are largely intact., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Grent-’t-Jong, Gajwani, Gross, Gumley, Lawrie, Schwannauer, Schultze-Lutter, Williams and Uhlhaas.)

Hippocampal dysfunctions are a core feature of schizophrenia, but conflicting evidence exists whether volumetric and morphological changes are present in early-stage psychosis and to what extent these deficits are related to clinical trajectories. In this study, we recruited individuals at clinical high risk for psychosis (CHR-P) (n = 108), patients with a first episode of psychosis (FEP) (n = 37), healthy controls (HC) (n = 70) as well as a psychiatric control group with substance abuse and affective disorders (CHR-N: n = 38). MRI-data at baseline were obtained and volumetric as well as vertex analyses of the hippocampus were carried out. Moreover, volumetric changes were examined in the amygdala, caudate, nucleus accumbens, pallidum, putamen and thalamus. In addition, we obtained follow-up functional and symptomatic assessments in CHR-P individuals to examine the question whether anatomical deficits at baseline predicted clinical trajectories. Our results show that the hippocampus is the only structure showing significant volumetric decrease in early-stage psychosis, with FEPs showing significantly smaller hippocampal volumes bilaterally alongside widespread shape changes in the vertex analysis. For the CHR-P group, volumetric decreases were confined to the left hippocampus. However, hippocampal alterations in the CHR-P group were not robustly associated with clinical outcomes, including the persistence of attenuated psychotic symptoms and functional trajectories. Accordingly, our findings highlight that dysfunctions in hippocampal anatomy are an important feature of early-stage psychosis which may, however, not be related to clinical outcomes in CHR-P participants., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: Suicidal thoughts and behaviours are prevalent in individuals with schizophrenia. However, research examining the prevalence and predictors of suicidality and self-harm in participants at clinical high-risk for psychosis (CHR-P) is limited and mostly focuses on help-seeking participants recruited through clinical pathways. The current study sought to assess the prevalence of suicidality and self-harm and identify predictors of current suicidal ideation in community-recruited CHR-P participants., Methods: Data were available for 130 CHR-P participants, 15 participants with first-episode psychosis (FEP), 47 participants not fulfilling CHR-P criteria (CHR-Ns) and 53 healthy controls. Current and lifetime suicidality and self-harm were assessed using the Mini-International Neuropsychiatric Interview and the Comprehensive Assessment of At-Risk Mental States (CAARMS). Multivariable logistic regression analysis was used to determine predictors of current suicidal ideation in the CHR-P group., Results: A considerable proportion of CHR-P participants disclosed current suicidal ideation (34.6%). Overall, FEP individuals were at greatest risk, with considerably high prevalence rates for current suicidal ideation (73.3%), lifetime self-harm behaviour (60.0%) and lifetime suicide attempt (60.0%). In the CHR-P sample, current suicidal ideation was predicted by lifetime suicide attempts, lower CAARMS severity, impaired social functioning and greater comorbidity., Conclusions: Our findings suggest that suicidality and self-harm are highly prevalent in community-recruited CHR-P and FEP individuals. Accordingly, these results highlight the importance of further research into the determinants of suicidality and self-harm during at-risk and early stages of psychosis, and the implementation of intervention strategies to reduce adverse outcomes in these populations., (© 2020 The Authors. Early Intervention in Psychiatry Published by John Wiley & Sons Australia, Ltd.)

Background: This study aimed to examine whether 40-Hz auditory steady-state responses (ASSRs) are impaired in participants at clinical high-risk for psychosis (CHR-P) and predict clinical outcomes., Methods: Magnetoencephalography data were collected during a 40-Hz ASSR paradigm for a group of 116 CHR-P participants, 33 patients with first-episode psychosis (15 antipsychotic-naïve), a psychosis risk-negative group (n = 38), and 49 healthy control subjects. Analysis of group differences of 40-Hz intertrial phase coherence and 40-Hz amplitude focused on right Heschl's gyrus, superior temporal gyrus, hippocampus, and thalamus after establishing significant activations during 40-Hz ASSR stimulation. Linear regression and linear discriminant analyses were used to predict clinical outcomes in CHR-P participants, including transition to psychosis and persistence of attenuated psychotic symptoms (APSs)., Results: CHR-P participants and patients with first-episode psychosis were impaired in 40-Hz amplitude in the right thalamus and hippocampus. In addition, patients with first-episode psychosis were impaired in 40-Hz amplitude in the right Heschl's gyrus, and CHR-P participants in 40-Hz intertrial phase coherence in the right Heschl's gyrus. The 40-Hz ASSR deficits were pronounced in CHR-P participants who later transitioned to psychosis (n = 13) or showed persistent APSs (n = 34). Importantly, both APS persistence and transition to psychosis were predicted by 40-Hz ASSR impairments, with ASSR activity in the right hippocampus, superior temporal gyrus, and middle temporal gyrus correctly classifying 69.2% individuals with nonpersistent APSs and 73.5% individuals with persistent APSs (area under the curve = 0.842), and right thalamus 40-Hz activity correctly classifying 76.9% transitioned and 53.6% nontransitioned CHR-P participants (area under the curve = 0.695)., Conclusions: Our data indicate that deficits in gamma-band entrainment in the primary auditory cortex and subcortical areas constitute a potential biomarker for predicting clinical outcomes in CHR-P participants., (Copyright © 2021 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Introduction: Duration of risk symptoms (DUR) in people at clinical high risk for psychosis (CHR-P) has been related to poorer clinical outcomes, such as reduced functioning, but it is currently unclear how different symptoms emerge as well as their link with cognitive deficits. To address these questions, we examined the duration of basic symptoms (BS) and attenuated psychotic symptoms (APS) in a sample of CHR-P participants to test the hypothesis that BS precede the manifestation of APS. As a secondary objective, we investigated the relationship between DUR, functioning and neuropsychological deficits., Methods: Data from 134 CHR-P participants were assessed with the Comprehensive Assessment of At-Risk Mental State and the Schizophrenia Proneness Interview, Adult Version. Global, role and social functioning and neurocognition were assessed and compared to a sample of healthy controls (n = 57)., Results: In CHR-P participants who reported both APS and BS, onset of BS and APS was not significantly related. When divided into short and long BS duration ( 8 years), CHR-P participants with a longer duration of BS showed evidence for an onset of BS preceding APS (n = 8, p = 0.003). However, in the short BS duration group, APS showed evidence of preceding BS (n = 56, p = 0.020). Finally, there were no significant effects of DUR on cognition or functioning measures., Conclusion: The present findings do not support the view that APS constitute a secondary phenomenon to BS. Moreover, our data could also not confirm that DUR has a significant effect on functioning and cognitive deficits. These findings are discussed in the context of current theories regarding emerging psychosis and the importance of DUR.

Poor functional outcomes are common in individuals at clinical high-risk for psychosis (CHR-P), but the contribution of cognitive deficits remains unclear. We examined the potential utility of cognitive variables in predictive models of functioning at baseline and follow-up with machine learning methods. Additional models fitted on baseline functioning variables were used as a benchmark to evaluate model performance. Data were available for 1) 146 CHR-P individuals of whom 118 completed a 6- and/or 12-month follow-up, 2) 47 participants not fulfilling CHR criteria (CHR-Ns) but displaying affective and substance use disorders and 3) 55 healthy controls (HCs). Predictors of baseline global assessment of functioning (GAF) scores were selected by L1-regularised least angle regression and then used to train classifiers to predict functional outcome in CHR-P individuals. In CHR-P participants, cognitive deficits together with clinical and functioning variables explained 41% of the variance in baseline GAF scores while cognitive variables alone explained 12%. These variables allowed classification of functional outcome with an average balanced accuracy (BAC) of 63% in both mixed- and cross-site models. However, higher accuracies (68%-70%) were achieved using classifiers fitted only on baseline functioning variables. Our findings suggest that cognitive deficits, alongside clinical and functioning variables, displayed robust relationships with impaired functioning in CHR-P participants at baseline and follow-up. Moreover, these variables allow for prediction of functional outcome. However, models based on baseline functioning variables showed a similar performance, highlighting the need to develop more accurate algorithms for predicting functional outcome in CHR-P participants., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Borderline Personality Disorder (BPD) is a psychiatric disorder associated with significant morbidity and mortality. However, the neurobiological alterations underlying the condition remain poorly understood. As a result, existing treatments remain inadequate. One of the main risk factors for the development of BPD is a history of childhood maltreatment. However, it is considered neither causative nor specific to the condition. Current theory is therefore increasingly moving toward a 'Gene x Environment' (GxE) model of the condition. The purpose of the current work was to conduct a systematic literature review, which comprehensively identifies all published molecular level GxE studies that have explored the role of specific genetic loci, in influencing the risk of BPD following exposure to childhood abuse or neglect., Methods: Four electronic databases were used to systematically search for molecular level GxE studies of any design, which focused on the development of BPD following exposure to childhood abuse or neglect, without language or date restrictions. Articles were screened independently by two reviewers and results were synthesized narratively., Results: A total of 473 articles were screened of which sixteen were selected for inclusion in our review. Implicated genes were categorised according to their influence on; Neurotransmitter Systems, Neurodevelopment and Neuroendocrine Systems., Conclusions: The identified studies have produced several relevant and statistically significant results. Of particular note, is the repeated finding that genes involved in HPA axis regulation, may be altered by exposure to childhood maltreatment, influencing subsequent susceptibility to BPD. This is both biologically plausible and of potential clinical significance., (Copyright © 2020. Published by Elsevier Ltd.)

Background: Adult psychiatric disorders are associated with both childhood traumatic experiences (CTEs) and neurodevelopmental disorders (NDDs). CTEs and NDDs frequently co-occur in childhood, but their combined risk effect on the emergence of juvenile mania symptoms has not yet been examined., Methods: In a population-representative Swedish twin study, CTEs and NDDs were assessed in 3,348 nine-year old twins born between 1998 and 2001, and treated as dichotomous predictors (any CTEs, any NDDs). Follow-up data were gathered at age 15 through parental reports of mania symptoms, yielding a symptom count score., Results: Both CTEs and NDDs at age 9 contributed uniquely to an increase in mania symptoms at age 15. Children with both risk factors had 1.6 times the rate of mania symptoms as children with CTEs-only (Incidence rate ratio [IRR] 1.63, 95% CI 1.37-1.93), and 1.3 times the rate of mania symptoms as children with NDDs-only (IRR 1.26, 95% CI 1.06-1.50). There was no evidence for an interactive effect of CTEs and NDDs. NDDs showed a trend towards having a larger effect on mania symptoms than CTEs (NDDs-only vs. CTEs-only: IRR 1.29, 95% CI 0.99-1.68)., Limitations: Although it is a strength of the study that the data on exposures and outcome were collected prospectively, parental recall of CTEs was required and CTEs may be under-reported., Conclusions: NDDs are at least as important as CTEs in the development of mania symptoms, and their risk is additive. Those with a history of both CTEs and NDDs should be monitored closely for the development of more severe psychiatric presentations., (Copyright © 2020. Published by Elsevier B.V.)

The current study examined the presence of abnormalities in cortical grey-matter (GM) in a sample of clinical high-risk (CHR) participants and examined relationships with psychosocial functioning and neurocognition. CHR-participants (n = 114), participants who did not fulfil CHR-criteria (CHR-negative) (n = 39) as well as a group of healthy controls (HC) (n = 49) were recruited. CHR-status was assessed using the Comprehensive Assessment of At-Risk Mental State (CAARMS) and the Schizophrenia Proneness Interview, Adult Version (SPI-A). The Brief Assessment of Cognition in Schizophrenia Battery (BACS) as well as tests for emotion recognition, working memory and attention were administered. In addition, role and social functioning as well as premorbid adjustment were assessed. No significant differences in GM-thickness and intensity were observed in CHR-participants compared to CHR-negative and HC. Circumscribed abnormalities in GM-intensity were found in the visual and frontal cortex of CHR-participants. Moreover, small-to-moderate correlations were observed between GM-intensity and neuropsychological deficits in the CHR-group. The current data suggest that CHR-participants may not show comprehensive abnormalities in GM. We discuss the implications of these findings for the pathophysiological theories of early stage-psychosis as well as methodological issues and the impact of different recruitment strategies., Competing Interests: Declaration of competing interest P.J.U. has received research support from Lilly and Lundbeck. S.M.L. has received lecture fees from Janssen, Otsuka and Sunovion. The remaining authors report no biomedical financial interests or potential conflicts of interest. The following are the supplementary data related to this article. Supplementary data to this article can be found online at https://doi.org/10.1016/j.schres.2019.08.034., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Alterations in autonomic functioning in individuals diagnosed with schizophrenia are well-documented. Yet, it is currently unclear whether these dysfunctions extend into the clinical high-risk state. Thus, we investigated resting heart rate (RHR) and heart rate variability (HRV) indices in individuals at clinical high-risk for psychosis (CHR-P). Methods: We recruited 117 CHR-P participants, 38 participants with affective disorders and substance abuse (CHR-N) as well as a group of 49 healthy controls. CHR-P status was assessed with the Comprehensive Assessment of At-Risk Mental States (CAARMS) and the Schizophrenia Proneness Instrument, Adult Version (SPI-A). We obtained 5 min, eyes-open resting-state MEG data, which was used for the extraction of cardiac field-related inter-beat-interval data and from which heart-rate and heart-rate variability measures were computed. Results: Compared to both CHR-N and healthy controls, CHR-P participants were characterized by an increased RHR, which was not explained by differences in psychopathological comorbidity and medication status. Increased RHR correlated with the presence of subthreshold psychotic symptoms and associated distress. No differences between groups were found for heart-rate variability measures, however. Furthermore, there was an association between motor-performance and psychophysiological measures. Conclusion: The current study provides evidence of alterations in autonomic functioning as disclosed by increased RHR in CHR-P participants. Future studies are needed to further evaluate this characteristic feature of CHR-P individuals and its potential predictive value for psychosis development., (Copyright © 2020 Kocsis, Gajwani, Gross, Gumley, Lawrie, Schwannauer, Schultze-Lutter, Grent-‘t-Jong and Uhlhaas.)

Importance: Psychotic disorders are characterized by impairments in neural oscillations, but the nature of the deficit, the trajectory across illness stages, and functional relevance remain unclear., Objectives: To examine whether changes in spectral power, phase locking, and functional connectivity in visual cortex are present during emerging psychosis and whether these abnormalities are associated with clinical outcomes., Design, Setting, and Participants: In this cross-sectional study, participants meeting clinical high-risk criteria for psychosis, participants with first-episode psychosis, participants with affective disorders and substance abuse, and a group of control participants were recruited. Participants underwent measurements with magnetoencephalography and magnetic resonance imaging. Data analysis was carried out between 2018 and 2019., Main Outcomes and Measures: Magnetoencephalographical activity was examined in the 1- to 90-Hz frequency range in combination with source reconstruction during a visual grating task. Event-related fields, power modulation, intertrial phase consistency, and connectivity measures in visual and frontal cortices were associated with neuropsychological scores, psychosocial functioning, and clinical symptoms as well as persistence of subthreshold psychotic symptoms at 12 months., Results: The study participants included those meeting clinical high-risk criteria for psychosis (n = 119; mean [SD] age, 22 [4.4] years; 32 men), 26 patients with first-episode psychosis (mean [SD] age, 24 [4.2] years; 16 men), 38 participants with affective disorders and substance abuse (mean [SD] age, 23 [4.7] years; 11 men), and 49 control participants (mean age [SD], 23 [3.6] years; 16 men). Clinical high-risk participants and patients with first-episode psychosis were characterized by reduced phase consistency of β/γ-band oscillations in visual cortex (d = 0.63/d = 0.93). Moreover, the first-episode psychosis group was also characterized by reduced occipital γ-band power (d = 1.14) and altered visual cortex connectivity (d = 0.74-0.84). Impaired fronto-occipital connectivity was present in both clinical high-risk participants (d = 0.54) and patients with first-episode psychosis (d = 0.84). Importantly, reductions in intertrial phase coherence predicted persistence of subthreshold psychosis in clinical high-risk participants (receiver operating characteristic area under curve = 0.728; 95% CI, 0.612-0.841; P = .001)., Conclusions and Relevance: High-frequency oscillations are impaired in the visual cortex during emerging psychosis and may be linked to behavioral and clinical impairments. Impaired phase consistency of γ-band oscillations was also associated with the persistence of subthreshold psychosis, suggesting that magnetoencephalographical measured neural oscillations could constitute a biomarker for clinical staging of emerging psychosis.

Child maltreatment may affect autonomic nervous system (ANS) responsivity, and ANS responsivity may influence the impact of child maltreatment on later outcomes including long-term mental/physical health. This review systematically evaluated the evidence regarding effects of maltreatment on ANS responsivity in children and examined how ANS responsivity may influence the association between maltreatment and psychopathology, with attention to relevant developmental issues. We searched the literature for relevant studies using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched five electronic databases, performed key word searches in relevant journals, hand searched reference sections of relevant articles, and contacted experts in the field. Articles were extracted according to inclusion criteria and their quality assessed. The search produced 1,388 articles; 22 met inclusion criteria. Most of the studies suggested blunted cardiovascular responsivity generally and sympathetic activation specifically in response to stress in maltreated children compared to nonmaltreated children. Findings around vagal responsivity and skin conductance were mixed. Limited evidence was found for ANS responsivity as a moderator or mediator of psychopathology risk among maltreated children. Maltreatment may be associated with blunted sympathetic activation in stressful situations. Differences in ANS responsivity may influence psychopathology risk among maltreated children. Further research is needed to confirm the nature and magnitude of such effects.

Background: The current study examined the pattern of neurocognitive impairments in a community-recruited sample of clinical high-risk (CHR) participants and established relationships with psychosocial functioning., Methods: CHR-participants (n = 108), participants who did not fulfil CHR-criteria (CHR-negatives) (n = 42) as well as a group of healthy controls (HCs) (n = 55) were recruited. CHR-status was assessed using the Comprehensive Assessment of At-Risk Mental States (CAARMS) and the Schizophrenia Proneness Instrument, Adult Version (SPI-A). The Brief Assessment of Cognition in Schizophrenia Battery (BACS) as well as tests for emotion recognition, working memory and attention were administered. In addition, role and social functioning as well as premorbid adjustment were assessed., Results: CHR-participants were significantly impaired on the Symbol-Coding and Token-Motor task and showed a reduction in total BACS-scores. Moreover, CHR-participants were characterised by prolonged response times (RTs) in emotion recognition as well as by reductions in both social and role functioning, GAF and premorbid adjustments compared with HCs. Neurocognitive impairments in emotion recognition accuracy, emotion recognition RT, processing speed and motor speed were associated with several aspects of functioning explaining between 4% and 12% of the variance., Conclusion: The current data obtained from a community sample of CHR-participants highlight the importance of dysfunctions in motor and processing speed and emotion recognition RT. Moreover, these deficits were found to be related to global, social and role functioning, suggesting that neurocognitive impairments are an important aspect of sub-threshold psychotic experiences and a possible target for therapeutic interventions.

Aim: Mental health-related stigma is considered a significant barrier to help-seeking and accessing care in those experiencing mental illness. Long duration of untreated psychosis is associated with poorer outcomes. The impact of stigma on the duration of untreated psychosis, in first-episode psychosis remains unexplored. To examine the association between mental health-related stigma and access to care in people experiencing first-episode psychosis in Birmingham, UK., Methods: We collected data on a prospective cohort of first-episode psychosis. The Stigma Scale was used as a measure of mental health-related stigma, and duration of untreated psychosis as a measure of delay in accessing care. We performed logistic and linear regression analyses to explore the relationship between mental health-related stigma and duration of untreated psychosis, adjusting for sex, age, educational level, religion and ethnicity., Results: On the 89 participants included in this study, linear regression analysis revealed that overall stigma and the discrimination sub-factor were significant predictors of longer duration of untreated psychosis, whereas logistic regression identified the disclosure sub-factor to be a significant predictor of longer duration of untreated psychosis., Conclusions: These findings demonstrate that stigmatizing views of mental illness from the patient's perspectives can result in delayed access to care. This emphasizes the importance of tackling mental health-related stigma to ensure early treatment and improved outcomes for people experiencing first-episode psychosis., (© 2018 John Wiley & Sons Australia, Ltd.)

Introduction: Identification of participants at clinical high-risk (CHR) for the development of psychosis is an important objective of current preventive efforts in mental health research. However, the utility of using web-based screening approaches to detect CHR participants at the population level has not been investigated., Methods: We tested a web-based screening approach to identify CHR individuals. Potential participants were invited to a website via e-mail invitations, flyers, and invitation letters involving both the general population and mental health services. Two thousand two hundred seventy-nine participants completed the 16-item version of the prodromal questionnaire (PQ-16) and a 9-item questionnaire of perceptual and cognitive aberrations (PCA) for the assessment of basic symptoms (BS) online. 52.3% of participants met a priori cut-off criteria for the PQ and 73.6% for PCA items online. One thousand seven hundred eighty-seven participants were invited for a clinical interview and n = 356 interviews were conducted (response rate: 19.9%) using the Comprehensive Assessment of At-Risk Mental State (CAARMS) and the Schizophrenia Proneness Interview, Adult Version (SPI-A). n = 101 CHR participants and n = 8 first-episode psychosis (FEP) were detected. ROC curve analysis revealed good to moderate sensitivity and specificity for predicting CHR status based on online results for both UHR and BS criteria (sensitivity/specificity: PQ-16 = 82%/46%; PCA = 94%/12%). Selection of a subset of 10 items from both PQ-16 and PCA lead to an improved of specificity of 57% while only marginally affecting sensitivity (81%). CHR participants were characterized by similar levels of functioning and neurocognitive deficits as clinically identified CHR groups., Conclusion: These data provide evidence for the possibility to identify CHR participants through population-based web screening. This could be an important strategy for early intervention and diagnosis of psychotic disorders., (© The Author(s) 2018. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

Background: Lifetime risk of suicide in first-episode psychosis far exceeds the general population, with the risk of suicide persisting long after first presentation. There is strong evidence to suggest that women more frequently attempt suicide, while men are at a greater risk of completing suicide. First-hand experiential evidence is needed in order to better understand men's motives for, and struggles with, suicidality in early psychosis., Methods: Semi-structured interviews were conducted with 7 participants. The interviews explored each respondent's account of their suicide attempt within the broader context of their life, in relation to their past, present and future. In line with the exploratory, inductive nature of the study, an Interpretative Phenomenological Analysis was used to explore the meaning of suicide attempts in these accounts., Results: Three super-ordinate themes emerged: Self-as-vulnerable (intra- and inter-personal relationships), appraisal of cumulative life events as unbearable and meaning of recovery marked by shared sense of hope and imagery for the future., Conclusions: Young men in the early stages of their treatment are seeking to find meaning for frightening, intrusive experiences with origins which often precede psychosis. These experiences permeate personal identity, relationships and recovery. Suicide was perceived as an escape from this conundrum, and was pursued angrily and impulsively. By contrast, the attainment of hope was marked by sharing one's burden and finding a sense of belonging. Specialized assertive outreach programmes may be beneficial in improving the social inclusion of young men who may be particularly marginalized., (© 2017 John Wiley & Sons Australia, Ltd.)

We examined alterations in E/I-balance in schizophrenia (ScZ) through measurements of resting-state gamma-band activity in participants meeting clinical high-risk (CHR) criteria (n = 88), 21 first episode (FEP) patients and 34 chronic ScZ-patients. Furthermore, MRS-data were obtained in CHR-participants and matched controls. Magnetoencephalographic (MEG) resting-state activity was examined at source level and MEG-data were correlated with neuropsychological scores and clinical symptoms. CHR-participants were characterized by increased 64-90 Hz power. In contrast, FEP- and ScZ-patients showed aberrant spectral power at both low- and high gamma-band frequencies. MRS-data showed a shift in E/I-balance toward increased excitation in CHR-participants, which correlated with increased occipital gamma-band power. Finally, neuropsychological deficits and clinical symptoms in FEP and ScZ-patients were correlated with reduced gamma band-activity, while elevated psychotic symptoms in the CHR group showed the opposite relationship. The current study suggests that resting-state gamma-band power and altered Glx/GABA ratio indicate changes in E/I-balance parameters across illness stages in ScZ., Competing Interests: TG, JG, JG, MW, RG, AG, SL, MS, FS, TN, DK, FL, WS, PU No competing interests declared, (© 2018, Grent-'t-Jong et al.)

Hypofunction of the N-methyl-d-aspartate receptor (NMDAR) has been implicated as a possible mechanism underlying cognitive deficits and aberrant neuronal dynamics in schizophrenia. To test this hypothesis, we first administered a sub-anaesthetic dose of S-ketamine (0.006 mg/kg/min) or saline in a single-blind crossover design in 14 participants while magnetoencephalographic data were recorded during a visual task. In addition, magnetoencephalographic data were obtained in a sample of unmedicated first-episode psychosis patients (n = 10) and in patients with chronic schizophrenia (n = 16) to allow for comparisons of neuronal dynamics in clinical populations versus NMDAR hypofunctioning. Magnetoencephalographic data were analysed at source-level in the 1-90 Hz frequency range in occipital and thalamic regions of interest. In addition, directed functional connectivity analysis was performed using Granger causality and feedback and feedforward activity was investigated using a directed asymmetry index. Psychopathology was assessed with the Positive and Negative Syndrome Scale. Acute ketamine administration in healthy volunteers led to similar effects on cognition and psychopathology as observed in first-episode and chronic schizophrenia patients. However, the effects of ketamine on high-frequency oscillations and their connectivity profile were not consistent with these observations. Ketamine increased amplitude and frequency of gamma-power (63-80 Hz) in occipital regions and upregulated low frequency (5-28 Hz) activity. Moreover, ketamine disrupted feedforward and feedback signalling at high and low frequencies leading to hypo- and hyper-connectivity in thalamo-cortical networks. In contrast, first-episode and chronic schizophrenia patients showed a different pattern of magnetoencephalographic activity, characterized by decreased task-induced high-gamma band oscillations and predominantly increased feedforward/feedback-mediated Granger causality connectivity. Accordingly, the current data have implications for theories of cognitive dysfunctions and circuit impairments in the disorder, suggesting that acute NMDAR hypofunction does not recreate alterations in neural oscillations during visual processing observed in schizophrenia.

Background: In 2008, the Mental Health Act (MHA) 2007 amendments to the MHA 1983 were implemented in England and Wales. The amendments were intended to remove perceived obstacles to the detention of high risk patients with personality disorders (PDs), sexual deviance and learning disabilities (LDs). The AMEND study aimed to test the hypothesis that the implementation of these changes would lead to an increase in numbers or proportions of patients with these conditions who would be assessed and detained under the MHA 2007., Method: A prospective, quantitative study of MHA assessments undertaken between July-October 2008-11 at three English sites. Data were collected from local forms used for MHA assessment documentation and patient electronic databases., Results: The total number of assessments in each four month period of data collection varied: 1034 in 2008, 1042 in 2009, 1242 in 2010 and 1010 in 2011 (n = 4415). Of the assessments 65.6% resulted in detention in 2008, 71.3% in 2009, 64.7% in 2010 and 63.5% in 2011. There was no significant change in the odds ratio of detention when comparing the 2008 assessments against the combined 2009, 2010 and 2011 data (OR = 1.025, Fisher's exact Χ 2 p = 0.735). Only patients with LD and 'any other disorder or disability of the mind' were significantly more likely to be assessed under the MHA post implementation (Χ 2  = 5.485, P = 0.018; Χ 2  = 24.962, P > 0.001 respectively). There was no significant change post implementation in terms of the diagnostic category of detained patients., Conclusions: In the first three years post implementation, the 2007 Act did not facilitate the compulsory care of patients with PDs, sexual deviance and LDs.

Background: Childhood maltreatment (CM) is strongly associated with psychiatric disorders in childhood and adulthood. Previous findings suggest that the association between CM and psychiatric disorders is partly causal and partly due to familial confounding, but few studies have investigated the mechanisms behind the association between CM and neurodevelopmental disorders (NDDs). Our objective was to determine whether maltreated children have an elevated number of NDDs and whether CM is a risk factor for an increased NDD 'load' and increased NDD symptoms when controlling for familial effects., Methods: We used a cross-sectional sample from a population-representative Swedish twin study, comprising 8,192 nine-year-old twins born in Sweden between 1997 and 2005. CM was defined as parent-reported exposure to emotional abuse/neglect, physical neglect, physical abuse, and/or sexual abuse. Four NDDs were measured with the Autism-Tics, AD/HD, and other comorbidities inventory., Results: Maltreated children had a greater mean number of NDDs than nonmaltreated children. In a co-twin control design, CM-discordant monozygotic twins did not differ significantly for their number of NDDs, suggesting that CM is not associated with an increased load of NDDs when genetic and shared environmental factors are taken into account. However, CM was associated with a small increase in symptoms of attention-deficit/hyperactivity disorder and autism spectrum disorder in CM-discordant MZ twins, although most of the covariance of CM with NDD symptoms was explained by common genetic effects., Conclusions: Maltreated children are at higher risk of having multiple NDDs. Our findings are, however, not consistent with the notion that CM causes the increased NDD load in maltreated children. Maltreated children should receive a full neurodevelopmental assessment, and clinicians should be aware that children with multiple NDDs are at higher risk of maltreatment., (© 2017 Association for Child and Adolescent Mental Health.)

Background: The transition from adolescence to adulthood is associated with the emergence of psychosis and other mental health problems, highlighting the importance of this developmental period for the understanding of developing psychopathology and individual differences in risk and resilience. The Youth Mental Health Risk and Resilience Study (YouR-Study) aims to identify neurobiological mechanisms and predictors of psychosis-risk with a state-of-the-art neuroimaging approach (Magnetoencephalography, Magnetic Resonance Spectroscopy, Magnetic Resonance Imaging) in combination with core psychological processes, such as affect regulation and attachment, that have been implicated in the development and maintenance of severe mental health problems., Methods/design: One hundred participants meeting clinical high-risk criteria (CHR) for psychosis through the Comprehensive Assessment of At-Risk Mental State and Schizophrenia Proneness Instrument, Adult Version, in the age range from 16 to 35 years of age will be recruited. Mental-state monitoring up to a total of 2 years will be implemented to detect transition to psychosis. In addition, a sample of n = 40 help-seeking participants will be recruited who do not meet CHR-criteria, a group of n = 50 healthy control participants and a sample of n = 25 patients with first-episode psychosis. MEG-activity will be obtained during auditory and visual tasks to examine neural oscillations and event-related fields. In addition, we will obtain estimates of GABA and Glutamate levels through Magnetic Resonance Spectroscopy (MRS) to examine relationships between neural synchrony and excitatory-inhibition (E/I) balance parameters. Neuroimaging will be complemented by detailed neuropsychological assessments as well as psychological measures investigating the impact of childhood abuse, attachment experiences and affect regulation., Discussion: The YouR-study could potentially provide important insights into the neurobiological mechanisms that confer risk for psychosis as well as biomarkers for early diagnosis of severe mental health problems. Moreover, we expect novel data related to the contribution of affect regulation and attachment-processes in the development of mental health problems, leading to an integrative model of early stage psychosis and the factors underlying risk and resilience of emerging psychopathology.

Engagement with psychiatric services is critical for ensuring successful outcomes in patients experiencing a first episode of psychosis (FEP). However, it is not known how sociodemographic factors and patient beliefs about the causes of mental illness affect engagement. This study explored predictors of engagement in a cohort of 103 FEP patients presenting to an early-intervention service. Beliefs that mental illness is caused by social stress or thinking odd thoughts predicted higher engagement scores. Patients with no qualifications were found to have higher engagement scores than those educated to a higher level. Ethnicity, gender, age and socioeconomic factors were not significantly correlated with engagement scores. Duration of untreated illness (DUI) significantly predicted higher engagement scores, but only for values >1220days. Duration of untreated psychosis (DUP) was not a significant predictor of patient engagement scores. Patient beliefs about the causes of mental illness are an important factor to be taken into consideration and may represent a target of interventions to increase engagement in FEP., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Purpose: There is substantial evidence to suggest that Black and minority ethnic (BME) patients are disproportionately detained under the Mental Health Act (MHA). We examined ethnic differences in patients assessed for detention and explored the effect of ethnicity after controlling for confounders., Methods: A prospective study of all MHA assessments conducted in 1 year (April 2009-March 2010) within Birmingham and Solihull Mental Health Foundation Trust, UK. Proportion of assessments and detentions within denominator population of service users and regional populations were calculated. Multiple regression analysis was conducted to determine which variables were associated with the outcome of MHA assessment and the role of ethnicity., Results: Of the 1115 assessments, 709 led to detentions (63.58 %). BME ethnic groups were statistically more likely to be assessed and detained under the MHA as compared to Whites, both in the service user and the ethnic population estimates in Birmingham, UK. MHA detention was predicted by having a serious mental illness, the presence of risk, older age and living alone. Ethnicity was not associated with detention under the MHA with age, diagnosis, risk and level of social support accounted for., Conclusion: The BME 'disproportionality' in detention rates seems to be due to higher rates of mental illness, greater risk and poorer levels of social support rather than ethnicity per se.

Background and Aims. Research on child maltreatment has largely overlooked the under-five age group and focuses primarily on quantitative measurement. This mixed-methods study of maltreated children (N = 92) entering care (age 6-60 months) combines a quantitative focus on the associations between care journey characteristics and mental health outcomes with a qualitative exploration of maltreatment in four different families. Methods. Care journey data was obtained from social care records; mental health and attachment assessments were carried out following entry to care; qualitative data comprised semistructured interviews with professionals, foster carers, and parents. Results. Significant associations were found between suspected sexual abuse and increased DAI inhibited attachment symptoms (p = 0.001) and between reported domestic violence and decreased DAI inhibited (p = 0.016) and disinhibited (p = 0.004) attachment symptoms. Qualitative results: two themes demonstrate the complexity of assessing maltreatment: (1) overlapping maltreatment factors occur in most cases and (2) maltreatment effects may be particularly challenging to isolate. Conclusions. Qualitative exploration has underscored the complexity of assessing maltreatment, indicating why expected associations were not found in this study and posing questions for the quantitative measurement of maltreatment in general. We therefore suggest a new categorisation of maltreatment and call for the complimentary research lenses of further mixed-methods approaches.

Background: Studies demonstrate ethnic variations in pathways to care during first episode psychosis (FEP). There are no extant studies, however, that have statistically examined the influence of culturally mediated illness attributions on these variations., Methods: We conducted an observational study of 123 (45 White; 35 Black; 43 Asian) patients recruited over a two-year period from an Early Intervention Service (EIS) in Birmingham, UK. Sociodemographic factors (age; sex; education; country of birth; religious practice; marital status; living alone), duration of untreated psychosis (DUP), service contacts (general practitioner; emergency services; faith-based; compulsory detention; criminal justice) and illness attributions ("individual;" "natural;" "social;" "supernatural;" "no attribution") were assessed., Results: Ethnic groups did not differ in DUP (p = 0.86). Asian patients were more likely to report supernatural illness attributions in comparison to White (Odds Ratio: 4.02; 95 % Confidence Intervals: 1.52, 10.62) and Black (OR: 3.48; 95 % CI: 1.25, 9.67) patients. In logistic regressions controlling for confounders and illness attributions, Black (OR: 14.00; 95 % CI: 1.30, 151.11) and Asian (OR: 13.29; 95 % CI: 1.26, 140.47) patients were more likely to consult faith-based institutions than White patients. Black patients were more likely to be compulsorily detained than White patients (OR: 4.56; 95 % CI: 1.40, 14.85)., Conclusion: Illness attributions and sociodemographic confounders do not fully explain the ethnic tendency to seek out faith-based institutions. While Asian and Black patients are more likely to seek help from faith-based organisations, this does not appear to lead to a delay in contact with mental health services.

Objective: Embedded in attachment theory is its association with affect regulation, which provides a framework for affective dysregulation in the emerging psychosis., Method: Fifty-one participants meeting criteria for ultra-high risk (UHR) of developing psychosis were recruited from a youth mental health service within the United Kingdom. At intake baseline, prior to starting therapeutic intervention, all clients were assessed on measures of affective dysregulation and attachment., Results: A large proportion of our sample (N = 51) reported clinically significant levels of depression (78%), state anxiety (59%), and social anxiety (65%). Eighty per cent of the UHR sample was insecurely attached. Insecure attachment was significantly associated with elevated depression and social anxiety. Attachment styles were associated with anxiety, depression, and social anxiety. There was no support for a mediating role of social anxiety between attachment styles and depression., Conclusion: Clinically significant levels of distress and anxiety experienced by the young people at high risk of psychosis. Clinical implications for the treatment of affective dysregulation in young people at UHR in relation to their attachment styles have been discussed., (© 2013 The British Psychological Society.)