Early life stress predicts thalamic hyperconnectivity: A transdiagnostic study of global connectivity

Abstract

Early life stress (ELS) is an established risk factor for psychiatric illness and is associated with altered functional connectivity within- and between intrinsic neural networks. The widespread nature of these disruptions suggests that broad imaging measures of neural connectivity, such as global based connectivity (GBC), may be particularly appropriate for studies of this population. GBC is designed to identify brain regions having maximal functional connectedness with the rest of the brain, and alterations in GBC may reflect a restriction or broadening of network synchronization. We evaluated whether ELS severity predicted GBC in a sample (N=46) with a spectrum of ELS exposure. Participants included healthy controls without ELS, those with at least moderate ELS but without psychiatric disorders, and a group of patients with ELS− related psychiatric disorders. The spatial distribution of GBC peaked in regions of the salience and default mode networks, and ELS severity predicted increased GBC of the left thalamus (corrected p < .005, r = .498). Thalamic connectivity was subsequently evaluated and revealed reduced connectivity with the salience network, particularly the dorsal anterior cingulate cortex (corrected p < .005), only in the patient group. These findings support a model of disrupted thalamic connectivity in ELS and trauma-related negative affect states, and underscore the importance of a transdiagnostic, dimensional neuroimaging approach to understanding the sequelae of trauma exposure.

Impact of juvenile chronic stress on adult cortico-accumbal function: Implications for cognition and addiction

“…Given the requirement of NMDA receptor-mediated activity within PFC circuits during cognitive tasks (Arnsten & Rubia, 2012), this would presumably result in less recruitment of the PFC as required for effective top-down control. In support of this, reduced neural activity within the PFC when performing a variety of executive function tasks is commonly observed in human adults reporting experience of chronic juvenile stressors (Table 2; e.g., Casement et al, 2015; Fonzo et al, 2016; Philip et al, 2013b; 2016). However, chronic juvenile stress is also associated with increased brain-derived neurotrophic factor (BDNF) in the PFC of adult rats (Table 1; Han et al, 2011b; Meng et al, 2011; Shao et al, 2013), which is surprising given that reduced gray matter, reduced dendritic length or elaboration, and reduced plasticity are often observed in the adult PFC following juvenile stress in both humans and animal models (Tables 1 & 2).…”

Transdiagnostic psychiatry: a systematic review

“…The vast majority of non‐interventional studies (79%) were cross‐sectional, and only 21% longitudinal. There was a large variability in study sample size, ranging from 15 participants in the smallest study to 91,199 in the largest (median: 148 participants).…”

“…Some studies used comorbid (as opposed to primary) diagnoses to validate the transdiagnostic construct. In about one third of studies (28%), the boundaries between primary and secondary diagnoses were not completely clear.…”

“…The largest transdiagnostic study published to date leveraged an electronic case register to include 353 mental disorders clustered across ten spectra, representing all ICD‐10 mental disorders except organic mental disorders. About one third of the studies (35%) included at least one non‐clinical sample.…”

Resting State Functional Connectivity of the Thalamus in North Korean Refugees with and without Posttraumatic Stress Disorder

“…Diffusion tensor imaging analyses, electrophysiological assessments, and perfusion studies have also shown that PTSD patients exhibit alterations in the thalamocortical pathway [8][9][10][11] . In addition, the thalamic hyper-connectivity has been reported to be associated with early life stress and anxiety in a trans-diagnostic study 12 . However, only a single study has investigated rsFC between the thalamus and cortical regions in PTSD using functional magnetic resonance imaging (fMRI) 13 .…”