Repeated Digitized Assessment of Risk and Symptom Profiles During Inpatient Treatment of Affective Disorder: Observational Study

Background: Predictive models have revealed promising results for the individual prognosis of treatment response and relapse risk as well as for differential diagnosis in affective disorders. Yet, in order to translate personalized predictive modeling from research contexts to psychiatric clinical routine, standardized collection of information of sufficient detail and temporal resolution in day-to-day clinical care is needed. Digital collection of self-report measures by patients is a time- and cost-efficient approach to gain such data throughout treatment. Objective: The objective of this study was to investigate whether patients with severe affective disorders were willing and able to participate in such efforts, whether the feasibility of such systems might vary depending on individual patient characteristics, and if digitally acquired assessments were of sufficient diagnostic validity. Methods: We implemented a system for longitudinal digital collection of risk and symptom profiles based on repeated self-reports via tablet computers throughout inpatient treatment of affective disorders at the Department of Psychiatry at the University of Münster. Tablet-handling competency and the speed of data entry were assessed. Depression severity was additionally assessed by a clinical interviewer at baseline and before discharge. Results: Of 364 affective disorder patients who were approached, 242 (66.5%) participated in the study; 88.8% of participants (215/242) were diagnosed with major depressive disorder, and 27 (11.2%) had bipolar disorder. During the duration of inpatient treatment, 79% of expected assessments were completed, with an average of 4 completed assessments per participant; 4 participants (4/242, 1.6%) dropped out of the study prematurely. During data entry, 89.3% of participants (216/242) did not require additional support. Needing support with tablet handling and slower data entry pace were predicted by older age, whereas depression severity at baseline did not influence these measures. Patient self-reporting of depression severity showed high agreement with standardized external assessments by a clinical interviewer. Conclusions: Our results indicate that digital collection of self-report measures is a feasible, accessible, and valid method for longitudinal data collection in psychiatric routine, which will eventually facilitate the identification of individual risk and resilience factors for affective disorders and pave the way toward personalized psychiatric care

Establishing the bidirectional relationship between depression and subclinical arteriosclerosis – rationale, design, and characteristics of the BiDirect Study

Background: Depression and cardiovascular diseases due to arteriosclerosis are both frequent and impairing conditions. Depression and (subclinical) arteriosclerosis appear to be related in a bidirectional way, and it is plausible to assume a partly joint causal relationship. However, the biological mechanisms and the behavioral pathways that lead from depression to arteriosclerosis and vice versa remain to be exactly determined. Methods/design: This study protocol describes the rationale and design of the prospective BiDirect Study that aims at investigating the mutual relationship between depression and (subclinical) arteriosclerosis. BiDirect is scheduled to follow-up three distinct cohorts of individuals ((i) patients with acute depression (N = 999), (ii) patients after an acute cardiac event (N = 347), and (iii) reference subjects from the general population (N = 912)). Over the course of 12 years, four personal examinations are planned to be conducted. The core examination program, which will remain identical across follow-ups, comprises a personal interview (e.g. medical diagnoses, health care utilization, lifestyle and risk behavior), a battery of self-administered questionnaires (e.g. depressive symptoms, readiness to change health behavior, perceived health-related quality of life), sensory (e.g. olfaction, pain) and neuropsychological (e.g. memory, executive functions, emotional processing, manual dexterity) assessments, anthropometry, body impedance measurement, a clinical work-up regarding the vascular status (e.g. electrocardiogram, blood pressure, intima media thickness), the taking of blood samples (serum and plasma, DNA), and structural and functional resonance imaging of the brain (e.g. diffusion tensor imaging, resting-state, emotional faces processing). The present report includes BiDirect-Baseline, the first data collection wave. Discussion: Due to its prospective character, the integration of three distinct cohorts, the long follow-up time window, the diligent diagnosis of depression taking depression subtypes into account, the consideration of relevant comorbidities and risk factors, the assessment of indicators of (subclinical) arteriosclerosis in different vascular territories, and the structural and functional brain imaging that is performed for a large number of participants, the BiDirect Study represents an innovative approach that combines population-based cohorts with sophisticated clinical work-up methods and that holds the potential to overcome many of the drawbacks characterizing earlier investigations.<br

Large-scale evidence for an association between low-grade peripheral inflammation and brain structural alterations in major depression in the BiDirect study

BACKGROUND: Preliminary research suggests that major depressive disorder (MDD) is associated with structural alterations in the brain, as well as with low-grade peripheral inflammation. However, even though a link between inflammatory processes and altered brain structural integrity has been purported by experimental research, well-powered studies to confirm this hypothesis in patients with MDD have been lacking. We aimed to investigate the potential association between structural brain alterations and low-grade inflammation as interrelated biological correlates of MDD. METHODS: In this cross-sectional study, 514 patients with MDD and 359 healthy controls underwent structural MRI. We used voxel-based morphometry to study local differences in grey matter volume. We also assessed serum levels of high-sensitivity C-reactive protein (hsCRP) in each participant. RESULTS: Compared with healthy controls (age [mean ± standard deviation] 52.57 ± 7.94 yr; 50% male), patients with MDD (49.14 ± 7.28 yr, 39% male) exhibited significantly increased hsCRP levels (Z = −5.562, p < 0.001) and significantly decreased grey matter volume in the prefrontal cortex and the insula. Prefrontal grey matter volume reductions were significantly associated with higher hsCRP levels in patients with MDD (x = 50, y = 50, z = 8; t1,501 = 5.15; k = 92; pFWE < 0.001). In the MDD sample, the significant negative association between hsCRP and grey matter appeared independent of age, sex, body mass index, current smoking status, antidepressant load, hospitalization and medical comorbidities. LIMITATIONS: This study had a cross-sectional design. CONCLUSION: The present study highlights the role of reduced grey matter volume and low-grade peripheral inflammation as interrelated biological correlates of MDD. The reported inverse association between peripheral low-grade inflammation and brain structural integrity in patients with MDD translates current knowledge from experimental studies to the bedside

Brain structural correlates of alexithymia in patients with major depressive disorder

BACKGROUND: Alexithymia is a risk factor for major depressive disorder (MDD) and has been associated with diminished treatment response. Neuroimaging studies have revealed structural aberrations of the anterior cingulate cortex and the fusiform gyrus in healthy controls with high levels of alexithymia. The present study tried to corroborate and extend these results to patients with MDD compared with healthy controls. METHODS: We investigated the relationship between alexithymia, depression and grey matter volume in 63 patients with MDD (mean age ± standard deviation = 42.43 yr ± 11.91; 33 female) and 46 healthy controls (45.35 yr ± 8.37; 22 female). We assessed alexithymia using the Toronto Alexithymia Scale. We conducted an alexithymia × group analysis of covariance; we used a region-of-interest approach, including the fusiform gyrus and anterior cingulate cortex, and conducted whole brain analysis using voxelbased morphometry. RESULTS: Our analysis revealed a significant alexithymia × group interaction in the fusiform gyrus (left, pFWE = 0.031; right, pFWE = 0.010). Higher alexithymia scores were associated with decreased grey matter volume in patients with MDD (pFWE = 0.009), but with increased grey matter volume of the fusiform gyrus in healthy controls (pFWE = 0.044). We found no significant main effects in the region-of-interest analysis. LIMITATIONS: Owing to the naturalistic nature of our study, patients with MDD and healthy controls differed significantly in their alexithymia scores. CONCLUSION: Our results showed the fusiform gyrus as a correlate of alexithymia. We also found differences related to alexithymia between patients with MDD and healthy controls in the fusiform gyrus. Our study encourages research related to the transition from risk to MDD in people with alexithymia

A meta-analysis of polygenic risk scores for mood disorders, neuroticism, and schizophrenia in antidepressant response

About two-thirds of patients with major depressive disorder (MDD) fail to achieve symptom remission after the initial antidepressant treatment. Despite a role of genetic factors was proven, the specific underpinnings are not fully understood yet. Polygenic risk scores (PRSs), which summarise the additive effect of multiple risk variants across the genome, might provide insights into the underlying genetics. This study aims to investigate the possible association of PRSs for bipolar disorder, MDD, neuroticism, and schizophrenia (SCZ) with antidepressant non-response or non-remission in patients with MDD. PRSs were calculated at eight genome-wide P-thresholds based on publicly available summary statistics of the largest genome-wide association studies. Logistic regressions were performed between PRSs and non-response or non-remission in six European clinical samples, adjusting for age, sex, baseline symptom severity, recruitment sites, and population stratification. Results were meta-analysed across samples, including up to 3,637 individuals. Bonferroni correction was applied. In the meta-analysis, no result was significant after Bonferroni correction. The top result was found for MDD-PRS and non-remission (p = 0.004), with patients in the highest vs. lowest PRS quintile being more likely not to achieve remission (OR=1.5, 95% CI=1.11–1.98, p = 0.007). Nominal associations were also found between MDD-PRS and non-response (p = 0.013), as well as between SCZ-PRS and non-remission (p = 0.035). Although PRSs are still not able to predict non-response or non-remission, our results are in line with previous works; methodological improvements in PRSs calculation may improve their predictive performance and have a meaningful role in precision psychiatry.SCOPUS: ar.jDecretOANoAutActifinfo:eu-repo/semantics/publishe

Elevated body weight modulates subcortical volume change and associated clinical response following electroconvulsive therapy

Background: Obesity is a frequent somatic comorbidity of major depression, and it has been associated with worse clinical outcomes and brain structural abnormalities. Converging evidence suggests that electroconvulsive therapy (ECT) induces both clinical improvements and increased subcortical grey matter volume in patients with depression. However, it remains unknown whether increased body weight modulates the clinical response and structural neuroplasticity that occur with ECT. Methods: To address this question, we conducted a longitudinal investigation of structural MRI data from the Global ECT-MRI Research Collaboration (GEMRIC) in 223 patients who were experiencing a major depressive episode (10 scanning sites). Structural MRI data were acquired before and after ECT, and we assessed change in subcortical grey matter volume using FreeSurfer and Quarc. Results: Higher body mass index (BMI) was associated with a significantly lower increase in subcortical grey matter volume following ECT. We observed significant negative associations between BMI and change in subcortical grey matter volume, with pronounced effects in the thalamus and putamen, where obese participants showed increases in grey matter volume that were 43.3% and 49.6%, respectively, of the increases found in participants with normal weight. As well, BMI significantly moderated the association between subcortical grey matter volume change and clinical response to ECT. We observed no significant association between BMI and clinical response to ECT. Limitations: Because only baseline BMI values were available, we were unable to study BMI changes during ECT and their potential association with clinical and grey matter volume change. Conclusion: Future studies should take into account the relevance of body weight as a modulator of structural neuroplasticity during ECT treatment and aim to further explore the functional relevance of this novel finding

Apolipoprotein E Homozygous ε4 Allele Status: A Deteriorating Effect on Visuospatial Working Memory and Global Brain Structure

THEORETICAL BACKGROUND: The Apolipoprotein E (APOE) ε4 genotype is known to be one of the strongest single-gene predictors for Alzheimer disease, which is characterized by widespread brain structural degeneration progressing along with cognitive impairment. The ε4 allele status has been associated with brain structural alterations and lower cognitive ability in non-demented subjects. However, it remains unclear to what extent the visuospatial cognitive domain is affected, from what age onward changes are detectable and if alterations may interact with cognitive deficits in major depressive disorder (MDD). The current work investigated the effect of APOE ε4 homozygosity on visuospatial working memory (vWM) capacity, and on hippocampal morphometry. Furthermore, potential moderating roles of age and MDD were assessed. METHODS: A sample of n = 31 homozygous ε4 carriers was contrasted with n = 31 non-ε4 carriers in a cross-sectional design. The sample consisted of non-demented, young to mid-age participants (mean age = 34.47; SD = 13.48; 51.6% female). Among them were n = 12 homozygous ε4 carriers and n = 12 non-ε4 carriers suffering from MDD (39%). VWM was assessed using the Corsi block-tapping task. Region of interest analyses of hippocampal gray matter density and volume were conducted using voxel-based morphometry (CAT12), and Freesurfer, respectively. RESULTS: Homozygous ε4 carriers showed significantly lower Corsi span capacity than non-ε4 carriers did, and Corsi span capacity was associated with higher gray matter density of the hippocampus. APOE group differences in hippocampal volume could be detected but were no longer present when controlling for total intracranial volume. Hippocampal gray matter density did not differ between APOE groups. We did not find any interaction effects of age and MDD diagnosis on hippocampal morphometry. CONCLUSION: Our results point toward a negative association of homozygous ε4 allele status with vWM capacity already during mid-adulthood, which emerges independently of MDD diagnosis and age. APOE genotype seems to be associated with global brain structural rather than hippocampus specific alterations in young- to mid-age participants