An exploration of actigraphy in the context of ketamine and treatment-resistant depression.

OBJECTIVES: This study explored the potential of non-parametric and complexity analysis metrics to detect changes in activity post-ketamine and their association with depressive symptomatology. METHODS: Individuals with treatment-resistant depression (TRD: n = 27, 16F, 35.9 ± 10.8 years) and healthy volunteers (HVs: n = 9, 4F, 36.4 ± 9.59 years) had their activity monitored during an inpatient, double-blind, crossover study where they received an infusion of ketamine or saline placebo. All participants were 18-65 years old, medication-free, and had a MADRS score ≥20. Non-parametric metrics averaged over each study day, metrics derived from complexity analysis, and traditionally calculated non-parametric metrics averaged over two weeks were calculated from the actigraphy time series. A separate analysis was conducted for a subsample (n = 17) to assess the utility of these metrics in a hospital setting. RESULTS: In HVs, lower intradaily variability was observed within daily rest/activity patterns post-ketamine versus post-placebo (F = 5.16(1,15), p = 0.04). No other significant effects of drug or drug-by-time or correlations between depressive symptomatology and activity were detected. CONCLUSIONS: Weak associations between non-parametric variables and ketamine were found but were not consistent across actigraphy measures. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT00088699.

Review: The use of functional magnetic resonance imaging (fMRI) in clinical trials and experimental research studies for depression.

Functional magnetic resonance imaging (fMRI) is a non-invasive technique that can be used to examine neural responses with and without the use of a functional task. Indeed, fMRI has been used in clinical trials and pharmacological research studies. In mental health, it has been used to identify brain areas linked to specific symptoms but also has the potential to help identify possible treatment targets. Despite fMRI's many advantages, such findings are rarely the primary outcome measure in clinical trials or research studies. This article reviews fMRI studies in depression that sought to assess the efficacy and mechanism of action of compounds with antidepressant effects. Our search results focused on selective serotonin reuptake inhibitors (SSRIs), the most commonly prescribed treatments for depression and ketamine, a fast-acting antidepressant treatment. Normalization of amygdala hyperactivity in response to negative emotional stimuli was found to underlie successful treatment response to SSRIs as well as ketamine, indicating a potential common pathway for both conventional and fast-acting antidepressants. Ketamine's rapid antidepressant effects make it a particularly useful compound for studying depression with fMRI; its effects on brain activity and connectivity trended toward normalizing the increases and decreases in brain activity and connectivity associated with depression. These findings highlight the considerable promise of fMRI as a tool for identifying treatment targets in depression. However, additional studies with improved methodology and study design are needed before fMRI findings can be translated into meaningful clinical trial outcomes.

Functional MRI markers for treatment-resistant depression: Insights and challenges.

Imaging studies of treatment-resistant depression (TRD) have examined brain activity, structure, and metabolite concentrations to identify critical areas of investigation in TRD as well as potential targets for treatment interventions. This chapter provides an overview of the main findings of studies using three imaging modalities: structural magnetic resonance imaging (MRI), functional MRI (fMRI), and magnetic resonance spectroscopy (MRS). Decreased connectivity and metabolite concentrations in frontal brain areas appear to characterize TRD, although results are not consistent across studies. Treatment interventions, including rapid-acting antidepressants and transcranial magnetic stimulation (TMS), have shown some efficacy in reversing these changes while alleviating depressive symptoms. However, comparatively few TRD imaging studies have been conducted, and these studies often have relatively small sample sizes or employ different methods to examine a variety of brain areas, making it difficult to draw firm conclusions from imaging studies about the pathophysiology of TRD. Larger studies with more unified hypotheses, as well as data sharing, could help TRD research and spur better characterization of the illness, providing critical new targets for treatment intervention.

Associations between peer stress in early adolescence and multiple event-related potentials elicited during social feedback processing.

Interpersonal stress in adolescence has been associated with alterations in neural responses to peer feedback, and increased vulnerability to psychopathology. However, it is unclear whether the associations of interpersonal problems with neural responses are global across event-related potentials (ERPs) or might result in alterations only in specific ERPs. We examined associations between multiple informants of peer stress (self-reported, parent-reported, and peer-reported) and multiple ERPs (N1, P2, RewP, and LPP) to social feedback in a sample of 46 early adolescents (aged 12-13 years). Reports of peer stress were only moderately correlated with one another, indicating different informants capture different aspects of peer stress. Regressions using informant reports to predict ERPs revealed greater parent-reported peer stress was associated with a smaller RewP, whereas self-reported stress was associated with a smaller P2, to acceptance. In contrast, greater peer-reported stress was associated with larger P2, RewP, and LPP to acceptance. Findings suggest that different sources of stress measurement are differentially associated with ERPs. Future research using social feedback-related ERPs should consider multiple sources of information as well as multiple ERP components across the time-course of feedback processing, to gain a clearer understanding of the effects of peer stress on neural responses to feedback.