Background: Social anxiety disorder (SAD) is a serious psychiatric condition with a high prevalence, and a typical onset during childhood/adolescence. The condition runs in families, but it is... Show moreBackground: Social anxiety disorder (SAD) is a serious psychiatric condition with a high prevalence, and a typical onset during childhood/adolescence. The condition runs in families, but it is largely unknown which neurobiological characteristics transfer this genetic vulnerability ('endophenotypes'). Using data from the Leiden Family Lab study on SAD, including two generations of families genetically enriched for SAD, we investigated whether social anxiety (SA) co-segregated with changes in intrinsic functional connectivity (iFC), and examined heritability.Methods: Functional MRI data were acquired during resting-state in 109 individuals (56 males; mean age: 31.5, range 9.2-61.5 years). FSL's tool MELODIC was used to perform independent component analysis. Six networks of interest (default mode, dorsal attention, executive control, frontoparietal, limbic and salience) were identified at the group-level and used to generate subject-specific spatial maps. Voxel-wise regression models, with SA-level as predictor and voxel-wise iFC as candidate endophenotypes, were performed to investigate the association with SA, within masks of the networks of interest. Subsequently, heritability was estimated.Findings: SA co-segregated with iFC within the dorsal attention network (positive association in left middle frontal gyrus and right postcentral gyrus) and frontoparietal network (positive association within left middle temporal gyrus) (cluster-forming-threshold z>2.3, cluster-corrected extent-threshold p<0.05). Furthermore, iFC of multiple voxels within these clusters was at least moderately heritable.Interpretation: These findings provide initial evidence for increased iFC as candidate endophenotype of SAD, particularly within networks involved in attention. These changes might underlie attentional biases commonly present in SAD. (C) 2021 The Authors. Published by Elsevier B.V. Show less
The main objective of this thesis was to investigate the serotonergic and cholinergic neurotransmitter systems, and the way these are altered in older age and Alzheimer’s disease. For that purpose,... Show moreThe main objective of this thesis was to investigate the serotonergic and cholinergic neurotransmitter systems, and the way these are altered in older age and Alzheimer’s disease. For that purpose, the neuroimaging technique resting state fMRI (RS-fMRI) was used to measure whole brain functional connectivity with and without pharmacological stimulation. The first part of the thesis concerns two pharmacological RS-fMRI studies that were executed in young adults. Pharmacological challenge effects of two selective serotonin reuptake inhibitors (sertraline and citalopram) and a cholinesterase inhibitor (galantamine) on brain connectivity were examined to gain more insight into the underlying neurotransmitter systems and the mechanisms of drug action in the central nervous system. The second part of this thesis was aimed at discovering changes in brain connectivity and serotonergic and cholinergic system functioning in aging and Alzheimer’s disease, by comparing brain network connections and the pharmacological response of this measure between young and older adults and patients with Alzheimer’s disease. Show less
Achterberg, M.; Bakermans, M.J.; IJzendoorn, M.H. van; Meulen, M. van der; Tottenham, N.; Crone, E.A.M. 2018
Connectivity between limbic/subcortical and prefrontal-cortical brain regions develops considerably across childhood, but less is known about the heritability of these networks at this age. We... Show moreConnectivity between limbic/subcortical and prefrontal-cortical brain regions develops considerably across childhood, but less is known about the heritability of these networks at this age. We tested the heritability of limbic/subcortical-cortical and limbic/subcortical-subcortical functional brain connectivity in 7- to 9-year-old twins (N = 220), focusing on two key limbic/subcortical structures: the ventral striatum and the amygdala, given their combined influence on changing incentivised behavior during childhood and adolescence. Whole brain analyses with ventral striatum (VS) and amygdala as seeds in genetically independent groups showed replicable functional connectivity patterns. The behavioral genetic analyses revealed that in general VS and amygdala connectivity showed distinct influences of genetics and environment. VS-prefrontal cortex connections were best described by genetic and unique environmental factors (the latter including measurement error), whereas amygdala-prefrontal cortex connectivity was mainly explained by environmental influences. Similarities were also found: connectivity between both the VS and amygdala and ventral anterior cingulate cortex (vACC) showed influences of shared environment, while connectivity with the orbitofrontal cortex (OFC) showed heritability. These findings may inform future interventions that target behavioral control and emotion regulation, by taking into account genetic dispositions as well as shared and unique environmental factors such as child rearing. Show less
As infants are fully dependent on their parents, correct perception and interpretation of infant signals is crucial for infant survival. It is therefore not surprising that specific brain circuits... Show moreAs infants are fully dependent on their parents, correct perception and interpretation of infant signals is crucial for infant survival. It is therefore not surprising that specific brain circuits and neuroendocrine processes have evolved to perceive infant signals correctly and to respond adequately. However, parents vary in their ability to respond to their infants in a sensitive way and several factors may be involved in parental sensitive responsiveness. One important factor influencing parenting behavior is the neuropeptide oxytocin. Of all the hormones involved in parenting and other social behaviors, oxytocin has received the most interest, as evidenced by the high number of scientific studies over the past decade (Bos, Panksepp, Bluthé, & Honk, 2012; Van IJzendoorn & Bakermans-Kranenburg, 2012). Many studies suggest that oxytocin is related to sensitive parenting (Bakermans-Kranenburg & Van IJzendoorn, 2008; Feldman, Weller, Zagoory-Sharon, & Levine, 2007), although the exact mechanism underlying this positive association is not entirely clear yet. Another factor that influences parenting behavior is adult state of mind with respect to attachment (Van IJzendoorn, 1995). In the current dissertation, the role of oxytocin and adult attachment in parenting is examined with a series of functional magnetic resonance imaging experiments. Show less
