Archives October 2021

Paper Publication: Intrinsic functional connectivity in late-life depression: trajectories over the course of pharmacotherapy in remitters and non-remitters

The study design protocol.

Previous studies in late-life depression (LLD) have found that patients have altered intrinsic functional connectivity in the dorsal default mode network (DMN) and executive control network (ECN). We aimed to detect connectivity differences across a treatment trial among LLD patients as a function of remission status. LLD patients (N=37) were enrolled into a 12-week trial of venlafaxine and underwent five functional magnetic resonance imaging resting state scans during treatment. Patients had no history of drug abuse, psychosis, dementia/neurodegenerative diseases or medical conditions with known effects on mood. We investigated whether there were differences in three networks: DMN, ECN and anterior salience network connectivity, as well as a whole brain centrality measure (eigenvector centrality). We found that remitters showed increases in ECN connectivity in the right precentral gyrus and decreases in DMN connectivity in the right inferior frontal gyrus and supramarginal gyrus. The ECN and DMN had regions (middle temporal gyrus and bilateral middle/inferior temporal/fusiform gyrus, respectively) that showed reversed effects (decreased ECN and increased DMN, respectively). Early changes in functional connectivity can occur after initial medication exposure. This study offers new data, indicating that functional connectivity changes differ depending on treatment response and can occur shortly after exposure to antidepressant medication.

Karim HT, Andreescu C, Tudorascu D, et al. Intrinsic functional connectivity in late-life depression: trajectories over the course of pharmacotherapy in remitters and non-remitters. Mol Psychiatry. 2017;22(3):450-457. doi:10.1038/mp.2016.55

The full paper can be found here

Paper Publication: MRI Predictors of Treatment Response in Late-Life Depression

In older adults, depression not only results in more years lived with disability than any other disease, but it also carries additional risk for suicide, medical comorbidities, and family care-giving burden. Because it can take many months to identify an effective treatment regimen, it is of upmost importance to shorten the window of time and identify early on what medication(s) and dosages will work effectively for individuals suffering from depression. Late-life depression (LLD) has been associated with greater burden of age-related changes, including atrophy, white matter ischemic changes, and alterations in functional connectivity (FC). Depression in midlife has been shown to alter affective reactivity and regulation, and functional magnetic resonance imaging (fMRI) studies in LLD have replicated the same abnormalities. Effective treatment can normalize these alterations. This article provides a review of the current literature using structural and functional neuroimaging to identify magnetic resonance imaging (MRI) predictors of treatment response in LLD. The majority of the literature on structural MRI has focused on the vascular depression hypothesis, and studies support the view that loss of brain volume and white matter integrity is associated with poorer treatment outcomes. Studies using fMRI have reported that lower task-based activity in the prefrontal cortex (PFC) and limbic regions is associated with poorer outcome. These imaging markers may be integrated into clinical decision-making to better treatment outcomes in the future.

Aizenstein HJ, Khalaf A, Walker SE, Andreescu C. Magnetic resonance imaging predictors of treatment response in late-life depression. J Geriatr Psychiatry Neurol. 2014;27(1):24-32. doi:10.1177/0891988713516541

The full published paper can be found here

Paper Publication: Emotion reactivity and regulation in late-life generalized anxiety disorder: Functional connectivity at baseline and post-treatment

Summarized findings showing differences in functional connectivity between non-anxious participants and elderly GAD during worry induction (left) and during worry reappraisal (right)

Generalized Anxiety Disorder (GAD) is one of the most prevalent mental disorders in the elderly, but its functional neuroanatomy is not well understood. Given the role of emotion dysregulation in GAD, we sought to describe the neural bases of emotion regulation in late-life GAD by analyzing the functional connectivity (FC) in the Salience Network and the Executive Control Network during worry induction and worry reappraisal. Twenty-eight elderly GAD and thirty-one non-anxious comparison participants were included. Twelve elderly GAD completed a 12-week pharmacotherapy trial. We used an in-scanner worry script that alternates blocks of worry induction and reappraisal. We assessed network FC, employing the following seeds: anterior insula (AI), dorso-lateral prefrontal cortex (dlPFC), the bed nucleus of stria terminalis (BNST), the paraventricular nucleus (PVN). GAD participants exhibited greater FC during worry induction between the left AI and the right orbito-frontal cortex (OFC), and between the BNST and the subgenual cingulate. During worry reappraisal, the non-anxious participants had greater FC between the left dlPFC and the medial PFC, as well as between the left AI and the medial PFC, while elderly GAD had greater FC between the PVN and the amygdala. Following twelve weeks of pharmacotherapy, GAD participants had greater connectivity between the dlPFC and several prefrontal regions during worry reappraisal. FC during worry induction and reappraisal points toward abnormalities in both worry generation and worry reappraisal. Following successful pharmacologic treatment, we observed greater connectivity in the prefrontal nodes of the Executive Control Network during reappraisal of worry.

You can read the full paper here

Paper Publication: New Research on Anxiety Disorders in the Elderly and an Update on Evidence-Based Treatments

Anxiety disorders are frequently encountered in the elderly, but they are largely undetected and untreated. Epidemiological studies indicate a prevalence ranging from 1.2 to 15 %. With the exception of generalized anxiety disorder and agoraphobia, which can often start in late life, most anxiety disorders in older patients are chronic and have their onset earlier in life. Anxiety disorders are an often unrecognized cause of distress, disability, and mortality risk in older adults, and they have been associated with cardiovascular disease, stroke, and cognitive decline. The mechanisms of anxiety in older adults differ from that in younger adults due to age-related neuropathology, as well as the loss and isolation so prominent in late life. Our review intends to provide a comprehensive summary of the most recent research done in the field of anxiety disorders in the elderly. Recent findings in clinical research, neuroimaging, neuroendocrinology, and neuropsychology are covered. An update on treatment options is discussed, including pharmacological and non-pharmacological alternatives.

Andreescu, C., Varon, D. New Research on Anxiety Disorders in the Elderly and an Update on Evidence-Based Treatments. Curr Psychiatry Rep 17, 53 (2015).

The full paper can be found Here