Publications by authors named "Danai Dima"

58 Publications

The Value of Web-Based Patient Education Materials on Transarterial Chemoembolization: Systematic Review.

JMIR Cancer 2021 May 7;7(2):e25357. Epub 2021 May 7.

Department of Radiology, Baystate Medical Center, University of Massachusetts Medical School, Springfield, MA, United States.

Background: Thousands of web searches are performed related to transarterial chemoembolization (TACE), given its palliative role in the treatment of liver cancer.

Objective: This study aims to assess the reliability, quality, completeness, readability, understandability, and actionability of websites that provide information on TACE for patients.

Methods: The five most popular keywords pertaining to TACE were searched on Google, Yahoo, and Bing. General website characteristics and the presence of Health On the Net Foundation code certification were documented. Website assessment was performed using the following scores: DISCERN, Journal of the American Medical Association, Flesch-Kincaid Grade Level, Flesch Reading Ease Score, and the Patient Education Materials Assessment Tool. A novel TACE content score was generated to evaluate website completeness.

Results: The search yielded 3750 websites. In total, 81 website entities belonging to 78 website domains met the inclusion criteria. A medical disclaimer was not provided on 28% (22/78) of website domains. Health On the Net code certification was present on 12% (9/78) of website domains. Authorship was absent on 88% (71/81) of websites, and sources were absent on 83% (67/81) of websites. The date of publication or of the last update was not listed on 58% (47/81) of websites. The median DISCERN score was 47.0 (IQR 40.5-54.0). The median TACE content score was 35 (IQR 27-43). The median readability grade level was in the 11th grade. Overall, 61% (49/81) and 16% (13/81) of websites were deemed understandable and actionable, respectively. Not-for-profit websites fared significantly better on the Journal of the American Medical Association, DISCERN, and TACE content scores.

Conclusions: The content referring to TACE that is currently available on the web is unreliable, incomplete, difficult to read, understandable but not actionable, and characterized by low overall quality. Websites need to revise their content to optimally educate consumers and support shared decision-making.

Trial Registration: PROSPERO International Prospective Register of Systematic Reviews CRD42020202747; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020202747.
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http://dx.doi.org/10.2196/25357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140383PMC
May 2021

State anxiety influences P300 and P600 event-related potentials over parietal regions in the hollow-mask illusion experiment.

Personal Neurosci 2021 16;4:e2. Epub 2021 Feb 16.

Department of Psychology, School of Arts and Social Sciences, City, University of London, London, UK.

The hollow-mask illusion is an optical illusion where a concave face is perceived as convex. It has been demonstrated that individuals with schizophrenia and anxiety are less susceptible to the illusion than controls. Previous research has shown that the P300 and P600 event-related potentials (ERPs) are affected in individuals with schizophrenia. Here, we examined whether individual differences in neuroticism and anxiety scores, traits that have been suggested to be risk factors for schizophrenia and anxiety disorders, affect ERPs of healthy participants while they view concave faces. Our results confirm that the participants were susceptible to the illusion, misperceiving concave faces as convex. We additionally demonstrate significant interactions of the concave condition with state anxiety in central and parietal electrodes for P300 and parietal areas for P600, but not with neuroticism and trait anxiety. The state anxiety interactions were driven by low-state anxiety participants showing lower amplitudes for concave faces compared to convex. The P300 and P600 amplitudes were smaller when a concave face activated a convex face memory representation, since the stimulus did not match the active representation. The opposite pattern was evident in high-state anxiety participants in regard to state anxiety interaction and the hollow-mask illusion, demonstrating larger P300 and P600 amplitudes to concave faces suggesting impaired late information processing in this group. This could be explained by impaired allocation of attentional resources in high-state anxiety leading to hyperarousal to concave faces that are unexpected mismatches to standard memory representations, as opposed to expected convex faces.
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http://dx.doi.org/10.1017/pen.2020.16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057463PMC
February 2021

Comorbid chronic tic disorder and tourette syndrome in children requiring inpatient mental health treatment.

Clin Child Psychol Psychiatry 2021 Jul 16;26(3):894-905. Epub 2021 Apr 16.

National and Specialist Acorn Lodge Inpatient Children's Unit, Child and Adolescent Mental Health Services, South London and the Maudsley NHS Foundation Trust, London, UK.

Objective: Children needing admission to an inpatient mental health unit often present with severe neuropsychiatric disorders characterised by complex psychopathology. We aimed to examine all admitted children with comorbid chronic tic disorder (CTD) and Tourette syndrome (TS) over a 10-year period and determine the clinical significance of these diagnoses.

Method: A retrospective, naturalistic study was conducted, comparing children with and without CTD/TS in terms of co-morbid diagnoses, medication use, access to education, aggression contributing to the admission, duration of admission, functional outcomes and satisfaction with treatment. Data were analysed using Chi-square/Fisher's exact test and -test for categorical and continuous variables, respectively, and subsequently with unadjusted and adjusted linear and logistic regression analyses.

Results: A relatively high proportion of children had co-morbid CTD/TS (19.7%). There was a significant association with co-morbid obsessive-compulsive disorder, intellectual disability and autism spectrum disorder but not attention deficit hyperactivity disorder. CTD/TS were associated with longer admissions even after adjustments for confounding but did not seem to be independently associated with other examined clinical characteristics.

Conclusions: The prevalence of CTD/TS in children needing inpatient treatment is significant. In our sample, comorbid CTD/TS seem to represent a marker of overall symptom severity as evidenced by longer admissions.
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http://dx.doi.org/10.1177/13591045211007918DOI Listing
July 2021

Cortical thickness across the lifespan: Data from 17,075 healthy individuals aged 3-90 years.

Hum Brain Mapp 2021 Feb 17. Epub 2021 Feb 17.

Laboratory of Psychiatric Neuroimaging, Departamento e Instituto de Psiquiatria, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.

Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3-90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes.
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http://dx.doi.org/10.1002/hbm.25364DOI Listing
February 2021

Subcortical volumes across the lifespan: Data from 18,605 healthy individuals aged 3-90 years.

Hum Brain Mapp 2021 Feb 11. Epub 2021 Feb 11.

Department of Psychology, Center for Brain Science, Harvard University, Cambridge, Massachusetts, USA.

Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.
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http://dx.doi.org/10.1002/hbm.25320DOI Listing
February 2021

Increased serum peripheral C-reactive protein is associated with reduced brain barriers permeability of TSPO radioligands in healthy volunteers and depressed patients: implications for inflammation and depression.

Brain Behav Immun 2021 01 5;91:487-497. Epub 2020 Nov 5.

Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

The relationship between peripheral and central immunity and how these ultimately may cause depressed behaviour has been the focus of a number of imaging studies conducted with Positron Emission Tomography (PET). These studies aimed at testing the immune-mediated model of depression that proposes a direct effect of peripheral cytokines and immune cells on the brain to elicit a neuroinflammatory response via a leaky blood-brain barrier and ultimately depressive behaviour. However, studies conducted so far using PET radioligands targeting the neuroinflammatory marker 18 kDa translocator protein (TSPO) in patient cohorts with depression have demonstrated mild inflammatory brain status but no correlation between central and peripheral immunity. To gain a better insight into the relationship between heightened peripheral immunity and neuroinflammation, we estimated blood-to-brain and blood-to-CSF perfusion rates for two TSPO radiotracers collected in two separate studies, one large cross-sectional study of neuroinflammation in normal and depressed cohorts (N = 51 patients and N = 25 controls) and a second study where peripheral inflammation in N = 7 healthy controls was induced via subcutaneous injection of interferon (IFN)-α. In both studies we observed a consistent negative association between peripheral inflammation, measured with c-reactive protein P (CRP), and radiotracer perfusion into and from the brain parenchyma and CSF. Importantly, there was no association of this effect with the marker of BBB leakage S100β, that was unchanged. These results suggest a different model of peripheral-to-central immunity interaction whereas peripheral inflammation may cause a reduction in BBB permeability. This effect, on the long term, is likely to disrupt brain homeostasis and induce depressive behavioural symptoms.
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http://dx.doi.org/10.1016/j.bbi.2020.10.025DOI Listing
January 2021

Greater male than female variability in regional brain structure across the lifespan.

Hum Brain Mapp 2020 Oct 12. Epub 2020 Oct 12.

FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain.

For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.
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http://dx.doi.org/10.1002/hbm.25204DOI Listing
October 2020

Treatment interruption and discontinuation of hormonal therapy in hormone receptor-positive breast cancer patients.

Breast Cancer Res Treat 2020 Dec 12;184(3):665-674. Epub 2020 Sep 12.

Tufts Clinical and Translational Science Institute (CTSI), Boston, MA, 02111, USA.

Purpose: To investigate predictors of treatment interruption and early discontinuation of adjuvant hormonal therapy (HT) in a retrospective cohort of women with newly diagnosed hormone receptor-positive (HR +) breast cancer.

Methods: Eligible cases were identified from a single institutional tumor registry from 2009 to 2015. Patients were followed from initiation of adjuvant HT for a minimum of one year through December 1, 2016. Predictors of treatment interruption or early discontinuation were analyzed with Cox proportional hazards regression models.

Results: With a median follow-up time of 3.0 years (IQR 1.5-4.5), 22 women (10.9%) discontinued HT early and 47 (23.4%) had at least one treatment interruption of > 14 days. Adjusted Cox proportional hazards regression models showed that women with pre-existing affective disorders were more likely to discontinue therapy early (HR 3.15; 95% CI 1.35-7.37), while those with pre-existing chronic pain disorders were at increased risk for treatment interruption (HR 2.24; 95% CI 1.20-4.19). HT-related symptoms were the most commonly reported reason for HT interruption or discontinuation. Women who experienced severe treatment-related symptoms were at increased risk for both HT interruption (HR 2.64; 95% CI 1.07-6.50) and HT discontinuation (HR 3.48; 95% CI 1.20-10.1).

Conclusions: This study showed that HT interruptions and discontinuation were common, often associated with HT-related symptoms. Clinicians caring for breast cancer patients on HT should monitor closely for treatment-emergent symptoms, especially women with pre-existing disorders, and support them to continue therapy through aggressive symptom management and other patient-centered approaches.
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http://dx.doi.org/10.1007/s10549-020-05892-zDOI Listing
December 2020

Evaluating Daratumumab in the Treatment of Multiple Myeloma: Safety, Efficacy and Place in Therapy.

Cancer Manag Res 2020 26;12:7891-7903. Epub 2020 Aug 26.

The John Conant Davis Myeloma and Amyloid Program, Division of Hematology-Oncology, Tufts Medical Center, Boston, MA 02111, USA.

Despite the tremendous advances in the treatment of multiple myeloma, mortality remains significant, highlighting the need for new effective strategies. In recent years, daratumumab, a novel human monoclonal antibody, binding CD38, has dramatically improved outcomes either as monotherapy or in combination with traditional regimens. Originally approved for relapsed/refractory multiple myeloma, this breakthrough medication is now being used as frontline therapy in patients with newly diagnosed multiple myeloma regardless of transplant eligibility, with trials showing promising results. Its tolerable side-effect profile and enhanced efficacy have led to its widespread incorporation into the management of multiple myeloma and further exploration about its use in other entities such as smoldering myeloma, MGUS, MGRS and amyloidosis. This comprehensive review will discuss daratumumab's mechanism of action and safety profile, as well as research which has defined its current approved indications, and ongoing clinical investigation that will define its future.
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http://dx.doi.org/10.2147/CMAR.S212526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7457558PMC
August 2020

Virtual Histology of Cortical Thickness and Shared Neurobiology in 6 Psychiatric Disorders.

JAMA Psychiatry 2021 Jan;78(1):47-63

Department of Psychiatry and Neuropsychology, School of Mental Health and Neuroscience, Maastricht University, the Netherlands.

Importance: Large-scale neuroimaging studies have revealed group differences in cortical thickness across many psychiatric disorders. The underlying neurobiology behind these differences is not well understood.

Objective: To determine neurobiologic correlates of group differences in cortical thickness between cases and controls in 6 disorders: attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and schizophrenia.

Design, Setting, And Participants: Profiles of group differences in cortical thickness between cases and controls were generated using T1-weighted magnetic resonance images. Similarity between interregional profiles of cell-specific gene expression and those in the group differences in cortical thickness were investigated in each disorder. Next, principal component analysis was used to reveal a shared profile of group difference in thickness across the disorders. Analysis for gene coexpression, clustering, and enrichment for genes associated with these disorders were conducted. Data analysis was conducted between June and December 2019. The analysis included 145 cohorts across 6 psychiatric disorders drawn from the ENIGMA consortium. The numbers of cases and controls in each of the 6 disorders were as follows: ADHD: 1814 and 1602; ASD: 1748 and 1770; BD: 1547 and 3405; MDD: 2658 and 3572; OCD: 2266 and 2007; and schizophrenia: 2688 and 3244.

Main Outcomes And Measures: Interregional profiles of group difference in cortical thickness between cases and controls.

Results: A total of 12 721 cases and 15 600 controls, ranging from ages 2 to 89 years, were included in this study. Interregional profiles of group differences in cortical thickness for each of the 6 psychiatric disorders were associated with profiles of gene expression specific to pyramidal (CA1) cells, astrocytes (except for BD), and microglia (except for OCD); collectively, gene-expression profiles of the 3 cell types explain between 25% and 54% of variance in interregional profiles of group differences in cortical thickness. Principal component analysis revealed a shared profile of difference in cortical thickness across the 6 disorders (48% variance explained); interregional profile of this principal component 1 was associated with that of the pyramidal-cell gene expression (explaining 56% of interregional variation). Coexpression analyses of these genes revealed 2 clusters: (1) a prenatal cluster enriched with genes involved in neurodevelopmental (axon guidance) processes and (2) a postnatal cluster enriched with genes involved in synaptic activity and plasticity-related processes. These clusters were enriched with genes associated with all 6 psychiatric disorders.

Conclusions And Relevance: In this study, shared neurobiologic processes were associated with differences in cortical thickness across multiple psychiatric disorders. These processes implicate a common role of prenatal development and postnatal functioning of the cerebral cortex in these disorders.
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http://dx.doi.org/10.1001/jamapsychiatry.2020.2694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7450410PMC
January 2021

What we learn about bipolar disorder from large-scale neuroimaging: Findings and future directions from the ENIGMA Bipolar Disorder Working Group.

Hum Brain Mapp 2020 Jul 29. Epub 2020 Jul 29.

Division of Mental Health and Addicition, Oslo University Hospital, Oslo, Norway.

MRI-derived brain measures offer a link between genes, the environment and behavior and have been widely studied in bipolar disorder (BD). However, many neuroimaging studies of BD have been underpowered, leading to varied results and uncertainty regarding effects. The Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Bipolar Disorder Working Group was formed in 2012 to empower discoveries, generate consensus findings and inform future hypothesis-driven studies of BD. Through this effort, over 150 researchers from 20 countries and 55 institutions pool data and resources to produce the largest neuroimaging studies of BD ever conducted. The ENIGMA Bipolar Disorder Working Group applies standardized processing and analysis techniques to empower large-scale meta- and mega-analyses of multimodal brain MRI and improve the replicability of studies relating brain variation to clinical and genetic data. Initial BD Working Group studies reveal widespread patterns of lower cortical thickness, subcortical volume and disrupted white matter integrity associated with BD. Findings also include mapping brain alterations of common medications like lithium, symptom patterns and clinical risk profiles and have provided further insights into the pathophysiological mechanisms of BD. Here we discuss key findings from the BD working group, its ongoing projects and future directions for large-scale, collaborative studies of mental illness.
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http://dx.doi.org/10.1002/hbm.25098DOI Listing
July 2020

Eculizumab-induced late erythroid maturation arrest: a case report.

Br J Haematol 2020 10 15;191(1):120-122. Epub 2020 Jul 15.

Division of Hematology-Oncology, Tufts Medical Center, The John Conant Davis Myeloma and Amyloid Program, Boston, MA, USA.

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http://dx.doi.org/10.1111/bjh.16936DOI Listing
October 2020

Functional outcomes and patient satisfaction following inpatient treatment for childhood-onset schizophrenia spectrum disorders vs non-psychotic disorders in children in the United Kingdom.

Early Interv Psychiatry 2021 Apr 20;15(2):412-419. Epub 2020 May 20.

National and Specialist Acorn Lodge Inpatient Children's Unit, Child and Adolescent Mental Health Clinical Academic Group, South London and the Maudsley NHS Foundation Trust, London, UK.

Aim: The aim of this study was to compare clinical characteristics and treatment outcomes between children with Childhood-onset schizophrenia spectrum disorders (COSS) and children with other severe non-psychotic psychiatric conditions (non-COSS), all admitted to a national mental health inpatient children's unit.

Methods: We conducted a retrospective study of all children discharged from a national children's inpatient unit in the United Kingdom, between 2009 and 2018. We compared functional and treatment outcomes and satisfaction with treatment in COSS with non-COSS in the whole sample and separately for male and female patients.

Results: A total of 211 children (55% boys) were included in the sample. The mean age on admission was 129.7 months (10.8 years; age range, 6-12).Twenty cases were diagnosed with COSS (9.5%). In the whole sample, COSS patients had significantly lower Children's Global Assessment Scale (CGAS) scores on admission compared to non-COSS (P = .006). There was a trend towards children with COSS as a group having a longer admission (M = 194.6 days, SD = 125.4) compared to non-COSS (M = 135.8 days, SD = 86.2), (P = .053). Females with COSS seemed to have more significant differences compared to females with non-COSS, in particular, longer admissions (P = .016) and worse CGAS scores at discharge (P = .04), whilst in males, these differences seemed to be attenuated.

Conclusions: Children with COSS have lower functioning at the point of inpatient admission and possibly longer admissions, but similar satisfaction with treatment at discharge from hospital compared with non-COSS. Females with COSS may have worse functional outcomes compared to non-COSS at discharge.
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http://dx.doi.org/10.1111/eip.12973DOI Listing
April 2021

Brain aging in major depressive disorder: results from the ENIGMA major depressive disorder working group.

Mol Psychiatry 2020 May 18. Epub 2020 May 18.

Department of Psychiatry, University of Münster, Münster, Germany.

Major depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in adult MDD patients, and whether this process is associated with clinical characteristics in a large multicenter international dataset. We performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 19 samples worldwide. Healthy brain aging was estimated by predicting chronological age (18-75 years) from 7 subcortical volumes, 34 cortical thickness and 34 surface area, lateral ventricles and total intracranial volume measures separately in 952 male and 1236 female controls from the ENIGMA MDD working group. The learned model coefficients were applied to 927 male controls and 986 depressed males, and 1199 female controls and 1689 depressed females to obtain independent unbiased brain-based age predictions. The difference between predicted "brain age" and chronological age was calculated to indicate brain-predicted age difference (brain-PAD). On average, MDD patients showed a higher brain-PAD of +1.08 (SE 0.22) years (Cohen's d = 0.14, 95% CI: 0.08-0.20) compared with controls. However, this difference did not seem to be driven by specific clinical characteristics (recurrent status, remission status, antidepressant medication use, age of onset, or symptom severity). This highly powered collaborative effort showed subtle patterns of age-related structural brain abnormalities in MDD. Substantial within-group variance and overlap between groups were observed. Longitudinal studies of MDD and somatic health outcomes are needed to further assess the clinical value of these brain-PAD estimates.
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http://dx.doi.org/10.1038/s41380-020-0754-0DOI Listing
May 2020

Neural Circuitry of Novelty Salience Processing in Psychosis Risk: Association With Clinical Outcome.

Schizophr Bull 2020 04;46(3):670-679

Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.

Psychosis has been proposed to develop from dysfunction in a hippocampal-striatal-midbrain circuit, leading to aberrant salience processing. Here, we used functional magnetic resonance imaging (fMRI) during novelty salience processing to investigate this model in people at clinical high risk (CHR) for psychosis according to their subsequent clinical outcomes. Seventy-six CHR participants as defined using the Comprehensive Assessment of At-Risk Mental States (CAARMS) and 31 healthy controls (HC) were studied while performing a novelty salience fMRI task that engaged an a priori hippocampal-striatal-midbrain circuit of interest. The CHR sample was then followed clinically for a mean of 59.7 months (~5 y), when clinical outcomes were assessed in terms of transition (CHR-T) or non-transition (CHR-NT) to psychosis (CAARMS criteria): during this period, 13 individuals (17%) developed a psychotic disorder (CHR-T) and 63 did not. Functional activation and effective connectivity within a hippocampal-striatal-midbrain circuit were compared between groups. In CHR individuals compared to HC, hippocampal response to novel stimuli was significantly attenuated (P = .041 family-wise error corrected). Dynamic Causal Modelling revealed that stimulus novelty modulated effective connectivity from the hippocampus to the striatum, and from the midbrain to the hippocampus, significantly more in CHR participants than in HC. Conversely, stimulus novelty modulated connectivity from the midbrain to the striatum significantly less in CHR participants than in HC, and less in CHR participants who subsequently developed psychosis than in CHR individuals who did not become psychotic. Our findings are consistent with preclinical evidence implicating hippocampal-striatal-midbrain circuit dysfunction in altered salience processing and the onset of psychosis.
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http://dx.doi.org/10.1093/schbul/sbz089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7147595PMC
April 2020

ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries.

Transl Psychiatry 2020 03 20;10(1):100. Epub 2020 Mar 20.

Department of Psychiatry & Behavioral Sciences, Stanford University, Stanford, CA, USA.

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors.
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http://dx.doi.org/10.1038/s41398-020-0705-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7083923PMC
March 2020

No Alterations of Brain Structural Asymmetry in Major Depressive Disorder: An ENIGMA Consortium Analysis.

Am J Psychiatry 2019 12 29;176(12):1039-1049. Epub 2019 Jul 29.

The Department of Language and Genetics, Max Planck Institute for Psycholinguistics, Nijmegen, the Netherlands (de Kovel, Francks); Orygen, the National Centre of Excellence in Youth Mental Health, Melbourne, Australia (Davey); the Department of Psychiatry, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam (Veltman); the Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USC, University of Southern California, Marina del Rey (Jahanshad, Thompson); the Laboratory of Affective, Cognitive, and Translational Neuroscience, Scientific Research Institute of Physiology and Basic Medicine, Novosibirsk, Russian Federation (Aftanas, Brack, Osipov); the Department of Neuroscience, Neuroimaging Center, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (Aleman); the Department of Psychiatry, University of Melbourne, Melbourne (Baune); the Institute for Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany (Bülow); the Laboratory of Psychiatric Neuroimaging (LIM-21), Departamento e Instituto de Psiquiatria, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil (Busatto Filho, Rosa); the Department of Psychiatry, Trinity College Dublin (Carballedo, Frodl); the Department of Psychiatry and the Weill Institute for Neurosciences, Division of Child and Adolescent Psychiatry, University of California, San Francisco (Connolly, Ho, Yang); the Department of Psychiatry, University of Minnesota Medical School, Minneapolis (Cullen, Mueller, Ubani, Schreiner); the Department of Psychiatry, University of Münster, Münster, Germany (Dannlowski, Dohm, Grotegerd, Leehr, Sindermann, Winter, Zaremba); the Department of Psychology, School of Arts and Social Sciences, City, University of London, London (Dima); the Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany (Erwin-Grabner; Goya-Maldonado, Schnell, Singh); the Department of Psychiatry and Psychotherapy, Otto von Guericke University Magdeburg, Magdeburg, Germany (Frodl); the Centre for Affective Disorders, Institute of Psychiatry, Psychology, and Neuroscience, King's College London (Fu); the Department of Psychology, Neuroscience, and Behaviour, McMaster University, Hamilton, Canada (Hall); the Department of Psychiatry, Yale School of Medicine, New Haven, Conn. (Alexander-Bloch, Glahn); the Psychopharmacology Research Unit, Department of Psychiatry, University of Oxford, Oxford, U.K. (Godlewska); the Department of Psychology, Stanford University, Stanford, Calif. (Gotlib, Ho); the Department of Psychiatry and Psychotherapy, University Medicine Greifswald (Grabe, Wittfeld); the Department of Psychiatry, Interdisciplinary Center Psychopathology and Emotion regulation, University Medical Center Groningen (Groenewold); the Section for Experimental Psychopathology and Neuroimaging, Department of General Psychiatry, Heidelberg University, Heidelberg, Germany (Gruber, Krämer, Simulionyte); the Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne, and Melbourne Health, Melbourne (Harrison); the Youth Mental Health Team, Brain and Mind Centre, University of Sydney, Sydney, Australia (Hatton, Hickie, Lagopoulos); the Department of Psychiatry and Psychotherapy, Philipps University Marburg, Marburg, Germany (Kircher, Krug, Nenadic, Yüksel); the Department of Neurology, University of Magdeburg, Magdeburg (Li); the Departments of Psychiatry and Paediatrics, University of Calgary, Calgary, Canada (MacMaster, McLellan); the Department of Psychiatry, Cumming School of Medicine, University of Calgary, Calgary (MacQueen); the Division of Psychiatry, University of Edinburgh, Edinburgh (Harris, McIntosh, Papmeyer, Whalley); Psychiatric Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia (Medland); the Department. of Psychiatry, Institute of Biomedical Research Sant Pau, Barcelona, Spain (Portella); the Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Amsterdam (Reneman, Schrantee); the Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford (Sacchet); West Region and Research Division, Institute of Mental Health, Singapore (Sim); Medical Research Council Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry, University of Cape Town, Cape Town, South Africa (Groenewold, Stein); Brain Function and Dysfunction, Leids Universitair Medisch Centrum, Leiden, the Netherlands (Van der Wee); the Department of Psychiatry, Leiden University Medical Center, Leiden (Van der Werff); the Division of Mind and Brain Research, Department of Psychiatry and Psychotherapy CCM, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin (Veer, H. Walter); the Institute of Information and Communication Technologies (Instituto ITACA), Universitat Politècnica de València, València, Spain (Gilabert); the Institute for Community Medicine, University Medicine Greifswald, Greifswald (Völzke); the Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany (M. Walter); the Department of Psychology, University of Minnesota, Minneapolis (Schreiner); the German Center for Neurodegenerative Diseases, Site Rostock/Greifswald (Grabe, Wittfeld); the Department of Neuroscience, Novosibirsk State University, Novosibirsk (Aftanas); the Department of Psychology, University of Groningen, Groningen (Aleman); the Center for Interdisciplinary Research on Applied Neurosciences, University of São Paulo, São Paulo (Busatto Filho, Rosa); the Department of Biomedical Sciences, Florida State University, Tallahassee (Connolly); the Department of Neuroimaging, Institute of Psychiatry, Psychology, and Neuroscience, King's College London (Dima); the Donders Institute for Brain, Cognition, and Behavior, Radboud University Nijmegen (Francks); the School of Psychology, University of East London, London (Fu); the Sunshine Coast Mind and Neuroscience Thompson Institute, Queensland, Australia (Lagopoulos); Strategic Clinical Network for Addictions and Mental Health, Alberta, Canada (MacMaster); the Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh (McIntosh); the Rehabilitation Services and Care Unit, Swiss Paraplegic Research, Nottwil, Switzerland (Papmeyer); CIBERSAM, Madrid (Portella); the Centre for Youth Mental Health, University of Melbourne, Melbourne (Davey, Schmaal); the Spinoza Center for Neuroimaging, Royal Netherlands Academy of Arts and Sciences, Amsterdam (Schrantee); Yong Loo Lin School of Medicine, National University of Singapore; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore (Sim); the School of Public Health, Boston University, Boston (Ubani); the Leiden Institute for Brain and Cognition, Leiden (Van der Werff); the German Center for Cardiovascular Research, partner site Greifswald, Greifswald (Völzke).

Objective: Asymmetry is a subtle but pervasive aspect of the human brain, and it may be altered in several psychiatric conditions. MRI studies have shown subtle differences of brain anatomy between people with major depressive disorder and healthy control subjects, but few studies have specifically examined brain anatomical asymmetry in relation to this disorder, and results from those studies have remained inconclusive. At the functional level, some electroencephalography studies have indicated left fronto-cortical hypoactivity and right parietal hypoactivity in depressive disorders, so aspects of lateralized anatomy may also be affected. The authors used pooled individual-level data from data sets collected around the world to investigate differences in laterality in measures of cortical thickness, cortical surface area, and subcortical volume between individuals with major depression and healthy control subjects.

Methods: The authors investigated differences in the laterality of thickness and surface area measures of 34 cerebral cortical regions in 2,256 individuals with major depression and 3,504 control subjects from 31 separate data sets, and they investigated volume asymmetries of eight subcortical structures in 2,540 individuals with major depression and 4,230 control subjects from 32 data sets. T-weighted MRI data were processed with a single protocol using FreeSurfer and the Desikan-Killiany atlas. The large sample size provided 80% power to detect effects of the order of Cohen's d=0.1.

Results: The largest effect size (Cohen's d) of major depression diagnosis was 0.085 for the thickness asymmetry of the superior temporal cortex, which was not significant after adjustment for multiple testing. Asymmetry measures were not significantly associated with medication use, acute compared with remitted status, first episode compared with recurrent status, or age at onset.

Conclusions: Altered brain macro-anatomical asymmetry may be of little relevance to major depression etiology in most cases.
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http://dx.doi.org/10.1176/appi.ajp.2019.18101144DOI Listing
December 2019

Interactive impact of childhood maltreatment, depression, and age on cortical brain structure: mega-analytic findings from a large multi-site cohort.

Psychol Med 2020 04 14;50(6):1020-1031. Epub 2019 May 14.

Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Germany.

Background: Childhood maltreatment (CM) plays an important role in the development of major depressive disorder (MDD). The aim of this study was to examine whether CM severity and type are associated with MDD-related brain alterations, and how they interact with sex and age.

Methods: Within the ENIGMA-MDD network, severity and subtypes of CM using the Childhood Trauma Questionnaire were assessed and structural magnetic resonance imaging data from patients with MDD and healthy controls were analyzed in a mega-analysis comprising a total of 3872 participants aged between 13 and 89 years. Cortical thickness and surface area were extracted at each site using FreeSurfer.

Results: CM severity was associated with reduced cortical thickness in the banks of the superior temporal sulcus and supramarginal gyrus as well as with reduced surface area of the middle temporal lobe. Participants reporting both childhood neglect and abuse had a lower cortical thickness in the inferior parietal lobe, middle temporal lobe, and precuneus compared to participants not exposed to CM. In males only, regardless of diagnosis, CM severity was associated with higher cortical thickness of the rostral anterior cingulate cortex. Finally, a significant interaction between CM and age in predicting thickness was seen across several prefrontal, temporal, and temporo-parietal regions.

Conclusions: Severity and type of CM may impact cortical thickness and surface area. Importantly, CM may influence age-dependent brain maturation, particularly in regions related to the default mode network, perception, and theory of mind.
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http://dx.doi.org/10.1017/S003329171900093XDOI Listing
April 2020

Polygenic risk for circulating reproductive hormone levels and their influence on hippocampal volume and depression susceptibility.

Psychoneuroendocrinology 2019 08 20;106:284-292. Epub 2019 Apr 20.

Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. Electronic address:

Altered reproductive hormone levels have been associated with the pathophysiology of depressive disorders and this risk may be imparted by their modulatory effect upon hippocampal structure and function. Currently it is unclear whether altered levels of reproductive hormones are causally associated with hippocampal volume reductions and the risk of depressive disorders. Here, we utilize genome-wide association study (GWAS) summary statistics from a GWAS focusing on reproductive hormones, consisting of 2913 individuals. Using this data, we generated polygenic risk scores (PRS) for estradiol, progesterone, prolactin and testosterone in the European RADIANT cohort consisting of 176 postpartum depression (PPD) cases (100% female, mean age: 41.6 years old), 2772 major depressive disorder (MDD) cases (68.6% female, mean age: 46.9 years old) and 1588 control participants (62.5% female, mean age: 42.4 years old), for which there was also a neuroimaging subset of 111 individuals (60.4% female, mean age: 50.0 years old). Only the best-fit PRS for estradiol showed a significant negative association with hippocampal volume, as well as many of its individual subfields; including the molecular layer and granule cell layer of the dentate gyrus, subiculum, CA1, CA2/3 and CA4 regions. Interestingly, several of these subfields are implicated in adult hippocampal neurogenesis. When we tested the same estradiol PRS for association with case-control status for PPD or MDD there was no significant relationship observed. Here, we provide evidence that genetic risk for higher plasma estradiol is negatively associated with hippocampal volume, but this does not translate into an increased risk of MDD or PPD. This work suggests that the relationship between reproductive hormones, the hippocampus, and depression is complex, and that there may not be a clear-cut pathway for etiology or risk moderation.
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http://dx.doi.org/10.1016/j.psyneuen.2019.04.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6597945PMC
August 2019

The polygenic nature of telomere length and the anti-ageing properties of lithium.

Neuropsychopharmacology 2019 03 18;44(4):757-765. Epub 2018 Dec 18.

Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

Telomere length is a promising biomarker for age-related disease and a potential anti-ageing drug target. Here, we study the genetic architecture of telomere length and the repositioning potential of lithium as an anti-ageing medication. LD score regression applied to the largest telomere length genome-wide association study to-date, revealed SNP-chip heritability estimates of 7.29%, with polygenic risk scoring capturing 4.4% of the variance in telomere length in an independent cohort (p = 6.17 × 10). Gene-enrichment analysis identified 13 genes associated with telomere length, with the most significant being the leucine rich repeat gene, LRRC34 (p = 3.69 × 10). In the context of lithium, we confirm that chronic use in a sample of 384 bipolar disorder patients is associated with longer telomeres (p = 0.03). As complementary evidence, we studied three orthologs of telomere length regulators in a Caenorhabditis elegans model of lithium-induced extended longevity and found all transcripts to be affected post-treatment (p < 0.05). Lithium may therefore confer its anti-ageing effects by moderating the expression of genes responsible for normal telomere length regulation. This is supported by our bipolar disorder sample, which shows that polygenic risk scores explain a higher proportion of the variance in telomere length amongst chronic lifetime lithium users (variance explained = 8.9%, p = 0.01), compared to non-users (p > 0.05). Consequently, this suggests that lithium may be catalysing the activity of endogenous mechanisms that promote telomere lengthening, whereby its efficacy eventually becomes limited by each individual's inherent telomere maintenance capabilities. Our work indicates a potential use of polygenic risk scoring for the prediction of adult telomere length and consequently lithium's anti-ageing efficacy.
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http://dx.doi.org/10.1038/s41386-018-0289-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6372618PMC
March 2019

Telomere length as a predictor of emotional processing in the brain.

Hum Brain Mapp 2019 04 4;40(6):1750-1759. Epub 2018 Dec 4.

Department of Psychology, School of Arts and Social Sciences, City, University of London, London, United Kingdom.

Shorter telomere length (TL) has been associated with the development of mood disorders as well as abnormalities in brain morphology. However, so far, no studies have considered the role TL may have on brain function during tasks relevant to mood disorders. In this study, we examine the relationship between TL and functional brain activation and connectivity, while participants (n = 112) perform a functional magnetic resonance imaging (fMRI) facial affect recognition task. Additionally, because variation in TL has a substantial genetic component we calculated polygenic risk scores for TL to test if they predict face-related functional brain activation. First, our results showed that TL was positively associated with increased activation in the amygdala and cuneus, as well as increased connectivity from posterior regions of the face network to the ventral prefrontal cortex. Second, polygenic risk scores for TL show a positive association with medial prefrontal cortex activation. The data support the view that TL and genetic loading for shorter telomeres, influence the function of brain regions known to be involved in emotional processing.
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http://dx.doi.org/10.1002/hbm.24487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6492163PMC
April 2019

Associations between polygenic risk scores for four psychiatric illnesses and brain structure using multivariate pattern recognition.

Neuroimage Clin 2018 9;20:1026-1036. Epub 2018 Oct 9.

Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; Department of Psychology, School of Arts and Social Sciences, City, University of London, London, UK. Electronic address:

Psychiatric illnesses are complex and polygenic. They are associated with widespread alterations in the brain, which are partly influenced by genetic factors. There have been some attempts to relate polygenic risk scores (PRS) - a measure of the overall genetic risk an individual carries for a disorder - to brain structure using univariate methods. However, PRS are likely associated with distributed and covarying effects across the brain. We therefore used multivariate machine learning in this proof-of-principle study to investigate associations between brain structure and PRS for four psychiatric disorders; attention deficit-hyperactivity disorder (ADHD), autism, bipolar disorder and schizophrenia. The sample included 213 individuals comprising patients with depression (69), bipolar disorder (33), and healthy controls (111). The five psychiatric PRSs were calculated based on summary data from the Psychiatric Genomics Consortium. T1-weighted magnetic resonance images were obtained and voxel-based morphometry was implemented in SPM12. Multivariate relevance vector regression was implemented in the Pattern Recognition for Neuroimaging Toolbox (PRoNTo). Across the whole sample, a multivariate pattern of grey matter significantly predicted the PRS for autism (r = 0.20, p = 0.03; MSE = 4.20 × 10, p = 0.02). For the schizophrenia PRS, the MSE was significant (MSE = 1.30 × 10, p = 0.02) although the correlation was not (r = 0.15, p = 0.06). These results lend support to the hypothesis that polygenic liability for autism and schizophrenia is associated with widespread changes in grey matter concentrations. These associations were seen in individuals not affected by these disorders, indicating that this is not driven by the expression of the disease, but by the genetic risk captured by the PRSs.
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http://dx.doi.org/10.1016/j.nicl.2018.10.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6197704PMC
February 2019

An fMRI study of visuo-vestibular interactions following vestibular neuritis.

Neuroimage Clin 2018 9;20:1010-1017. Epub 2018 Oct 9.

Neuro-otology Unit, Division of Brain Sciences, Charing Cross Hospital, Imperial College London, London W6 8RP, UK. Electronic address:

Vestibular neuritis (VN) is characterised by acute vertigo due to a sudden loss of unilateral vestibular function. A considerable proportion of VN patients proceed to develop chronic symptoms of dizziness, including visually induced dizziness, specifically during head turns. Here we investigated whether the development of such poor clinical outcomes following VN, is associated with abnormal visuo-vestibular cortical processing. Accordingly, we applied functional magnetic resonance imaging to assess brain responses of chronic VN patients and compared these to controls during both congruent (co-directional) and incongruent (opposite directions) visuo-vestibular stimulation (i.e. emulating situations that provoke symptoms in patients). We observed a focal significant difference in BOLD signal in the primary visual cortex V1 between patients and controls in the congruent condition (small volume corrected level of p < .05 FWE). Importantly, this reduced BOLD signal in V1 was negatively correlated with functional status measured with validated clinical questionnaires. Our findings suggest that central compensation and in turn clinical outcomes in VN are partly mediated by adaptive mechanisms associated with the early visual cortex.
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http://dx.doi.org/10.1016/j.nicl.2018.10.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6197146PMC
February 2019

Cortical Brain Abnormalities in 4474 Individuals With Schizophrenia and 5098 Control Subjects via the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) Consortium.

Biol Psychiatry 2018 11 14;84(9):644-654. Epub 2018 May 14.

Division of Mental Health and Addiction, NORMENT, K.G. Jebsen Centre for Psychosis Research, Oslo University Hospital, Oslo, Norway.

Background: The profile of cortical neuroanatomical abnormalities in schizophrenia is not fully understood, despite hundreds of published structural brain imaging studies. This study presents the first meta-analysis of cortical thickness and surface area abnormalities in schizophrenia conducted by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Schizophrenia Working Group.

Methods: The study included data from 4474 individuals with schizophrenia (mean age, 32.3 years; range, 11-78 years; 66% male) and 5098 healthy volunteers (mean age, 32.8 years; range, 10-87 years; 53% male) assessed with standardized methods at 39 centers worldwide.

Results: Compared with healthy volunteers, individuals with schizophrenia have widespread thinner cortex (left/right hemisphere: Cohen's d = -0.530/-0.516) and smaller surface area (left/right hemisphere: Cohen's d = -0.251/-0.254), with the largest effect sizes for both in frontal and temporal lobe regions. Regional group differences in cortical thickness remained significant when statistically controlling for global cortical thickness, suggesting regional specificity. In contrast, effects for cortical surface area appear global. Case-control, negative, cortical thickness effect sizes were two to three times larger in individuals receiving antipsychotic medication relative to unmedicated individuals. Negative correlations between age and bilateral temporal pole thickness were stronger in individuals with schizophrenia than in healthy volunteers. Regional cortical thickness showed significant negative correlations with normalized medication dose, symptom severity, and duration of illness and positive correlations with age at onset.

Conclusions: The findings indicate that the ENIGMA meta-analysis approach can achieve robust findings in clinical neuroscience studies; also, medication effects should be taken into account in future genetic association studies of cortical thickness in schizophrenia.
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http://dx.doi.org/10.1016/j.biopsych.2018.04.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6177304PMC
November 2018

A systematic review of associations between functional MRI activity and polygenic risk for schizophrenia and bipolar disorder.

Brain Imaging Behav 2019 Jun;13(3):862-877

Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

Genetic factors account for up to 80% of the liability for schizophrenia (SCZ) and bipolar disorder (BD). Genome-wide association studies have successfully identified several genes associated with increased risk for both disorders. This has allowed researchers to model the aggregate effect of genes associated with disease status and create a polygenic risk score (PGRS) for each individual. The interest in imaging genetics using PGRS has grown in recent years, with several studies now published. We have conducted a systematic review to examine the effects of PGRS of SCZ, BD and cross psychiatric disorders on brain function and connectivity using fMRI data. Results indicate that the effect of genetic load for SCZ and BD on brain function affects task-related recruitment, with frontal areas having a more prominent role, independent of task. Additionally, the results suggest that the polygenic architecture of psychotic disorders is not regionally confined but impacts on the task-dependent recruitment of multiple brain regions. Future imaging genetics studies with large samples, especially population studies, would be uniquely informative in mapping the spatial distribution of the genetic risk to psychiatric disorders on brain processes during various cognitive tasks and may lead to the discovery of biological pathways that could be crucial in mediating the link between genetic factors and alterations in brain networks.
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http://dx.doi.org/10.1007/s11682-018-9879-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6538577PMC
June 2019

Multimodal Brain Changes in First-Episode Mania: A Voxel-Based Morphometry, Functional Magnetic Resonance Imaging, and Connectivity Study.

Schizophr Bull 2019 03;45(2):464-473

Barcelona Bipolar Disorders Unit, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain.

Background: Brain structural and functional changes in bipolar disorder (BD) are well-established findings, but it is uncertain whether these changes are already present in first episode mania (FEM).

Methods: We compared 31 FEM subjects, with 31 healthy individuals matched for age, sex, and premorbid IQ. Whole-brain voxel-wise morphometry, functional magnetic resonance imaging during the n-back task, and a functional connectivity analysis were performed.

Results: There were no volumetric differences between the 2 groups. During the 2-back task, FEM patients did not perform differently from controls and activated similar regions, but they showed less deactivation in the ventromedial prefrontal cortex (vmPFC), the anterior hub of the default mode network (DMN). They showed preserved functional connectivity between the vmPFC and other regions of the DMN, but increased connectivity with the superior frontal gyrus.

Conclusions: The absence of volumetric changes in FEM patients suggests that these changes could be related to progression of the illness. On the other hand, the failure of deactivation of the anterior hub of the DMN is present from the onset of the illness and may represent a core pathophysiological feature of BD.
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http://dx.doi.org/10.1093/schbul/sby047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6403052PMC
March 2019

Test-retest reliability and longitudinal analysis of automated hippocampal subregion volumes in healthy ageing and Alzheimer's disease populations.

Hum Brain Mapp 2018 04 16;39(4):1743-1754. Epub 2018 Jan 16.

Institute of Psychiatry, Psychology and Neuroscience, King's College London, Institute of Psychiatry, London, United Kingdom.

The hippocampal formation is a complex brain structure that is important in cognitive processes such as memory, mood, reward processing and other executive functions. Histological and neuroimaging studies have implicated the hippocampal region in neuropsychiatric disorders as well as in neurodegenerative diseases. This highly plastic limbic region is made up of several subregions that are believed to have different functional roles. Therefore, there is a growing interest in imaging the subregions of the hippocampal formation rather than modelling the hippocampus as a homogenous structure, driving the development of new automated analysis tools. Consequently, there is a pressing need to understand the stability of the measures derived from these new techniques. In this study, an automated hippocampal subregion segmentation pipeline, released as a developmental version of Freesurfer (v6.0), was applied to T1-weighted magnetic resonance imaging (MRI) scans of 22 healthy older participants, scanned on 3 separate occasions and a separate longitudinal dataset of 40 Alzheimer's disease (AD) patients. Test-retest reliability of hippocampal subregion volumes was assessed using the intra-class correlation coefficient (ICC), percentage volume difference and percentage volume overlap (Dice). Sensitivity of the regional estimates to longitudinal change was estimated using linear mixed effects (LME) modelling. The results show that out of the 24 hippocampal subregions, 20 had ICC scores of 0.9 or higher in both samples; these regions include the molecular layer, granule cell layer of the dentate gyrus, CA1, CA3 and the subiculum (ICC > 0.9), whilst the hippocampal fissure and fimbria had lower ICC scores (0.73-0.88). Furthermore, LME analysis of the independent AD dataset demonstrated sensitivity to group and individual differences in the rate of volume change over time in several hippocampal subregions (CA1, molecular layer, CA3, hippocampal tail, fissure and presubiculum). These results indicate that this automated segmentation method provides a robust method with which to measure hippocampal subregions, and may be useful in tracking disease progression and measuring the effects of pharmacological intervention.
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http://dx.doi.org/10.1002/hbm.23948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6866454PMC
April 2018

Telomere Length and Bipolar Disorder.

Neuropsychopharmacology 2018 01;43(2):454

This corrects the article DOI: 10.1038/npp.2017.125.
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http://dx.doi.org/10.1038/npp.2017.239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5729573PMC
January 2018
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