At-risk Mental State For Psychosis Research Articles

Basal-Forebrain Cholinergic Nuclei Alterations are Associated With Medication and Cognitive Deficits Across the Schizophrenia Spectrum.

The cholinergic system is altered in schizophrenia. Particularly, patients' volumes of basal-forebrain cholinergic nuclei (BFCN) are lower and correlated with attentional deficits. It is unclear, however, if and how BFCN changes and their link to cognitive symptoms extend across the schizophrenia spectrum, including individuals with at-risk mental state for psychosis (ARMS) or during first psychotic episode (FEP). To address this question, we assessed voxel-based morphometry (VBM) of structural magnetic resonance imaging data of anterior and posterior BFCN subclusters as well as symptom ratings, including cognitive, positive, and negative symptoms, in a large multi-site dataset (n = 4) comprising 68 ARMS subjects, 98 FEP patients (27 unmedicated and 71 medicated), 140 patients with established schizophrenia (SCZ; medicated), and 169 healthy controls. In SCZ, we found lower VBM measures for the anterior BFCN, which were associated with the anticholinergic burden of medication and correlated with patients' cognitive deficits. In contrast, we found larger VBM measures for the posterior BFCN in FEP, which were driven by unmedicated patients and correlated at-trend with cognitive deficits. We found no BFCN changes in ARMS. Altered VBM measures were not correlated with positive or negative symptoms. Results demonstrate complex (posterior vs. anterior BFCN) and non-linear (larger vs. lower VBM) differences in BFCN across the schizophrenia spectrum, which are specifically associated both with medication, including its anticholinergic burden, and cognitive symptoms. Data suggest an altered trajectory of BFCN integrity in schizophrenia, influenced by medication and relevant for cognitive symptoms.

Use of a targeted, computer/web-based guided self-help psychoeducation toolkit for distressing hallucinations (MUSE) in people with an at-risk mental state for psychosis: protocol for a randomised controlled feasibility trial

IntroductionIndividuals who access at-risk mental state (ARMS) services often have unusual sensory experiences and levels of distress that lead them to seek help. The Managing Unusual Sensory Experiences (MUSE) treatment...

A dopamine receptor D2 genetic polymorphism associated with transition to mental disorders in a cohort of individuals with at-risk mental state for psychosis.

To test the association of 45 single nucleotide polymorphisms (SNPs) with transition to psychiatric disorders in a cohort of individuals at ultrahigh risk (UHR) mental state for psychosis. Through general population screening, 88 non-help-seeking UHR subjects and 130 healthy control individuals were genotyped for 45 SNPs related to psychosis. They were followed for a mean of 2.5 years, and conversion to psychotic and to general psychiatric disorders was assessed. Genotype frequencies between controls, converters, and non-converters were analyzed. There were no differences in sociodemographics between controls and UHR. Also, UHR converters and non-converters had no differences in their baseline symptoms scores. The dopamine receptor D2 gene (DRD2) SNP rs6277 was significantly more common among UHR who transitioned to psychosis (p < 0.001) and to UHR who transitioned to any psychiatric disorders (p = 0.001) when compared to UHR who did not transition. The rs6277 T allele was related to psychiatric morbidity in a dose-response fashion, being significantly more frequent in UHR converters than UHR non-converters and control subjects (p = 0.003). Our findings suggest that rs6277 could potentially constitute a genetic marker of transition to psychiatric disorders in subjects with at-risk mental states, warranting further investigation in larger samples.

Machine learning-based ability to classify psychosis and early stages of disease through parenting and attachment-related variables is associated with social cognition

BackgroundRecent views posited that negative parenting and attachment insecurity can be considered as general environmental factors of vulnerability for psychosis, specifically for individuals diagnosed with psychosis (PSY). Furthermore, evidence highlighted a tight relationship between attachment style and social cognition abilities, a key PSY behavioral phenotype. The aim of this study is to generate a machine learning algorithm based on the perceived quality of parenting and attachment style-related features to discriminate between PSY and healthy controls (HC) and to investigate its ability to track PSY early stages and risk conditions, as well as its association with social cognition performance.MethodsPerceived maternal and paternal parenting, as well as attachment anxiety and avoidance scores, were trained to separate 71 HC from 34 PSY (20 individuals diagnosed with schizophrenia + 14 diagnosed with bipolar disorder with psychotic manifestations) using support vector classification and repeated nested cross-validation. We then validated this model on independent datasets including individuals at the early stages of disease (ESD, i.e. first episode of psychosis or depression, or at-risk mental state for psychosis) and with familial high risk for PSY (FHR, i.e. having a first-degree relative suffering from psychosis). Then, we performed factorial analyses to test the group x classification rate interaction on emotion perception, social inference and managing of emotions abilities.ResultsThe perceived parenting and attachment-based machine learning model discriminated PSY from HC with a Balanced Accuracy (BAC) of 72.2%. Slightly lower classification performance was measured in the ESD sample (HC-ESD BAC = 63.5%), while the model could not discriminate between FHR and HC (BAC = 44.2%). We observed a significant group x classification interaction in PSY and HC from the discovery sample on emotion perception and on the ability to manage emotions (both p = 0.02). The interaction on managing of emotion abilities was replicated in the ESD and HC validation sample (p = 0.03).ConclusionOur results suggest that parenting and attachment-related variables bear significant classification power when applied to both PSY and its early stages and are associated with variability in emotion processing. These variables could therefore be useful in psychosis early recognition programs aimed at softening the psychosis-associated disability.

Obsessive-Compulsive Symptoms and Other Symptoms of the At-risk Mental State for Psychosis: A Network Perspective.

BackgroundThe high prevalence of obsessive-compulsive symptoms (OCS) among subjects at Ultra-High Risk (UHR) for psychosis is well documented. However, the network structure spanning the relations between OCS and symptoms of the at risk mental state for psychosis as assessed with the Comprehensive Assessment of At Risk Mental States (CAARMS) has not yet been investigated. This article aimed to use a network approach to investigate the associations between OCS and CAARMS symptoms in a large sample of individuals with different levels of risk for psychosis. MethodThree hundred and forty-one UHR and 66 healthy participants were included, who participated in the EU-GEI study. Data analysis consisted of constructing a network of CAARMS symptoms, investigating central items in the network, and identifying the shortest pathways between OCS and positive symptoms. ResultsStrong associations between OCS and anxiety, social isolation and blunted affect were identified. Depression was the most central symptom in terms of the number of connections, and anxiety was a key item in bridging OCS to other symptoms. Shortest paths between OCS and positive symptoms revealed that unusual thought content and perceptual abnormalities were connected mainly via anxiety, while disorganized speech was connected via blunted affect and cognitive change. ConclusionsFindings provide valuable insight into the central role of depression and the potential connective component of anxiety between OCS and other symptoms of the network. Interventions specifically aimed to reduce affective symptoms might be crucial for the development and prospective course of symptom co-occurrence.

Identifying patients at risk of psychosis: a qualitative study of GP views in South West England.

BackgroundEarly intervention in people with an at-risk mental state for psychosis can decrease the rates of transition to psychosis. GPs play a key role in the identification of this patient group but very few studies have explored GPs’ awareness of patients who are at risk of psychosis.AimTo explore GPs’ views and experiences of identifying patients with an at-risk mental state for psychosis, and the barriers and facilitators to identification.Design and settingIn-depth semi-structured interviews were held with GPs working in South West England primary care. The interviews were conducted between March and July 2019.MethodA topic guide was used to ensure consistency across interviews. This guide was revised to incorporate a definition of the at-risk mental state for psychosis, as after conducting a few interviews it became clear that some GPs were not familiar with this construct. Interviews were audiorecorded and analysed thematically.ResultsA total of 20 GPs were interviewed. Some GPs were not familiar with the concept of being at risk of developing psychosis, and perceived that they may not have the right skills to identify this patient group. Other barriers related to patients not presenting or disclosing psychotic symptoms, and limitations imposed by scarce resources on the structure and provision of NHS services, such as lack of continuity of care and high thresholds for accessing specialised services.ConclusionIdentifying people at risk of psychosis in primary care is difficult. Provision of GP training, development of policies that support continuity of care, and improved access to specialised services could help improve the identification of this patient group.

Can reduced leftward asymmetry of white matter integrity be a marker of transition to psychosis in at-risk mental state?

As a biomarker for the degree of psychosis development, the lateral asymmetry of white matter (WM) integrity in each area of the cerebrum has been investigated; as a result, a reduced leftward asymmetry of WM integrity has been reported in patients with schizophrenia. Although individuals with an at-risk mental state for psychosis (ARMS) who subsequently develop psychosis are believed to have poorer social functioning, only a few studies have actually examined the associations between WM abnormalities and social functioning. The aim of the present study was to clarify the possibly predictive association between a reduced asymmetry of WM integrity and impairments in social functioning in patients with ARMS. Thirty ARMS subjects underwent MRI scanning and were assessed using the Social Functioning Scale (SFS). We examined the fractional anisotropy (FA) values in the cingulum bundle (CB) and the uncinate fasciculus (UF) using a tract-specific analysis. Lateral asymmetry was assessed using the laterality index (LI). The LI of the FA value was positive (leftward) in the CB and negative (rightward) in the UF. Although the LI was not correlated with the Scale of Prodromal Symptoms (SOPS) score, the LI in the CB was positively correlated with the SFS score. In ARMS patients, the degree of reduced leftward asymmetry in the CB might affect deteriorations in social functioning and may be useful as a biomarker for predicting future outcomes at an early stage of psychosis.

Impaired self-recognition in individuals with no full-blown psychotic symptoms represented across the continuum of psychosis: a meta-analysis.

Impairments in self-recognition (i.e. recognition of own thoughts and actions) have been repeatedly shown in individuals with schizophrenia. According to classical clinical characterizations, schizophrenia is included in a continuum encompassing a large range of genetic statuses, psychotic states and symptoms. The current meta-analysis aims to determine whether self-recognition is affected by individuals within the psychosis continuum. Three populations were considered: people with an at-risk mental state for psychosis (ARMS), hallucination-prone individuals and unaffected relatives of patients with schizophrenia. Eleven studies contrasted self-recognition between these three populations (n = 386) and healthy controls (n = 315) and four studies used correlational analysis to estimate comparable effects (n = 629). Eligible studies used experimental paradigms including source-monitoring and self-monitoring. We observed significantly reduced self-recognition accuracy in these populations [g = -0.44 (-0.71 to -0.17), p = 0.002] compared to controls. No influence of the type of population, experimental paradigm or study design was observed. The present analysis argues for self-recognition deficits in populations with no full-blown psychotic symptoms represented across the continuum of psychosis.

Voxel-Based Morphometry Correlates of an Agitated-Aggressive Syndrome in the At-Risk Mental State for Psychosis and First Episode Psychosis

There are mixed reports on structural neuroimaging correlates of aggression in schizophrenia with weak evidence due to cohort overlaps and lack of replications. To our knowledge, no study examined volumetric neuroimaging correlates of aggression in early stages of psychosis. An agitated-aggressive syndrome is present in at-risk mental state (ARMS) and in first-episode psychosis (FEP) – it is unclear whether this syndrome is associated with structural brain abnormalities in early stages of psychosis. Using three-dimensional magnetic resonance imaging and a whole brain voxel-based morphometry approach, we examined 56 ARMS patients, 55 FEP patients and 25 healthy controls. We operationalized aggression using the Excited Component of the Brief Psychiatric Rating Scale (BPRS-EC) and dichotomized our patient group by median split into “BPRS-EC high” (n = 49) and “BPRS-EC low” groups (n = 62). The “BPRS-EC high” group had significantly smaller left lingual gyrus volume than HC. This finding was not present in the “BPRS-EC low” group. In addition, grey matter volume in the left lingual gyrus showed a negative linear correlation with BPRS-EC over all subjects (ρ = −0.318; p = 0.0001) and in the patient group (ρ = −0.202; p = 0.033). These findings provide first hints on structural brain abnormalities associated with an agitated-aggressive syndrome in ARMS and FEP patients.

Federated multi-site longitudinal study of at-risk mental state for psychosis in Japan

There has been recent accumulation of evidence and clinical guidance regarding the at-risk mental state (ARMS) for psychosis. However, most studies have been observational cohort and intervention studies of Western populations. To assess the validity of the ARMS concept and the transition rate to psychosis in a non-Western nation, we retrospectively combined and analyzed clinical data of individuals diagnosed with ARMS who were prospectively followed-up at three specialized clinical services for ARMS in Japan. In total, we included 309 individuals with ARMS, of whom 43 developed overt psychosis. We estimated cumulative transition rates to psychosis with the Kaplan-Meier method, obtaining rates of 12% at 12, 16% at 24, 19% at 36, and 20% at 48 months. Only two individuals reported past cannabis use. Despite several differences among the three sites, transition rates did not differ among them. Furthermore, the transition rate of children aged between 14 and 17 years did not differ from that of individuals aged 18 years or older. Regression analysis revealed that meeting the brief limited intermittent psychotic symptoms (BLIPS) criterion was associated with an increased risk of transition to psychosis, whereas genetic risk factors were not. Although antipsychotic prescription was relatively frequent in this cohort, there was no evidence supporting frequent use of antipsychotics for this population. In conclusion, our findings support the assertion that the current concept of ARMS is applicable in Japan. Development of local clinical guidelines and training for clinicians is necessary to disseminate this concept to more clinical settings.

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

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

Interpersonal Sensitivity in Youth for the At-Risk Mental State for Psychosis in Karachi, Pakistan

&#x0D; &#x0D; &#x0D; Individuals having high interpersonal sensitivity are sensitive to relationships and self-deficits in comparison to others. Studies report that high interpersonal sensitivity can cause low self-esteem and feelings of insecurity. The objective of the study was to assess the interpersonal sensitivity in people with an at-risk mental state (ARMS) for psychosis compared to the individuals not at risk. A total sample of 50 individuals aged 18 to 35 years was recruited from Bahria University, Karwan- e-Hayat and Karachi Psychiatric Hospital: 25 with ARMS and 25 participants who were not ARMS, according to scores on Schizophrenia Proneness Inventory-Adult (SPI-A). All of the participants then responded to self-report questionnaire on Interpersonal Sensitivity Measure. Results showed a significant difference (p&lt; .001), between both the groups where individuals screened positive for ARMS reported higher sensitivity to interpersonal relations compared to those who were not at risk. The findings of the present study indicate that increased sensitivity to social interactions is a manifestation of the potentially early phase of psychosis. Early intervention to those identified as sensitive to interpersonal relations can help avert serious disorders.&#x0D; &#x0D; &#x0D;

Pre-onset risk characteristics for mania among young people at clinical high risk for psychosis

IntroductionPsychosis and mania share conceptual, genetic and clinical features, which suggest the possibility that they have common antecedents. Participants identified to be at-risk for psychosis might also be at-risk for mania. We aimed to identify the rate and predictors of transition to mania in a cohort of youth with clinical or familial risk for psychosis. MethodsAmong a cohort of 416 young people with an at-risk mental state for psychosis defined using the Ultra-High-Risk (UHR) criteria, 74.7% were followed up between 5 and 13years from their baseline assessment. We undertook a matched case-control examination of those who developed mania over the follow-up period compared to those who did not develop mania or psychosis. Transition to mania was determined using either a structured clinical interview, or diagnoses from a state-wide public mental health contact registry. Clinical characteristics and risk factors were examined at baseline using information from structured interviews, clinical file notes, rating scales and unstructured assessments. ResultsEighteen participants developed mania (UHR-Manic transition or UHR-M, 4.3%). In comparison with participants matched on age, gender and baseline-study who developed neither mania nor psychosis, more UHR-M participants had subthreshold manic symptoms or were prescribed antidepressants at baseline. They also had lower global functioning. DiscussionIn addition to the UHR criteria, features such as subthreshold manic symptoms and antidepressant use may help identify at-risk groups that predict the onset of mania in addition to transition to psychosis. Presence of manic symptoms may also indicate syndrome specificity early in the prodromal phase.

Alpha oscillations underlie working memory abnormalities in the psychosis high-risk state

Working memory (WM) functioning, known to be modulated by neural oscillations, is impaired in schizophrenic psychoses. It remains unclear whether in the psychosis high-risk state, WM encoding is altered or whether patients are impaired at shielding their WM against distractors. We employed single-trial analyses of neurophysiological and behavioral data recorded during a WM paradigm, designed to include predictable distractors, on 18 patients with an at-risk mental state for psychosis (ARMS, 26.1±5.45 years) and 21 healthy controls (HCs, 25.5±3.95 years). Strong distractors were associated with reduced WM accuracy (p=0.036), but only ARMS patients required more processing time for strong distractors (p=0.002). Increased parieto-occipital alpha amplitude preceding distractor presentations was associated with enhanced accuracy only in HCs (p=0.009). During encoding, increased intertrial alpha phase locking values were associated with increased performance. Reduced shielding mechanisms against distractors in ARMS patients could lead to defective WM maintenance, which may result in significant confusion that may contribute to the formation of psychotic symptoms.

Interpersonal sensitivity in the at-risk mental state for psychosis in Karachi, Pakistan

IntroductionInterpersonal sensitivity can be explained as a personality trait in which there is an excessive and expanded awareness of the behavior and emotions of others. Individuals having high interpersonal sensitivity are sensitive to interpersonal relationships and self-deficiencies in comparison to others. Studies report that high interpersonal sensitivity can cause low self-esteem and feelings of insecurity.ObjectivesThe objective of this study was to examine the level of interpersonal sensitivity in individuals with an at-risk mental state (ARMS) for psychosis compared to the individuals not at risk for psychosis.MethodsA total sample of 50 individuals was recruited from Bahria University, Karwan-e-Hayat and Karachi Psychiatric Hospital: 25 with ARMS for psychosis and 25 participants who were not ARMS, according to scores on Schizophrenia Proneness Inventory-Adult (SPI-A). All of the participants then responded to self-report questionnaire on Interpersonal Sensitivity Measure.ResultsResults showed that the group with ARMS had a significantly higher interpersonal sensitivity on average (112.5) as compared to healthy individuals (91.8). Results show significant difference in both of the groups (t = –5.049; P &lt; .0001) indicating that interpersonal sensitivity in people with ARMS was relatively high compared to those who were not at risk.ConclusionThis study suggests that being ‘hypersensitive’ to interpersonal interactions is a psychological feature of the potentially prodromal phase of psychosis. Addressing difficulties in interpersonal relationships and offering early psychotherapeutic interventions can be beneficial, not only in averting serious illness, but preventing loss to individual and national productivity.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Can neuropsychological testing facilitate differential diagnosis between at-risk mental state for psychosis and adult attention deficit hyperactivity disorder?

IntroductionPatients with an at-risk mental state (ARMS) for psychosis and patients with attention deficit hyperactivity disorder (ADHD) have many overlapping symptoms and hence can be difficult to differentiate clinically.ObjectivesThe aim of this study was to investigate whether the differential diagnosis between ARMS and ADHD could be improved by neuropsychological testing.MethodsA total of 157 ARMS and 122 adult ADHD patients were recruited via the Basel Früherkennung von Psychosen (FePsy) study and the ADHD Special Consultations Unit of the University of Basel Psychiatric Hospital, respectively. Verbal learning and memory was tested with the California Verbal Learning Test (CVLT), sustained attention with the Continuous performance test (CPT) and problem solving abilities with the Tower of Hanoi task. Group differences in neuropsychological performance were analyzed using generalized linear models, which included age and gender as covariates.ResultsAdult ADHD patients recalled significantly fewer words in the CVLT (both after short and long delay) and had significantly more false alarms and omissions and longer reaction times in the CPT than ARMS patients.ConclusionsAdult ADHD patients show larger deficits than ARMS patients in the domains of verbal memory and sustained attention, but not in problem solving abilities. This in line with current meta-analyses, which found that impairments in the domains of attention and verbal memory are of medium effect size in adult ADHD patients and of small effect size in ARMS patients. Our results suggest that measures of these domains can be exploited to improve the differential diagnosis between adult ADHD and ARMS patients.Disclosure of interestThe author has not supplied his/her declaration of competing interest.

The Importance of Metamemory Functioning to the Pathogenesis of Psychosis.

Many studies up to date have implied that biases in the metacognition of memory, so called metamemory, contribute to the development and maintenance of positive symptoms in schizophrenia. However, no study exists which has longitudinally followed patients experiencing positive symptoms. The present article therefore reviews cross-sectional studies on retrospective metamemory abilities in participants within different stages of a schizophrenia spectrum disorder, with heterogeneous symptom severities, creating a pseudo-longitudinal overview. Summarized, a deterioration of these abilities correlating with psychosis development can be inferred. The reviewed publications indicate that metamemory biases can already be found in patients with an at-risk mental state for psychosis (ARMS). Patients in their first episode of psychosis (FEP) seem to be more severely impaired than ARMS-patients but similarly affected compared to chronic patients. The contribution of these biases to the pathogenesis of psychosis is discussed, giving consideration to relations with other cognitive- and metacognitive functions, neurochemical processes and neural correlates. It is hypothesized that the biases represent early cognitive markers of the beginning and persisting psychotic state. An early treatment program could help patients to ameliorate the general course of illness or even to prevent the risk of a transition to psychosis.

SU71. Effects of Cannabidiol on Mediotemporal and Dorsostriatal Activity During Encoding and Recall, in the At-Risk Mental State for Psychosis

SU71. Effects of Cannabidiol on Mediotemporal and Dorsostriatal Activity During Encoding and Recall, in the At-Risk Mental State for Psychosis

The access and waiting-time standard for first-episode psychosis: an opportunity for identification and treatment of psychosis risk states?

Expansion of early intervention services to identify and clinically manage at-risk mental state for psychosis has been recently commissioned by NHS England. Although this is a welcome development for preventive psychiatry, further clarity is required on thresholds for definition of such risk states and their ability to predict subsequent outcomes. Intervention studies for these risk states have demonstrated that a variety of interventions, including those with fewer adverse effects than antipsychotic medication, may potentially be effective but they should be interpreted with caution.

Stigma toward psychosis and its formulation process: prejudice and discrimination against early stages of schizophrenia

BackgroundStigma toward psychosis can prevent social attendance and help-seeking behavior. Early detection and intervention has been shown to improve patient outcome in schizophrenia. The aim of this study was to reveal the characteristics and formulation process of stigma toward each clinical stage of schizophrenia, taking people's backgrounds into consideration. MethodsThe participants consisted of three groups: general public, patients with mental illness, and psychiatric professionals. We performed a survey examining stigmas toward people with psychotic-like-experiences (PLE), at-risk mental state for psychosis (ARMS), schizophrenia, or depression. Prejudice was measured using a 21-item questionnaire, and discrimination was measured using the Social Distance Scale. ResultsThe participants consisted of 149 people from the general public, 97 patients, and 119 psychiatric professionals. Generally, a similar pattern was observed among the groups in which prejudice and discrimination against PLE was mildest, followed by that against ARMS and depression, and finally schizophrenia. When the stigma of the general public was compared with that of psychiatric professionals, the prejudice and discrimination against PLE of the general public were both lower than those of the psychiatric professionals. However, the prejudice of the general public was stronger than that of the professionals for ARMS. Furthermore, the discrimination of the general public was stronger than that of the professionals for schizophrenia. ConclusionsThe stigmas of mental illness differed according to the clinical stage, although the pattern of severity was similar among the three groups. A formulation process is suggested in which stigma toward schizophrenia develops from an attitudinal property (prejudice) against ARMS and a behavioral property (discrimination) against schizophrenia.