scholarly journals Thinner cortex is associated with psychosis onset in individuals at Clinical High Risk for Developing Psychosis: An ENIGMA Working Group mega-analysis

2021 ◽  
Author(s):  
Maria Jalbrzikowski ◽  
Rebecca A. Hayes ◽  
Stephen J. Wood ◽  
Dorte Nordholm ◽  
Juan H. Zhou ◽  
...  
Keyword(s):  
High Risk ◽  
Surface Area ◽  
Cortical Thickness ◽  
Working Group ◽  
Large Scale ◽  
Meta Analysis ◽  
Clinical High Risk ◽  
Postnatal Brain ◽  
Mri Scans ◽  
Subcortical Volume

AbstractImportanceThe ENIGMA clinical high risk for psychosis (CHR) initiative, the largest pooled CHR-neuroimaging sample to date, aims to discover robust neurobiological markers of psychosis risk in a sample with known heterogeneous outcomes.ObjectiveWe investigated baseline structural neuroimaging differences between CHR subjects and healthy controls (HC), and between CHR participants who later developed a psychotic disorder (CHR-PS+) and those who did not (CHR-PS-). We assessed associations with age by group and conversion status, and similarities between the patterns of effect size maps for psychosis conversion and those found in other large-scale psychosis studies.Design, Setting, and ParticipantsBaseline T1-weighted MRI data were pooled from 31 international sites participating in the ENIGMA CHR Working Group. MRI scans were processed using harmonized protocols and analyzed within a mega- and meta-analysis framework from January-October 2020.Main Outcome(s) and Measure(s)Measures of regional cortical thickness (CT), surface area (SA), and subcortical volumes were extracted from T1-weighted MRI scans. Independent variables were group (CHR, HC) and conversion status (CHR-PS+, CHR-PS-, HC).ResultsThe final dataset consisted of 3,169 participants (CHR=1,792, HC=1,377, age range: 9.5 to 39.8 years, 45% female). Using longitudinal clinical information, we identified CHR-PS+ (N=253) and CHR-PS-(N=1,234). CHR exhibited widespread thinner cortex compared to HC (average d=-0.125, range: −0.09 to −0.17), but not SA or subcortical volume. Thinner cortex in the fusiform, superior temporal, and paracentral regions was associated with psychosis conversion (average d=-0.22). Age showed a stronger negative association with left fusiform and left paracentral CT in HC, compared to CHR-PS+. Regional CT psychosis conversion effect sizes resembled patterns of CT alterations observed in other ENIGMA studies of psychosis.Conclusions and RelevanceWe provide evidence for widespread subtle CT reductions in CHR. The pattern of regions displaying greater CT alterations in CHR-PS+ were similar to those reported in other large-scale investigations of psychosis. Additionally, a subset of these regions displayed abnormal age associations. Widespread CT disruptions coupled with abnormal age associations in CHR may point to disruptions in postnatal brain developmental processes.Key PointsQuestionHow do baseline brain morphometric features relate to later psychosis conversion in individuals at clinical high risk (CHR)?FindingsIn the largest coordinated international analysis to date, reduced baseline cortical thickness, but not cortical surface area or subcortical volume, was more pronounced in CHR, in a manner highly consistent with thinner cortex in established psychosis. Regions that displayed greater cortical thinning in future psychosis converters additionally displayed abnormal associations with age.MeaningCHR status and later transition to psychosis is robustly associated with reduced cortical thickness. Abnormal age associations and specificity to cortical thickness may point to aberrant postnatal brain development in CHR, including pruning and myelination.

scholarly journals M156. CORTICAL NEUROANATOMICAL SIGNATURE OF SCHIZOTYPY IN 2,695 INDIVIDUALS ASSESSED IN A WORLDWIDE ENIGMA STUDY

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S195-S195
Author(s):  
Mathilde Antoniades ◽  
Igor Nenadic ◽  
Tilo Kircher ◽  
Alex Krug ◽  
Tina Meller ◽  
...  
Keyword(s):  
Surface Area ◽  
Cortical Thickness ◽  
Orbitofrontal Cortex ◽  
Working Group ◽  
Large Scale ◽  
Partial Correlation ◽  
Meta Analysis ◽  
Healthy Individuals ◽  
Frontal Pole ◽  
Mri Scans

Abstract Background Cortical neuroanatomical abnormalities have been reported along a continuum between individuals with chronic schizophrenia, first-episode psychosis, clinical high risk for psychosis, and healthy individuals self-reporting subclinical psychotic-like experiences (or schizotypy). Recently, the Schizophrenia Working Group within the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) consortium provided meta-analytic evidence for robust cortical thickness abnormalities in schizophrenia, while also indicating that these abnormalities are influenced by illness severity and treatment with antipsychotic medications. In this context, schizotypy research allows the investigation of cortical neuroanatomy associated with the expression of subclinical psychotic-like symptoms without the potential influence of a psychotic illness, its severity, or the use of antipsychotics. This study presents the first large-scale imaging meta-analysis of cortical thickness in schizotypy using standardized methods from 23 datasets worldwide. Methods Cortical thickness and surface area were assessed in MRI scans of 2,695 healthy individuals (mean [range] age of 29.1 [17–55.8], 46.3% male) who had also completed validated self-report schizotypy questionnaires. Each site processed their local T1-weighted MRI scans using FreeSurfer and, following the protocol outlined in the ENIGMA Schizophrenia Working Group study, extracted cortical thickness for 70 Desikan-Killiany (DK) atlas regions (34 regions per hemisphere + left and right hemisphere mean thickness). At each site, partial correlation analyses were performed between regional cortical thickness by ROI and total schizotypy scores in R, predicting the left, right and mean cortical thickness, adjusting for sex, age and site. Random-effects meta-analyses of partial correlation effect sizes for each of the DK atlas regions were performed using R’s metafor package. False discovery rate (pFDR < .05) was used to control for multiple comparisons. Results We found significant positive associations between subclinical psychotic-like experiences and mean cortical thickness of the medial orbitofrontal cortex (r = .077; pFDR = .006) and the frontal pole (r = .073; pFDR = .006). When assessed separately by hemisphere, meta-analysis revealed a significant positive association between subclinical psychotic-like experiences and cortical thickness of the left medial orbitofrontal cortex (r = .066; pFDR = .044), and at trend-level with the right medial orbitofrontal cortex (r = .062; pFDR = .053) and the left frontal pole (r = .062; pFDR = .053). No significant associations were observed for surface area. Discussion Worldwide cooperative analyses of large-scale brain imaging data support a profile of cortical thickness abnormalities involving prefrontal cortical regions positively related to schizotypy in healthy individuals. These findings are not secondary to potential influences of disease chronicity or antipsychotic medication on the neuroanatomical correlates of psychotic-like experiences. The directionality of the observed meta-analytical effects in schizotypy is opposite to those previously reported in patients with schizophrenia (i.e., thinner cortex). The present findings of increased thickness may indicate early microstructural deficits (e.g. in myelination) that contribute to vulnerability for psychosis. Alternatively, these may reflect mechanisms of resilience associated with the expression of subclinical manifestations of psychotic symptoms in otherwise healthy individuals.

Meta-analyzing the prevalence and prognostic effect of antipsychotic exposure in clinical high-risk (CHR): when things are not what they seem

2020 ◽  
pp. 1-9
Author(s):  
Andrea Raballo ◽  
Michele Poletti ◽  
Antonio Preti
Keyword(s):  
High Risk ◽  
Meta Analysis ◽  
Prognostic Impact ◽  
Clinical High Risk ◽  
Qualitative Synthesis ◽  
Prognostic Effect ◽  
Inverse Variance ◽  
Arcsine Transformation ◽  
Estimate Prevalence

Abstract Background The clinical high-risk (CHR) for psychosis paradigm is changing psychiatric practice. However, a widespread confounder, i.e. baseline exposure to antipsychotics (AP) in CHR samples, is systematically overlooked. Such exposure might mitigate the initial clinical presentation, increase the heterogeneity within CHR populations, and confound the evaluation of transition to psychosis at follow-up. This is the first meta-analysis examining the prevalence and the prognostic impact on transition to psychosis of ongoing AP treatment at baseline in CHR cohorts. Methods Major databases were searched for articles published until 20 April 2020. The variance-stabilizing Freeman-Tukey double arcsine transformation was used to estimate prevalence. The binary outcome of transition to psychosis by group was estimated with risk ratio (RR) and the inverse variance method was used for pooling. Results Fourteen studies were eligible for qualitative synthesis, including 1588 CHR individuals. Out of the pooled CHR sample, 370 individuals (i.e. 23.3%) were already exposed to AP at the time of CHR status ascription. Transition toward full-blown psychosis at follow-up intervened in 112 (29%; 95% CI 24–34%) of the AP-exposed CHR as compared to 235 (16%; 14–19%) of the AP-naïve CHR participants. AP-exposed CHR had higher RR of transition to psychosis (RR = 1.47; 95% CI 1.18–1.83; z = 3.48; p = 0.0005), without influence by age, gender ratio, overall sample size, duration of the follow-up, or quality of the studies. Conclusions Baseline AP exposure in CHR samples is substantial and is associated with a higher imminent risk of transition to psychosis. Therefore, such exposure should be regarded as a non-negligible red flag for clinical risk management.

scholarly journals Longitudinal outcome of attenuated positive symptoms, negative symptoms, functioning and remission in people at clinical high risk for psychosis: a meta-analysis

2021 ◽  
Vol 36 ◽  
pp. 100909
Author(s):  
Gonzalo Salazar de Pablo ◽  
Filippo Besana ◽  
Vincenzo Arienti ◽  
Ana Catalan ◽  
Julio Vaquerizo-Serrano ◽  
...  
Keyword(s):  
High Risk ◽  
Negative Symptoms ◽  
Meta Analysis ◽  
Positive Symptoms ◽  
Clinical High Risk ◽  
Longitudinal Outcome

scholarly journals Autism Spectrum Disorder and Clinical High Risk for Psychosis: A Systematic Review and Meta-analysis

2021 ◽  
Author(s):  
Julio Vaquerizo-Serrano ◽  
Gonzalo Salazar de Pablo ◽  
Jatinder Singh ◽  
Paramala Santosh
Keyword(s):  
Systematic Review ◽  
High Risk ◽  
Literature Search ◽  
Meta Analysis ◽  
Autism Spectrum ◽  
Clinical High Risk ◽  
Psychotic Experiences ◽  
Attenuated Psychosis Syndrome ◽  
The Mean ◽  
Spectrum Disorders

AbstractPsychotic experiences can occur in autism spectrum disorders (ASD). Some of the ASD individuals with these experiences may fulfil Clinical High-Risk for Psychosis (CHR-P) criteria. A systematic literature search was performed to review the information on ASD and CHR-P. A meta-analysis of the proportion of CHR-P in ASD was conducted. The systematic review included 13 studies. The mean age of ASD individuals across the included studies was 11.09 years. The Attenuated Psychosis Syndrome subgroup was the most frequently reported. Four studies were meta-analysed, showing that 11.6% of CHR-P individuals have an ASD diagnosis. Symptoms of prodromal psychosis may be present in individuals with ASD. The transition from CHR-P to psychosis is not affected by ASD.

scholarly journals Quantifying the Polygenic Architecture of the Human Cerebral Cortex: Extensive Genetic Overlap between Cortical Thickness and Surface Area

2020 ◽  
Vol 30 (10) ◽  
pp. 5597-5603 ◽  
Author(s):  
Dennis van der Meer ◽  
Oleksandr Frei ◽  
Tobias Kaufmann ◽  
Chi-Hua Chen ◽  
Wesley K Thompson ◽  
...  
Keyword(s):  
Surface Area ◽  
Cortical Thickness ◽  
Large Scale ◽  
Gaussian Mixture ◽  
Total Surface Area ◽  
Brain Morphology ◽  
Genetic Determinants ◽  
Genetic Predictors ◽  
Genetic Overlap ◽  
Causal Variants

Abstract The thickness of the cerebral cortical sheet and its surface area are highly heritable traits thought to have largely distinct polygenic architectures. Despite large-scale efforts, the majority of their genetic determinants remain unknown. Our ability to identify causal genetic variants can be improved by employing brain measures that better map onto the biology we seek to understand. Such measures may have fewer variants but with larger effects, that is, lower polygenicity and higher discoverability. Using Gaussian mixture modeling, we estimated the number of causal variants shared between mean cortical thickness and total surface area, as well as the polygenicity and discoverability of regional measures. We made use of UK Biobank data from 30 880 healthy White European individuals (mean age 64.3, standard deviation 7.5, 52.1% female). We found large genetic overlap between total surface area and mean thickness, sharing 4016 out of 7941 causal variants. Regional surface area was more discoverable (P = 2.6 × 10−6) and less polygenic (P = 0.004) than regional thickness measures. These findings may serve as a roadmap for improved future GWAS studies; knowledge of which measures are most discoverable may be used to boost identification of genetic predictors and thereby gain a better understanding of brain morphology.

scholarly journals S154. TOBACCO SMOKING AND CLINICAL HIGH RISK: A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE EVIDENCE

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S94-S95
Author(s):  
Andrea De Micheli ◽  
Albertine van Lawick van Pabst ◽  
Enass Yossef ◽  
Philip McGuire ◽  
Paolo Fusar-Poli
Keyword(s):  
Systematic Review ◽  
High Risk ◽  
Physical Health ◽  
Tobacco Use ◽  
Citation Index ◽  
Meta Analysis ◽  
Assessment Tools ◽  
Clinical High Risk ◽  
Increased Risk ◽  
Russian Science Citation Index

Abstract Background There is converging evidence that youths at clinical high risk (CHR) are not only likely to develop the first episode of psychosis but also to develop poor physical outcomes. Some physical health risk factors - such as smoking - have been shown to increase the probability of a frank onset of psychosis in those at risk. A meta-analysis conducted in psychotic patients confirmed that daily tobacco use is associated with an increased risk of psychosis. A significant association between any attenuated psychotic symptoms (that characterize CHR state) and cigarette smoking has been recently shown in a study conducted in South London. Nowadays, it is not completely clear how these findings would translate to the CHR population but a better understanding of how physical health parameters could affect psychopathological outcomes could be beneficial for these vulnerable clinical populations. To shed light on the percentage of smokers in CHR populations, an updated systematic review and meta-analysis of the literature has been carried out. Our main aim was to test whether the probability of being a smoker was higher in the CHR subjects or in the control group. Methods The literature search was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We systematically scrutinized from literature inception to 2019 the following on-line databases: Web of Science Core Collection, BIOSIS Citation Index, KCL-Korean Journal Database, MEDLINE, Russian Science Citation Index, SCiELO Citation Index. We have considered all the relevant studies reporting the smoking status in CHR subjects and in control groups. We used the odds ratio (OR) as effect size measure and data were pooled using a random effect approach. Results Preliminary data show that CHR individuals were more likely to use tobacco that matched healthy controls. Specifically, the overall OR of 2.016 (p<.001 95%CI=1.476–2.749) indicated a higher likelihood that CHR individuals would use tobacco compared to controls. Heterogeneity was not significant (I²=30.193 p=0.11). The visual inspection of funnel plots did not reveal a clear suggestion for publication bias and the Egger’s test was non-significant (p=0.10). Discussion Our systematic review and meta-analysis suggest that is crucial to investigate physical health outcomes such as tobacco use as part of clinical practice in CHR services. Unfortunately, current CHR assessment tools are entirely based on the measurement of psychopathological features and do not include an assessment of these parameters on a regular basis.

Brain Cortical Thickness and Surface Area Correlates of Neurocognitive Performance in Patients with Schizophrenia, Bipolar Disorder, and Healthy Adults

2011 ◽  
Vol 17 (6) ◽  
pp. 1080-1093 ◽  
Author(s):  
C.B. Hartberg ◽  
K. Sundet ◽  
L.M. Rimol ◽  
U.K. Haukvik ◽  
E.H. Lange ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Working Memory ◽  
Surface Area ◽  
Cortical Thickness ◽  
Negative Relationship ◽  
Anterior Cingulate ◽  
Neurocognitive Functioning ◽  
Healthy Controls ◽  
Neurocognitive Performance ◽  
Mri Scans

AbstractRelationships between cortical brain structure and neurocognitive functioning have been reported in schizophrenia, but findings are inconclusive, and only a few studies in bipolar disorder have addressed this issue. This is the first study to directly compare relationships between cortical thickness and surface area with neurocognitive functioning in patients with schizophrenia (n = 117) and bipolar disorder (n = 121) and healthy controls (n = 192). MRI scans were obtained, and regional cortical thickness and surface area measurements were analyzed for relationships with test scores from 6 neurocognitive domains. In the combined sample, cortical thickness in the right rostral anterior cingulate was inversely related to working memory, and cortical surface area in four frontal and temporal regions were positively related to neurocognitive functioning. A positive relationship between left transverse temporal thickness and processing speed was specific to schizophrenia. A negative relationship between right temporal pole thickness and working memory was specific to bipolar disorder. In conclusion, significant cortical structure/function relationships were found in a large sample of healthy controls and patients with schizophrenia or bipolar disorder. The differences that were found between schizophrenia and bipolar may indicate differential relationship patterns in the two disorders, which may be of relevance for understanding the underlying pathophysiology. (JINS, 2011, 17, 1080–1093)

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