Psychiatry - Research Publications

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    Combining Clinical With Cognitive or Magnetic Resonance Imaging Data for Predicting Transition to Psychosis in Ultra High-Risk Patients: Data From the PACE 400 Cohort.
    Hartmann, S ; Cearns, M ; Pantelis, C ; Dwyer, D ; Cavve, B ; Byrne, E ; Scott, I ; Yuen, HP ; Gao, C ; Allott, K ; Lin, A ; Wood, SJ ; Wigman, JTW ; Amminger, GP ; McGorry, PD ; Yung, AR ; Nelson, B ; Clark, SR (Elsevier BV, 2023-12-03)
    BACKGROUND: Multimodal modeling that combines biological and clinical data shows promise in predicting transition to psychosis in individuals who are at ultra-high risk. Individuals who transition to psychosis are known to have deficits at baseline in cognitive function and reductions in gray matter volume in multiple brain regions identified by magnetic resonance imaging. METHODS: In this study, we used Cox proportional hazards regression models to assess the additive predictive value of each modality-cognition, cortical structure information, and the neuroanatomical measure of brain age gap-to a previously developed clinical model using functioning and duration of symptoms prior to service entry as predictors in the Personal Assessment and Crisis Evaluation (PACE) 400 cohort. The PACE 400 study is a well-characterized cohort of Australian youths who were identified as ultra-high risk of transitioning to psychosis using the Comprehensive Assessment of At Risk Mental States (CAARMS) and followed for up to 18 years; it contains clinical data (from N = 416 participants), cognitive data (n = 213), and magnetic resonance imaging cortical parameters extracted using FreeSurfer (n = 231). RESULTS: The results showed that neuroimaging, brain age gap, and cognition added marginal predictive information to the previously developed clinical model (fraction of new information: neuroimaging 0%-12%, brain age gap 7%, cognition 0%-16%). CONCLUSIONS: In summary, adding a second modality to a clinical risk model predicting the onset of a psychotic disorder in the PACE 400 cohort showed little improvement in the fit of the model for long-term prediction of transition to psychosis.
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    Childhood trauma is prevalent and associated with co-occurring depression, anxiety, mania and psychosis in young people attending Australian youth mental health services
    Bendall, S ; Eastwood, O ; Spelman, T ; McGorry, P ; Hickie, I ; Yung, AR ; Amminger, P ; Wood, SJ ; Pantelis, C ; Purcell, R ; Phillips, L (SAGE PUBLICATIONS LTD, 2023-12)
    OBJECTIVES: Childhood trauma is common and associated with mental ill health. While high rates of trauma are observed across individual disorders, there is evidence that trauma is associated with an admixture of affective, anxiety and psychotic symptoms in adults. Given that early onset of mental disorder and trauma exposure herald poor outcomes, it is important to examine trauma prevalence rates in youth mental health services and to determine whether this trauma-related clustering is present in help-seeking young people. METHODS: We used data from the Transitions Study, a longitudinal investigation of young people attending headspace youth mental health services in Australia between January 2011 and August 2012. Participants were 775 young people aged 12-25. Childhood trauma was assessed using the Childhood Trauma Questionnaire. Multinomial regression was used to assess whether reported childhood trauma was more strongly associated with the co-occurrence of depression, anxiety, mania and psychosis symptoms than with any one in isolation. RESULTS: Approximately 84% of participants reported some form of abuse (emotional: 68%; physical: 32%; sexual: 22%) or neglect (emotional: 65%; physical: 46%). Exposure to multiple trauma types was common. Childhood trauma was significantly associated with each symptom domain. More severe childhood trauma was more strongly associated with the co-occurrence of symptoms than with any one symptom domain in isolation, such that more severely trauma-exposed young people were more likely to experience increased symptom clustering. CONCLUSIONS: Childhood trauma is pervasive in youth mental health services and associated with a symptom profile that cuts across traditional diagnostic boundaries.
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    Neuroanatomical heterogeneity and homogeneity in individuals at clinical high risk for psychosis
    Baldwin, H ; Radua, J ; Antoniades, M ; Haas, SS ; Frangou, S ; Agartz, I ; Allen, P ; Andreassen, OA ; Atkinson, K ; Bachman, P ; Baeza, I ; Bartholomeusz, CF ; Chee, MWL ; Colibazzi, T ; Cooper, RE ; Corcoran, CM ; Cropley, VL ; Ebdrup, BH ; Fortea, A ; Glenthoj, LB ; Hamilton, HK ; Haut, KM ; Hayes, RA ; He, Y ; Heekeren, K ; Kaess, M ; Kasai, K ; Katagiri, N ; Kim, M ; Kindler, J ; Klaunig, MJ ; Koike, S ; Koppel, A ; Kristensen, TD ; Bin Kwak, Y ; Kwon, JS ; Lawrie, SM ; Lebedeva, I ; Lee, J ; Lin, A ; Loewy, RL ; Mathalon, DH ; Michel, C ; Mizrahi, R ; Moller, P ; Nelson, B ; Nemoto, T ; Nordholm, D ; Omelchenko, MA ; Pantelis, C ; Raghava, JM ; Rossberg, J ; Roessler, W ; Salisbury, DF ; Sasabayashi, D ; Schall, U ; Smigielski, L ; Sugranyes, G ; Suzuki, M ; Takahashi, T ; Tamnes, CK ; Tang, J ; Theodoridou, A ; Thomopoulos, S ; Tomyshev, AS ; Uhlhaas, PJ ; Vaernes, TG ; van Amelsvoort, TAMJ ; Van Erp, TGM ; Waltz, JA ; Westlye, LT ; Wood, SJ ; Zhou, JH ; McGuire, P ; Thompson, PM ; Jalbrzikowski, M ; Hernaus, D ; Fusar-Poli, P (SPRINGERNATURE, 2022-07-26)
    Individuals at Clinical High Risk for Psychosis (CHR-P) demonstrate heterogeneity in clinical profiles and outcome features. However, the extent of neuroanatomical heterogeneity in the CHR-P state is largely undetermined. We aimed to quantify the neuroanatomical heterogeneity in structural magnetic resonance imaging measures of cortical surface area (SA), cortical thickness (CT), subcortical volume (SV), and intracranial volume (ICV) in CHR-P individuals compared with healthy controls (HC), and in relation to subsequent transition to a first episode of psychosis. The ENIGMA CHR-P consortium applied a harmonised analysis to neuroimaging data across 29 international sites, including 1579 CHR-P individuals and 1243 HC, offering the largest pooled CHR-P neuroimaging dataset to date. Regional heterogeneity was indexed with the Variability Ratio (VR) and Coefficient of Variation (CV) ratio applied at the group level. Personalised estimates of heterogeneity of SA, CT and SV brain profiles were indexed with the novel Person-Based Similarity Index (PBSI), with two complementary applications. First, to assess the extent of within-diagnosis similarity or divergence of neuroanatomical profiles between individuals. Second, using a normative modelling approach, to assess the 'normativeness' of neuroanatomical profiles in individuals at CHR-P. CHR-P individuals demonstrated no greater regional heterogeneity after applying FDR corrections. However, PBSI scores indicated significantly greater neuroanatomical divergence in global SA, CT and SV profiles in CHR-P individuals compared with HC. Normative PBSI analysis identified 11 CHR-P individuals (0.70%) with marked deviation (>1.5 SD) in SA, 118 (7.47%) in CT and 161 (10.20%) in SV. Psychosis transition was not significantly associated with any measure of heterogeneity. Overall, our examination of neuroanatomical heterogeneity within the CHR-P state indicated greater divergence in neuroanatomical profiles at an individual level, irrespective of psychosis conversion. Further large-scale investigations are required of those who demonstrate marked deviation.
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    The Relationship Between Grey Matter Volume and Clinical and Functional Outcomes in People at Clinical High Risk for Psychosis.
    Tognin, S ; Richter, A ; Kempton, MJ ; Modinos, G ; Antoniades, M ; Azis, M ; Allen, P ; Bossong, MG ; Perez, J ; Pantelis, C ; Nelson, B ; Amminger, P ; Riecher-Rössler, A ; Barrantes-Vidal, N ; Krebs, M-O ; Glenthøj, B ; Ruhrmann, S ; Sachs, G ; Rutten, BPF ; de Haan, L ; van der Gaag, M ; EU-GEI High Risk Study Group, ; Valmaggia, LR ; McGuire, P (Oxford University Press (OUP), 2022-01)
    OBJECTIVE: To examine the association between baseline alterations in grey matter volume (GMV) and clinical and functional outcomes in people at clinical high risk (CHR) for psychosis. METHODS: 265 CHR individuals and 92 healthy controls were recruited as part of a prospective multi-center study. After a baseline assessment using magnetic resonance imaging (MRI), participants were followed for at least two years to determine clinical and functional outcomes, including transition to psychosis (according to the Comprehensive Assessment of an At Risk Mental State, CAARMS), level of functioning (according to the Global Assessment of Functioning), and symptomatic remission (according to the CAARMS). GMV was measured in selected cortical and subcortical regions of interest (ROI) based on previous studies (ie orbitofrontal gyrus, cingulate gyrus, gyrus rectus, inferior temporal gyrus, parahippocampal gyrus, striatum, and hippocampus). Using voxel-based morphometry, we analysed the relationship between GMV and clinical and functional outcomes. RESULTS: Within the CHR sample, a poor functional outcome (GAF < 65) was associated with relatively lower GMV in the right striatum at baseline (P < .047 after Family Wise Error correction). There were no significant associations between baseline GMV and either subsequent remission or transition to psychosis. CONCLUSIONS: In CHR individuals, lower striatal GMV was associated with a poor level of overall functioning at follow-up. This finding was not related to effects of antipsychotic or antidepressant medication. The failure to replicate previous associations between GMV and later psychosis onset, despite studying a relatively large sample, is consistent with the findings of recent large-scale multi-center studies.
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    Association of Structural Magnetic Resonance Imaging Measures With Psychosis Onset in Individuals at Clinical High Risk for Developing Psychosis An ENIGMA Working Group Mega-analysis
    Jalbrzikowski, M ; Hayes, RA ; Wood, SJ ; Nordholm, D ; Zhou, JH ; Fusar-Poli, P ; Uhlhaas, PJ ; Takahashi, T ; Sugranyes, G ; Kwak, YB ; Mathalon, DH ; Katagiri, N ; Hooker, CI ; Smigielski, L ; Colibazzi, T ; Via, E ; Tang, J ; Koike, S ; Rasser, PE ; Michel, C ; Lebedeva, I ; Hegelstad, WTV ; de la Fuente-Sandoval, C ; Waltz, JA ; Mizrahi, R ; Corcoran, CM ; Resch, F ; Tamnes, CK ; Haas, SS ; Lemmers-Jansen, ILJ ; Agartz, I ; Allen, P ; Amminger, GP ; Andreassen, OA ; Atkinson, K ; Bachman, P ; Baeza, I ; Baldwin, H ; Bartholomeusz, CF ; Borgwardt, S ; Catalano, S ; Chee, MWL ; Chen, X ; Cho, KIK ; Cooper, RE ; Cropley, VL ; Dolz, M ; Ebdrup, BH ; Fortea, A ; Glenthoj, LB ; Glenthoj, BY ; de Haan, L ; Hamilton, HK ; Harris, MA ; Haut, KM ; He, Y ; Heekeren, K ; Heinz, A ; Hubl, D ; Hwang, WJ ; Kaess, M ; Kasai, K ; Kim, M ; Kindler, J ; Klaunig, MJ ; Koppel, A ; Kristensen, TD ; Kwon, JS ; Lawrie, SM ; Lee, J ; Leon-Ortiz, P ; Lin, A ; Loewy, RL ; Ma, X ; McGorry, P ; McGuire, P ; Mizuno, M ; Moller, P ; Moncada-Habib, T ; Munoz-Samons, D ; Nelson, B ; Nemoto, T ; Nordentoft, M ; Omelchenko, MA ; Oppedal, K ; Ouyang, L ; Pantelis, C ; Pariente, JC ; Raghava, JM ; Reyes-Madrigal, F ; Roach, BJ ; Rossberg, JI ; Rossler, W ; Salisbury, DF ; Sasabayashi, D ; Schall, U ; Schiffman, J ; Schlagenhauf, F ; Schmidt, A ; Sorensen, ME ; Suzuki, M ; Theodoridou, A ; Tomyshev, AS ; Tor, J ; Vaernes, TG ; Velakoulis, D ; Venegoni, GD ; Vinogradov, S ; Wenneberg, C ; Westlye, LT ; Yamasue, H ; Yuan, L ; Yung, AR ; van Amelsvoort, TAMJ ; Turner, JA ; van Erp, TGM ; Thompson, PM ; Hernaus, D (AMER MEDICAL ASSOC, 2021-07)
    IMPORTANCE: The ENIGMA clinical high risk (CHR) for psychosis initiative, the largest pooled neuroimaging sample of individuals at CHR to date, aims to discover robust neurobiological markers of psychosis risk. OBJECTIVE: To investigate baseline structural neuroimaging differences between individuals at CHR and healthy controls as well as between participants at CHR who later developed a psychotic disorder (CHR-PS+) and those who did not (CHR-PS-). DESIGN, SETTING, AND PARTICIPANTS: In this case-control study, baseline T1-weighted magnetic resonance imaging (MRI) data were pooled from 31 international sites participating in the ENIGMA Clinical High Risk for Psychosis Working Group. CHR status was assessed using the Comprehensive Assessment of At-Risk Mental States or Structured Interview for Prodromal Syndromes. MRI scans were processed using harmonized protocols and analyzed within a mega-analysis and meta-analysis framework from January to October 2020. MAIN OUTCOMES AND MEASURES: Measures of regional cortical thickness (CT), surface area, and subcortical volumes were extracted from T1-weighted MRI scans. Independent variables were group (CHR group vs control group) and conversion status (CHR-PS+ group vs CHR-PS- group vs control group). RESULTS: Of the 3169 included participants, 1428 (45.1%) were female, and the mean (SD; range) age was 21.1 (4.9; 9.5-39.9) years. This study included 1792 individuals at CHR and 1377 healthy controls. Using longitudinal clinical information, 253 in the CHR-PS+ group, 1234 in the CHR-PS- group, and 305 at CHR without follow-up data were identified. Compared with healthy controls, individuals at CHR exhibited widespread lower CT measures (mean [range] Cohen d = -0.13 [-0.17 to -0.09]), but not surface area or subcortical volume. Lower CT measures in the fusiform, superior temporal, and paracentral regions were associated with psychosis conversion (mean Cohen d = -0.22; 95% CI, -0.35 to 0.10). Among healthy controls, compared with those in the CHR-PS+ group, age showed a stronger negative association with left fusiform CT measures (F = 9.8; P < .001; q < .001) and left paracentral CT measures (F = 5.9; P = .005; q = .02). Effect sizes representing lower CT associated with psychosis conversion resembled patterns of CT differences observed in ENIGMA studies of schizophrenia (ρ = 0.35; 95% CI, 0.12 to 0.55; P = .004) and individuals with 22q11.2 microdeletion syndrome and a psychotic disorder diagnosis (ρ = 0.43; 95% CI, 0.20 to 0.61; P = .001). CONCLUSIONS AND RELEVANCE: This study provides evidence for widespread subtle, lower CT measures in individuals at CHR. The pattern of CT measure differences in those in the CHR-PS+ group was similar to those reported in other large-scale investigations of psychosis. Additionally, a subset of these regions displayed abnormal age associations. Widespread disruptions in CT coupled with abnormal age associations in those at CHR may point to disruptions in postnatal brain developmental processes.
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    Cognitive functioning throughout adulthood and illness stages in individuals with psychotic disorders and their unaffected siblings
    Velthorst, E ; Mollon, J ; Murray, RM ; de Haan, L ; Germeys, IM ; Glahn, DC ; Arango, C ; van der Ven, E ; Di Forti, M ; Bernardo, M ; Guloksuz, S ; Delespaul, P ; Mezquida, G ; Amoretti, S ; Bobes, J ; Saiz, PA ; Garcia-Portilla, MP ; Santos, JL ; Jimenez-Lopez, E ; Sanjuan, J ; Aguilar, EJ ; Arrojo, M ; Carracedo, A ; Lopez, G ; Gonzalez-Penas, J ; Parellada, M ; Atbasoglu, C ; Saka, MC ; Ucok, A ; Alptekin, K ; Akdede, B ; Binbay, T ; Altinyazar, V ; Ulas, H ; Yalincetin, B ; Gumus-Akay, G ; Beyaz, BC ; Soygur, H ; Cankurtaran, ES ; Kaymak, SU ; Maric, NP ; Mihaljevic, MM ; Petrovic, SA ; Mirjanic, T ; Del-Ben, CM ; Ferraro, L ; Gayer-Anderson, C ; Jones, PB ; Jongsma, HE ; Kirkbride, JB ; La Cascia, C ; Lasalvia, A ; Tosato, S ; Llorca, P-M ; Menezes, PR ; Morgan, C ; Quattrone, D ; Menchetti, M ; Selten, J-P ; Szoke, A ; Tarricone, I ; Tortelli, A ; McGuire, P ; Valmaggia, L ; Kempton, MJ ; van der Gaag, M ; Riecher-Rossler, A ; Bressan, RA ; Barrantes-Vidal, N ; Nelson, B ; McGorry, P ; Pantelis, C ; Krebs, M-O ; Ruhrmann, S ; Sachs, G ; Rutten, BPF ; van Os, J ; Alizadeh, BZ ; van Amelsvoort, T ; Bartels-Velthuis, AA ; Bruggeman, R ; van Beveren, NJ ; Luykx, JJ ; Cahn, W ; Simons, CJP ; Kahn, RS ; Schirmbeck, F ; van Winkel, R ; Reichenberg, A (SPRINGERNATURE, 2021-08)
    Important questions remain about the profile of cognitive impairment in psychotic disorders across adulthood and illness stages. The age-associated profile of familial impairments also remains unclear, as well as the effect of factors, such as symptoms, functioning, and medication. Using cross-sectional data from the EU-GEI and GROUP studies, comprising 8455 participants aged 18 to 65, we examined cognitive functioning across adulthood in patients with psychotic disorders (n = 2883), and their unaffected siblings (n = 2271), compared to controls (n = 3301). An abbreviated WAIS-III measured verbal knowledge, working memory, visuospatial processing, processing speed, and IQ. Patients showed medium to large deficits across all functions (ES range = -0.45 to -0.73, p < 0.001), while siblings showed small deficits on IQ, verbal knowledge, and working memory (ES = -0.14 to -0.33, p < 0.001). Magnitude of impairment was not associated with participant age, such that the size of impairment in older and younger patients did not significantly differ. However, first-episode patients performed worse than prodromal patients (ES range = -0.88 to -0.60, p < 0.001). Adjusting for cannabis use, symptom severity, and global functioning attenuated impairments in siblings, while deficits in patients remained statistically significant, albeit reduced by half (ES range = -0.13 to -0.38, p < 0.01). Antipsychotic medication also accounted for around half of the impairment in patients (ES range = -0.21 to -0.43, p < 0.01). Deficits in verbal knowledge, and working memory may specifically index familial, i.e., shared genetic and/or shared environmental, liability for psychotic disorders. Nevertheless, potentially modifiable illness-related factors account for a significant portion of the cognitive impairment in psychotic disorders.
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    Impact of Comorbid Affective Disorders on Longitudinal Clinical Outcomes in Individuals at Ultra-high Risk for Psychosis
    Schirmbeck, F ; van der Burg, NC ; Blankers, M ; Vermeulen, JM ; McGuire, P ; Valmaggia, LR ; Kempton, MJ ; van der Gaag, M ; Riecher-Rossler, A ; Bressan, RA ; Barrantes-Vidal, N ; Nelson, B ; Amminger, GP ; McGorry, P ; Pantelis, C ; Krebs, M-O ; Ruhrmann, S ; Sachs, G ; Rutten, BPF ; van Os, J ; Nordentoft, M ; Glenthoj, B ; Fusar-Poli, P ; de Haan, L (OXFORD UNIV PRESS, 2022-01)
    INTRODUCTION: Diagnoses of anxiety and/or depression are common in subjects at Ultra-High Risk for Psychosis (UHR) and associated with extensive functional impairment. Less is known about the impact of affective comorbidities on the prospective course of attenuated psychotic symptoms (APS). METHOD: Latent class mixed modelling identified APS trajectories in 331 UHR subjects assessed at baseline, 6, 12, and 24 months follow-up. The prognostic value of past, baseline, and one-year DSM-IV depressive or anxiety disorders on trajectories was investigated using logistic regression, controlling for confounders. Cox proportional hazard analyses investigated associations with transition risk. RESULTS: 46.8% of participants fulfilled the criteria for a past depressive disorder, 33.2% at baseline, and 15.1% at one-year follow-up. Any past, baseline, or one-year anxiety disorder was diagnosed in 42.9%, 37.2%, and 27.0%, respectively. Participants were classified into one of three latent APS trajectory groups: (1) persistently low, (2) increasing, and (3) decreasing. Past depression was associated with a higher risk of belonging to the increasing trajectory group, compared to the persistently low (OR = 3.149, [95%CI: 1.298-7.642]) or decreasing group (OR = 3.137, [1.165-8.450]). In contrast, past (OR = .443, [.179-1.094]) or current (OR = .414, [.156-1.094]) anxiety disorders showed a trend-level association with a lower risk of belonging to the increasing group compared to the persistently low group. Past depression was significantly associated with a higher risk of transitioning to psychosis (HR = 2.123, [1.178-3.828]). CONCLUSION: A past depressive episode might be a particularly relevant risk factor for an unfavorable course of APS in UHR individuals. Early affective disturbances may be used to advance detection, prognostic, and clinical strategies.
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    Stress reactivity as a putative mechanism linking childhood trauma with clinical outcomes in individuals at ultra-high-risk for psychosis: Findings from the EU-GEI High Risk Study
    Paetzold, I ; Myin-Germeys, I ; Schick, A ; Nelson, B ; Velthorst, E ; Schirmbeck, F ; van Os, J ; Morgan, C ; Hartmann, J ; van der Gaag, M ; de Haan, L ; Valmaggia, L ; McGuire, P ; Kempton, M ; Reininghaus, U (CAMBRIDGE UNIV PRESS, 2021-05-28)
    AIMS: Childhood trauma is associated with an elevated risk for psychosis, but the psychological mechanisms involved remain largely unclear. This study aimed to investigate emotional and psychotic stress reactivity in daily life as a putative mechanism linking childhood trauma and clinical outcomes in individuals at ultra-high-risk (UHR) for psychosis. METHODS: Experience sampling methodology was used to measure momentary stress, affect and psychotic experiences in the daily life of N = 79 UHR individuals in the EU-GEI High Risk Study. The Childhood Trauma Questionnaire was used to assess self-reported childhood trauma. Clinical outcomes were assessed at baseline, 1- and 2-year follow-up. RESULTS: The association of stress with positive (β = -0.14, p = 0.010) and negative affect (β = 0.11, p = 0.020) was modified by transition status such that stress reactivity was greater in individuals who transitioned to psychosis. Moreover, the association of stress with negative affect (β = 0.06, p = 0.019) and psychotic experiences (β = 0.05, p = 0.037) was greater in individuals exposed to high v. low levels of childhood trauma. We also found evidence that decreased positive affect in response to stress was associated with reduced functioning at 1-year follow-up (B = 6.29, p = 0.034). In addition, there was evidence that the association of childhood trauma with poor functional outcomes was mediated by stress reactivity (e.g. indirect effect: B = -2.13, p = 0.026), but no evidence that stress reactivity mediated the association between childhood trauma and transition (e.g. indirect effect: B = 0.14, p = 0.506). CONCLUSIONS: Emotional and psychotic stress reactivity may be potential mechanisms linking childhood trauma with clinical outcomes in UHR individuals.
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    Obsessive-Compulsive Symptoms and Other Symptoms of the At-risk Mental State for Psychosis: A Network Perspective
    Ong, HL ; Isvoranu, A-M ; Schirmbeck, F ; McGuire, P ; Valmaggia, L ; Kempton, MJ ; van der Gaag, M ; Riecher-Rossler, A ; Bressan, RA ; Barrantes-Vidal, N ; Nelson, B ; Amminger, GP ; McGorry, P ; Pantelis, C ; Krebs, M-O ; Nordentoft, M ; Glenthoj, B ; Ruhrmann, S ; Sachs, G ; Rutten, BPF ; van Os, J ; de Haan, L ; Borsboom, D (OXFORD UNIV PRESS, 2021-07)
    BACKGROUND: The 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. METHOD: Three 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. RESULTS: Strong 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. CONCLUSIONS: Findings 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.
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    From Speech Illusions to Onset of Psychotic Disorder: Applying Network Analysis to an Experimental Measure of Aberrant Experiences
    Boyette, L-L ; Isvoranu, A-M ; Schirmbeck, F ; Velthorst, E ; Simons, CJP ; Barrantes-Vidal, N ; Bressan, R ; Kempton, MJ ; Krebs, M-O ; McGuire, P ; Nelson, B ; Nordentoft, M ; Riecher-Rössler, A ; Ruhrmann, S ; Rutten, BP ; Sachs, G ; Valmaggia, LR ; van der Gaag, M ; Borsboom, D ; de Haan, L ; van Os, J ; McGuire, P ; Valmaggia, LR ; Kempton, MJ ; Calem, M ; Tognin, S ; Modinos, G ; de Haan, L ; van der Gaag, M ; Velthorst, E ; Kraan, TC ; van Dam, DS ; Burger, N ; Nelson, B ; McGorry, P ; Amminger, GP ; Pantelis, C ; Politis, A ; Goodall, J ; Riecher-Rössler, A ; Borgwardt, S ; Studerus, E ; Bressan, R ; Gadelha, A ; Brietzke, E ; Asevedo, G ; Asevedo, E ; Zugman, A ; Barrantes-Vidal, N ; Domínguez-Martínez, T ; Cristóbal-Narváez, P ; Kwapil, TR ; Monsonet, M ; Hinojosa, L ; Kazes, M ; Daban, C ; Bourgin, J ; Gay, O ; Mam-Lam-Fook, C ; Krebs, M-O ; Nordholm, D ; Randers, L ; Krakauer, K ; Glenthøj, L ; Glenthøj, B ; Nordentoft, M ; Ruhrmann, S ; Gebhard, D ; Arnhold, J ; Klosterkötter, J ; Sachs, G ; Lasser, I ; Winklbaur, B ; Delespaul, PA ; Rutten, BP ; van Os, J (Oxford University Press (OUP), 2020-01-01)
    Abstract Aberrant perceptional experiences are a potential early marker of psychosis development. Earlier studies have found experimentally assessed speech illusions to be associated with positive symptoms in patients with psychotic disorders, but findings for attenuated symptoms in individuals without psychotic disorders have been inconsistent. Also, the role of affect is unclear. The aim of this study was to use the network approach to investigate how speech illusions relate to individual symptoms and onset of a psychotic disorder. We estimated a network model based on data from 289 Clinical High-Risk (CHR) subjects, participating in the EU-GEI project. The network structure depicts statistical associations between (affective and all) speech illusions, cross-sectional individual attenuated positive and affective symptoms, and transition to psychotic disorder after conditioning on all other variables in the network. Speech illusions were assessed with the White Noise Task, symptoms with the BPRS and transition during 24-month follow-up with the CAARMS. Affective, not all, speech illusions were found to be directly, albeit weakly, associated with hallucinatory experiences. Hallucinatory experiences, in turn, were associated with delusional ideation. Bizarre behavior was the only symptom in the network steadily predictive of transition. Affective symptoms were highly interrelated, with depression showing the highest overall strength of connections to and predictability by other symptoms. Both speech illusions and transition showed low overall predictability by symptoms. Our findings suggest that experimentally assessed speech illusions are not a mere consequence of psychotic symptoms or disorder, but that their single assessment is likely not useful for assessing transition risk.