Can Depression be Diagnosed by Response to Mother's Face? A Personalized Attachment-Based Paradigm for Diagnostic fMRI

OBJECTIVE: Objective measurement of depression remains elusive. Depression has been associated with insecure attachment, and both have been associated with changes in brain reactivity in response to viewing standard emotional and neutral faces. In this study, we developed a method to calculate predicted scores for the Beck Depression Inventory II (BDI-II) using personalized stimuli: fMRI imaging of subjects viewing pictures of their own mothers. METHODS: 28 female subjects ages 18-30 (14 healthy controls and 14 unipolar depressed diagnosed by MINI psychiatric interview) were scored on the Beck Depression Inventory II (BDI-II) and the Adult Attachment Interview (AAI) coherence of mind scale of global attachment security. Subjects viewed pictures of Mother (M), Friend (F) and Stranger (S), during functional magnetic resonance imaging (fMRI). Using a principal component regression method (PCR), a predicted Beck Depression Inventory II (BDI-II) score was obtained from activity patterns in the paracingulate gyrus (Brodmann area 32) and compared to clinical diagnosis and the measured BDI-II score. The same procedure was performed for AAI coherence of mind scores. RESULTS: Activity patterns in BA-32 identified depressed subjects. The categorical agreement between the derived BDI-II score (using the standard clinical cut-score of 14 on the BDI-II) and depression diagnosis by MINI psychiatric interview was 89%, with sensitivity 85.7% and specificity 92.8%. Predicted and measured BDI-II scores had a correlation of 0.55. Prediction of attachment security was not statistically significant. CONCLUSIONS: Brain activity in response to viewing one's mother may be diagnostic of depression. Functional magnetic resonance imaging using personalized paradigms has the potential to provide objective assessments, even when behavioral measures are not informative. Further, fMRI based diagnostic algorithms may enhance our understanding of the neural mechanisms of depression by identifying distinctive neural features of the illness

A Meta-Analysis of fMRI Studies on Emotion Processing in Major Depressive Disorder

The processing of an emotional stimulus involves a multi-step process that includes appraising and identifying a stimulus as well as producing an affective state in response. Many individuals with depressive disorders such as major depressive disorder (MDD) experience impairments related to emotion processing, likely caused by changes in the structure and function of brain regions important for emotion processing. However, the precise neural differences underlying emotion processing impairments in MDD remain unclear given conflicting findings in the neuroimaging literature. This lack of clarity has hindered the development of novel neurostimulation treatments for MDD, which require targeting of specific brain areas. In an effort to better identify specific areas of the brain to target for stimulation treatment, I conducted a meta-analysis of the functional magnetic resonance imaging (fMRI) literature to date regarding emotion processing in MDD. The meta-analysis of fMRI studies examined emotion processing in healthy controls and individuals with MDD using the tool GingerALE. Results showed clusters of hyperactivity in the amygdala and portions of the ventral basal ganglia, a finding that held true when limiting the analysis to only those studies that utilized negative stimuli. Additional exploratory results showed a cluster of hypoactivity in the right dorsolateral prefrontal cortex. These results help to shed light on neural changes underlying emotion processing in MDD, and may serve to inform future neurostimulation clinical trials

Amygdala responsivity related to memory of emotionally neutral stimuli constitutes a trait factor for depression

Contains fulltext : 96622.pdf (Publisher’s version ) (Closed access)Episodic memory impairment is considered to be a core cognitive deficit of Major Depressive Disorder (MDD) and has motivated a line of research investigating the role of the amygdala and the hippocampus in depression. While functional neuroimaging studies have focused on memory for emotional but not for neutral stimuli, in order to probe amygdala function, structural imaging studies have tied episodic memory to hippocampal function. We therefore investigated the neural correlates of episodic memory formation for neutral stimuli in 20 patients with a first depressive episode, 20 patients recovered from a first episode and 20 healthy controls. Because there is evidence that the amygdala exhibits hyperactive responses even to neutral stimuli in depressed subjects, we specifically explored the potential role of the amygdala in forming episodic memories with neutral content. Both patient groups showed stronger subsequent memory effects in the amygdala when compared to controls, in the absence of any differences in hippocampal activity between groups. Patients with a first episode of MDD showed increased activity related to episodic memory formation in a fronto-limbic network. These state-related activations may be related to a compensatory mechanism, which is supported by the absence of any differences in memory performance between groups. These findings represent initial evidence for a neurocognitive trait or vulnerability marker of depression-amygdala involvement in episodic memory formation of neutral stimuli

State and trait characteristics of early course major depressive disorder

Contains fulltext : 109595.pdf (Publisher’s version ) (Open Access)Radboud Universiteit Nijmegen, 21 december 2012Promotores : Buitelaar, J.K., Fernandez, G.S.E. Co-promotor : Tendolkar, I

A Longitudinal Investigation of Psychological and Neural Mechanisms of Weight Loss

Although obesity is fundamentally a problem of energy balance wherein calorie intake exceeds calorie output, there is a multitude of psychological and neural factors inherent in eating and overeating. Behavioral and neuroimaging research suggests a relationship between emotion regulation and eating behavior. However, the connections among psychological characteristics, brain function, and weight loss maintenance are poorly understood. Accordingly, in the present study, fMRI was used to examine how two psychological characteristics, emotion amplification and rumination, are related to (a) neural response to food images both before (baseline [BL]) and after (3M) participants undergo a three-month behavioral weight loss intervention, and (b) initial weight loss and weight loss maintenance. Emotion amplification was associated with decreased activation in dorsolateral prefrontal cortex (DLPFC) from BL to 3M. Rumination was associated with decreased activation in DLPFC from BL to 3M and increased activation in lateral prefrontal cortex, anterior cingulate cortex, parahippocampal gyrus, and amygdala from BL to 3M. Rumination was also inversely correlated with BL post-meal activation in DLPFC and caudate; activation in these two regions was prospectively associated with more weight loss from BL to 3M. Findings suggest that emotion amplification and rumination contribute to how food stimuli are processed at a neural level. Potential mechanisms for behavioral regulation and treatment implications are discussed

Autobiographical and hippocampus-dependent spatial memory in depression

Depression is associated with deficits in the recollection of specific autobiographical memories, a phenomenon referred to as overgeneral memory. Neither the modifiability nor the neural correlates of overgeneral memory are currently well understood. The aim of this thesis was to increase the understanding of autobiographical memory specificity and overgeneral memory in depression. Part one of the thesis is a literature review investigating whether interventions for treating and preventing depression are effective in improving autobiographical memory specificity. Nineteen studies of varying methodological strength were identified and included in the review. There is evidence that memory specificity improves over the course of treatment for depression, but further research is required to establish the causal effects of different interventions and the effectiveness of prevention strategies. Part two of the thesis presents an empirical study aimed at establishing the association between overgeneral memory and allocentric spatial memory as a measure of hippocampal function in depression. Depressed and non-depressed adults completed measures of autobiographical memory and allocentric spatial memory. The depression group showed impairment in autobiographical memory, but not in allocentric spatial memory, and there was no association between performance on the two memory tasks. The data was collected in the context of a joint project (Williams, 2017). Part three of the thesis is a critical appraisal of the research. It offers reflections on study design and recruitment, benefits of a joint project, exclusion criteria and generalizability, challenges in measuring autobiographical memory, and the role of a clinical researcher in the National Health Service

Deep brain stimulation mediates neurotrophin signaling in an animal model of antidepressant resistance

Chronic adrenocorticotropic hormone administration at circadian nadir produces an antidepressant resistance animal model that does not present with an altered plasma corticosterone profile nor changes in hippocampal brain derived neurotrophic factor and its receptor. Acute and chronic infralimbic deep brain stimulation elicited an antidepressant response in this animal model, which appears to be associated with changes in gene and protein expression of key intracellular mediators of neurotrophic factor signaling. Together, these findings stand to make important positive impacts on treatment strategies for one of the most debilitating and prevalent disorders of the modern era and suggest that antidepressant treatment response may involve mechanisms distinct from chronic stress-mediated induction of depression-like behavioral phenotypes