BackgroundMajor depressive disorder (MDD) is a heterogeneous psychiatric disorder. Childhood trauma (CT, emotional/physical/sexual abuse or neglect before the age of 18) is one of the largest and... Show moreBackgroundMajor depressive disorder (MDD) is a heterogeneous psychiatric disorder. Childhood trauma (CT, emotional/physical/sexual abuse or neglect before the age of 18) is one of the largest and most consistent risk factors for development and poor course of MDD. Overactivity of the HPA-axis and the stress hormone cortisol is thought to play a role in the vulnerability for MDD following exposure to CT. Rodent experiments showed that antagonism of the glucocorticoid receptor (GR) at adult age reversed the effects of early life stress. Similarly, we aim to target MDD in individuals with CT exposure using the GR antagonist mifepristone.MethodsThe RESET-medication study is a placebo-controlled double-blind randomized controlled trial (RCT) which aims to include 158 adults with MDD and CT. Participants will be randomized (1:1) to a 7-day treatment arm of mifepristone (1200 mg/day) or a control arm (placebo). Participants are allowed to receive usual care for MDD including antidepressants. Measurements include three face-to-face meetings at baseline (T0), day 8 (T1), week 6 (T2), and two online follow-up meetings at 12 weeks (T3) and 6 months (T4). A subgroup of participants (N = 80) are included in a fMRI sub-study (T0, T2). The main study outcome will be depressive symptom severity as measured with the Inventory of Depressive Symptomatology—Self Rated (IDS-SR) at T2. Secondary outcomes include, among others, depressive symptom severity at other time points, disability, anxiety, sleep and subjective stress. To address underlying mechanisms mifepristone plasma levels, cortisol, inflammation, epigenetic regulation and fMRI measurements are obtained.DiscussionThe RESET-medication study will provide clinical evidence whether GR antagonism is a disease-modifying treatment for MDD in individuals exposed to CT. If effective, this hypothesis-driven approach may extend to other psychiatric disorders where CT plays an important role. Show less
Introduction: Major depressive disorder (MDD) is common, and recurrence rates are high. Preventive Cognitive Therapy (PCT), has been shown to prolong time to recurrence and reduce risk of... Show moreIntroduction: Major depressive disorder (MDD) is common, and recurrence rates are high. Preventive Cognitive Therapy (PCT), has been shown to prolong time to recurrence and reduce risk of recurrence(s) over 2-10 years in patients with recurrent depression. Objective: The aim of the study was to examine the effectiveness of PCT over 20 years on time to first recurrence, cumulative proportion of first recurrences, percentage of depression-free time, mean severity of recurrences, and the number of recurrences within a patient. Methods: Adults remitted from recurrent MDD were randomized to PCT or Treatment As Usual (TAU). Clinical outcomes were assessed using the SCID over 20 years. We used Cox regression analyses, Kaplan-Meier analyses, ANOVA, and negative binomial regression and tested for interaction with the number of previous episodes. Results: There was a significant interaction effect for number of previous episodes with treatment condition on time to first recurrence (Wald[1, n = 172] = 8.840, p = 0.003). For participants with more than 3 previous episodes, the mean time to recurrence was 4.8 years for PCT versus 1.6 years for TAU; the cumulative proportion of first recurrences was 87.5% for PCT and 100% for TAU. For participants with more than 3 previous episodes, exploratory analyses suggest that PCT had 53% less recurrences and percentage of depression-free time was significantly higher compared to TAU. There were no significant effects on mean severity. Conclusions: Up to 20 years, for MDD patients with more than 3 previous episodes, those who received PCT had significantly longer time to a first recurrence and lower recurrence risk and may have less recurrences and more depression-free time compared to TAU. This suggests long term protective effects of PCT up to 20-years. Show less
Background: Structural brain alterations are observed in major depressive disorder (MDD). However, MDD is a highly heterogeneous disorder and specific clinical or biological characteristics of... Show moreBackground: Structural brain alterations are observed in major depressive disorder (MDD). However, MDD is a highly heterogeneous disorder and specific clinical or biological characteristics of depression might relate to specific structural brain alterations. Clinical symptom subtypes of depression, as well as immuno-metabolic dysregulation associated with subtypes of depression, have been associated with brain alterations. Therefore, we examined if specific clinical and biological characteristics of depression show different brain alterations compared to overall depression. Method: Individuals with and without depressive and/or anxiety disorders from the Netherlands Study of Depression and Anxiety (NESDA) (328 participants from three timepoints leading to 541 observations) and the Mood Treatment with Antidepressants or Running (MOTAR) study (123 baseline participants) were included. Symptom profiles (atypical energy-related profile, melancholic profile and depression severity) and biological indices (inflammatory, metabolic syndrome, and immuno-metabolic indices) were created. The associations of the clinical and biological profiles with depression-related structural brain measures (anterior cingulate cortex [ACC], orbitofrontal cortex, insula, and nucleus accumbens) were examined dimensionally in both studies and meta-analysed. Results: Depression severity was negatively associated with rostral ACC thickness (B = -0.55, pFDR = 0.03), and melancholic symptoms were negatively associated with caudal ACC thickness (B = -0.42, pFDR = 0.03). The atypical energy-related symptom profile and immuno-metabolic indices did not show a consistent association with structural brain measures across studies. Conclusion: Overall depression- and melancholic symptom severity showed a dose-response relationship with reduced ACC thickness. No associations between immuno-metabolic dysregulation and structural brain alterations were found, suggesting that although both are associated with depression, distinct mechanisms may be involved. Show less
Dijkstra, F.M.; Loo, A.J. van de; Abdulahad, S.; Bosma, E.R.; Hartog, M.; Huls, H.; ... ; Verster, J.C. 2022
Background: Intranasal esketamine demonstrates rapid improvement of depressive symptoms. However, transient adverse effects (dissociation, sedation and dizziness) may occur, which could impact... Show moreBackground: Intranasal esketamine demonstrates rapid improvement of depressive symptoms. However, transient adverse effects (dissociation, sedation and dizziness) may occur, which could impact driving performance. Aims: To evaluate the effects of 84 mg intranasal esketamine on driving performance in unipolar major depressive disorder (MDD) or persistent depressive disorder (PDD) patients. Methods: The study consisted of two parts. Part A was a single-blind, double-dummy, randomized three-period, cross-over study to compare effects of esketamine versus placebo on next morning driving, 18 +/- 2 h post-treatment. Alcohol was administered to demonstrate assay sensitivity. In Part B, same-day driving, 6 +/- 0.5 hours post-treatment, was assessed during twice weekly esketamine administration for 3 weeks. Twenty-seven patients with mild-to-moderate MDD or PDD without psychotic features completed a 100 km on-the-road driving test on a public highway in normal traffic. The primary outcome was standard deviation of lateral position (SDLP; cm; weaving of car). Results: In Part A, alcohol impaired driving performance compared to placebo: Least-square means (95% CI), p-value for delta SDLP (cm) compared with placebo: (Delta SDLP = + 1.83 (1.03; 2.62), p < 0.001), whereas esketamine did not: (Delta SDLP = -0.23 (-1.04; 0.58), p = 0.572). In Part B, weekly driving tests showed no differences between placebo baseline SDLP and after esketamine administration over 3 weeks: Day 11: (Delta SDLP = -0.96 (-3.72; 1.81), p = 0.493), Day 18: (Delta SDLP = -0.56 (-3.33; 2.20), p = 0.686) and Day 25: (Delta SDLP = -1.05 (-3.82; 1.71), p = 0.451). Conclusions: In this study, esketamine did not impair on-road driving performance the next morning following a single dose, or on same day after repeated administration. Show less
Background: Affective disorders involve dysregulation of major biological stress systems (hypothalamic-pituitary adrenal (HPA)-axis, immune system, autonomic nervous system (ANS)).... Show moreBackground: Affective disorders involve dysregulation of major biological stress systems (hypothalamic-pituitary adrenal (HPA)-axis, immune system, autonomic nervous system (ANS)). Suchdysregulationshave rarely beensimultaneously examined across different stress systems.Methods: In the Netherlands Study of Depression and Anxiety (n=2789), we investigated whether current or remitted depressive and/or anxiety disorders (based on the CIDI semi-structured interview), including specific symptom profiles, were associated with separate markers and cumulative indexes of the HPA-axis (cortisol awakening response, evening cortisol, dexamethasone suppression test cortisol), immune system (C-reactive protein, interleukin-6, tumor necrosis factor-alpha), and ANS (heart rate, respiratory sinus arrhythmia, pre-ejection period).Results: Depressive andanxiety disorderswere significantlyassociated with changes in three biological stress systemsincluding HPA-axis hyperactivity, increased inflammatory activity, and a higher ANS tone, particularly for integrative and cumulative indexes of these stress systems (pFDR <.05) vs. controls. The strongest associations were seen with current disorders andcumulative indexes of the HPA-axis (13=.124, pFDR=.001), the immune system (13 =.057, pFDR=.032), and total cumulative index across stress systems (13=.102, pFDR=.004). Atypical, energy-related depression severity was linked to immune system markers (pFDR<0.001), melancholic depression severity to HPA-axis markers (pFDR=.032), and anxiety arousal severity to both HPA-axis and immune system markers (pFDR<0.05). Findings were partially explained by poorer lifestyle, more chronic diseases, or (especially for ANS-function) antidepressant use. Limitations: Cross-sectional analyses limit examination of temporal associations.Conclusion: Patients withdepressive and anxiety disorders showed consistent dysregulation across biological stress systems, particularly for current episodes.To understand stress system functionality in affective disorders, an integrated approach capturing cumulative stress indices within and across biological stress systems is important. Show less
Background: Ambulatory assessments offer opportunities to evaluate daily dynamics of sleep and momentary affect using mobile technologies. This study examines day-to-day bidirectional associations... Show moreBackground: Ambulatory assessments offer opportunities to evaluate daily dynamics of sleep and momentary affect using mobile technologies. This study examines day-to-day bidirectional associations between sleep and affect using mobile monitoring, and evaluates whether these associations differ between people without and with current or remitted depression/anxiety.Methods: Two-week ecological momentary assessment (EMA) and actigraphy data of 359 participants with current (n = 93), remitted (n = 176) or no (n = 90) CIDI depression/anxiety diagnoses were obtained from the Netherlands Study of Depression and Anxiety. Objective sleep duration (SD) and efficiency were obtained from actigraphy data. Self-reported SD, sleep quality (SQ), positive affect (PA) and negative affect (NA) were assessed by electronic diaries through EMA.Results: A bidirectional longitudinal association was found between self-reported SQ and affect, while no asso-ciation was found for self-reported SD and objective SD and efficiency. Better SQ predicted affect the same day (higher PA: b = 0.035, p < 0.001; lower NA: b =-0.022, p < 0.001), while lower NA on the preceding day predicted better SQ (b =-0.102, p = 0.001). The presence of current depression/anxiety disorders moderated the association between better SQ and subsequent lower NA; it was stronger for patients compared to controls (p = 0.003).Limitations: Observational study design can only point to areas of interest for interventions.Conclusions: This 2-week ambulatory monitoring study shows that, especially among depression/anxiety patients, better self-reported SQ predicts higher PA and lower NA the same day, while lower NA predicts better self-reported SQ. The value of mobile technologies to monitor and potentially intervene in patients to improve their affect should be explored. Show less
Hebbrecht, K.; Stuivenga, M.; Birkenhager, T.; Morrens, M.; Fried, E.I.; Sabbe, B.; Giltay, E.J. 2020
BackgroundMajor depressive disorder (MDD) shows large heterogeneity of symptoms between patients, but within patients, particular symptom clusters may show similar trajectories. While symptom... Show moreBackgroundMajor depressive disorder (MDD) shows large heterogeneity of symptoms between patients, but within patients, particular symptom clusters may show similar trajectories. While symptom clusters and networks have mostly been studied using cross-sectional designs, temporal dynamics of symptoms within patients may yield information that facilitates personalized medicine. Here, we aim to cluster depressive symptom dynamics through dynamic time warping (DTW) analysis.MethodsThe 17-item Hamilton Rating Scale for Depression (HRSD-17) was administered every 2weeks for a median of 11weeks in 255 depressed inpatients. The DTW analysis modeled the temporal dynamics of each pair of individual HRSD-17 items within each patient (i.e., 69,360 calculated "DTW distances"). Subsequently, hierarchical clustering and network models were estimated based on similarities in symptom dynamics both within each patient and at the group level.ResultsThe sample had a mean age of 51 (SD 15.4), and 64.7% were female. Clusters and networks based on symptom dynamics markedly differed across patients. At the group level, five dynamic symptom clusters emerged, which differed from a previously published cross-sectional network. Patients who showed treatment response or remission had the shortest average DTW distance, indicating denser networks with more synchronous symptom trajectories.ConclusionsSymptom dynamics over time can be clustered and visualized using DTW. DTW represents a promising new approach for studying symptom dynamics with the potential to facilitate personalized psychiatric care. Show less
Baeten, R.F.; Rossum, E.F.C. van; Rijke, Y.B. de; Sabbe, B.G.C.; Mast, R.C. van der; Belge, J.B.; ... ; Diermen, L. van 2020
Background: There is substantial evidence showing changes in hypothalamic pituitary adrenal (HPA)-axis ac-tivity in patients with major depressive disorder (MDD). Also, there seem to be differences... Show moreBackground: There is substantial evidence showing changes in hypothalamic pituitary adrenal (HPA)-axis ac-tivity in patients with major depressive disorder (MDD). Also, there seem to be differences in HPA-axis func-tioning between MDD subgroups. It is however unclear whether hair cortisol concentrations (HCC), which are a stable marker of long-term cortisol levels, are suitable as a biomarker for identifying subgroups in MDD. Methods: We were able to attain valid HCC from a scalp hair sample of sixty-two patients with a major de-pressive episode right before electroconvulsive therapy (ECT). HCC were our main biological outcome measure. We created subgroups using depression severity as defined by the Hamilton Depression Rating Scale, the pre-sence/absence of psychotic symptoms, the presence of melancholia as defined by the CORE and catatonia as defined by the Bush-Francis Catatonia Rating Scale. Results: Our analyses of the total group showed a median HCC of 4.4 pg/mg. We found patients with catatonia (N = 10) to have substantially higher median HCC (8.3 pg/mg) than patients without catatonia (3.8 pg/mg). Although presence of melancholia and depression severity were not significantly associated with HCC, more severe psychomotor agitation was associated with higher HCC. Pre-treatment HCC was not associated with ECT outcome. Strengths and limitations: A complicating factor in interpretation of our results was the large variability in HCC. This could be related to potential confounders such as cardiometabolic and other comorbidities, that were however addressed to the extent possible. Conclusions: HCC is a potential biomarker for MDD patients with severe agitation and/or catatonia. ClinicalTrials.gov: Identifier: NCT02562846. Show less
Objectives Gaining knowledge of dynamic processes of mechanisms underlying mindfulness-based cognitive therapy (MBCT) for recurrent depression could help to improve treatment efficacy. The current... Show moreObjectives Gaining knowledge of dynamic processes of mechanisms underlying mindfulness-based cognitive therapy (MBCT) for recurrent depression could help to improve treatment efficacy. The current study examined the overall course and week-to-week associations of mindfulness and positive/negative affect during MBCT for recurrent depression. Methods Using data from the MOMENT study, 235 patients with recurrent depression in (partial) remission allocated to MBCT were included. Prior to each MBCT session, self-reports were obtained on mindfulness, positive affect, and negative affect. Results Autoregressive latent trajectory (ALT) modeling revealed that, across the MBCT course, larger increases in mindfulness were associated with larger increases in positive affect (r = .80,p < .050). Higher general levels of negative affect were associated with smaller increases in mindfulness over time (r = -.26,p < .001). Week-to-week effects showed no reciprocal cross-lagged effects between mindfulness and positive affect or negative affect, except for positive affect at session 2 which was positively associated with mindfulness at session 3 (r = .11,p < .050). Conclusions The current study supports a positive association in strength of increase between mindfulness and positive affect, while higher general levels of negative affect might be associated with smaller increases of mindfulness during MBCT for recurrent depression. For future research, experience sampling methods (ESMs) are recommended to capture dynamics on a smaller time scale. ALT modeling techniques are advised to be better able to interpret the processes of stability and change during MBCT for recurrent depression. Show less
Hebbrecht, K.; Stuivenga, M.; Birkenhager, T.; Mast, R.C. van der; Sabbe, B.; Giltay, E.J. 2020
Background:Although differences in symptom profiles and outcome between depressive patients with an underlying major depressive disorder (MDD) and bipolar depression (BD) have been reported,... Show moreBackground:Although differences in symptom profiles and outcome between depressive patients with an underlying major depressive disorder (MDD) and bipolar depression (BD) have been reported, studies with sequential short-interval assessments in a real-life inpatient setting are scarce.Objectives:To examine potential differences in symptom profile and course of depressive symptomatology in depressive inpatients with underlying MDD and BD.Methods:A cohort of 276 consecutive inpatients with MDD (n= 224) or BD (n= 52) was followed during their hospitalization using routine outcome monitoring (ROM), which included a structured diagnostic interview at baseline (Mini-International Neuropsychiatric Interview Plus [MINI-Plus]) and repeated 17-item Hamilton Depression Rating Scale every 2 weeks. MDD and BD were compared regarding their symptom profiles and time to response and remission. Furthermore, the concordance between the MINI-Plus and clinical diagnosis was analyzed.Results:Patients were on average 52 and 47 years old in the MDD and BD group, respectively, and 66 versus 64% were female. Compared to patients with BD, patients with MDD scored higher on weight loss (p= 0.02), whereas the BD group showed a higher long-term likelihood of response (hazard ratio = 1.93, 95% confidence interval 1.16-3.20,pfor interaction with time = 0.04). Although the same association was seen for remission, the interaction with time was not significant (p= 0.48). Efficiency between the MINI-Plus and clinical diagnosis of BD was high (0.90), suggesting that the MINI-Plus is an adequate ROM diagnostic tool.Conclusions:In routine clinical inpatient care, minor differences in the symptom profile and the course of depressive symptomatology may be helpful in distinguishing MDD and BD, particularly when using sequential ROM assessments. Show less
BACKGROUND: The prevalence of depression is higher in individuals with autoimmune diseases, but the mechanisms underlying the observed comorbidities are unknown. Shared genetic etiology is a... Show moreBACKGROUND: The prevalence of depression is higher in individuals with autoimmune diseases, but the mechanisms underlying the observed comorbidities are unknown. Shared genetic etiology is a plausible explanation for the overlap, and in this study we tested whether genetic variation in the major histocompatibility complex (MHC), which is associated with risk for autoimmune diseases, is also associated with risk for depression.METHODS: We fine-mapped the classical MHC (chr6: 29.6-33.1 Mb), imputing 216 human leukocyte antigen (HLA) alleles and 4 complement component 4 (C4) haplotypes in studies from the Psychiatric Genomics Consortium Major Depressive Disorder Working Group and the UK Biobank. The total sample size was 45,149 depression cases and 86,698 controls. We tested for association between depression status and imputed MHC variants, applying both a region-wide significance threshold (3.9 x 10(-6) ) and a candidate threshold (1.6 x 10(-4) ).RESULTS: No HLA alleles or C4 haplotypes were associated with depression at the region-wide threshold. HLAB*08:01 was associated with modest protection for depression at the candidate threshold for testing in HLA genes in the meta-analysis (odds ratio = 0.98, 95% confidence interval = 0.97-0.99).CONCLUSIONS: We found no evidence that an increased risk for depression was conferred by HLA alleles, which play a major role in the genetic susceptibility to autoimmune diseases, or C4 haplotypes, which are strongly associated with schizophrenia. These results suggest that any HLA or C4 variants associated with depression either are rare or have very modest effect sizes. Show less
Background: The large between-person differences in symptomatology suggest that major depressive disorder (MDD) is a heterogeneous psychiatric disorder. However, symptom-specific prospective... Show moreBackground: The large between-person differences in symptomatology suggest that major depressive disorder (MDD) is a heterogeneous psychiatric disorder. However, symptom-specific prospective studies are scarce. We hypothesized that chronicity (i.e., being depressed for 24 months during a patient's preceding 48 months at baseline) and neuroticism at baseline would predict adverse course trajectories over 9 years of follow up with differential magnitudes for individual depressive symptoms.Methods: In total, 560 patients with a current MDD were included from the Netherlands Study of Depression and Anxiety (NESDA-cohort). We used a multivariate linear mixed model with repeated measures, with a history of chronicity and neuroticism separately as main independent variables and with Inventory of Depressive Symptomatology self-report (IDS-SR) item scores as outcome variables. For each individual symptom, the model was adjusted for age, gender, and baseline depression severity.Results: Patients were on average 42.7 (SD = 12.1) years old and 64.7% were women. Patients with chronic depression or high levels of neuroticism showed similar absolute rates of decline over time compared to their counterparts. However, because symptoms had higher starting points for mood, cognitive, and somatic/vegetative symptoms (in that order), symptom severity remained higher over time. Chronicity and neuroticism were especially linked to persistent low self-esteem and high interpersonal sensitivity.Limitations: Neuroticism is partly state dependent and likely affected by depression severity.Conclusions: Chronicity and neuroticism predict long-term persistence of diverse psychiatric symptoms, in particular low self-esteem and high interpersonal sensitivity. Show less
Ballegooijen, W. van; Eikelenboom, M.; Fokkema, M.; Riper, H.; Hemert, A.M. van; Kerkhof, A.J.F.M.; ... ; Smit, J.H. 2019
Background: Suicidality could be associated with specific combinations of biological, social and psychologicalfactors. Therefore, depressive episodes with suicidal ideation could be different from... Show moreBackground: Suicidality could be associated with specific combinations of biological, social and psychologicalfactors. Therefore, depressive episodes with suicidal ideation could be different from depressive episodeswithout suicidal ideation in terms of latent variable structures.Methods: In this study we compared latent variable structures between suicidal and non-suicidal depressedpatients using confirmatory factor analysis (CFA), following a measurement invariance test procedure. Patients(N = 919) suffering from major depressive disorder were selected from the Netherlands Study of Depression andAnxiety (NESDA) and split into a group that showed no symptoms of suicidal ideation (non-SI; N = 691) and asuicidal ideation (SI) group that had one or more symptoms of suicidal ideation (N = 228). Depression andanxiety symptoms were measured using the short form of the Mood and Anxiety Symptoms Questionnaire(MASQ-D30).Results: CFA implied a difference in latent variable structures between the non-SI sample (CFI 0.957; RMSEA0.041) and the SI sample (CFI 0.900; RMSEA 0.056). Subsequent multiple-group CFA showed violations ofmeasurement invariance. The General distress and Anhedonic depression subscales were best indicated byhopelessness and lack of optimism in the SI sample and by dissatisfaction and not feeling lively in the non-SIsample. Overall, the SI sample had higher scores and lower inter-item correlations on the Anhedonic depressionitems.Limitations: We have included very mild cases of suicidal ideation in our SI sample.Conclusions: On a latent variable level, depression with suicidal ideation differs from depression without suicidalideation. Results encourage further research into the symptom structure of depression among suicidal patients Show less
Background: Psychiatric disorders are highly heterogeneous, defined based on symptoms with little connection to potential underlying biological mechanisms. A possible approach to dissect biological... Show moreBackground: Psychiatric disorders are highly heterogeneous, defined based on symptoms with little connection to potential underlying biological mechanisms. A possible approach to dissect biological heterogeneity is to look for biologically meaningful subtypes. A recent study Drysdale et al. (2017) showed promising results along this line by simultaneously using resting state fMRI and clinical data and identified four distinct subtypes of depression with different clinical profiles and abnormal resting state fMRI connectivity. These subtypes were predictive of treatment response to transcranial magnetic stimulation therapy.Objective: Here, we attempted to replicate the procedure followed in the Drysdale a al. study and their findings in a different clinical population and a more heterogeneous sample of 187 participants with depression and anxiety. We aimed to answer the following questions: 1) Using the same procedure, can we find a statistically significant and reliable relationship between brain connectivity and clinical symptoms? 2) Is the observed relationship similar to the one found in the original study? 3) Can we identify distinct and reliable subtypes? 4) Do they have similar clinical profiles as the subtypes identified in the original study?Methods: We followed the original procedure as closely as possible, including a canonical correlation analysis to find a low dimensional representation of clinically relevant resting state fMRI features, followed by hierarchical clustering to identify subtypes. We extended the original procedure using additional statistical tests, to test the statistical significance of the relationship between resting state fMRI and clinical data, and the existence of distinct subtypes. Furthermore, we examined the stability of the whole procedure using resampling.Results and conclusion: As in the original study, we found extremely high canonical correlations between functional connectivity and clinical symptoms, and an optimal three-cluster solution. However, neither canonical correlations nor clusters were statistically significant. On the basis of our extensive evaluations of the analysis methodology used and within the limits of comparison of our sample relative to the sample used in Drysdale et al., we argue that the evidence for the existence of the distinct resting state connectivity-based subtypes of depression should be interpreted with caution. Show less
Individuals suffering from depression often have difficulty trusting others. Previous research has shown a relationship between trust formation and pupil mimicry - the synchronization of pupil... Show moreIndividuals suffering from depression often have difficulty trusting others. Previous research has shown a relationship between trust formation and pupil mimicry - the synchronization of pupil sizes between individuals. The current study therefore examined whether pupil mimicry is weaker in depressed individuals and an underlying factor of their low levels of trust. Forty-two patients with major depressive disorder (MDD) and 40 healthy control subjects played trust games with virtual partners. Images of these partners' eye regions were presented to participants before they had to make a monetary investment decision. Partners' pupils either dilated, constricted, or remained static over the course of 4-s interactions. During the task, participants' pupil sizes were recorded with eye-tracking equipment to assess mimicry. The results confirm that patients with MDD were somewhat less trusting than controls and used another's pupillary cues differently when deciding to trust. Specifically, whereas healthy controls trusted partners with dilating pupils more than partners with constricting pupils, patients with MDD particularly trusted partners whose pupils changed in size less, regardless of whether partners' pupils were dilating or constricting. This difference in investment behavior was unrelated to differences in pupil mimicry, which was equally apparent in both groups and fostered trust to the same extent. Whereas lower levels of trust observed in patients with MDD could not be explained by differences in pupil mimicry, our data show that pupil dilation mimicry might help people to trust. These findings provide further evidence for the important role of pupil size and pupil mimicry in interpersonal trust formation and shed light on the pathophysiology of clinically low trust in patients with MDD. Show less
