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Contains fulltext : 288241.pdf (Publisher’s version ) (Open Access) Emotional information is better remembered than neutral information. Extensive evidence indicates that the amygdala and its interactions with other cerebral regions play an important role in the memory-enhancing effect of emotional arousal. While the cerebellum has been found to be involved in fear conditioning, its role in emotional enhancement of episodic memory is less clear. To address this issue, we used a whole-brain functional MRI approach in 1,418 healthy participants. First, we identified clusters significantly activated during enhanced memory encoding of negative and positive emotional pictures. In addition to the well-known emotional memory-related cerebral regions, we identified a cluster in the cerebellum. We then used dynamic causal modeling and identified several cerebellar connections with increased connection strength corresponding to enhanced emotional memory, including one to a cluster covering the amygdala and hippocampus, and bidirectional connections with a cluster covering the anterior cingulate cortex. The present findings indicate that the cerebellum is an integral part of a network involved in emotional enhancement of episodic memory.

Musashi RNA-binding proteins (MSIs) retain a pivotal role in stem cell maintenance, tumorigenesis, and nervous system development. Recently, we showed in C. elegans that Musashi (MSI-1) actively promotes forgetting upon associative learning via a 3’UTR-dependent translational expression of the Arp2/3 actin branching complex. Here, we investigated the evolutionary conserved role of MSI proteins and the effect of their pharmacological inhibition on memory. Expression of human Musashi 1 (MSI1) and Musashi 2 (MSI2) under the endogenous Musashi promoter fully rescued the phenotype of msi-1(lf) worms. Furthermore, pharmacological inhibition of human MSI1 and MSI2 activity using (-)- gossypol resulted in improved memory retention, without causing locomotor, chemotactic, or learning deficits. No drug effect was observed in msi-1(lf) treated worms. Using Western blotting and confocal microscopy, we found no changes in MSI-1 protein abundance following (-)- gossypol treatment, suggesting that Musashi gene expression remains unaltered and that the compound exerts its inhibitory effect post-translationally. Additionally, (-)- gossypol suppressed the previously seen rescue of the msi-1(lf) phenotype in worms expressing human MSI1 specifically in the AVA neuron, indicating that (-)- gossypol can regulate the Musashi pathway in a memory-related neuronal circuit in worms. Finally, treating aged worms with (-)- gossypol reversed physiological age-dependent memory decline. Taken together, our findings indicate that pharmacological inhibition of Musashi might represent a promising approach for memory modulation.

The hippocampus is a heterogeneous structure, comprising histologically distinguishable subfields. These subfields are differentially involved in memory consolidation, spatial navigation and pattern separation, complex functions often impaired in individuals with brain disorders characterized by reduced hippocampal volume, including Alzheimer’s disease (AD) and schizophrenia. Given the structural and functional heterogeneity of the hippocampal formation, we sought to characterize the subfields’ genetic architecture. T1-weighted brain scans (n = 21,297, 16 cohorts) were processed with the hippocampal subfields algorithm in FreeSurfer v6.0. We ran a genome-wide association analysis on each subfield, co-varying for whole hippocampal volume. We further calculated the single-nucleotide polymorphism (SNP)-based heritability of 12 subfields, as well as their genetic correlation with each other, with other structural brain features and with AD and schizophrenia. All outcome measures were corrected for age, sex and intracranial volume. We found 15 unique genome-wide significant loci across six subfields, of which eight had not been previously linked to the hippocampus. Top SNPs were mapped to genes associated with neuronal differentiation, locomotor behaviour, schizophrenia and AD. The volumes of all the subfields were estimated to be heritable (h2 from 0.14 to 0.27, all p –16) and clustered together based on their genetic correlations compared with other structural brain features. There was also evidence of genetic overlap of subicular subfield volumes with schizophrenia. We conclude that hippocampal subfields have partly distinct genetic determinants associated with specific biological processes and traits. Taking into account this specificity may increase our understanding of hippocampal neurobiology and associated pathologies.

Extensive pharmacologic, genetic, and epigenetic research has linked the glucocorticoid receptor (GR) to memory processes, and to risk and symptoms of posttraumatic stress disorder (PTSD). In the present study we investigated the epigenetic pattern of 12 genes involved in the regulation of GR signaling in two African populations of heavily traumatized individuals: Survivors of the rebel war in northern Uganda (n = 463) and survivors of the Rwandan genocide (n = 350). The strongest link between regional methylation and PTSD risk and symptoms was observed for NTRK2, which encodes the transmembrane receptor tropomyosin-related kinase B, binds the brain-derived neurotrophic factor, and has been shown to play an important role in memory formation. NTRK2 methylation was not related to trauma load, suggesting that methylation differences preexisted the trauma. Because NTRK2 methylation differences were predominantly associated with memory-related PTSD symptoms, and because they seem to precede traumatic events, we next investigated the relationship between NTRK2 methylation and memory in a sample of nontraumatized individuals (n = 568). We found that NTRK2 methylation was negatively associated with recognition memory performance. Furthermore, fMRI analyses revealed NTRK2 methylation-dependent differences in brain network activity related to recognition memory. The present study demonstrates that NTRK2 is epigenetically linked to memory functions in nontraumatized subjects and to PTSD risk and symptoms in traumatized populations.

Background: An infection with SARS-CoV-2 can lead to long-term health problems known as Long Covid or Post Covid-19 condition. Whereas Long Covid symptoms may induce stress and depressive symptoms, it is also possible that stress and depressive symptoms can contribute to some of the symptoms. Importantly, stress levels and depressive symptoms have been found to be increased during the pandemic and may be also increased after infection. When investigating the prevalence of Long Covid symptoms it seems therefore important to use well-matched controls and to take stress levels and depressive symptoms into account.Methods: We conducted a survey study in over 11’000 subjects in the framework of the Swiss Corona Stress Study (4th survey, November 2021) and assessed stress levels and depressive symptoms (PHQ-9) along with physical and neurological symptoms of the past two weeks. From the 1’428 participants reporting at least one SARS-CoV-2 positive PCR test (98% non-hospitalized), we created 3 non-overlapping groups based on the date of the last reported positive test: at least 9 months before the study (n=774); between 9 and 3 months before the study (n=238); within 3 months before the study (n=416). For each group, we selected an equally sized subset of matched participants from the study pool of 9’651 subjects who didn’t report any SARS-CoV-2 positive test. Results: We found that the prevalence of several physical/neurological symptoms was significantly higher in SARS-CoV-2 positives as compared to the negative controls at all 3 time points. For participants who report having been tested positive at least 9 months ago, the top 3 symptoms as compared to negative controls were loss of smell/taste (prevalence positives: 20%, prevalence negatives: 1%, p=4.0E-20), rapid physical exhaustion (prevalence positives: 29%, prevalence negatives: 15%, p=2.3E-10) and fever (prevalence positives: 10%, prevalence negatives: 3%, p=1.9E-8). Stress levels and depressive symptoms were significantly associated with increased prevalence for most of the symptoms in both SARS-CoV-2 positives and negative controls. However, a history of SARS-CoV-2 infection was not significantly associated with heightened levels of stress or depressive symptoms at any of the investigated time intervals, and a higher prevalence of symptoms in these participants was also observed under adjustment for psychological state measures. Conclusion: The present results indicate that SARS-CoV-2 positivity is associated with higher prevalence of physical or neurological symptoms independently from stress levels or depressive symptoms.

The last survey of the Swiss Corona Stress Study in November 2020 has shown that the proportion of respondents with moderately severe to severe depressive symptoms was 18%, with the youngest group of 14-24 year olds being the most affected at 29%. Between 8 and 24 March 2021, an additional survey was conducted in the German speaking part of Northwestern Switzerland among 393 high school students with the majority being between 16 and 19 years old. The anonymous survey was completed by 97.5% of the students. The proportion of respondents with moderately severe to severe depressive symptoms was 27%. In this survey, additional questions were asked about school, social life and vaccination. The most significant stressor associated with depressive symptoms was perceived school pressure. 46% of the respondents indicated they were very or extremely stressed because of the pressure of school. Furthermore, the perception that school pressure has increased due to the pandemic (missed material due to closures, quarantine) was strongly correlated with depressive symptoms. Other factors included worries about poorer education or job opportunities and worries about damage to the social network. An additional factor analysis confirmed that stressors related to school build up the factor with the strongest correlation with depressive symptoms (with a large effect size).Other results- 69% of respondents would get vaccinated if the vaccine were available to them.- 41% of respondents would see the change to distance learning as a relief, 46% as a burden and 13% neither.- Only 4% of respondents said they were not at all afraid of infecting their parents/grandparents or another close person belonging to a risk group.- 29% of respondents have at least a moderate to severe fear of suffering from Long-COVID in case of infection.

Cannabis contains a multitude of different compounds. One of them, cannabidiol – a non-psychoactive substance – might counteract negative effects of Δ-9-Tetrahydrocannabinol on hippocampus-dependent memory impairment. The aim of the present study was to investigate the effect of vaping cannabidiol on verbal episodic memory in healthy young subjects. We used a double-blind, placebo-controlled, randomized crossover trial in 39 healthy young subjects. Participants received once a single dose of cannabidiol e-liquid (0.25 ml, 5% cannabidiol, 12.5 mg cannabidiol) and once placebo for vaping after learning 15 unrelated nouns. The primary outcome measure was the short delay verbal memory performance (number of correctly free recalled nouns) 20 min after learning. 34 participants (mean age: 22.26 [3.04]) completed all visits and entered analyses (17 received cannabidiol and 17 received placebo first). Cannabidiol enhanced verbal episodic memory performance (placebo: 7.03 [2.34]; cannabidiol 7.71 [2.48]; adjusted group difference 0.68, 95% CI 0.01 to 1.35; R2β = .028, p = .048). Importantly, we did not detect medication effects on secondary outcome measures attention or working memory performance, suggesting that CBD has no negative impact on these basic cognitive functions. The results are in line with the idea that vaping cannabidiol interacts with the central endocannabinoid system and is capable to modulate memory processes, a phenomenon with possible therapeutic potential. Further studies are needed to investigate optimal dose-response and time-response relationships.

Smartphone-based virtual reality (VR) applications (apps) might help to counter low utilization rates of available treatments for fear of heights. Demonstration of effectiveness in real-life situations of such apps is crucial, but lacking so far. Objective of this study was to develop a stand-alone, smartphone-based VR exposure app—Easy Heights—and to test its effectiveness in a real-life situation. We performed a single-blind, parallel group, randomized controlled trial. We recruited 70 participants with fear of heights, aged 18–60 years. Primary outcome was performance in a real-life Behavioral Avoidance Test (BAT) on a lookout tower after a single 1-h app use (phase 1) and after additional repeated (6 × 30 min) app use at home (phase 2). After phase 2, but not phase 1, participants in the Easy Heights condition showed significantly higher BAT scores compared to participants in the control condition (Cohen’s d = 1.3, p = 0.0001). Repeated use of our stand-alone, smartphone-based VR exposure app reduces avoidance behavior and fear, providing a low-threshold treatment for fear of heights.

The results of the third survey of the Swiss Corona Stress Study refer to the period from November 11-19, 2020, during which 11,612 people from all over Switzerland participated. Stress levels have increased significantly compared to the first survey during lockdown in April 2020. While the proportion of people reporting maximum stress levels was around 11% during the April lockdown, it rose to 20% in the second pandemic wave in November. The increase in stress was accompanied by an increase in depressive symptoms. The main drivers of psychological stress and depressive symptoms included burden due to a Covid-19-related change in work, school, or education, Covid-19-related financial losses, and fears about the future. These stressors have increased significantly, compared to the time of the April lockdown. Further factors were the fear that someone in the closest circle would become seriously ill or die from COVID-19, as well as the burden of social restrictions and burden from an increase in conflicts at home. While the proportion of respondents with moderately severe or severe (PHQ-9 ≥15) depressive symptoms was 3% before the pandemic, 9% during the April lockdown, and 12% during May, it increased to 18% in November. The risk for moderately severe or severe depressive symptoms was associated with age (with younger people showing the highest risk) and was increased in people experiencing financial losses due to the pandemic. In addition, people from the French-speaking part of Switzerland, which was most affected by the pandemic during the second wave, were at higher risk than people from the rest of Switzerland.

Purpose: The COVID-19 pandemic and governmental counter measurements, confinement in particular, have changed the routines of everyday life of people all over the world. To assess the psychological consequences of daily life changes during COVID-19 pandemic in the Iranian population.Method: We performed an anonymous online survey in the first 3 weeks of March 2020. Participants had to rate their stress levels and depressive symptoms during the last two weeks and before the pandemic retrospectively. The changes in psychological measurements and its association with socio-demographic factors and burdens due to confinement were assessed.Results: Overall, among the 3210 subjects who participated in our study, we observed an increase in both stress levels and average depression score. However, about 23% of subjects reported a decrease in their stress levels during the pandemic. The burden of childcare at home, restrictions in private life, and the burden of thoughts about the future were positively correlated with changes in stress levels and depression scores. On the other hand, feeling relieved in the pandemic condition, and enjoying more family time associated with less change in stress levels and depression scores. Being religious and older age were identified as resilience factors, whereas being a student, seeking a job, and having a psychiatric disorder history were identified as risk factors for depression.Conclusion: Stress levels and depressive symptoms have increased during COVID-19 pandemic and this increase is in relation to different social and personal burdens due to confinement strategy.

Background Recognition memory is an essential ability for functioning in everyday life. Establishing robust brain networks linked to recognition memory performance can help to understand the neural basis of recognition memory itself and the interindividual differences in recognition memory performance. Methods We analysed behavioural and whole-brain fMRI data from 1′410 healthy young adults during the testing phase of a picture-recognition task. Using independent component analysis (ICA), we decomposed the fMRI contrast for previously seen vs. new (old-new) pictures into networks of brain activity. This was done in two independent samples (training sample: N = 645, replication sample: N = 665). Next, we investigated the relationship between the identified brain networks and interindividual differences in recognition memory performance by conducting a prediction analysis. We estimated the prediction accuracy in a third independent sample (test sample: N = 100). Results We identified 12 robust and replicable brain networks using two independent samples. Based on the activity of those networks we could successfully estimate interindividual differences in recognition memory performance with high accuracy in a third independent sample (r = 0.5, p = 1.29 × 10−07). Conclusion Given the robustness of the ICA decomposition as well as the high prediction estimate, the identified brain networks may be considered as potential biomarkers of recognition memory performance in healthy young adults and can be further investigated in the context of health and disease.

Although in vivo exposure therapy is highly effective in the treatment of specific phobias, only a minority of patients seeks therapy. Exposure to virtual objects has been shown to be better tolerated, equally efficacious, but the technology has not been made widely accessible yet. We developed an augmented reality (AR) application (app) to reduce fear of spiders and performed a randomized controlled trial comparing the effects of our app (six 30-min sessions at home over a two-week period) with no intervention. Primary outcome was subjective fear, measured by a Subjective Units of Distress Scale (SUDS) in a Behavioural Approach Test (BAT) in a real-life spider situation at six weeks follow-up. Between Oct 7, 2019, and Dec 6, 2019, 66 individuals were enrolled and randomized. The intervention led to significantly lower subjective fear in the BAT compared to the control group (intervention group, baseline: 7.12 [SD 2.03] follow-up: 5.03 [SD 2.19] vs. control group, baseline: 7.06 [SD 2.34], follow-up 6.24 [SD 2.21]; adjusted group difference -1.24, 95 % CI -2.17 to -0.31; Cohen’s d = 0.57, p = 0.010). The repeated use of the AR app reduces subjective fear in a real-life spider situation, providing a low-threshold and low-cost treatment for fear of spiders.

The neural cell adhesion molecule 1 (NCAM-1) has been implicated in several brain-related biological processes, including neuronal migration, axonal branching, fasciculation, and synaptogenesis, with a pivotal role in synaptic plasticity. Here, we investigated the evolutionary conserved role of NCAM-1 in learning and memory. First, we investigated sustained changes in ncam-1 expression following aversive olfactory conditioning in C. elegans using molecular genetic methods. Furthermore, we examined the link between epigenetic signatures of the NCAM1 gene and memory in two human samples of healthy individuals (N = 568 and N = 319) and in two samples of traumatized individuals (N = 350 and N = 463). We found that olfactory conditioning in C. elegans induced ncam-1 expression and that loss of ncam-1 function selectively impaired associative long-term memory, without causing acquisition, sensory, or short-term memory deficits. Reintroduction of the C. elegans or human NCAM1 fully rescued memory impairment, suggesting a conserved role of NCAM1 for memory. In parallel, DNA methylation of the NCAM1 promoter in two independent healthy Swiss cohorts was associated with memory performance. In two independent Sub-Saharan populations of conflict zone survivors who had faced severe trauma, DNA methylation at an alternative promoter of the NCAM1 gene was associated with traumatic memories. Our results support a role of NCAM1 in associative memory in nematodes and humans, and might, ultimately, be helpful in elucidating diagnostic markers or suggest novel therapy targets for memory-related disorders, like PTSD.

In Switzerland by 2045, we expect 2.7 Mio citizens aged 65+ of whom 1.0 Mio. aged 80+. A priority and focus of personalized health research is therefore aging biology to extend healthy life expectancy. Novel molecular and imaging features will emerge as candidate targets for risk prediction and screening of chronic diseases. It is of utmost importance to test the clinical and public health utility of candidate biomarkers evolving from this research in citizen reference cohorts. We will build a Swiss Aging Citizen Reference (SACR), a testable and scalable reference cohort offering interoperable, searchable, and accessible data. 1000 participants from existing Swiss citizen cohorts will be combined and analyzed for DNA methylation and MRI brain imaging. SACR will serve as a testbed for clinical and public health utility of candidate biomarkers. As for a proof-of-concept study, we will conduct an agnostic search for structural and functional brain features associated with epigenetic aging acceleration to examine the potential of epigenetic age acceleration as the intermediate aging biomarker and to better understand the aging mechanism in brain.

Summary Activity-dependent persistent changes in neuronal intrinsic excitability and synaptic strength are underlying learning and memory. Voltage-gated potassium (Kv) channels are potential regulators of memory and may be linked to age-dependent neuronal disfunction. MinK-related peptides (MiRPs) are conserved transmembrane proteins modulating Kv channels; however, their possible role in the regulation of memory and age-dependent memory decline are unknown. Here, we show that, in C. elegans, mps-2 is the sole member of the MiRP family that controls exclusively long-term associative memory (LTAM) in AVA neuron. In addition, we demonstrate that mps-2 also plays a critical role in age-dependent memory decline. In young adult worms, mps-2 is transcriptionally upregulated by CRH-1/cyclic AMP (cAMP)-response-binding protein (CREB) during LTAM, although the mps-2 baseline expression is CREB independent and instead, during aging, relies on nhr-66, which acts as an age-dependent repressor. Deletion of nhr-66 or its binding element in the mps-2 promoter prevents age-dependent transcriptional repression of mps-2 and memory decline. Finally, MPS-2 acts through the modulation of the Kv2.1/KVS-3 and Kv2.2/KVS-4 heteromeric potassium channels. Altogether, we describe a conserved MPS-2/KVS-3/KVS-4 pathway essential for LTAM and also for a programmed control of physiological age-dependent memory decline.

Only a small proportion of what we see can later be recalled. Up to date it is unknown how far differences in visual exploration during encoding affect the strength of episodic memories. Here, we identified individual gaze characteristics by analyzing eye tracking data in a picture encoding task performed by 967 healthy subjects during fMRI. We found a positive correlation between fixation frequency during visual exploration and subsequent free recall performance. Brain imaging results showed a positive correlation of fixation frequency with activations in regions related to vision and memory, including the medial temporal lobe. To investigate if higher fixation frequency is causally linked to better memory, we experimentally manipulated visual exploration patterns in an independent population of 64 subjects. Doubling the number of fixations within a given exploration time increased subsequent free recall performance by 19%. Our findings provide evidence for a causal relationship between fixation frequency and episodic memory for visual information.

The mental consequences of the COVID-19 pandemic and the strict lockdown measures implemented by governments world-wide to fight it are currently unknown. We performed an online survey study in Switzerland and analyzed data acquired during confinement (wave 1) and during partial lifting of measures (partial deconfinement) (wave 2). Wave 1: Data from over 10’000 individuals living in Switzerland were collected between April 6 and 8, 2020, starting 3 weeks after the beginning of confinement. While 24.4% of the participants reported no change in stress levels, 49.6% of the participants reported an increase in stress levels during confinement as compared to the time before the COVID-19 pandemic. We identified several potential sources for people feeling more stressed during confinement, such as the burden related to changes at work or school, problems with childcare or not being able to spend more time with others. The changes in stress levels were highly correlated with changes in depressive symptoms. 57% of the participants reported an increase in depressive symptoms. Further, the prevalence of moderately severe or severe depressive symptoms (PHQ-9 score ≥ 15) increased from 3.4% before the COVID-19 pandemic to 9.1% during confinement. Interestingly, 26% of participants showed a decrease in stress level during confinement, suggesting that for those individuals the confinement involved a reduction of stressors and/or resulted in more time for recovery. Finally, we identified several behaviors amenable to change that were related to a reduced increase in stress level and depressive symptoms during confinement. Wave 2: Data from over 10’000 individuals living in Switzerland were collected between May 11 and June 1, 2020 during partial deconfinement. As for wave 1, we observed diverse reactions with regard to stress levels: While 28% of the participants reported no change in stress levels, 40% of the participants reported an increase in stress levels during partial deconfinement as compared to the time before the COVID-19 pandemic. We identified similar sources for people feeling more stressed as during confinement and the changes in stress levels were highly correlated with changes in depressive symptoms. 49.5% of the participants reported an increase in depressive symptoms. Further, the prevalence of moderately severe or severe depressive symptoms (PHQ-9 score ≥ 15) remained elevated with a prevalence rate of 11.7%. With regard to changeable behaviors during the pandemic, we found (as in wave 1) that spending more time pursuing new projects, spending more time pursuing hobbies at home, and light physical exercise were related to less stress increase.A comparison between the two waves indicated that while the waves did not substantially differ in the distributions of changes in stress levels or depressive symptoms, they did differ with regard to the distribution of anxiety ratings. Specifically, anxiety levels decreased from wave 1 to wave 2. Finally, we identified risk and resilience factors with regard to the development of depressive symptoms (present in both waves): A history of a prior psychiatric disorder was a risk factor for developing moderately severe or severe depressive symptoms during the pandemic. In a resilient group of people who had none or only minimal depressive symptoms before and during the pandemic, older people (≥ 55 years), men and individuals with no history of prior psychiatric disorder were overrepresented. Thus, advanced age, male gender and the absence of prior psychiatric disorder were identified as resilience factors.

We have established the COgnitive Science Metrics Online Survey (COSMOS) platform that contains a digital psychometrics toolset in the guise of applied games measuring a wide range of cognitive functions. Here we are outlining this online research endeavor designed for automatized psychometric data collection and scalable assessment: Once set up, the low costs and expenditure associated with individual psychometric testing allow substantially increased study cohorts and thus contribute to enhancing study outcome reliability. We are leveraging gamification of the data acquisition method to make the tests suitable for online administration. By putting a strong focus on entertainment and individually tailored feedback, we aim to maximize subjects’ incentives for repeated and continued participation. The objective of measuring repeatedly is obtaining more revealing multi-trial average scores and measures from various operationalizations of the same psychological construct instead of relying on single-shot measurements. COSMOS is set up to acquire an automatically and continuously growing dataset that can be used to answer a wide variety of research questions.Following the principles of the open science movement, this data set will also be made accessible to other publicly-funded researchers, given that all precautions for individual data protection are fulfilled. We have developed a secure hosting platform and a series of digital gamified testing instruments that can measure theory of mind, attention, working memory, episodic long- and short-term memory, spatial memory, reaction times, eye-hand coordination, impulsivity, humor appreciation, altruism, fairness, strategic thinking, decision making and risk-taking behavior. Furthermore, some of the game-based testing instruments also offer the possibility of using classical questionnaire items. A subset of these gamified tests is already implemented in the COSMOS platform, publicly accessible and currently undergoing evaluation and calibration as normative data is being collected. In summary, our approach can be used to accomplish a detailed and reliable psychometric characterization of thousands of individuals to supply various studies with large-scale neuro-cognitive phenotypes. Our game-based online testing strategy can also guide recruitment for studies as they allow very efficient screening and sample composition. Finally, this setup also allows to evaluate potential cognitive training effects and whether improvements are merely task specific or if generalization effects occur in or even across cognitive domains.

Depressive symptoms exist on a continuum, the far end of which is found in depressive disorders. Utilizing the continuous spectrum of depressive symptoms may therefore contribute to the understanding of the biological underpinnings of depression. Gene set enrichment analysis (GSEA) is an important tool for the identification of gene groups linked to complex traits, and was applied in the present study on genome-wide association study (GWAS) data of depression scores and their brain-level structural correlates in healthy young individuals. On symptom level (i.e. depression scores), robust enrichment was identified for two gene sets: NCAM1 Interactions and Collagen Formation. Depression scores were also associated with decreased fractional anisotropy (FA) - a brain white matter property - within the forceps minor and the left superior temporal longitudinal fasciculus. Within each of these tracts, mean FA value of depression score-associated voxels was used as a phenotype in a subsequent GSEA. The NCAM1 Interactions gene set was significantly enriched in these tracts. By linking the NCAM1 Interactions gene set to depression scores and their structural brain correlates in healthy participants, the current study contributes to the understanding of the molecular underpinnings of depressive symptomatology.