Browsing by Author "Crossley, Nicolas A."

Now showing 1 - 7 of 7
  • Thumbnail Image
    Item
    Childhood adversity increases risk of psychotic experiences in patients with substance use disorder
    (ELSEVIER IRELAND LTD, 2022) Borquez-Infante, Ignacio; Vasquez, Javiera; Dupre, Sofia; Undurraga, Eduardo A.; Crossley, Nicolas A.; Undurraga, Juan
    Introduction: Adverse childhood experiences (ACEs) increase the risk of psychotic experiences (PE), but little is known about heterogeneities of this association in different developmental stages, dimensions, or whether they are affected by substance use disorder (SUD). This study examines the association between different types of ACEs at various developmental stages and lifetime PE in patients with SUD in Chile.Methods: We included 399 consenting adults in outpatient or residential SUD treatment programs. Sociodemo-graphic data and information about PE and ACEs were obtained by trained clinical psychologists.Results: Patients reporting PE experienced more ACEs compared to patients without PE (4.2 versus 3.4). They also experienced more complex adversities (41.8% versus 25.1%), had more psychiatric comorbidities (85% versus 70.4%), and reported using more substances (mean 4.5 versus 3.9). Adjusted association between ACEs and PE showed the highest OR for arrests (1.88), sexual abuse (1.81), alcohol abuse by parents (1.48), school exclusion (1.39), foster or residential care (18.3).Conclusion: Early exposure to ACEs is a risk factor for later PE among patients with SUD. Type of ACE and the period when they occurred is important, suggesting the existence of critical periods where the individual is more susceptible to adverse environmental stimuli.
  • Thumbnail Image
    Item
    Dysconnectivity in Schizophrenia Revisited: Abnormal Temporal Organization of Dynamic Functional Connectivity in Patients With a First Episode of Psychosis
    (2023) Ramirez-Mahaluf, Juan P.; Tepper, Angeles; Maria Alliende, Luz; Mena, Carlos; Castaneda, Carmen Paz; Iruretagoyena, Barbara; Nachar, Ruben; Reyes-Madrigal, Francisco; Leon-Ortiz, Pablo; Mora-Duran, Ricardo; Ossandon, Tomas; Gonzalez-Valderrama, Alfonso; Undurraga, Juan; De la Fuente-Sandoval, Camilo; Crossley, Nicolas A.
    Background and Hypothesis Abnormal functional connectivity between brain regions is a consistent finding in schizophrenia, including functional magnetic resonance imaging (fMRI) studies. Recent studies have highlighted that connectivity changes in time in healthy subjects. We here examined the temporal changes in functional connectivity in patients with a first episode of psychosis (FEP). Specifically, we analyzed the temporal order in which whole-brain organization states were visited. Study Design Two case-control studies, including in each sample a subgroup scanned a second time after treatment. Chilean sample included 79 patients with a FEP and 83 healthy controls. Mexican sample included 21 antipsychotic-naive FEP patients and 15 healthy controls. Characteristics of the temporal trajectories between whole-brain functional connectivity meta-states were examined via resting-state functional MRI using elements of network science. We compared the cohorts of cases and controls and explored their differences as well as potential associations with symptoms, cognition, and antipsychotic medication doses. Study Results We found that the temporal sequence in which patients' brain dynamics visited the different states was more redundant and segregated. Patients were less flexible than controls in changing their network in time from different configurations, and explored the whole landscape of possible states in a less efficient way. These changes were related to the dose of antipsychotics the patients were receiving. We replicated the relationship with antipsychotic medication in the antipsychotic-naive FEP sample scanned before and after treatment. Conclusions We conclude that psychosis is related to a temporal disorganization of the brain's dynamic functional connectivity, and this is associated with antipsychotic medication use.
  • Thumbnail Image
    Item
    Exploring causal mechanisms of psychosis risk
    (2024) Oliver, Dominic; Chesney, Edward; Cullen, Alexis E.; Davies, Cathy; Englund, Amir; Gifford, George; Kerins, Sarah; Lalousis, Paris Alexandros; Logeswaran, Yanakan; Merritt, Kate; Zahid, Uzma; Crossley, Nicolas A.; McCutcheon, Robert A.; McGuire, Philip; Fusar-Poli, Paolo
    Robust epidemiological evidence of risk and protective factors for psychosis is essential to inform preventive interventions. Previous evidence syntheses have classified these risk and protective factors according to their strength of association with psychosis. In this critical review we appraise the distinct and overlapping mechanisms of 25 key environmental risk factors for psychosis, and link these to mechanistic pathways that may contribute to neurochemical alterations hypothesised to underlie psychotic symptoms. We then discuss the implications of our findings for future research, specifically considering interactions between factors, exploring universal and subgroup-specific factors, improving understanding of temporality and risk dynamics, standardising operationalisation and measurement of risk and protective factors, and developing preventive interventions targeting risk and protective factors.
  • Thumbnail Image
    Item
    Obesity and brain structure in schizophrenia - ENIGMA study in 3021 individuals
    (2022) McWhinney, Sean R.; Brosch, Katharina; Calhoun, Vince D.; Crespo-Facorro, Benedicto; Crossley, Nicolas A.; Dannlowski, Udo; Dickie, Erin; Dietze, Lorielle M. F.; Donohoe, Gary; Du Plessis, Stefan; Ehrlich, Stefan; Emsley, Robin; Furstova, Petra; Glahn, David C.; Gonzalez-Valderrama, Alfonso; Grotegerd, Dominik; Holleran, Laurena; Kircher, Tilo T. J.; Knytl, Pavel; Kolenic, Marian; Lencer, Rebekka; Nenadic, Igor; Opel, Nils; Pfarr, Julia-Katharina; Rodrigue, Amanda L.; Rootes-Murdy, Kelly; Ross, Alex J.; Sim, Kang; Skoch, Antonin; Spaniel, Filip; Stein, Frederike; Svancer, Patrik; Tordesillas-Gutierrez, Diana; Undurraga, Juan; Vaquez-Bourgon, Javier; Voineskos, Aristotle; Walton, Esther; Weickert, Thomas W.; Weickert, Cynthia Shannon; Thompson, Paul M.; van Erp, Theo G. M.; Turner, Jessica A.; Hajek, Tomas
    Schizophrenia is frequently associated with obesity, which is linked with neurostructural alterations. Yet, we do not understand how the brain correlates of obesity map onto the brain changes in schizophrenia. We obtained MRI-derived brain cortical and subcortical measures and body mass index (BMI) from 1260 individuals with schizophrenia and 1761 controls from 12 independent research sites within the ENIGMA-Schizophrenia Working Group. We jointly modeled the statistical effects of schizophrenia and BMI using mixed effects. BMI was additively associated with structure of many of the same brain regions as schizophrenia, but the cortical and subcortical alterations in schizophrenia were more widespread and pronounced. Both BMI and schizophrenia were primarily associated with changes in cortical thickness, with fewer correlates in surface area. While, BMI was negatively associated with cortical thickness, the significant associations between BMI and surface area or subcortical volumes were positive. Lastly, the brain correlates of obesity were replicated among large studies and closely resembled neurostructural changes in major depressive disorders. We confirmed widespread associations between BMI and brain structure in individuals with schizophrenia. People with both obesity and schizophrenia showed more pronounced brain alterations than people with only one of these conditions. Obesity appears to be a relevant factor which could account for heterogeneity of brain imaging findings and for differences in brain imaging outcomes among people with schizophrenia.
  • Thumbnail Image
    Item
    Parsing neurobiological heterogeneity of the clinical high-risk state for psychosis: A pseudo-continuous arterial spin labelling study
    (2023) Oliver, Dominic; Davies, Cathy; Zelaya, Fernando; Selvaggi, Pierluigi; De Micheli, Andrea; Catalan, Ana; Baldwin, Helen; Arribas, Maite; Modinos, Gemma; Crossley, Nicolas A.; Allen, Paul; Egerton, Alice; Jauhar, Sameer; Howes, Oliver D.; McGuire, Philip; Fusar-Poli, Paolo
    IntroductionThe impact of the clinical high-risk for psychosis (CHR-P) construct is dependent on accurately predicting outcomes. Individuals with brief limited intermittent psychotic symptoms (BLIPS) have higher risk of developing a first episode of psychosis (FEP) compared to individuals with attenuated psychotic symptoms (APS). Supplementing subgroup stratification with information from candidate biomarkers based on neurobiological parameters, such as resting-state, regional cerebral blood flow (rCBF), may help refine risk estimates. Based on previous evidence, we hypothesized that individuals with BLIPS would exhibit increased rCBF compared to APS in key regions linked to dopaminergic pathways. MethodsData from four studies were combined using ComBat (to account for between-study differences) to analyse rCBF in 150 age- and sex-matched subjects (n = 30 healthy controls [HCs], n = 80 APS, n = 20 BLIPS and n = 20 FEP). Global gray matter (GM) rCBF was examined in addition to region-of-interest (ROI) analyses in bilateral/left/right frontal cortex, hippocampus and striatum. Group differences were assessed using general linear models: (i) alone; (ii) with global GM rCBF as a covariate; (iii) with global GM rCBF and smoking status as covariates. Significance was set at p < 0.05. ResultsWhole-brain voxel-wise analyses and Bayesian ROI analyses were also conducted. No significant group differences were found in global [F(3,143) = 1,41, p = 0.24], bilateral frontal cortex [F(3,143) = 1.01, p = 0.39], hippocampus [F(3,143) = 0.63, p = 0.60] or striatum [F(3,143) = 0.52, p = 0.57] rCBF. Similar null findings were observed in lateralized ROIs (p > 0.05). All results were robust to addition of covariates (p > 0.05). No significant clusters were identified in whole-brain voxel-wise analyses (p > 0.05(FWE)). Weak-to-moderate evidence was found for an absence of rCBF differences between APS and BLIPS in Bayesian ROI analyses. ConclusionOn this evidence, APS and BLIPS are unlikely to be neurobiologically distinct. Due to this and the weak-to-moderate evidence for the null hypothesis, future research should investigate larger samples of APS and BLIPS through collaboration across large-scale international consortia.
  • No Thumbnail Available
    Item
    Premorbid school performance trajectories in patients with treatment-resistant schizophrenia prescribed clozapine in the public health system in Chile: a case-control study, 2007–2020
    (2025) Conejeros Pavez, Jose Daniel Hernan; Blanco Vasquez, Javiera Alejandra; Diaz, Camila; Mena, Cristian; Undurraga, Juan; Gonzalez-Valderrama, Alfonso; Claro Larrain, Susana; Undurraga Fourcade, Eduardo Andres; Crossley, Nicolas A.
    BackgroundThe premorbid phase of treatment-resistant schizophrenia (TRS) may reveal underlying mechanisms and inform early interventions. According to the neurodevelopmental hypothesis, treatment resistance may be linked to pronounced developmental impairments. We examined school grades and attendance trajectories in children who later developed TRS.MethodsThis case-control study analyzed school grade point average and attendance among all individuals born after 1990 and started on clozapine in Chile’s public health system as a proxy for TRS. Control groups included children later diagnosed with treatment-responsive schizophrenia, bipolar disorder, and unaffected classmates. Linear mixed models accounted for individual and school-level confounders.ResultsWe included 1072 children (9929 observations, 29.3% female) subsequently diagnosed with TRS, 323 (2802 observations, 25.7% female) with schizophrenia, 175 (1784 observations, 53.8% female) bipolar disorder, and 273,260 (533,335 observations, 47% female) unaffected classmates. Children who later developed TRS had worse grades across levels than their classmates (−0.26 SD [−0.2, −0.4]), but not treatment-responsive schizophrenia. All severe mental illness groups showed grade declines in later school levels, with TRS showing steeper linear decline than treatment-responsive schizophrenia (group×age of −0.03; 95%CI −0.04, −0.01) and steeper quadratic decline than bipolar disorder (group×age2 of −0.005; −0.01, −0.001). Attendance declined over time in the two groups developing schizophrenia compared to their classmates. Those developing TRS experienced the sharpest drop (group×age compared to schizophrenia −0.03; −0.05, −0.01 and bipolar disorder −0.027; −0.049, −0.006).ConclusionsTRS may stem from a more aggressive pathological process or pronounced late-maturation abnormality, rather than an early premorbid impairment, suggesting an intervention target.
  • No Thumbnail Available
    Item
    Robust and replicable functional brain signatures of 22q11.2 deletion syndrome and associated psychosis: a deep neural network-based multi-cohort study
    (2024) Supekar, Kaustubh; de los Angeles, Carlo; Ryali, Srikanth; Kushan, Leila; Schleifer, Charlie; Repetto, Gabriela; Crossley, Nicolas A.; Simon, Tony; Bearden, Carrie E.; Menon, Vinod
    A major genetic risk factor for psychosis is 22q11.2 deletion (22q11.2DS). However, robust and replicable functional brain signatures of 22q11.2DS and 22q11.2DS-associated psychosis remain elusive due to small sample sizes and a focus on small single-site cohorts. Here, we identify functional brain signatures of 22q11.2DS and 22q11.2DS-associated psychosis, and their links with idiopathic early psychosis, using one of the largest multi-cohort data to date. We obtained multi-cohort clinical phenotypic and task-free fMRI data from 856 participants (101 22q11.2DS, 120 idiopathic early psychosis, 101 idiopathic autism, 123 idiopathic ADHD, and 411 healthy controls) in a case-control design. A novel spatiotemporal deep neural network (stDNN)-based analysis was applied to the multi-cohort data to identify functional brain signatures of 22q11.2DS and 22q11.2DS-associated psychosis. Next, stDNN was used to test the hypothesis that the functional brain signatures of 22q11.2DS-associated psychosis overlap with idiopathic early psychosis but not with autism and ADHD. stDNN-derived brain signatures distinguished 22q11.2DS from controls, and 22q11.2DS-associated psychosis with very high accuracies (86-94%) in the primary cohort and two fully independent cohorts without additional training. Robust distinguishing features of 22q11.2DS-associated psychosis emerged in the anterior insula node of the salience network and the striatum node of the dopaminergic reward pathway. These features also distinguished individuals with idiopathic early psychosis from controls, but not idiopathic autism or ADHD. Our results reveal that individuals with 22q11.2DS exhibit a highly distinct functional brain organization compared to controls. Additionally, the brain signatures of 22q11.2DS-associated psychosis overlap with those of idiopathic early psychosis in the salience network and dopaminergic reward pathway, providing substantial empirical support for the theoretical aberrant salience-based model of psychosis. Collectively, our findings, replicated across multiple independent cohorts, advance the understanding of 22q11.2DS and associated psychosis, underscoring the value of 22q11.2DS as a genetic model for probing the neurobiological underpinnings of psychosis and its progression.