The role of immuno-metabolic depression features in the effects of light therapy in patients with depression and type 2 diabetes mellitus: A randomized controlled trial.

OBJECTIVE: Immuno-metabolic depression (IMD) is proposed to be a form of depression encompassing atypical, energy-related symptoms (AES), low-grade inflammation and metabolic dysregulations. Light therapy may alleviate AES by modulating inflammatory and metabolic pathways. We investigated whether light therapy improves clinical and biological IMD features and whether effects of light therapy on AES or depressive symptom severity are moderated by baseline IMD features. Associations between changes in symptoms and biomarkers were explored. METHODS: In secondary analyses, clinical trial data was used from 77 individuals with depression and type 2 diabetes mellitus (T2DM) randomized to four weeks of light therapy or placebo. AES severity and depressive symptom severity were based on the Inventory of Depressive Symptomatology. Biomarkers included 73 metabolites (Nightingale) summarized in three principal components and CRP, IL-6, TNF-α, INF-γ. Linear regression analyses were performed. RESULTS: Light therapy had no effect on AES severity, inflammatory markers and metabolite principle components versus placebo. None of these baseline features moderated the effects of light therapy on AES severity. Only a principle component reflecting metabolites implicated in glucose homeostasis moderated the effects of light therapy on depressive symptom severity (ßinteraction = 0.65, P = 0.001, FDR = 0.003). Changes in AES were not associated with changes in biomarkers. CONCLUSION: Findings do not support the efficacy of light therapy in reducing IMD features in patients with depression and T2DM. We find limited evidence that light therapy is a more beneficial depression treatment among those with more IMD features. Changes in clinical and biological IMD features did not align over four-weeks' time. TRIAL REGISTRATION: The Netherlands Trial Register (NTR) NTR4942.

Insulin resistance as a marker for the immune-metabolic subtype of depression.

OBJECTIVE: Insulin resistance (IR), a marker of metabolic dysregulation and pro-inflammatory state, moderates the antidepressant treatment effect in patients with type 2 diabetes (T2D) and is therefore a potential marker for personalized treatment. Based on data from a light therapy trial (NTR4942), we aimed to evaluate whether 1) depression symptoms differ according to the level of IR, and 2) improvement of specific depression symptoms drive the positive effects of light therapy in those with higher IR. METHODS: This secondary analysis in 59 individuals with depression and T2D explored differences in depressive symptom profile (30-item Inventory of Depressive Symptomatology (IDS)) at baseline and in response to light therapy (versus placebo), between lower and higher IR individuals, using Likelihood Ratio tests and Linear-by-linear association. IR was measured using the gold standard, a hyperinsulinemic-euglycaemic clamp. RESULTS: At baseline, higher IR individuals reported more symptoms of irritability (p=0.024) anhedonia (no interest in people and activities: p=0.011; absence of pleasure and enjoyment: p=0.021), fatigue (fatigue: p=0.036; physical fatigue: p=0.035) and hypersomnia (p=0.029) relative to persons with lower IR, who reported more insomnia (nightly awakening: p=0.041; early morning awakening: p=0.012). Light therapy led to an improvement across IDS symptoms in higher IR individuals, while in lower IR individuals, light therapy improved early morning awakening (p=0.005) and interest in people and activities (p=0.015), but worsened mood (feeling sad: p=0.001; feeling irritable: p=0.002; interpersonal sensitivity: p=0.014). CONCLUSIONS: Results add to the hypothesis of an immune-metabolic subtype of depression, and suggest that IR might be a promising focus for precision medicine.

Effects of dietary interventions on depressive symptom profiles: results from the MooDFOOD depression prevention study.

BACKGROUND: Dietary interventions did not prevent depression onset nor reduced depressive symptoms in a large multi-center randomized controlled depression prevention study (MooDFOOD) involving overweight adults with subsyndromal depressive symptoms. We conducted follow-up analyses to investigate whether dietary interventions differ in their effects on depressive symptom profiles (mood/cognition; somatic; atypical, energy-related). METHODS: Baseline, 3-, 6-, and 12-month follow-up data from MooDFOOD were used (n = 933). Participants received (1) placebo supplements, (2) food-related behavioral activation (F-BA) therapy with placebo supplements, (3) multi-nutrient supplements (omega-3 fatty acids and a multi-vitamin), or (4) F-BA therapy with multi-nutrient supplements. Depressive symptom profiles were based on the Inventory of Depressive Symptomatology. RESULTS: F-BA therapy was significantly associated with decreased severity of the somatic (B = -0.03, p = 0.014, d = -0.10) and energy-related (B = -0.08, p = 0.001, d = -0.13), but not with the mood/cognition symptom profile, whereas multi-nutrient supplementation was significantly associated with increased severity of the mood/cognition (B = 0.05, p = 0.022, d = 0.09) and the energy-related (B = 0.07, p = 0.002, d = 0.12) but not with the somatic symptom profile. CONCLUSIONS: Differentiating depressive symptom profiles indicated that food-related behavioral interventions are most beneficial to alleviate somatic symptoms and symptoms of the atypical, energy-related profile linked to an immuno-metabolic form of depression, although effect sizes were small. Multi-nutrient supplements are not indicated to reduce depressive symptom profiles. These findings show that attention to clinical heterogeneity in depression is of importance when studying dietary interventions.

Using Smartphones and Wearable Devices to Monitor Behavioral Changes During COVID-19.

BACKGROUND: In the absence of a vaccine or effective treatment for COVID-19, countries have adopted nonpharmaceutical interventions (NPIs) such as social distancing and full lockdown. An objective and quantitative means of passively monitoring the impact and response of these interventions at a local level is needed. OBJECTIVE: We aim to explore the utility of the recently developed open-source mobile health platform Remote Assessment of Disease and Relapse (RADAR)-base as a toolbox to rapidly test the effect and response to NPIs intended to limit the spread of COVID-19. METHODS: We analyzed data extracted from smartphone and wearable devices, and managed by the RADAR-base from 1062 participants recruited in Italy, Spain, Denmark, the United Kingdom, and the Netherlands. We derived nine features on a daily basis including time spent at home, maximum distance travelled from home, the maximum number of Bluetooth-enabled nearby devices (as a proxy for physical distancing), step count, average heart rate, sleep duration, bedtime, phone unlock duration, and social app use duration. We performed Kruskal-Wallis tests followed by post hoc Dunn tests to assess differences in these features among baseline, prelockdown, and during lockdown periods. We also studied behavioral differences by age, gender, BMI, and educational background. RESULTS: We were able to quantify expected changes in time spent at home, distance travelled, and the number of nearby Bluetooth-enabled devices between prelockdown and during lockdown periods (P<.001 for all five countries). We saw reduced sociality as measured through mobility features and increased virtual sociality through phone use. People were more active on their phones (P<.001 for Italy, Spain, and the United Kingdom), spending more time using social media apps (P<.001 for Italy, Spain, the United Kingdom, and the Netherlands), particularly around major news events. Furthermore, participants had a lower heart rate (P<.001 for Italy and Spain; P=.02 for Denmark), went to bed later (P<.001 for Italy, Spain, the United Kingdom, and the Netherlands), and slept more (P<.001 for Italy, Spain, and the United Kingdom). We also found that young people had longer homestay than older people during the lockdown and fewer daily steps. Although there was no significant difference between the high and low BMI groups in time spent at home, the low BMI group walked more. CONCLUSIONS: RADAR-base, a freely deployable data collection platform leveraging data from wearables and mobile technologies, can be used to rapidly quantify and provide a holistic view of behavioral changes in response to public health interventions as a result of infectious outbreaks such as COVID-19. RADAR-base may be a viable approach to implementing an early warning system for passively assessing the local compliance to interventions in epidemics and pandemics, and could help countries ease out of lockdown.

Sleep, circadian rhythm, and physical activity patterns in depressive and anxiety disorders: A 2-week ambulatory assessment study.

BACKGROUND: Actigraphy may provide a more valid assessment of sleep, circadian rhythm (CR), and physical activity (PA) than self-reported questionnaires, but has not been used widely to study the association with depression/anxiety and their clinical characteristics. METHODS: Fourteen-day actigraphy data of 359 participants with current (n = 93), remitted (n = 176), or no (n = 90) composite international diagnostic interview depression/anxiety diagnoses were obtained from the Netherlands Study of Depression and Anxiety. Objective estimates included sleep duration (SD), sleep efficiency, relative amplitude (RA) between day-time and night-time activity, mid sleep on free days (MSF), gross motor activity (GMA), and moderate-to-vigorous PA (MVPA). Self-reported measures included insomnia rating scale, SD, MSF, metabolic equivalent total, and MVPA. RESULTS: Compared to controls, individuals with current depression/anxiety had a significantly different objective, but not self-reported, PA and CR: lower GMA (23.83 vs. 27.4 milli-gravity/day, p = .022), lower MVPA (35.32 vs. 47.64 min/day, p = .023), lower RA (0.82 vs. 0.83, p = .033). In contrast, self-reported, but not objective, sleep differed between people with current depression/anxiety compared to those without current disorders; people with current depression/anxiety reported both shorter and longer SD and more insomnia. More depressive/anxiety symptoms and number of depressive/anxiety diagnoses were associated with larger disturbances of the actigraphy measures. CONCLUSION: Actigraphy provides ecologically valid information on sleep, CR, and PA that enhances data from self-reported questionnaires. As those with more severe or comorbid forms showed the lowest PA and most CR disruptions, the potential for adjunctive behavioral and chronotherapy interventions should be explored, as well as the potential of actigraphy to monitor treatment response to such interventions.