To review the role of the precuneus in major depression We will review the literature involving the precuneus in the pathophysiology of depression. We will also report a recent study of our group using structural MRI and VBM analyses to assess the role of precuneus in Autobiographical Memory (AM). Visual perspective during AM retrieval was assessed in two independent datasets of 45 and 20 healthy young adults with two different AM retrieval tasks. Precuneus, a medial part of the parietal cortex, is a central component of the default mode network. Results from our VBM study show that the precuneus volume in healthy subjects is correlated with the ability to retrieve autobiographical memories with a first-person perspective. Consistent with its role in integration of self-relevant mental simulations with past experiences and visuo-spatial processes during AM retrieval, the precuneus may subserve emotion regulation processes in healthy subjects and depressed patients. The precuneus and the default mode network show abnormal connectivity in depressed patients that may indicate abnormal self-processing in depression. Abnormal activity and connectivity of the precuneus within the default mode network is associated with impairment in self-processing in depression and may be related to the tendency of depressed patients to retrieve AM using third-person perspective. Further studies are needed to evaluate if impaired function or structure of the precuneus may predict the clinical response to antidepressant treatment.
To describe a new framework 'SENSO' (sensitivity to social signal) that emphasizes that acute depressed patients show abnormal cognitive, emotional and biological responses to positive and negative social signals with impaired monitoring of social acceptance. We will review evidence that Major Depression is associated with increasing vulnerability to social rejection and social stress. We will also discuss a recent meta-analysis realized by our group evaluating neural correlates of social exclusion tasks in healthy subjects. Major Depression is clearly precipitated by major social life-events. These social events increase the need for subjects to monitor their level of social acceptance and induce stress response. Self-propagatory processes (i.e. excessive reassurance seeking, negative feedback seeking) generate in depressed patients a vicious circle leading to increase sensitivity to social rejection. Social exclusion tasks in healthy subjects induce increased activation in ventromedial prefrontal cortex, subgenual cortex and insula, regions implicated in self-processing and production of negative emotion. Results of our literature review and of our meta-analysis stress the importance of studying interpersonal processes and their neural correlates in depressive phenomena. They emphasize the role of salient and default mode networks in the pathophysiology of major depression.
Increased Self-focus, the tendency to excessively appraise stimuli as strongly related to oneself, is a core feature of major depression. In major depressive disorder increased self-focus is associated with abnormal dorsal and ventral medial prefrontal activity as well as increased dorsolateral prefrontal activity. Objective Although Lemogne et al, 2010 suggested that Medial Prefrontal Activity does not change after reduction of depressive symptoms, sensitivity of brain regions involved in self-referential processing to antidepressant is unknown. The main goal here was to assess with fMRI early effects of agomelatine, on self-referential processing in depressed patients. Methods 25 acute depressed patients and 14 healthy controls were scanned before and after 7 days treatment, while performing self-referential processing task using emotional pictures. Patients were randomized to agomelatine 25mg/day (n=13) or placebo (n=12), healthy controls received placebo. Subjects were asked to evaluate pictures according to different conditions: Self (Does the picture relate to you?); General (Is the picture positive or negative?). Depression was assessed with Hamilton Scale. Results Depressed patients compared to controls at baseline showed hyperactivity in dorsolateral prefrontal cortex, dorsal anterior cingulate and ventrolateral prefrontal cortex (VLPFC). After 7 days treatment, Agomelatine, compared to placebo, normalized the hyperactivity of VLPFC to healthy volunteers’ level. Conclusion Agomelatine targets specific brain structures, namely VLPFC, involved in automatic regulation of emotion during self-referential processing. These changes in brain activity at day 7 could contribute to the early clinical effects of agomelatine, suggesting an early set up of the brain for long term response and remission of depression.
Objectives To define neural correlates of cognitive dysfunction in major depression and to disentangle the role of cognitive, default mode and limbic networks in emotional and cognitive problems of depressed patients Material and Methods We will review brain imaging studies of executive function and rumination in depression. We will also describe results of a recent study conducted in healthy volunteers (n=41) using cognitive tasks related to ruminative processes. During fMRI acquisition subjects were asked to read sentences and to engage in an analytical or an experiential self-referential task. Results Several studies using executive tasks related cognitive effort in depressed patients with increased activation of the dorsolateral prefrontal cortex. This hyperactivity of lateral prefrontal cortex is associated with abnormal deactivation of medial brain structures such as the medial prefrontal cortex. Consistent with this review, our study in healthy volunteers showed that subjects with High score in rumination showed lower activity in medial brain structures in relation with difficulties to differentiate analytical and experiential self-focus. Conclusion Overall these findings support the hypothesis of abnormal interaction in cognitive and default mode network in depression and may help to refine our understanding of how rumination promotes depression through maladaptive self-focus.
During the past two decades, it has been amply documented that neuropsychiatric disorders (NPDs) disproportionately account for burden of illness attributable to chronic non-communicable medical disorders globally. It is also likely that human capital costs attributable to NPDs will disproportionately increase as a consequence of population aging and beneficial risk factor modification of other common and chronic medical disorders (e.g., cardiovascular disease). Notwithstanding the availability of multiple modalities of antidepressant treatment, relatively few studies in psychiatry have primarily sought to determine whether improving cognitive function in MDD improves patient reported outcomes (PROs) and/or is cost effective. The mediational relevance of cognition in MDD potentially extrapolates to all NPDs, indicating that screening for, measuring, preventing, and treating cognitive deficits in psychiatry is not only a primary therapeutic target, but also should be conceptualized as a transdiagnostic domain to be considered regardless of patient age and/or differential diagnosis.
