Chronic pain predicts a worse response to depression treatment, regardless of thyroid function or psychotropics prescribed.

BACKGROUND: Chronic pain (CP) and thyroid hormones' (TH) abnormalities are associated with depression, but the impact of pain and TH fluctuation on the response to depression treatment is uncertain. METHODS: Eighty-eight patients with major depression were evaluated before and after 6 months of specific treatment, through scales of symptoms' severity (HAM-D-17), psychomotor disturbance (CORE), and quality of life (WHOQOL-Bref). We reviewed psychiatric medications and measured TSH, T3 and T4. We used Generalized Estimating Equations to assess the interaction effect between CP and treatment time on depression severity and TH levels, and Bonferroni to compare means. RESULTS: 47.7 % of the patients had CP. Patients with and without CP did not differ at baseline. At follow-up, those with CP experienced a more modest decrease in symptoms' severity and no improvement in any domain of psychomotor disturbance, contrasting with a decrease of over 40 % from the baseline values of CORE in patients without CP (non-CP). Initial and final scores were respectively: HAM-D CP 24.06 and 19.3, Δ = -4.75; HAM-D non-CP 22.92 and 14.7, Δ = -8.21; CORE CP 5.36 and 5.24, Δ = -0.12; CORE non-CP 5.8 and 3.22, Δ = -2.57. There was no interaction with TH or life quality. Model adjustments for psychotropic drugs received and sensitivity analysis excluding somatic symptoms from severity scales did not impact the results. LIMITATIONS: Findings may not replicate in mildly depressed patients from primary care. Pain scales were not applied. CONCLUSIONS: Individuals with chronic pain showed a suboptimal response to depression treatment, regardless of the medications used or TH levels.

The relationship of white matter microstructure with psychomotor disturbance and relapse in remitted psychotic depression.

BACKGROUND: Psychomotor disturbance is common in psychotic depression and is associated with relapse. In this analysis, we examined whether white matter microstructure is associated with relapse probability in psychotic depression and, if so, whether white matter microstructure accounts for the association between psychomotor disturbance and relapse. METHODS: We used tractography to characterize diffusion-weighted MRI data in 80 participants enrolled in a randomized clinical trial that compared efficacy and tolerability of sertraline plus olanzapine with sertraline plus placebo in the continuation treatment of remitted psychotic depression. Cox proportional hazard models tested the relationships between psychomotor disturbance (processing speed and CORE score) at baseline, white matter microstructure (fractional anisotropy [FA] and mean diffusivity [MD]) in 15 selected tracts at baseline, and relapse probability. RESULTS: CORE was significantly associated with relapse. Higher mean MD was significantly associated with relapse in the each of the following tracts: corpus callosum, left striato-frontal, left thalamo-frontal, and right thalamo-frontal. CORE and MD were each associated with relapse in the final models. LIMITATIONS: As a secondary analysis with a small sample size, this study was not powered for its aims, and is vulnerable to types I and II statistical errors. Further, the sample size was not sufficient to test the interaction of the independent variables and randomized treatment group with relapse probability. CONCLUSIONS: While both psychomotor disturbance and MD were associated with psychotic depression relapse, MD did not account for the relationship between psychomotor disturbance and relapse. The mechanism by which of psychomotor disturbance increases the risk of relapse requires further investigation. CLINICAL TRIAL REGISTRATION: Study of the Pharmacotherapy of Psychotic Depression II (STOP-PD II); NCT01427608. URL: https://clinicaltrials.gov/ct2/show/NCT01427608.

Spontaneous beta power, motor-related beta power and cortical thickness in major depressive disorder with psychomotor disturbance.

INTRODUCTION: The psychomotor disturbance is a common symptom in patients with major depressive disorder (MDD). The neurological mechanisms of psychomotor disturbance are intricate, involving alterations in the structure and function of motor-related regions. However, the relationship among changes in the spontaneous activity, motor-related activity, local cortical thickness, and psychomotor function remains unclear. METHOD: A total of 140 patients with MDD and 68 healthy controls performed a simple right-hand visuomotor task during magnetoencephalography (MEG) scanning. All patients were divided into two groups according to the presence of psychomotor slowing. Spontaneous beta power, movement-related beta desynchronization (MRBD), absolute beta power during movement and cortical characteristics in the bilateral primary motor cortex were compared using general linear models with the group as a fixed effect and age as a covariate. Finally, the moderated mediation model was tested to examine the relationship between brain metrics with group differences and psychomotor performance. RESULTS: The patients with psychomotor slowing showed higher spontaneous beta power, movement-related beta desynchronization and absolute beta power during movement than patients without psychomotor slowing. Compared with the other two groups, significant decreases were found in cortical thickness of the left primary motor cortex in patients with psychomotor slowing. Our moderated mediation model showed that the increased spontaneous beta power indirectly affected impaired psychomotor performance by abnormal MRBD, and the indirect effects were moderated by cortical thickness. CONCLUSION: These results suggest that patients with MDD have aberrant cortical beta activity at rest and during movement, combined with abnormal cortical thickness, contributing to the psychomotor disturbance observed in this patient population.

Actigraphically measured psychomotor slowing in depression: systematic review and meta-analysis.

Psychomotor slowing is a key feature of depressive disorders. Despite its great clinical importance, the pathophysiology and prevalence across different diagnoses and mood states are still poorly understood. Actigraphy allows unbiased, objective, and naturalistic assessment of physical activity as a marker of psychomotor slowing. Yet, the true effect-sizes remain unclear as recent, large systematic reviews are missing. We conducted a novel meta-analysis on actigraphically measured slowing in depression with strict inclusion and exclusion criteria for diagnosis ascertainment and sample duplications. Medline/PubMed and Web-of-Science were searched with terms combining mood-keywords and actigraphy-keywords until September 2021. Original research measuring actigraphy for ⩾24 h in at least two groups of depressed, remitted, or healthy participants and applying operationalized diagnosis was included. Studies in somatically ill patients, N < 10 participants/group, and studies using consumer-devices were excluded. Activity-levels between groups were compared using random-effects models with standardized-mean-differences and several moderators were examined. In total, 34 studies (n = 1804 patients) were included. Patients had lower activity than controls [standardized mean difference (s.m.d.) = -0.78, 95% confidence interval (CI) -0.99 to -0.57]. Compared to controls, patients with unipolar and bipolar disorder had lower activity than controls whether in depressed (unipolar: s.m.d. = -0.82, 95% CI -1.07 to -0.56; bipolar: s.m.d. = -0.94, 95% CI -1.41 to -0.46), or remitted/euthymic mood (unipolar: s.m.d. = -0.28, 95% CI -0.56 to 0.0; bipolar: s.m.d. = -0.92, 95% CI -1.36 to -0.47). None of the examined moderators had any significant effect. To date, this is the largest meta-analysis on actigraphically measured slowing in mood disorders. They are associated with lower activity, even in the remitted/euthymic mood-state. Studying objective motor behavior via actigraphy holds promise for informing screening and staging of affective disorders.

Factor analysis of the CORE measure of psychomotor disturbance in psychotic depression: Findings from the STOP-PD II study.

The CORE instrument is commonly used to measure psychomotor disturbance. We examined the factor structure of the CORE in 266 adults with an acute episode psychotic depression, a disorder with a high rate of psychomotor disturbance. Exploratory factor analysis identified a two-factor solution: Factor 1 corresponded to the CORE's retardation and non-interactiveness items and Factor 2 corresponded to its agitation items. Internal consistency was excellent for Factor 1 but questionable for Factor 2. These findings suggest that the CORE's retardation and non-interactiveness items should be combined in one subscale when assessing patients with an acute episode of psychotic depression.

Association between psychomotor disturbance and treatment outcome in psychotic depression: a STOP-PD II report.

BACKGROUND: Little is known about the relationship between psychomotor disturbance (PMD) and treatment outcome of psychotic depression. This study examined the association between PMD and subsequent remission and relapse of treated psychotic depression. METHODS: Two hundred and sixty-nine men and women aged 18-85 years with an episode of psychotic depression were treated with open-label sertraline plus olanzapine for up to 12 weeks. Participants who remained in remission or near-remission following an 8-week stabilization phase were eligible to participate in a 36-week randomized controlled trial (RCT) that compared the efficacy and tolerability of sertraline plus olanzapine (n = 64) with sertraline plus placebo (n = 62). PMD was measured with the psychiatrist-rated sign-based CORE at acute phase baseline and at RCT baseline. Spearman's correlations and logistic regression analyses were used to analyze the association between CORE total score at acute phase baseline and remission/near-remission and CORE total score at RCT baseline and relapse. RESULTS: Higher CORE total score at acute phase baseline was associated with lower frequency of remission/near-remission. Higher CORE total score at RCT baseline was associated with higher frequency of relapse, in the RCT sample as a whole, as well as in each of the two randomized groups. CONCLUSIONS: PMD is associated with poorer outcome of psychotic depression treated with sertraline plus olanzapine. Future research needs to examine the neurobiology of PMD in psychotic depression in relation to treatment outcome.

Can psychomotor disturbance predict ect outcome in depression?

Psychomotor symptoms are core features of melancholic depression. This study investigates whether psychomotor disturbance predicts the outcome of electroconvulsive therapy (ECT) and how the treatment modulates psychomotor disturbance. In 73 adults suffering from major depressive disorder psychomotor functioning was evaluated before, during and after ECT using the observer-rated CORE measure and objective measures including accelerometry and a drawing task. Regression models were fitted to assess the predictive value of melancholic depression (CORE ≥ 8) and the psychomotor variables on ECT outcome, while effects on psychomotor functioning were evaluated through linear mixed models. Patients with CORE-defined melancholic depression (n = 41) had a 4.9 times greater chance of reaching response than those (n = 24) with non-melancholic depression (Chi-Square = 7.5, P = 0.006). At baseline, both higher total CORE scores (AUC = 0.76; P = 0.001) and needing more cognitive (AUC = 0.78; P = 0.001) and motor time (AUC = 0.76; P = 0.003) on the drawing task corresponded to superior ECT outcomes, as did lower daytime activity levels (AUC = 0.76) although not significantly so after Bonferroni correction for multiple testing. A greater CORE-score reduction in the first week of ECT was associated with higher ECT effectiveness. ECT reduced CORE-assessed psychomotor symptoms and improved activity levels only in those patients showing the severer baseline retardation. Although the sample was relatively small, psychomotor symptoms were clearly associated with beneficial outcome of ECT in patients with major depression, indicating that monitoring psychomotor deficits can help personalise treatment.

Association between core-assigned melancholia and the melancholia subscale of the HAM-D.

BACKGROUND: Clinical observation and research data suggest that major depression (MD) is a heterogeneous disorder, possibly representing a group of different clinical entities. The identification of more homogeneous subtypes of depression could enhance research and enable development of more specific treatments. A melancholic subtype of MD, defined by the presence of observable psychomotor disturbance (PMD), is proposed to be more homogeneous and associated with biological determinants. The aim of this study was to investigate the homogeneity of this melancholic subtype in terms of symptoms by searching for an association between melancholia and a unidimensional subscale of the Hamilton Depression Rating Scale (HAM-D) proposed to have biological validity (HAM-D6). METHODS: A cross-sectional assessment of 385 outpatients presenting with a unipolar major depressive episode was carried out to evaluate depressive symptoms using the HAM-D and melancholic or nonmelancholic subtype, according to the CORE measure of PMD. RESULTS: Melancholic patients exhibited more severe depressive symptoms, mainly associated with the HAM-D6. The items of this melancholia subscale represent 42.3% of the total HAM-D and were responsible for 59.4% of between-group differences. Correlation analysis showed similar results. LIMITATIONS: Most patients received previous treatment, and some were not at the nadir of the episode when assessed. This could have lowered the CORE measure sensibility. CONCLUSION: Melancholic depression, as assigned by the CORE measure, represents a more severe and homogeneous subtype of MD. This observation may allow identification of proper biomarkers and development of more specific treatments.