Cognitive functioning and lifetime major depressive disorder in UK Biobank

Abstract Background. Cognitive impairment associated with lifetime major depressive disorder (MDD) is well-supported by meta-analytic studies, but population-based estimates remain scarce. Previous UK Biobank studies have only shown limited evidence of cognitive differences related to probable MDD. Using updated cognitive and clinical assessments in UK Biobank, this study investigated population-level differences in cognitive functioning associated with lifetime MDD. Methods. Associations between lifetime MDD and cognition (performance on six tasks and general cognitive functioning [g-factor]) were investigated in UK Biobank (N-range 7,457–14,836, age 45–81 years, 52% female), adjusting for demographics, education, and lifestyle. Lifetime MDD classifications were based on the Composite International Diagnostic Interview. Within the lifetime MDD group, we additionally investigated relationships between cognition and (a) recurrence, (b) current symptoms, (c) severity of psychosocial impairment (while symptomatic), and (d) concurrent psychotropic medication use. Results. Lifetime MDD was robustly associated with a lower g-factor (β = −0.10, PFDR = 4.7 × 10−5), with impairments in attention, processing speed, and executive functioning (β ≥ 0.06). Clinical characteristics revealed differential profiles of cognitive impairment among case individuals; those who reported severe psychosocial impairment and use of psychotropic medication performed worse on cognitive tests. Severe psychosocial impairment and reasoning showed the strongest association (β = −0.18, PFDR = 7.5 × 10−5). Conclusions. Findings describe small but robust associations between lifetime MDD and lower cognitive performance within a population-based sample. Overall effects were of modest effect size, suggesting limited clinical relevance. However, deficits within specific cognitive domains were more pronounced in relation to clinical characteristics, particularly severe psychosocial impairment.

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Cognitive functioning and lifetime Major Depressive Disorder in UK Biobank

10.1101/19006031 ◽

2019 ◽

Author(s):

L De Nooij ◽

MA Harris ◽

MJ Adams ◽

T-K Clarke ◽

X Shen ◽

...

Keyword(s):

Major Depressive Disorder ◽

Cognitive Impairment ◽

Depressive Disorder ◽

Cognitive Functioning ◽

Psychotropic Medication ◽

Clinical Characteristics ◽

Population Based ◽

Uk Biobank ◽

Major Depressive ◽

Psychosocial Impairment

AbstractBackgroundCognitive impairment associated with lifetime Major Depressive Disorder (MDD) is well-supported by meta-analytic studies, but population-based estimates remain scarce. Previous UK Biobank studies have only shown limited evidence of cognitive differences related to probable MDD. Using updated cognitive and clinical assessments in UK Biobank, this study investigated population-level differences in cognitive functioning associated with lifetime MDD.MethodsAssociations between lifetime MDD and cognition (performance on six tasks and general cognitive functioning (g-factor)) were investigated in UK Biobank (N-range 7,457-14,836, age 45-81 years, 52% female), adjusting for demographics, education and lifestyle. Lifetime MDD classifications were based on the Composite International Diagnostic Interview. Within the lifetime MDD group, we additionally investigated relationships between cognition and (i) recurrence, (ii) current symptoms, (iii) severity of psychosocial impairment (while symptomatic), and (iv) concurrent psychotropic medication use.ResultsLifetime MDD was robustly associated with a lower g-factor (β = −0.10, PFDR = 4.7×10−5), with impairments in attention, processing speed and executive functioning (β ≥ 0.06). Clinical characteristics revealed differential profiles of cognitive impairment among case individuals; those who reported severe psychosocial impairment and use of psychotropic medication performed worse on cognitive tests. Severe psychosocial impairment and reasoning showed the strongest association (β = −0.18, PFDR = 7.5×10−5).ConclusionsFindings describe small but robust associations between lifetime MDD and lower cognitive performance within a population based sample. Overall effects were of modest effect size, suggesting limited clinical relevance. However, deficits within specific cognitive domains were more pronounced in relation to clinical characteristics, particularly severe psychosocial impairment.

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Genetic association study of psychotic experiences in UK Biobank

10.1101/583468 ◽

2019 ◽

Cited By ~ 3

Author(s):

Sophie E. Legge ◽

Hannah J. Jones ◽

Kimberley M. Kendall ◽

Antonio F. Pardiñas ◽

Georgina Menzies ◽

...

Keyword(s):

Bipolar Disorder ◽

Major Depressive Disorder ◽

Depressive Disorder ◽

Neurodevelopmental Disorders ◽

Population Based ◽

Uk Biobank ◽

Psychotic Experiences ◽

Psychotic Experience ◽

Major Depressive ◽

Genome Wide

AbstractPsychotic experiences, such as hallucinations and delusions, are reported by approximately 5%-10% of the general population, though only a small proportion of individuals develop psychotic disorders such as schizophrenia or bipolar disorder. Studying the genetic aetiology of psychotic experiences in the general population, and its relationship with the genetic aetiology of other disorders, may increase our understanding of their pathological significance. Using the population-based UK Biobank sample, we performed the largest genetic association study of psychotic experiences in individuals without a psychotic disorder. We conducted three genome-wide association studies (GWAS) for (i) any psychotic experience (6123 cases vs. 121,843 controls), (ii) distressing psychotic experiences (2143 cases vs. 121,843 controls), and (iii) multiple occurrence psychotic experiences (3337 cases vs. 121,843 controls). Analyses of polygenic risk scores (PRS), genetic correlation, and copy number variation (CNV) were conducted to assess whether genetic liability to psychotic experiences is shared with schizophrenia and/or other neuropsychiatric disorders and traits. GWAS analyses identified four loci associated with psychotic experiences including a locus in Ankyrin-3 (ANK3, OR=1.16,p=3.06 × 10−8) with any psychotic experience and a locus in cannabinoid receptor 2 gene (CNR2,OR=0.66,p=3.78×10−8) with distressing psychotic experiences. PRS analyses identified associations between psychotic experiences and genetic liability for schizophrenia, major depressive disorder, and bipolar disorder, and these associations were stronger for distressing psychotic experiences. Genetic correlation analysis identified significant genetic correlations between psychotic experiences and major depressive disorder, schizophrenia, autism spectrum disorder and a cross-disorder GWAS. Individuals reporting psychotic experiences had an increased burden of CNVs previously associated with schizophrenia (OR=2.04,p=2.49×10−4) and of those associated with neurodevelopmental disorders more widely (OR=1.75,p=1.41×10−3). In conclusion, we identified four genome-wide significant loci in the largest GWAS of psychotic experiences from the population-based UK Biobank sample and found support for a shared genetic aetiology between psychotic experiences and schizophrenia, but also major depressive disorder, bipolar disorder and neurodevelopmental disorders.

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Age of onset and course of major depressive disorder: associations with psychosocial functioning outcomes in adulthood

Psychological Medicine ◽

10.1017/s0033291714001640 ◽

2014 ◽

Vol 45 (3) ◽

pp. 505-514 ◽

Cited By ~ 29

Author(s):

S. Wilson ◽

B. M. Hicks ◽

K. T. Foster ◽

M. McGue ◽

W. G. Iacono

Keyword(s):

Major Depressive Disorder ◽

Depressive Disorder ◽

Psychosocial Functioning ◽

Age Of Onset ◽

Large Population ◽

Early Adulthood ◽

Population Based ◽

Major Depressive ◽

Psychosocial Impairment ◽

Severe Group

BackgroundMajor depressive disorder (MDD) that onsets by adolescence is associated with various deficits in psychosocial functioning. However, adolescent-onset MDD often follows a recurrent course that may drive its associated impairment.MethodTo tease apart these two clinical features, we examined the relative associations of age of onset (adolescent versus adult) and course (recurrent versus single episodes) of MDD with a broad range of psychosocial functioning outcomes assessed in early adulthood. Participants comprised a large, population-based sample of male and female twins from the Minnesota Twin Family Study (MTFS; n = 1252) assessed prospectively from ages 17 to 29 years.ResultsA recurrent course of MDD predicted impairment in several psychosocial domains in adulthood, regardless of whether the onset was in adolescence or adulthood. By contrast, adolescent-onset MDD showed less evidence of impairment in adulthood after accounting for recurrence. Individuals with both an adolescent onset and recurrent episodes of MDD represented a particularly severe group with pervasive psychosocial impairment in adulthood.ConclusionsThe negative implications of adolescent-onset MDD for psychosocial functioning in adulthood seem to be due primarily to its frequently recurrent course, rather than its early onset, per se. The results highlight the importance of considering both age of onset and course for understanding MDD and its implications for functioning, and also in guiding targeted intervention efforts.

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Supplemental Material for Cognitive Functioning in the First-Episode of Major Depressive Disorder: A Systematic Review and Meta-Analysis

Neuropsychology ◽

10.1037/neu0000319.supp ◽

2016 ◽

Keyword(s):

Systematic Review ◽

Major Depressive Disorder ◽

Depressive Disorder ◽

Cognitive Functioning ◽

Meta Analysis ◽

First Episode ◽

Major Depressive

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Clinical Characteristics of Major Depressive Disorder without Comorbid Psychiatric Diseases Using MMPI-2-RF

10.26226/morressier.5cf632c1af72dec2b0554904 ◽

2019 ◽

Author(s):

Jiyoung Kim

Keyword(s):

Major Depressive Disorder ◽

Depressive Disorder ◽

Clinical Characteristics ◽

Psychiatric Diseases ◽

Major Depressive

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The overlap of genetic susceptibility to schizophrenia and cardiometabolic disease can be used to identify metabolically different groups of individuals

Scientific Reports ◽

10.1038/s41598-020-79964-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Rona J. Strawbridge ◽

Keira J. A. Johnston ◽

Mark E. S. Bailey ◽

Damiano Baldassarre ◽

Breda Cullen ◽

...

Keyword(s):

Bipolar Disorder ◽

Major Depressive Disorder ◽

Depressive Disorder ◽

European Ancestry ◽

Cardiometabolic Disease ◽

Metabolic Profiles ◽

Genome Wide Association Studies ◽

Uk Biobank ◽

Major Depressive ◽

Increased Risk

AbstractUnderstanding why individuals with severe mental illness (Schizophrenia, Bipolar Disorder and Major Depressive Disorder) have increased risk of cardiometabolic disease (including obesity, type 2 diabetes and cardiovascular disease), and identifying those at highest risk of cardiometabolic disease are important priority areas for researchers. For individuals with European ancestry we explored whether genetic variation could identify sub-groups with different metabolic profiles. Loci associated with schizophrenia, bipolar disorder and major depressive disorder from previous genome-wide association studies and loci that were also implicated in cardiometabolic processes and diseases were selected. In the IMPROVE study (a high cardiovascular risk sample) and UK Biobank (general population sample) multidimensional scaling was applied to genetic variants implicated in both psychiatric and cardiometabolic disorders. Visual inspection of the resulting plots used to identify distinct clusters. Differences between these clusters were assessed using chi-squared and Kruskall-Wallis tests. In IMPROVE, genetic loci associated with both schizophrenia and cardiometabolic disease (but not bipolar disorder or major depressive disorder) identified three groups of individuals with distinct metabolic profiles. This grouping was replicated within UK Biobank, with somewhat less distinction between metabolic profiles. This work focused on individuals of European ancestry and is unlikely to apply to more genetically diverse populations. Overall, this study provides proof of concept that common biology underlying mental and physical illness may help to stratify subsets of individuals with different cardiometabolic profiles.

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Clinical laboratory tests and five-year incidence of major depressive disorder: a prospective cohort study of 433,890 participants from the UK Biobank

Translational Psychiatry ◽

10.1038/s41398-021-01505-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Michael Wainberg ◽

Stefan Kloiber ◽

Breno Diniz ◽

Roger S. McIntyre ◽

Daniel Felsky ◽

...

Keyword(s):

Public Health ◽

Major Depressive Disorder ◽

Cohort Study ◽

Confidence Interval ◽

Depressive Disorder ◽

Blood Cell ◽

Biological Processes ◽

Uk Biobank ◽

Major Depressive ◽

The Uk

AbstractPrevention of major depressive disorder (MDD) is a public health priority. Identifying biomarkers of underlying biological processes that contribute to MDD onset may help address this public health need. This prospective cohort study encompassed 383,131 white British participants from the UK Biobank with no prior history of MDD, with replication in 50,759 participants of other ancestries. Leveraging linked inpatient and primary care records, we computed adjusted odds ratios for 5-year MDD incidence among individuals with values below or above the 95% confidence interval (<2.5th or >97.5th percentile) on each of 57 laboratory measures. Sensitivity analyses were performed across multiple percentile thresholds and in comparison to established reference ranges. We found that indicators of liver dysfunction were associated with increased 5-year MDD incidence (even after correction for alcohol use and body mass index): elevated alanine aminotransferase (AOR = 1.35, 95% confidence interval [1.16, 1.58]), aspartate aminotransferase (AOR = 1.39 [1.19, 1.62]), and gamma glutamyltransferase (AOR = 1.52 [1.31, 1.76]) as well as low albumin (AOR = 1.28 [1.09, 1.50]). Similar observations were made with respect to endocrine dysregulation, specifically low insulin-like growth factor 1 (AOR = 1.34 [1.16, 1.55]), low testosterone among males (AOR = 1.60 [1.27, 2.00]), and elevated glycated hemoglobin (HbA1C; AOR = 1.23 [1.05, 1.43]). Markers of renal impairment (i.e. elevated cystatin C, phosphate, and urea) and indicators of anemia and macrocytosis (i.e. red blood cell enlargement) were also associated with MDD incidence. While some immune markers, like elevated white blood cell and neutrophil count, were associated with MDD (AOR = 1.23 [1.07, 1.42]), others, like elevated C-reactive protein, were not (AOR = 1.04 [0.89, 1.22]). The 30 significant associations validated as a group in the multi-ancestry replication cohort (Wilcoxon p = 0.0005), with a median AOR of 1.235. Importantly, all 30 significant associations with extreme laboratory test results were directionally consistent with an increased MDD risk. In sum, markers of liver and kidney dysfunction, growth hormone and testosterone deficiency, innate immunity, anemia, macrocytosis, and insulin resistance were associated with MDD incidence in a large community-based cohort. Our results support a contributory role of diverse biological processes to MDD onset.

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Cognition and Its Association with Psychosocial and Occupational Functioning during Treatment with Escitalopram in Patients with Major Depressive Disorder: A CAN-BIND-1 Report: La Cognition Et Son Association Avec Le Fonctionnement Psychosocial Et Professionnel Durant Le Traitement Par Escitalopram Chez Des Patients Souffrant De Trouble Dépressif Majeur: Une Étude Can-Bind-1

The Canadian Journal of Psychiatry ◽

10.1177/0706743720974823 ◽

2020 ◽

pp. 070674372097482

Author(s):

Shane J. McInerney ◽

Trisha Chakrabarty ◽

Malgorzata Maciukiewicz ◽

Benicio N. Frey ◽

Glenda M. MacQueen ◽

...

Keyword(s):

Major Depressive Disorder ◽

Depressive Disorder ◽

Cognitive Functioning ◽

Symptom Severity ◽

Cognitive Change ◽

Cognitive Domain ◽

Depression Symptom ◽

Major Depressive ◽

Occupational Functioning ◽

The Impact

Objectives: Major depressive disorder (MDD) is associated with impairments in both cognition and functioning. However, whether cognitive deficits significantly contribute to impaired psychosocial and occupational functioning, independent of other depressive symptoms, is not well established. We examined the relationship between cognitive performance and functioning in depressed patients before and after antidepressant treatment using secondary data from the first Canadian Biomarker Integration Network in Depression-1 study. Methods: Cognition was assessed at baseline in unmedicated, depressed participants with MDD ( n = 207) using the Central Nervous System Vital Signs computerized battery, psychosocial functioning with the Sheehan Disability Scale (SDS), and occupational functioning with the Lam Employment Absence and Productivity Scale (LEAPS). Cognition ( n = 181), SDS ( n = 175), and LEAPS ( n = 118) were reassessed after participants received 8 weeks of open-label escitalopram monotherapy. A series of linear regressions were conducted to determine (1) whether cognitive functioning was associated with psychosocial and occupational functioning prior to treatment, after adjusting for overall depressive symptom severity and (2) whether changes in cognitive functioning after an 8-week treatment phase were associated with changes in psychosocial and occupational functioning, after adjusting for changes in overall symptom severity. Results: Baseline global cognitive functioning, after adjusting for depression symptom severity and demographic variables, was associated with the SDS work/study subscale (β = −0.17; P = 0.03) and LEAPS productivity subscale (β = −0.17; P = 0.05), but not SDS total (β = 0.19; P = 0.12) or LEAPS total (β = 0.41; P = 0.17) scores. Although LEAPS and SDS scores showed significant improvements after 8 weeks of treatment ( P < 0.001), there were no significant associations between changes in cognitive domain scores and functional improvements. Conclusion: Cognition was associated with occupational functioning at baseline, but changes in cognition were not associated with psychosocial or occupational functional improvements following escitalopram treatment. We recommend the use of more comprehensive functional assessments to determine the impact of cognitive change on functional outcomes in future research.

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