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Introduction: Ketamine demonstrates robust and rapidly occurring antidepressant effects in patients with difficult-to-treat major depressive disorder. Ketamine's antidepressant effects and its impact on functional networks in non-resistant forms of major depressive disorder are expected to provide valuable insight into ketamine's mechanism of action related to depression., Methods: This study employs an existing network model of major depressive disorder to investigate the effects of ketamine on resting state connectivity in a therapy-non-resistant major depressive disorder population. In a randomized, double-blind, placebo-controlled, cross-over study, 0.5 mg/kg racemic ketamine or 0.9%NaCl was administered intravenously in 16 MDD patients. We applied resting-state functional magnetic resonance imaging (rs-fMRI) to explore changes in functional brain connectivity directly at 50, 80 and 165 min (acute) and 24 h (delayed) following ketamine administration. A clinician-rated 10-item scale (MADRS) was administered at 165 min and 24 h after ketamine administration. Connections-of-interest (COIs) were based on the previously published corticolimbic-insular-striatalpallidal-thalamic (CLIPST) circuitry model of major depressive disorder., Results: Compared with placebo, ketamine significantly ( p < 0.0014) reduced the mean (SD) MADRS total score from 21.2 (5.9) pre-dose to 10.3 (4.6) 24 h post-dose. At both acute ( p < 0.0172) and delayed ( p < 0.0488) time points, significant rs-fMRI connectivity changes occurred only in MDD-related COIs as proposed by the CLIPST model. No changes in functional connectivity were found in non-CLIPST connections., Discussion: This study demonstrates that ketamine specifically affects depression-related circuitry. Analyzing functional connectivity based on a neurocircuitry model of a specific CNS disease and drug action may be an effective approach that could result in a more targeted analysis in future pharmaco-fMRI studies in CNS drug development., Competing Interests: Author KN was employed by the company Sumitomo Pharma Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that this study received funding from Sumitomo Pharma Co., Ltd. The funder had the following involvement in the study: conceptualization of the study design and publication., (Copyright © 2025 Recourt, Van Gerven, Drenth, van der Grond, Nishigori, Van Der Wee and Jacobs.)

Through education, a social group transmits accumulated knowledge, skills, customs, and values to its members. So far, to the best of our knowledge, the association between educational attainment and neural correlates of emotion processing has been left unexplored. In a retrospective analysis of The Netherlands Study of Depression and Anxiety (NESDA) functional magnetic resonance imaging (fMRI) study, we compared two groups of fourteen healthy volunteers with intermediate and high educational attainment, matched for age and gender. The data concerned event-related fMRI of brain activation during perception of facial emotional expressions. The region of interest (ROI) analysis showed stronger right amygdala activation to facial expressions in participants with lower relative to higher educational attainment (HE). The psychophysiological interaction analysis revealed that participants with HE exhibited stronger right amygdala-right insula connectivity during perception of emotional and neutral facial expressions. This exploratory study suggests the relevance of educational attainment on the neural mechanism of facial expressions processing.

Depressive and anxiety disorders are often first diagnosed during adolescence and it is known that they persist into adulthood. Previous studies often tried to dissociate depressive and anxiety disorders, but high comorbidity makes this difficult and maybe even impossible. The goal of this study was to use neuroimaging to test what the unique contribution is of depression and anxiety symptomatology on emotional processing and amygdala activation, and to compare the results with a healthy control group. We included 25 adolescents with depressive and/or anxiety disorders and 26 healthy adolescents. Participants performed an emotional face processing task while in the MRI scanner. We were particularly interested in the relation between depression/anxiety symptomatology and patterns of amygdala activation. There were no significant differences in activation patterns between the control group and the clinical group on whole brain level and ROI level. However, we found that dimensional scores on an anxiety but not a depression subscale significantly predicted brain activation in the right amygdala when processing fearful, happy and neutral faces. These results suggest that anxiety symptoms are a better predictor for differentiating activation patterns in the amygdala than depression symptoms. Although the current study includes a relatively large sample of treatment naïve adolescents with depression/anxiety disorders, results might be influenced by differences between studies in recruitment strategies or methodology. Future research should include larger samples with a more equal distribution of adolescents with a clinical diagnosis of depression and/or anxiety. To conclude, this study shows that abnormal amygdala responses to emotional faces in depression and anxiety seems to be more dependent on anxiety symptoms than on depression symptoms, and thereby highlights the need for more research to better characterize clinical groups in future studies.

There is a high degree of intra-individual variation in how individuals respond to stress. This becomes evident when exploring the development of posttraumatic symptoms or stress-related disorders after exposure to trauma. Whether or not an individual develops posttraumatic symptoms after experiencing a traumatic event is partly dependent on a person's resilience. Resilience can be broadly defined as the dynamic process encompassing positive adaptation within the context of significant adversity. Even though research into the neurobiological basis of resilience is still in its early stages, these insights can have important implications for the prevention and treatment of stress-related disorders. Neuroimaging studies contribute to our knowledge of intra-individual variability in resilience and the development of posttraumatic symptoms or other stress-related disorders. This review provides an overview of neuroimaging findings related to resilience. Structural, resting-state, and task-related neuroimaging results associated with resilience are discussed. There are a limited number of studies available and neuroimaging research of resilience is still in its infancy. The available studies point at brain circuitries involved in stress and emotion regulation, with more efficient processing and regulation associated with resilience.

Sleep complaints increase profoundly with age; prevalence estimates of insomnia in the elderly reach up to 37%. The three major types of nocturnal complaints are difficulties initiating (DIS) and maintaining (DMS) sleep and early morning awakening (EMA), of which the latter appears most characteristic for aging. The neural correlates associated with these complaints have hardly been investigated, hampering the development of rational treatment and prevention. A recent study on structural brain correlates of insomnia showed that overall severity, but not duration, of insomnia complaints is associated with lower gray matter (GM) density in part of the left orbitofrontal cortex (OFC). Following up on this, we investigated, in an independent sample of people not diagnosed with insomnia, whether individual differences in GM density are associated with differences in DIS, DMS, and EMA. Sixty five healthy participants (mean age = 41 years, range 18-56) filled out questionnaires and underwent structural magnetic resonance imaging. Three compound Z-scores were computed for questionnaire items relating to DIS, DMS, and EMA. Whole-brain voxel-based morphometry was used to investigate their association with GM density. Results show that participants with lower GM density in a region where the left inferior OFC borders the insula report more EMA, but not DIS or DMS. This is the first study to investigate structural brain correlates of specific sleep characteristics that can translate into complaints in insomniacs. The selective association of EMA with orbitofrontal GM density makes our findings particularly relevant to elderly people, where EMA represents the most characteristic complaint. It is hypothesized that low GM density in aforementioned orbitofrontal area affects its role in sensing comfort. An intact ability to evaluate comfort may be crucial to maintain sleep, especially at the end of the night when sleep is vulnerable because homeostatic sleep propensity has dissipated.

Recently, both increases and decreases in resting-state functional connectivity have been found in major depression. However, these studies only assessed functional connectivity within a specific network or between a few regions of interest, while comorbidity and use of medication was not always controlled for. Therefore, the aim of the current study was to investigate whole-brain functional connectivity, unbiased by a priori definition of regions or networks of interest, in medication-free depressive patients without comorbidity. We analyzed resting-state fMRI data of 19 medication-free patients with a recent diagnosis of major depression (within 6 months before inclusion) and no comorbidity, and 19 age- and gender-matched controls. Independent component analysis was employed on the concatenated data sets of all participants. Thirteen functionally relevant networks were identified, describing the entire study sample. Next, individual representations of the networks were created using a dual regression method. Statistical inference was subsequently done on these spatial maps using voxel-wise permutation tests. Abnormal functional connectivity was found within three resting-state networks in depression: (1) decreased bilateral amygdala and left anterior insula connectivity in an affective network, (2) reduced connectivity of the left frontal pole in a network associated with attention and working memory, and (3) decreased bilateral lingual gyrus connectivity within ventromedial visual regions. None of these effects were associated with symptom severity or gray matter density. We found abnormal resting-state functional connectivity not previously associated with major depression, which might relate to abnormal affect regulation and mild cognitive deficits, both associated with the symptomatology of the disorder.