Centre for Youth Mental Health - Research Publications
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ItemNo Preview AvailableCortisol Levels in Childhood Associated with Emergence of Attenuated Psychotic Symptoms in Early Adulthood(PERGAMON-ELSEVIER SCIENCE LTD, 2021-09)
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ItemNo Preview AvailableInterrelationships between depressive symptoms and positive and negative symptoms of recent onset schizophrenia spectrum disorders: A network analytical approach(PERGAMON-ELSEVIER SCIENCE LTD, 2021-08)OBJECTIVE: There is a need to better understand the interrelationships between positive and negative symptoms of recent-onset schizophrenia spectrum disorders (SSD) and co-occurring depressive symptoms. Aims were to determine: (1) whether depressive symptoms are best conceptualised as distinct from, or intrinsic to, positive and negative symptoms; and (2) bridging symptoms. METHODS: Network analysis was applied to data from 198 individuals with depressive and psychotic symptoms in SSD from the Psychosis Recent Onset GRoningen Survey (PROGR-S). Measures were: Montgomery-Åsberg Depression Rating Scale and Positive and Negative Syndrome Scale. RESULTS: Positive symptoms were just as likely to be associated with depressive and negative symptoms, and had more strong associations with depressive than negative symptoms. Negative symptoms were more likely to be associated with depressive than positive symptoms, and had more strong associations with depressive than positive symptoms. Suspiciousness and stereotyped thinking bridged between positive and depressive symptoms, and apparent sadness and lassitude between negative and depressive symptoms. CONCLUSIONS: Depressive symptoms might be best conceptualised as intrinsic to positive and negative symptoms pertaining to deficits in motivation and interest in the psychotic phase of SSD. Treatments targeting bridges between depressive and positive symptoms, and depressive and such negative symptoms, might prevent or improve co-occurring depressive symptoms, or vice-versa, in the psychotic phase of SSD.
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ItemNo Preview AvailableAssociation of Structural Magnetic Resonance Imaging Measures With Psychosis Onset in Individuals at Clinical High Risk for Developing Psychosis An ENIGMA Working Group Mega-analysis(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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ItemNo Preview AvailableImproved social functioning following social recovery therapy in first episode psychosis: Do social cognition and neurocognition change following therapy, and do they predict treatment response?(ELSEVIER, 2021-02)UNLABELLED: There is a need to develop and refine psychosocial interventions to improve functioning in First Episode Psychosis (FEP). Social cognition and neurocognition are closely linked to functioning in psychosis; examinations of cognition pre- and post- psychosocial intervention may provide insights into the mechanisms of these interventions, and identify which individuals are most likely to benefit. METHOD: Cognition was assessed within a multi-site trial of Social Recovery Therapy (SRT) for individuals with FEP experiencing poor functioning (<30 h weekly structured activity). Fifty-nine participants were randomly allocated to the therapy group (SRT + Early intervention), and 64 were allocated to treatment as usual group (TAU - early intervention care). Social cognition and neurocognition were assessed at baseline and 9 months; assessors were blind to group allocation. It was hypothesized that social cognition would improve following therapy, and those with better social cognition prior to therapy would benefit the most from SRT. RESULTS: There was no significant impact of SRT on individual neurocognitive or social cognitive variables, however, joint models addressing patterns of missingness demonstrate improvement across a number of cognitive outcomes following SRT. Further, regression analyses showed those who had better social cognition at baseline were most likely to benefit from the therapy (ß = 0.350; 95% CI = 0.830 to 8.891; p = .019). CONCLUSION: It is not clear if SRT impacts on social cognitive or neurocognitive function, however, SRT may be beneficial in those with better social cognition at baseline.
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ItemNo Preview AvailableHeterogeneity and Classification of Recent Onset Psychosis and Depression: A Multimodal Machine Learning Approach(OXFORD UNIV PRESS, 2021-07)Diagnostic heterogeneity within and across psychotic and affective disorders challenges accurate treatment selection, particularly in the early stages. Delineation of shared and distinct illness features at the phenotypic and brain levels may inform the development of more precise differential diagnostic tools. We aimed to identify prototypes of depression and psychosis to investigate their heterogeneity, with common, comorbid transdiagnostic symptoms. Analyzing clinical/neurocognitive and grey matter volume (GMV) data from the PRONIA database, we generated prototypic models of recent-onset depression (ROD) vs. recent-onset psychosis (ROP) by training support-vector machines to separate patients with ROD from patients with ROP, who were selected for absent comorbid features (pure groups). Then, models were applied to patients with comorbidity, ie, ROP with depressive symptoms (ROP+D) and ROD participants with sub-threshold psychosis-like features (ROD+P), to measure their positions within the affective-psychotic continuum. All models were independently validated in a replication sample. Comorbid patients were positioned between pure groups, with ROP+D patients being more frequently classified as ROD compared to pure ROP patients (clinical/neurocognitive model: χ2 = 14.874; P < .001; GMV model: χ2 = 4.933; P = .026). ROD+P patient classification did not differ from ROD (clinical/neurocognitive model: χ2 = 1.956; P = 0.162; GMV model: χ2 = 0.005; P = .943). Clinical/neurocognitive and neuroanatomical models demonstrated separability of prototypic depression from psychosis. The shift of comorbid patients toward the depression prototype, observed at the clinical and biological levels, suggests that psychosis with affective comorbidity aligns more strongly to depressive rather than psychotic disease processes. Future studies should assess how these quantitative measures of comorbidity predict outcomes and individual responses to stratified therapeutic interventions.
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ItemNo Preview AvailableThe association between migrant status and transition in an ultra-high risk for psychosis population(SPRINGER HEIDELBERG, 2021-06)PURPOSE: Migrant status is one of the most replicated and robust risk factors for developing a psychotic disorder. This study aimed to determine whether migrant status in people identified as Ultra-High Risk for Psychosis (UHR) was associated with risk of transitioning to a full-threshold psychotic disorder. METHODS: Hazard ratios for the risk of transition were calculated from five large UHR cohorts (n = 2166) and were used to conduct a meta-analysis using the generic inverse-variance method using a random-effects model. RESULTS: 2166 UHR young people, with a mean age of 19.1 years (SD ± 4.5) were included, of whom 221 (10.7%) were first-generation migrants. A total of 357 young people transitioned to psychosis over a median follow-up time of 417 days (I.Q.R.147-756 days), representing 17.0% of the cohort. The risk of transition to a full-threshold disorder was not increased for first-generation migrants, (HR = 1.08, 95% CI 0.62-1.89); however, there was a high level of heterogeneity between studies The hazard ratio for second-generation migrants to transition to a full-threshold psychotic disorder compared to the remainder of the native-born population was 1.03 (95% CI 0.70-1.51). CONCLUSIONS: This meta-analysis did not find a statistically significant association between migrant status and an increased risk for transition to a full-threshold psychotic disorder; however, several methodological issues could explain this finding. Further research should focus on examining the risk of specific migrant groups and also ensuring that migrant populations are adequately represented within UHR clinics.
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ItemMultimodal prognosis of negative symptom severity in individuals at increased risk of developing psychosis(SPRINGERNATURE, 2021-05-24)Negative symptoms occur frequently in individuals at clinical high risk (CHR) for psychosis and contribute to functional impairments. The aim of this study was to predict negative symptom severity in CHR after 9 months. Predictive models either included baseline negative symptoms measured with the Structured Interview for Psychosis-Risk Syndromes (SIPS-N), whole-brain gyrification, or both to forecast negative symptoms of at least moderate severity in 94 CHR. We also conducted sequential risk stratification to stratify CHR into different risk groups based on the SIPS-N and gyrification model. Additionally, we assessed the models' ability to predict functional outcomes in CHR and their transdiagnostic generalizability to predict negative symptoms in 96 patients with recent-onset psychosis (ROP) and 97 patients with recent-onset depression (ROD). Baseline SIPS-N and gyrification predicted moderate/severe negative symptoms with significant balanced accuracies of 68 and 62%, while the combined model achieved 73% accuracy. Sequential risk stratification stratified CHR into a high (83%), medium (40-64%), and low (19%) risk group regarding their risk of having moderate/severe negative symptoms at 9 months follow-up. The baseline SIPS-N model was also able to predict social (61%), but not role functioning (59%) at above-chance accuracies, whereas the gyrification model achieved significant accuracies in predicting both social (76%) and role (74%) functioning in CHR. Finally, only the baseline SIPS-N model showed transdiagnostic generalization to ROP (63%). This study delivers a multimodal prognostic model to identify those CHR with a clinically relevant negative symptom severity and functional impairments, potentially requiring further therapeutic consideration.
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ItemNo Preview AvailableImpaired olfactory ability associated with larger left hippocampus and rectus volumes at earliest stages of schizophrenia: A sign of neuroinflammation?(ELSEVIER IRELAND LTD, 2020-07)Impaired olfactory identification has been reported as a first sign of schizophrenia during the earliest stages of illness, including before illness onset. The aim of this study was to examine the relationship between volumes of these regions (amygdala, hippocampus, gyrus rectus and orbitofrontal cortex) and olfactory ability in three groups of participants: healthy control participants (Ctls), patients with first-episode schizophrenia (FE-Scz) and chronic schizophrenia patients (Scz). Exploratory analyses were performed in a sample of individuals at ultra-high risk (UHR) for psychosis in a co-submission paper (Masaoka et al., 2020). The relationship to brain structural measures was not apparent prior to psychosis onset, but was only evident following illness onset, with a different pattern of relationships apparent across illness stages (FE-Scz vs Scz). Path analysis found that lower olfactory ability was related to larger volumes of the left hippocampus and gyrus rectus in the FE-Scz group. We speculate that larger hippocampus and rectus in early schizophrenia are indicative of swelling, potentially caused by an active neurochemical or immunological process, such as inflammation or neurotoxicity, which is associated with impaired olfactory ability. The volumetric decreases in the chronic stage of Scz may be due to degeneration resulting from an active immune process and its resolution.
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ItemListening to voices: understanding and self-management of auditory verbal hallucinations in young adults(CAMBRIDGE UNIV PRESS, 2021-06)Aims Auditory Verbal Hallucinations (AVH) are a hallmark of psychosis, but affect many other clinical populations. Patients’ understanding and self-management of AVH may differ between diagnostic groups, change over time, and influence clinical outcomes. We aimed to explore patients’ understanding and self-management of AVH in a young adult clinical population. Method 35 participants reporting frequent AVH were purposively sampled from a youth mental health service, to capture experiences across psychosis and non-psychosis diagnoses. Diary and photo-elicitation methodologies were used – participants were asked to complete diaries documenting experiences of AVH, and to take photographs representing these experiences. In-depth, unstructured interviews were held, using participant-produced materials as a topic guide. Conventional content analysis was conducted, deriving results from the data in the form of themes. Result Three themes emerged: (1)Searching for answers, forming identities – voice-hearers sought to explain their experiences, resulting in the construction of identities for voices, and descriptions of relationships with them. These identities were drawn from participants’ life-stories (e.g., reflecting trauma), and belief-systems (e.g., reflecting supernatural beliefs, or mental illness). Some described this process as active / volitional. Participants described re-defining their own identities in relation to those constructed for AVH (e.g. as diseased, 'chosen', or persecuted), others considered AVH explicitly as aspects of, or changes in, their personality. (2)Coping strategies and goals – patients’ self-management strategies were diverse, reflecting the diverse negative experiences of AVH. Strategies were related to a smaller number of goals, e.g. distraction, soothing overwhelming emotions, 'reality-checking', and retaining agency. (3)Outlook – participants formed an overall outlook reflecting their self-efficacy in managing AVH. Resignation and hopelessness in connection with disabling AVH are contrasted with outlooks of “acceptance” or integration, which were described as positive, ideal, or mature. Conclusion Trans-diagnostic commonalities in understanding and self-management of AVH are highlighted - answer-seeking and identity-formation processes; a diversity of coping strategies and goals; and striving to accept the symptom. Descriptions of “voices-as-self”, and dysfunctional relationships with AVH, could represent specific features of voice-hearing in personality disorder, whereas certain supernatural/paranormal identities and explanations were clearly delusional. However, no aspect of identity-formation was completely unique to psychosis or non-psychosis diagnostic groups. The identity-formation process, coping strategies, and outlooks can be seen as a framework both for individual therapies and further research.
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