0000000000043016
AUTHOR
Julia Linke
Reward anticipation revisited- evidence from an fMRI study in euthymic bipolar I patients and healthy first-degree relatives.
Abstract Background Symptomatic phases in bipolar disorder (BD) are hypothesized to result from a hypersensitive behavioral activation system (BAS) being sensitive to potential rewards. However, studies on the neuronal underpinnings of reward anticipation in BD are scarce with contradictory findings and possibly confounded by effects of dopaminergic medication, necessitating further research on dysfunctional motivation in BD. Moreover, its role as vulnerability marker for BD is unclear. Methods Functional imaging was conducted in 16 euthymic BD-I patients free from dopaminergic medication and 19 healthy first-degree relatives using a monetary incentive delay task and compared to parallelize…
Effects of valence and arousal on implicit approach/ avoidance tendencies: A fMRI study.
To date, it is still a matter of debate, whether valence or valence and arousal interactively foster implicit approach and avoidance tendencies, and which neural circuitries underlie these effects. To address these questions, we investigated the effects of valence and arousal on implicit approach/avoidance tendencies during fMRI in healthy volunteers (N=46). The implicit approach of positive social scenes was associated with shorter response preparation times and increased activation of the lingual, parahippocampal and fusiform gyri. Valence and arousal did not influence reaction times interactively, but we observed increased activation of prefrontal, motor, temporal, middle cingulate and p…
Impact of antenatal glucocorticoid therapy and risk of preterm delivery on intelligence in term-born children
Context: Women at risk of preterm delivery are routinely treated with synthetic glucocorticoids (sGCs). Although this therapy substantially reduces neonatal morbidity, concerns remain whether sGC excess may disrupt neurodevelopmental trajectories underlying cognitive functioning. Objective: The present study is the first to disentangle direct effects of antenatal sGC treatment on possible long-term cognitive disadvantages from those of pregnancy complications and prematurity. Design, Setting, and Participants: This cross-sectional study included a mixed-sex cohort of 222 term-born children (aged 6–11 years) consisting of three groups: children of mothers admitted to hospital for threatening…
A Multilevel Functional Study of aSNAP25At-Risk Variant for Bipolar Disorder and Schizophrenia
The synaptosomal-associated protein SNAP25 is a key player in synaptic vesicle docking and fusion and has been associated with multiple psychiatric conditions, including schizophrenia, bipolar disorder, and attention-deficit/hyperactivity disorder. We recently identified a promoter variant inSNAP25,rs6039769, that is associated with early-onset bipolar disorder and a higher gene expression level in human prefrontal cortex. In the current study, we showed that this variant was associated both in males and females with schizophrenia in two independent cohorts. We then combinedin vitroandin vivoapproaches in humans to understand the functional impact of the at-risk allele. Thus, we showedin vi…
Neurodevelopmental subtypes of bipolar disorder are related to cortical folding patterns: An international multicenter study
Objectives Brain sulcation is an indirect marker of neurodevelopmental processes. Studies of the cortical sulcation in bipolar disorder have yielded mixed results, probably due to high variability in clinical phenotype. We investigated whole-brain cortical sulcation in a large sample of selected patients with high neurodevelopmental load. Methods A total of 263 patients with bipolar disorder I and 320 controls were included in a multicentric magnetic resonance imaging (MRI) study. All subjects underwent high-resolution T1-weighted brain MRI. Images were processed with an automatized pipeline to extract the global sulcal index (g-SI) and the local sulcal indices (l-SIs) from 12 a priori dete…
Cerebellar parcellation in schizophrenia and bipolar disorder
International audience; Objective: The cerebellum is involved in cognitive processing and emotion control. Cerebellar alterations could explain symptoms of schizophrenia spectrum disorder (SZ) and bipolar disorder (BD). In addition, literature suggests that lithium might influence cerebellar anatomy. Our aim was to study cerebellar anatomy in SZ and BD, and investigate the effect of lithium.Methods: Participants from 7 centers worldwide underwent a 3T MRI. We included 182 patients with SZ, 144 patients with BD, and 322 controls. We automatically segmented the cerebellum using the CERES pipeline. All outputs were visually inspected.Results: Patients with SZ showed a smaller global cerebellar…
Mental Imagery Training Increases Wanting of Rewards and Reward Sensitivity and Reduces Depressive Symptoms.
High reward sensitivity and wanting of rewarding stimuli help to identify and motivate repetition of pleasant activities. This behavioral activation is thought to increase positive emotions. Therefore, both mechanisms are highly relevant for resilience against depressive symptoms. Yet, these mechanisms have not been targeted by psychotherapeutic interventions. In the present study, we tested a mental imagery training comprising eight 10-minute sessions every second day and delivered via the Internet to healthy volunteers (N = 30, 21 female, mean age of 23.8 years, Caucasian) who were preselected for low reward sensitivity. Participants were paired according to age, sex, reward sensitivity, …
Further Neuroimaging Evidence for the Deficit Subtype of Schizophrenia
The clinical heterogeneity of schizophrenia has hindered neurobiological investigations aimed at identifying neural correlates of the disorder.To identify network-based biomarkers across the spectrum of impairment present in schizophrenia by separately evaluating individuals with deficit and nondeficit subtypes of this disorder.A university hospital network-based neuroimaging study was conducted between February 1, 2007, and February 28, 2012. Participants included patients with schizophrenia (n = 128) and matched healthy controls (n = 130) from two academic centers and patients with bipolar I disorder (n = 39) and matched healthy controls (n = 43) from a third site. Patients with schizophr…
Impaired anatomical connectivity and related executive functions: differentiating vulnerability and disease marker in bipolar disorder.
Background Bipolar 1 disorder (BD1) has been associated with impaired set shifting, increased risk taking, and impaired integrity of frontolimbic white matter. However, it remains unknown to what extent these findings are related to each other and whether these abnormalities represent risk factors or consequences of the illness. Methods We addressed the first question by comparing 19 patients with BD1 and 19 healthy control subjects (sample 1) with diffusion tensor imaging, the Intra-Extra Dimensional Set Shift Task, and the Cambridge Gambling Task. The second question we approached by applying the same protocol to 22 healthy first-degree relatives of patients with BD1 and 22 persons withou…
Lithium prevents grey matter atrophy in patients with bipolar disorder: an international multicenter study
AbstractBackgroundLithium (Li) is the gold standard treatment for bipolar disorder (BD). However, its mechanisms of action remain unknown but include neurotrophic effects. We here investigated the influence of Li on cortical and local grey matter (GM) volumes in a large international sample of patients with BD and healthy controls (HC).MethodsWe analyzed high-resolution T1-weighted structural magnetic resonance imaging scans of 271 patients with BD type I (120 undergoing Li) and 316 HC. Cortical and local GM volumes were compared using voxel-wise approaches with voxel-based morphometry and SIENAX using FSL. We used multiple linear regression models to test the influence of Li on cortical an…
Increased impulsivity as a vulnerability marker for bipolar disorder: Evidence from self-report and experimental measures in two high-risk populations
Abstract Background Heightened impulsivity has been suggested as a possible risk factor for bipolar disorder (BD). However, studies on high-risk populations are scarce and have mainly focused on individuals with a genetic risk. The present study investigated two high-risk samples for BD with regard to several aspects of the impulsivity construct. Methods Unaffected relatives of BD patients (genetically defined high-risk group, N=29) and participants scoring high on the Hypomanic Personality Scale (psychometrically defined high-risk sample, N=25) were being compared to respective control groups (N=27 and N=25) using a multi-method approach. Participants were accessed on the Barratt Impulsive…
Bipolar disorder: A neural network perspective on a disorder of emotion and motivation
Bipolar disorder (BD) is a severe, chronic disease with a heritability of 60-80%. BD is frequently misdiagnosed due to phenomenological overlap with other psychopathologies, an important issue that calls for the identification of biological and psychological vulnerability and disease markers. Altered structural and functional connectivity, mainly between limbic and prefrontal brain areas, have been proposed to underlie emotional and motivational dysregulation in BD and might represent relevant vulnerability and disease markers. In the present laboratory review we discuss functional and structural neuroimaging findings on emotional and motivational dysregulation from our research group in BD…
Correction: Widespread white matter microstructural abnormalities in bipolar disorder: evidence from mega- and meta-analyses across 3033 individuals
Fronto-limbic white matter (WM) abnormalities are assumed to lie at the heart of the pathophysiology of bipolar disorder (BD); however, diffusion tensor imaging (DTI) studies have reported heterogeneous results and it is not clear how the clinical heterogeneity is related to the observed differences. This study aimed to identify WM abnormalities that differentiate patients with BD from healthy controls (HC) in the largest DTI dataset of patients with BD to date, collected via the ENIGMA network. We gathered individual tensor-derived regional metrics from 26 cohorts leading to a sample size of N = 3033 (1482 BD and 1551 HC). Mean fractional anisotropy (FA) from 43 regions of interest (ROI) a…
Corpus callosum area in patients with bipolar disorder with and without psychotic features: an international multicentre study
Background Previous studies have reported MRI abnormalities of the corpus callosum (CC) in patients with bipolar disorder (BD), although only a few studies have directly compared callosal areas in psychotic versus nonpsychotic patients with this disorder. We sought to compare regional callosal areas in a large international multicentre sample of patients with BD and healthy controls. Methods We analyzed anatomic T-1 MRI data of patients with BD-I and healthy controls recruited from 4 sites (France, Germany, Ireland and the United States). We obtained the mid-sagittal areas of 7 CC subregions using an automatic CC delineation. Differences in regional callosal areas between patients and contr…
Widespread white matter microstructural abnormalities in bipolar disorder: evidence from mega- and meta-analyses across 3033 individuals
Fronto-limbic white matter (WM) abnormalities are assumed to lie at the heart of the pathophysiology of bipolar disorder (BD);\ud however, diffusion tensor imaging (DTI) studies have reported heterogeneous results and it is not clear how the clinical\ud heterogeneity is related to the observed differences. This study aimed to identify WM abnormalities that differentiate patients with\ud BD from healthy controls (HC) in the largest DTI dataset of patients with BD to date, collected via the ENIGMA network. We gathered\ud individual tensor-derived regional metrics from 26 cohorts leading to a sample size of N = 3033 (1482 BD and 1551 HC). Mean\ud fractional anisotropy (FA) from 43 regions of i…
Aberrant probabilistic reinforcement learning in first-degree relatives of individuals with bipolar disorder
Contains fulltext : 215845.pdf (Publisher’s version ) (Closed access) Background: Motivational dysregulation represents a core vulnerability factor for bipolar disorder. Whether this also comprises aberrant learning of stimulus-reinforcer contingencies is less clear. Methods: To answer this question, we compared healthy first-degree relatives of individuals with bipolar disorder (n = 42) known to convey an increased risk of developing a bipolar spectrum disorder and healthy individuals (n = 97). Further, we investigated the effects of the behavioral activation system (BAS) on reinforcement learning across the entire sample. All participants were assessed with a probabilistic learning task t…
Aberrant Subnetwork and Hub Dysconnectivity in Adult Bipolar Disorder: A Multicenter Graph Theory Analysis
Abstract Neuroimaging evidence implicates structural network-level abnormalities in bipolar disorder (BD); however, there remain conflicting results in the current literature hampered by sample size limitations and clinical heterogeneity. Here, we set out to perform a multisite graph theory analysis to assess the extent of neuroanatomical dysconnectivity in a large representative study of individuals with BD. This cross-sectional multicenter international study assessed structural and diffusion-weighted magnetic resonance imaging data obtained from 109 subjects with BD type 1 and 103 psychiatrically healthy volunteers. Whole-brain metrics, permutation-based statistics, and connectivity of h…
Shape analysis of the cingulum, uncinate and arcuate fasciculi in patients with bipolar disorder
Background: Abnormal maturation of brain connectivity is supposed to underlie the dysfunctional emotion regulation in patients with bipolar disorder (BD). To test this hypothesis, white matter integrity is usually investigated using measures of water diffusivity provided by MRI. Here we consider a more intuitive aspect of the morphometry of the white matter tracts: the shape of the fibre bundles, which is associated with neurodevelopment. We analyzed the shape of 3 tracts involved in BD: the cingulum (CG), uncinate fasciculus (UF) and arcuate fasciculus (AF). Methods: We analyzed diffusion MRI data in patients with BD and healthy controls. The fibre bundles were reconstructed using Q-ball–b…
A MULTI-LEVEL FUNCTIONAL STUDY OF A SNAP25 AT-RISK VARIANT FOR BIPOLAR DISORDER AND SCHIZOPHRENIA
Background The synaptosomal associated protein SNAP25 is crucial for synaptic vesicle docking and fusion and has been associated with multiple psychiatric conditions. We recently identified a promoter variant in SNAP25, rs6039769, associated with bipolar disorder and gene expression in prefrontal cortex. Methods Here, we performed a genetic association study using this variation on two independent cohorts of 288 and 173 subjects with schizophrenia and 315 unaffected control individuals. We replicated our results using data from the schizophrenia group of the Psychiatric Genomics Consortium (PGC). Functional consequences combined both in vitro and post-mortem gene expression analysis on 30 p…