Markers of Psychosis Risk in the General Population

Taylor, Jerome; Calkins, Monica E.; Gur, Raquel E.

doi:10.1016/j.biopsych.2020.02.002

Cited by 30 publications

(25 citation statements)

References 159 publications

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“…Multiple neuroimaging studies compared brain morphology in ultra-high risk (UHR) for psychosis to healthy controls or first-episode psychosis patients [24][25][26][27]. In contrast to case-control brain imaging studies, which have focused on UHR and first-episode psychosis [28], the nonclinical spectrum (i.e., the occurrence of sparse PLE in healthy subjects) has received less attention despite recent findings of dimensional relations on the phenotype level [29,30]. A continuous relationship between infrequent psychotic-like or subclinical symptoms towards a clinical spectrum [31][32][33] permits a hypothesised relation to neural markers that have been associated with CHR or disease status.…”

Section: Introductionmentioning

confidence: 99%

Distress severity in perceptual anomalies moderates the relationship between prefrontal brain structure and psychosis proneness in nonclinical individuals

Evermann

Schmitt

Meller

et al. 2021

Eur Arch Psychiatry Clin Neurosci

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In the general population, psychosis risk phenotypes occur independently of attenuated prodromal syndromes. Neurobiological correlates of vulnerability could help to understand their meaningfulness. Interactions between the occurrence of psychotic-like experiences (PLE) and other psychological factors e.g., distress related to PLE, may distinguish psychosis-prone individuals from those without risk of future psychotic disorder. We aimed to investigate whether (a) correlates of total PLE and distress, and (b) symptom dimension-specific moderation effects exist at the brain structural level in non-help-seeking adults reporting PLE below and above the screening criterion for clinical high-risk (CHR). We obtained T1-weighted whole-brain MRI scans from 104 healthy adults from the community without psychosis CHR states for voxel-based morphometry (VBM). Brain structural associations with PLE and PLE distress were analysed with multiple linear regression models. Moderation of PLE by distress severity of two types of positive symptoms from the Prodromal Questionnaire (PQ-16) screening inventory was explored in regions-of-interest after VBM. Total PQ-16 score was positively associated with grey matter volume (GMV) in prefrontal regions, occipital fusiform and lingual gyri (p < 0.05, FDR peak-level corrected). Overall distress severity and GMV were not associated. Examination of distress severity on the positive symptom dimensions as moderators showed reduced strength of the association between PLE and rSFG volume with increased distress severity for perceptual PLE. In this study, brain structural variation was related to PLE level, but not distress severity, suggesting specificity. In healthy individuals, positive relationships between PLE and prefrontal volumes may indicate protective features, which supports the insufficiency of PLE for the prediction of CHR. Additional indicators of vulnerability, such as distress associated with perceptual PLE, change the positive brain structure relationship. Brain structural findings may strengthen clinical objectives through disentanglement of innocuous and risk-related PLE.

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Section: Introductionmentioning

confidence: 99%

Distress severity in perceptual anomalies moderates the relationship between prefrontal brain structure and psychosis proneness in nonclinical individuals

Evermann

Schmitt

Meller

et al. 2021

Eur Arch Psychiatry Clin Neurosci

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“…Indeed, psychosis is also frequent during mood episodes in BD, severe depression, substance use disorder and neurodegenerative disorders ( 16 – 18 ). Intriguingly, some SCZ-like psychopathological abnormalities (i.e., paranoid delusional thinking and auditory hallucinations) are expressed in an attenuated form in 5–8% of the otherwise healthy population, especially in individuals with schizotypal or schizoid personality traits ( 13 , 19 ). This extensive overlapping of symptoms and genetic risk factors with other psychiatric and neurological conditions is suggestive of a common underlying neuropathophysiology for these disorders, which, rather than discrete diagnoses, may represent a continuum that extends to the general population ( 13 , 19 , 20 ).…”

Section: Introductionmentioning

confidence: 99%

Maternal Immune Activation and the Development of Dopaminergic Neurotransmission of the Offspring: Relevance for Schizophrenia and Other Psychoses

2020

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Prenatal infections have been linked to the development of schizophrenia (SCZ) and other neurodevelopmental disorders in the offspring, and work in animal models indicates that this is to occur through the maternal inflammatory response triggered by infection. Several studies in animal models demonstrated that acute inflammatory episodes are sufficient to trigger brain alterations in the adult offspring, especially in the mesolimbic dopamine (DA) system, involved in the pathophysiology of SCZ and other disorders involving psychosis. In the current review, we synthesize the literature on the clinical studies implicating prenatal infectious events in the development of SCZ. Then, we summarize evidence from animal models of maternal immune activation (MIA) and the behavioral and molecular alterations relevant for the function of the DAergic system. Furthermore, we discuss the evidence supporting the involvement of maternal cytokines, such as interleukin 6 (IL-6) and leptin (a hormone with effects on inflammation) in mediating the effects of MIA on the fetal brain, leading to the long-lasting effects on the offspring. In particular, IL-6 has been involved in mediating the effects of MIA animal models in the offspring through actions on the placenta, induction of IL-17a, or triggering the decrease in non-heme iron (hypoferremia). Maternal infection is very likely interacting with additional genetic and environmental risk factors in the development of SCZ; systematically investigating how these interactions produce specific phenotypes is the next step in understanding the etiology of complex psychiatric disorders.

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“…Third, our findings may not generalize to inpatient settings because only 10% of youth in TEOSS were inpatient when the study antipsychotic was initiated. Finally, psychosis exists on a spectrum (Alameda et al 2019;Burton et al 2019;Taylor et al 2020), and because TEOSS only includes youth with schizophrenia, schizoaffective disorder, and schizophreniform disorder, our results may not generalize to nonschizophrenia/schizoaffective psychosis spectrum disorders, like unspecified psychotic disorder.…”

Section: Response Time In Teoss 49mentioning

confidence: 80%

Time to Clinical Response in the Treatment of Early Onset Schizophrenia Spectrum Disorders Study

Taylor

Appel

Eli

et al. 2021

Journal of Child and Adolescent Psychopharmacology

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Objectives: We investigated the time course of clinical response in the Treatment of Early Onset Schizophrenia Spectrum Disorders Study (TEOSS). Methods: TEOSS randomized 119 predominantly outpatient youth ages 8-19 years with schizophrenia or schizoaffective disorder to 8 weeks of treatment with molindone, risperidone, or olanzapine. We used proportional hazards regression to determine whether these three antipsychotics differed in the time until clinical response, defined as the time from treatment initiation to the point of achieving a Clinical Global Impressions-Improvement (CGI-I) scale score of 1 (''very much improved'') or 2 (''much improved'') that was maintained until week 8. Results: Of the 116 youth who initiated treatment, 56 (48%) achieved clinical response. Among clinical responders, the median (-interquartile range) time until clinical response was 4.0 (-4.0) weeks for olanzapine, 4.5 (-4.0) weeks for risperidone, and 6.0 (-4.0) weeks for molindone. There were no significant differences in time course for clinical response between medications ( p = 0.84). Youth without symptom improvement (CGI-I ‡ 4) after 3 weeks were more likely to be clinical nonresponders at week 8 (relative risk ratio = 1.98, 95% confidence interval 1.29-3.05), compared with youth with atleast-minimal symptom improvement after 3 weeks when looking at all antipsychotics combined. Conclusion: To our knowledge, our study is the first to investigate medication differences in treatment response timing in early onset schizophrenia spectrum disorders. Clinical response times for molindone, risperidone, and olanzapine were not significantly different. Furthermore, while lack of early improvement predicted clinical nonresponse, whether or not to continue antipsychotic treatment after 3 or more weeks without symptom improvement should be based on clinical judgment after weighing potential risks, benefits, and alternatives. ClinicalTrials.gov Identifier: NCT00053703

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Markers of Psychosis Risk in the General Population

Cited by 30 publications

References 159 publications

Distress severity in perceptual anomalies moderates the relationship between prefrontal brain structure and psychosis proneness in nonclinical individuals

Distress severity in perceptual anomalies moderates the relationship between prefrontal brain structure and psychosis proneness in nonclinical individuals

Maternal Immune Activation and the Development of Dopaminergic Neurotransmission of the Offspring: Relevance for Schizophrenia and Other Psychoses

Time to Clinical Response in the Treatment of Early Onset Schizophrenia Spectrum Disorders Study

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