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1.
Depress Anxiety ; 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36345264

RESUMO

BACKGROUND: Ambulatory assessments offer opportunities to study physical activity level (PAL) and affect at the group and person-level. We examined bidirectional associations between PAL and affect in a 3-h timeframe and evaluated whether associations differ between people with and without 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) Composite International Diagnostic Interview depression/anxiety diagnoses were obtained from the Netherlands Study of Depression and Anxiety. Positive affect (PA) and negative affect (NA) were assessed by EMA 5 times per day. Average PAL between EMA assessments were calculated from actigraphy data. RESULTS: At the group-level, higher PAL was associated with subsequent higher PA (b = 0.109, p < .001) and lower NA (b = -0.043, p < .001), while higher PA (b = 0.066, p < .001) and lower NA (b = -0.053, p < .001) were associated with subsequent higher PAL. The association between higher PAL and subsequent lower NA was stronger for current depression/anxiety patients than controls (p = .01). At the person-level, analyses revealed heterogeneity in bidirectional associations. CONCLUSIONS: Higher PAL may improve affect, especially among depression/anxiety patients. As the relationships vary at the person-level, ambulatory assessments may help identify who would benefit from behavioral interventions.

2.
J Affect Disord ; 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36372132

RESUMO

BACKGROUND: In a substantial subgroup of depressed patients, atypical, energy-related depression symptoms (e.g. increased appetite/weight, hypersomnia, loss of energy) tend to cluster with immuno-metabolic dysregulations (e.g. increased BMI and inflammatory markers). This clustering is proposed to reflect a more homogeneous depression pathology. This study examines to what extent energy-related symptoms are associated and share demographic, lifestyle and clinical characteristics. METHODS: Data were available from 13,965 participants from eight Dutch cohorts with DSM-5 lifetime major depression assessed by the Lifetime Depression Assessment Self-report (LIDAS) questionnaire. Information on four energy-related depression symptoms were extracted: energy loss, increased appetite, increased weight, and hypersomnia. Tetrachoric correlations between these symptoms, and associations of these symptoms with sociodemographic (sex, age, education), lifestyle (physical activity, BMI, smoking) and clinical characteristics (age of onset, episode duration, history, treatment and recency, and self-reported comorbidity) were computed. RESULTS: Correlations between energy-related symptoms were overall higher than those with other depression symptoms and varied from 0.90 (increased appetite vs increased weight) to 0.11 (increased appetite vs energy loss). All energy-related symptoms were strongly associated with higher BMI and a more severe clinical profile. Patients with increased appetite were more often smokers, and only patients with increased appetite or weight more often had a self-reported diagnosis of PTSD (OR = 1.17, p = 2.91E-08) and eating disorder (OR = 1.40, p = 4.08E-17). CONCLUSIONS: The symptom-specific associations may have consequences for a profile integrating these symptoms, which can be used to reflect immuno-metabolic depression. They indicate the need to study immuno-metabolic depression at individual symptom resolution as a starting point.

4.
Nat Med ; 28(10): 2027-2037, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36192553

RESUMO

The Coronavirus Disease 2019 (COVID-19) pandemic has threatened global mental health, both indirectly via disruptive societal changes and directly via neuropsychiatric sequelae after SARS-CoV-2 infection. Despite a small increase in self-reported mental health problems, this has (so far) not translated into objectively measurable increased rates of mental disorders, self-harm or suicide rates at the population level. This could suggest effective resilience and adaptation, but there is substantial heterogeneity among subgroups, and time-lag effects may also exist. With regard to COVID-19 itself, both acute and post-acute neuropsychiatric sequelae have become apparent, with high prevalence of fatigue, cognitive impairments and anxiety and depressive symptoms, even months after infection. To understand how COVID-19 continues to shape mental health in the longer term, fine-grained, well-controlled longitudinal data at the (neuro)biological, individual and societal levels remain essential. For future pandemics, policymakers and clinicians should prioritize mental health from the outset to identify and protect those at risk and promote long-term resilience.


Assuntos
COVID-19 , Pandemias , Ansiedade/epidemiologia , Ansiedade/psicologia , COVID-19/epidemiologia , Depressão/epidemiologia , Humanos , Saúde Mental , SARS-CoV-2
5.
JMIR Mhealth Uhealth ; 10(10): e40667, 2022 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-36194451

RESUMO

BACKGROUND: Gait is an essential manifestation of depression. However, the gait characteristics of daily walking and their relationships with depression have yet to be fully explored. OBJECTIVE: The aim of this study was to explore associations between depression symptom severity and daily-life gait characteristics derived from acceleration signals in real-world settings. METHODS: We used two ambulatory data sets (N=71 and N=215) with acceleration signals collected by wearable devices and mobile phones, respectively. We extracted 12 daily-life gait features to describe the distribution and variance of gait cadence and force over a long-term period. Spearman coefficients and linear mixed-effects models were used to explore the associations between daily-life gait features and depression symptom severity measured by the 15-item Geriatric Depression Scale (GDS-15) and 8-item Patient Health Questionnaire (PHQ-8) self-reported questionnaires. The likelihood-ratio (LR) test was used to test whether daily-life gait features could provide additional information relative to the laboratory gait features. RESULTS: Higher depression symptom severity was significantly associated with lower gait cadence of high-performance walking (segments with faster walking speed) over a long-term period in both data sets. The linear regression model with long-term daily-life gait features (R2=0.30) fitted depression scores significantly better (LR test P=.001) than the model with only laboratory gait features (R2=0.06). CONCLUSIONS: This study indicated that the significant links between daily-life walking characteristics and depression symptom severity could be captured by both wearable devices and mobile phones. The daily-life gait patterns could provide additional information for predicting depression symptom severity relative to laboratory walking. These findings may contribute to developing clinical tools to remotely monitor mental health in real-world settings.


Assuntos
Depressão , Marcha , Aceleração , Idoso , Humanos , Estudos Retrospectivos , Caminhada
6.
Transl Psychiatry ; 12(1): 433, 2022 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-36198681

RESUMO

Despite advances in identifying the genetic basis of psychiatric and neurological disorders, fundamental questions about their evolutionary origins remain elusive. Here, introgressed variants from archaic humans such as Neandertals can serve as an intriguing research paradigm. We compared the number of associations for Neandertal variants to the number of associations of frequency-matched non-archaic variants with regard to human CNS disorders (neurological and psychiatric), nervous system drug prescriptions (as a proxy for disease), and related, non-disease phenotypes in the UK biobank (UKBB). While no enrichment for Neandertal genetic variants were observed in the UKBB for psychiatric or neurological disease categories, we found significant associations with certain behavioral phenotypes including pain, chronotype/sleep, smoking and alcohol consumption. In some instances, the enrichment signal was driven by Neandertal variants that represented the strongest association genome-wide. SNPs within a Neandertal haplotype that was associated with smoking in the UKBB could be replicated in four independent genomics datasets.Our data suggest that evolutionary processes in recent human evolution like admixture with Neandertals significantly contribute to behavioral phenotypes but not psychiatric and neurological diseases. These findings help to link genetic variants in a population to putative past beneficial effects, which likely only indirectly contribute to pathology in modern day humans.


Assuntos
Homem de Neandertal , Animais , Variação Genética , Genoma , Haplótipos , Humanos , Homem de Neandertal/genética , Fenótipo
7.
Environ Int ; 168: 107491, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36081220

RESUMO

BACKGROUND: Exposure to ambient air pollution, even at low levels, is a major environmental health risk. The peripheral blood transcriptome provides a potential avenue for the elucidation of ambient air pollution related biological perturbations. We assessed the association between long-term estimates for seven priority air pollutants and perturbations in peripheral blood transcriptomics data collected in the Dutch National Twin Register (NTR) and Netherlands Study of Depression and Anxiety (NESDA) cohorts. METHODS: In both the discovery (n = 2438) and replication (n = 1567) cohort, outdoor concentration of 7 air pollutants (NO2, NOx, particulate matter (PM2.5, PM2.5abs, PM10, PMcoarse), and ultrafine particles) was predicted with land use regression models. Gene expression was assessed by Affymetrix U219 arrays. Multi-variable univariate mixed-effect models were applied to test for an association between the air pollutants and the transcriptome. Functional analysis was conducted in DAVID. RESULTS: In the discovery cohort, we observed for 335 genes (374 probes with FDR < 5 %) a perturbation in peripheral blood gene expression that was associated with long-term average levels of PM2.5. For 69 genes pooled effect estimates from the NTR and NESDA cohorts were significant. Identified genes play a role in biological pathways related to cell signaling and immune response. Sixty-two out of 69 genes had a similar direction of effect in an analysis in which we regressed the probes on differential PM2.5 exposure within monozygotic twin pairs, indicating that the observed differences in gene expression were likely driven by differences in air pollution, rather than by confounding by genetic factors. CONCLUSION: Our results indicate that PM2.5 can elicit a response in cell signaling and the immune system, both hallmarks of environmental diseases. The differential effect that we observed between air pollutants may aid in the understanding of differential health effects that have been observed with these exposures.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Poluição do Ar/análise , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Expressão Gênica , Humanos , Imunidade , Material Particulado/análise , Material Particulado/toxicidade , Transdução de Sinais
8.
Neuroimage Clin ; 36: 103180, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36088843

RESUMO

OBJECTIVE: Major depressive disorder has been associated with lower prefrontal thickness and hippocampal volume, but it is unknown whether this association also holds for depressive symptoms in the general population. We investigated associations of depressive symptoms and depression status with brain structures across population-based and patient-control cohorts, and explored whether these associations are similar over the lifespan and across sexes. METHODS: We included 3,447 participants aged 18-89 years from six population-based and two clinical patient-control cohorts of the European Lifebrain consortium. Cross-sectional meta-analyses using individual person data were performed for associations of depressive symptoms and depression status with FreeSurfer-derived thickness of bilateral rostral anterior cingulate cortex (rACC) and medial orbitofrontal cortex (mOFC), and hippocampal and total grey matter volume (GMV), separately for population-based and clinical cohorts. RESULTS: Across patient-control cohorts, depressive symptoms and presence of mild-to-severe depression were associated with lower mOFC thickness (rsymptoms = -0.15/ rstatus = -0.22), rACC thickness (rsymptoms = -0.20/ rstatus = -0.25), hippocampal volume (rsymptoms = -0.13/ rstatus = 0.13) and total GMV (rsymptoms = -0.21/ rstatus = -0.25). Effect sizes were slightly larger for presence of moderate-to-severe depression. Associations were similar across age groups and sex. Across population-based cohorts, no associations between depression and brain structures were observed. CONCLUSIONS: Fitting with previous meta-analyses, depressive symptoms and depression status were associated with lower mOFC, rACC thickness, and hippocampal and total grey matter volume in clinical patient-control cohorts, although effect sizes were small. The absence of consistent associations in population-based cohorts with mostly mild depressive symptoms, suggests that significantly lower thickness and volume of the studied brain structures are only detectable in clinical populations with more severe depressive symptoms.

9.
NPJ Digit Med ; 5(1): 133, 2022 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-36057688

RESUMO

The use of remote measurement technologies (RMTs) across mobile health (mHealth) studies is becoming popular, given their potential for providing rich data on symptom change and indicators of future state in recurrent conditions such as major depressive disorder (MDD). Understanding recruitment into RMT research is fundamental for improving historically small sample sizes, reducing loss of statistical power, and ultimately producing results worthy of clinical implementation. There is a need for the standardisation of best practices for successful recruitment into RMT research. The current paper reviews lessons learned from recruitment into the Remote Assessment of Disease and Relapse- Major Depressive Disorder (RADAR-MDD) study, a large-scale, multi-site prospective cohort study using RMT to explore the clinical course of people with depression across the UK, the Netherlands, and Spain. More specifically, the paper reflects on key experiences from the UK site and consolidates these into four key recruitment strategies, alongside a review of barriers to recruitment. Finally, the strategies and barriers outlined are combined into a model of lessons learned. This work provides a foundation for future RMT study design, recruitment and evaluation.

10.
J Affect Disord ; 317: 149-155, 2022 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-36031004

RESUMO

BACKGROUND: Existing studies on disease course usually apply relatively short follow-up periods and narrow definitions of disease course resulting in too optimistic views on disease prognosis. This study explores the relevance of using a longer and broader (cross-disorder) perspective. METHODS: Respondents with a 12-month disorder at baseline and available at 3-, 6- and 9-year follow-up were selected (major depressive disorder, MDD: n = 208; anxiety disorder: n = 220) from a general population study (N = 6646). DSM-IV disorders were assessed with the Composite International Diagnostic Interview. Disease course was described using a short and narrow perspective (i.e., 3-year follow-up, and considering presence of the index disorder only) and a long and broad perspective (9-year follow-up, and considering presence of any mood, anxiety or substance use disorder as outcome). RESULTS: The recovery rates of both MDD and anxiety disorder reduced by half when the perspective switched from short and narrow (MDD: 74.0 %; anxiety disorder: 79.5 %) to long and broad (35.6 % and 40.0 % respectively). At 9-year follow-up, the rates of a persistent disorder (a disorder at each follow-up assessment) tripled when the perspective switched from narrow to broad (MDD: from 4.8 % to 13.9 %; anxiety disorder: from 4.5 % to 15.5 %). LIMITATIONS: The findings are not generalizable to the most severe depressed and anxious patients. CONCLUSIONS: Most people with MDD or anxiety disorder in the general population have a rather favourable prognosis when a narrow perspective is applied, but an unfavourable prognosis when a long-term and broad perspective is applied. Consequently, MDD and anxiety disorder should not merely be perceived as episodic disorders, and require longer-term disease monitoring and management.


Assuntos
Transtorno Depressivo Maior , Ansiedade/diagnóstico , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/epidemiologia , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/epidemiologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Progressão da Doença , Humanos , Prognóstico
12.
BJPsych Open ; 8(5): e162, 2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36039783

RESUMO

BACKGROUND: Mental health was only modestly affected in adults during the early months of the COVID-19 pandemic on the group level, but interpersonal variation was large. AIMS: We aim to investigate potential predictors of the differences in changes in mental health. METHOD: Data were aggregated from three Dutch ongoing prospective cohorts with similar methodology for data collection. We included participants with pre-pandemic data gathered during 2006-2016, and who completed online questionnaires at least once during lockdown in The Netherlands between 1 April and 15 May 2020. Sociodemographic, clinical (number of mental health disorders and personality factors) and COVID-19-related variables were analysed as predictors of relative changes in four mental health outcomes (depressive symptoms, anxiety and worry symptoms, and loneliness), using multivariate linear regression analyses. RESULTS: We included 1517 participants with (n = 1181) and without (n = 336) mental health disorders. Mean age was 56.1 years (s.d. 13.2), and 64.3% were women. Higher neuroticism predicted increases in all four mental health outcomes, especially for worry (ß = 0.172, P = 0.003). Living alone and female gender predicted increases in depressive symptoms and loneliness (ß = 0.05-0.08), whereas quarantine and strict adherence with COVID-19 restrictions predicted increases in anxiety and worry symptoms (ß = 0.07-0.11).Teleworking predicted a decrease in anxiety symptoms (ß = -0.07) and higher age predicted a decrease in anxiety (ß = -0.08) and worry symptoms (ß = -0.10). CONCLUSIONS: Our study showed neuroticism as a robust predictor of adverse changes in mental health, and identified additional sociodemographic and COVID-19-related predictors that explain longitudinal variability in mental health during the COVID-19 pandemic.

13.
Transl Psychiatry ; 12(1): 274, 2022 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-35821204

RESUMO

The serotonin-transporter-linked promoter region (5-HTTLPR) has been widely investigated as contributing to depression vulnerability. Nevertheless, empirical research provides wide contrasting findings regarding its involvement in the etiopathogenesis of the disorder. Our hypothesis was that such discrepancy can be explained considering time as moderating factor. We explored this hypothesis, exploiting a meta analytic approach. We searched PubMed, PsychoINFO, Scopus and EMBASE databases and 1096 studies were identified and screened, resulting in 22 studies to be included in the meta-analyses. The effect of the 5-HTTLPR x stress interaction on depression risk was found to be moderated by the following temporal factors: the duration of stress (i.e. chronic vs. acute) and the time interval between end of stress and assessment of depression (i.e. within 1 year vs. more than 1 year). When stratifying for the duration of stress, the effect of the 5-HTTLPR x stress interaction emerged only in the case of chronic stress, with a significant subgroup difference (p = 0.004). The stratification according to time interval revealed a significant interaction only for intervals within 1 year, though no difference between subgroups was found. The critical role of time interval clearly emerged when considering only chronic stress: a significant effect of the 5-HTTLPR and stress interaction was confirmed exclusively within 1 year and a significant subgroup difference was found (p = 0.01). These results show that the 5-HTTLPR x stress interaction is a dynamic process, producing different effects at different time points, and indirectly confirm that s-allele carriers are both at higher risk and more capable to recover from depression. Overall, these findings expand the current view of the interplay between 5-HTTLPR and stress adding the temporal dimension, that results in a three-way interaction: gene x environment x time.


Assuntos
Depressão , Interação Gene-Ambiente , Depressão/genética , Genótipo , Proteínas da Membrana Plasmática de Transporte de Serotonina , Estresse Psicológico/complicações , Estresse Psicológico/genética
14.
Brain Behav Immun ; 106: 21-29, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35870669

RESUMO

BACKGROUND: Childhood trauma (CT) is robustly associated with psychiatric disorders including major depressive and anxiety disorders across the life span. The innate immune system may play a role in the relation between CT and stress-related psychopathology. However, whether CT influences the innate production capacity of cytokine levels following ex vivo stimulation by lipopolysaccharide (LPS), is currently unknown. METHODS: Using data from the Netherlands Study of Depression and Anxiety (NESDA, n=1237), we examined whether CT (emotional neglect, emotional, physical, and sexual abuse before the age of 16), assessed by the Childhood Trauma Interview, was associated with levels in supernatants of interferon (IFN)γ, interleukin-2 (IL-2), IL-4, IL-6, IL-8, IL-10, IL-18, monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein (MIP)-1α, MIP-1ß, matrix metalloproteinase-2 (MMP-2), TNFα and TNFß after ex vivo stimulation with LPS. Cytokines were analysed individually and cumulatively (overall inflammation index and number of cytokines in high-risk quartile (HRQ)) using linear regression analyses. RESULTS: After adjustment for demographic, lifestyle, and health-related covariates, total CT severity was associated with the overall inflammation index (ß = 0.085, PFDR = 0.011), the number of cytokines in HRQ (ß = 0.063, PFDR = 0.036), and individual markers of IL-2 (ß = 0.067, PFDR = 0.036), IL-6 (ß = 0.091 PFDR = 0.011), IL-8 (ß = 0.085 PFDR = 0.011), IL-10 (ß = 0.094 PFDR = 0.011), MCP-1 (ß = 0.081 PFDR = 0.011), MIP-1α (ß = 0.061 PFDR = 0.047), MIP1-ß (ß = 0.077 PFDR = 0.016), MMP-2 (ß = 0.070 PFDR = 0.027), and TNFß (ß = 0.078 PFDR = 0.016). Associations were strongest for individuals with severe CT, reporting multiple types or higher frequencies of trauma. Half of the findings persisted after adjustment for psychiatric status. The findings were consistent across different CT types. CONCLUSION: Childhood Trauma is associated with increased LPS-stimulated cytokine levels, with evidence for a dose-response relationship. Our results highlight a dysregulated innate immune system capacity in adults with CT, which could contribute to an increased vulnerability for psychopathology and somatic disorders across the lifespan.


Assuntos
Experiências Adversas da Infância , Ansiedade , Depressão , Imunidade Inata , Adulto , Ansiedade/imunologia , Transtornos de Ansiedade/imunologia , Quimiocina CCL2 , Quimiocina CCL3 , Quimiocina CCL4 , Citocinas/metabolismo , Depressão/imunologia , Transtorno Depressivo Maior/imunologia , Humanos , Inflamação , Interferons , Interleucina-10 , Interleucina-18 , Interleucina-2 , Interleucina-4 , Interleucina-6 , Interleucina-8 , Lipopolissacarídeos , Metaloproteinase 2 da Matriz , Países Baixos/epidemiologia , Fator de Necrose Tumoral alfa
15.
J Affect Disord ; 312: 268-274, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35760189

RESUMO

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 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.


Assuntos
Transtorno Depressivo Maior , Transtornos de Ansiedade , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Depressão , Transtorno Depressivo Maior/diagnóstico , Giro do Cíngulo/metabolismo , Humanos
16.
J Affect Disord ; 312: 322-330, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35760192

RESUMO

BACKGROUND: Childhood trauma (CT) is a risk factor for depressive and anxiety disorders. However, whether CT is more strongly linked to specific clinical features of these disorders remains inconclusive. The current study comprehensively examined cross-sectional and longitudinal associations between CT and depressive/anxiety symptomatology in a large adult sample with current and remitted depressive and/or anxiety disorders. METHODS: Baseline (n = 1803), 2-year (n = 1735), 4-year (n = 1585), and 6-year follow-up (n = 1475) data from the Netherlands Study of Depression and Anxiety were used. CT (emotional neglect, emotional/physical/sexual abuse) was assessed at baseline, while depressive/anxiety symptomatology with relevant dimensions (e.g., mood/cognitive, melancholic, general distress, and somatic depression) was assessed at each wave using self-reported questionnaires. Linear regressions and linear mixed models determined cross-sectional and longitudinal associations. RESULTS: Individuals with CT, especially, severe CT, compared to those without CT, had significantly higher scores in overall depressive symptomatology (Cohen's d = 0.674), mood/cognitive depression (d = 0.691), melancholic depression (d = 0.587), general distress (d = 0.561), and somatic depression severity (d = 0.549). Differences were lower, but still highly significant for anxiety (d = 0.418), worry (d = 0.362), and fear/phobic symptomatology (d = 0.359). Effects were consistent across CT types and maintained over six years. LIMITATIONS: Retrospectively-reported CT. CONCLUSIONS: CT is a risk factor for depressive and anxiety symptomatology across all dimensions and enduring over multiple years. Screening for CT is essential to identify individuals at risk for more severe and chronic manifestations of affective disorders.


Assuntos
Experiências Adversas da Infância , Adulto , Ansiedade/epidemiologia , Ansiedade/psicologia , Transtornos de Ansiedade/psicologia , Estudos Transversais , Depressão/epidemiologia , Depressão/psicologia , Humanos , Estudos Longitudinais , Países Baixos/epidemiologia , Estudos Retrospectivos
17.
J Affect Disord ; 307: 254-263, 2022 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-35381295

RESUMO

BACKGROUND: Altered metabolism of acylcarnitines - transporting fatty acids to mitochondria - may link cellular energy dysfunction to depression. We examined the potential causal role of acylcarnitine metabolism in depression by leveraging genomics and Mendelian randomization. METHODS: Summary statistics were obtained from large GWAS: the Fenland Study (N = 9363), and the Psychiatric Genomics Consortium (246,363 depression cases and 561,190 controls). Two-sample Mendelian randomization analyses tested the potential causal link of 15 endogenous acylcarnitines with depression. RESULTS: In univariable analyses, genetically-predicted lower levels of short-chain acylcarnitines C2 (odds ratio [OR] 0.97, 95% confidence intervals [CIs] 0.95-1.00) and C3 (OR 0.97, 95%CIs 0.96-0.99) and higher levels of medium-chain acylcarnitines C8 (OR 1.04, 95%CIs 1.01-1.06) and C10 (OR 1.04, 95%CIs 1.02-1.06) were associated with increased depression risk. No reverse potential causal role of depression genetic liability on acylcarnitines levels was found. Multivariable analyses showed that the association with depression was driven by the medium-chain acylcarnitines C8 (OR 1.04, 95%CIs 1.02-1.06) and C10 (OR 1.04, 95%CIs 1.02-1.06), suggesting a potential causal role in the risk of depression. Causal estimates for C8 (OR = 1.05, 95%CIs = 1.02-1.07) and C10 (OR = 1.05, 95%CIs = 1.02-1.08) were confirmed in follow-up analyses using genetic instruments derived from a GWAS meta-analysis including up to 16,841 samples. DISCUSSION: Accumulation of medium-chain acylcarnitines is a signature of inborn errors of fatty acid metabolism and age-related metabolic conditions. Our findings point to a link between altered mitochondrial energy production and depression pathogenesis. Acylcarnitine metabolism represents a promising access point for the development of novel therapeutic approaches for depression.


Assuntos
Carnitina , Depressão , Carnitina/análogos & derivados , Causalidade , Depressão/genética , Genômica , Humanos
18.
PLoS One ; 17(4): e0263769, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35421108

RESUMO

BACKGROUND: Social functioning is often impaired in schizophrenia (SZ) and Alzheimer's disease (AD). However, commonalities and differences in social dysfunction among these patient groups remain elusive. MATERIALS AND METHODS: Using data from the PRISM study, behavioral (all subscales and total score of the Social Functioning Scale) and affective (perceived social disability and loneliness) indicators of social functioning were measured in patients with SZ (N = 56), probable AD (N = 50) and age-matched healthy controls groups (HC, N = 29 and N = 28). We examined to what extent social functioning differed between disease and age-matched HC groups, as well as between patient groups. Furthermore, we examined how severity of disease and mood were correlated with social functioning, irrespective of diagnosis. RESULTS: As compared to HC, both behavioral and affective social functioning seemed impaired in SZ patients (Cohen's d's 0.81-1.69), whereas AD patients mainly showed impaired behavioral social function (Cohen's d's 0.65-1.14). While behavioral indices of social functioning were similar across patient groups, SZ patients reported more perceived social disability than AD patients (Cohen's d's 0.65). Across patient groups, positive mood, lower depression and anxiety levels were strong determinants of better social functioning (p's <0.001), even more so than severity of disease. CONCLUSIONS: AD and SZ patients both exhibit poor social functioning in comparison to age- and sex matched HC participants. Social dysfunction in SZ patients may be more severe than in AD patients, though this may be due to underreporting by AD patients. Across patients, social functioning appeared as more influenced by mood states than by severity of disease.


Assuntos
Doença de Alzheimer , Esquizofrenia , Humanos , Solidão , Esquizofrenia/diagnóstico , Ajustamento Social , Interação Social
20.
BMC Psychiatry ; 22(1): 136, 2022 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-35189842

RESUMO

BACKGROUND: Major Depressive Disorder (MDD) is prevalent, often chronic, and requires ongoing monitoring of symptoms to track response to treatment and identify early indicators of relapse. Remote Measurement Technologies (RMT) provide an opportunity to transform the measurement and management of MDD, via data collected from inbuilt smartphone sensors and wearable devices alongside app-based questionnaires and tasks. A key question for the field is the extent to which participants can adhere to research protocols and the completeness of data collected. We aimed to describe drop out and data completeness in a naturalistic multimodal longitudinal RMT study, in people with a history of recurrent MDD. We further aimed to determine whether those experiencing a depressive relapse at baseline contributed less complete data. METHODS: Remote Assessment of Disease and Relapse - Major Depressive Disorder (RADAR-MDD) is a multi-centre, prospective observational cohort study conducted as part of the Remote Assessment of Disease and Relapse - Central Nervous System (RADAR-CNS) program. People with a history of MDD were provided with a wrist-worn wearable device, and smartphone apps designed to: a) collect data from smartphone sensors; and b) deliver questionnaires, speech tasks, and cognitive assessments. Participants were followed-up for a minimum of 11 months and maximum of 24 months. RESULTS: Individuals with a history of MDD (n = 623) were enrolled in the study,. We report 80% completion rates for primary outcome assessments across all follow-up timepoints. 79.8% of people participated for the maximum amount of time available and 20.2% withdrew prematurely. We found no evidence of an association between the severity of depression symptoms at baseline and the availability of data. In total, 110 participants had > 50% data available across all data types. CONCLUSIONS: RADAR-MDD is the largest multimodal RMT study in the field of mental health. Here, we have shown that collecting RMT data from a clinical population is feasible. We found comparable levels of data availability in active and passive forms of data collection, demonstrating that both are feasible in this patient group.


Assuntos
Transtorno Depressivo Maior , Aplicativos Móveis , Doença Crônica , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/epidemiologia , Humanos , Estudos Prospectivos , Recidiva , Smartphone
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