TY - JOUR
AU - G. Fanelli
AU - J. Bralten
AU - B. Franke
AU - Roth Mota
AU - A. R. Atti
AU - D. De Ronchi
AU - A. M. Monteleone
AU - L. Grassi
AU - A. Serretti
AU - C. Fabbri
A1 - 
AB - BACKGROUND: Major depressive disorder (MDD) and insulin resistance-related conditions are major contributors to global disability. Their co-occurrence complicates clinical outcomes, increasing mortality and symptom severity. AIMS: In this study, we investigated the association of insulin resistance-related conditions and related polygenic scores (PGSs) with MDD clinical profile and treatment outcomes, using primary care records from UK Biobank. METHOD: We identified MDD cases and insulin resistance-related conditions, as well as measures of depression treatment outcomes (e.g. resistance) from the records. Clinical-demographic variables were derived from self-reports, and insulin resistance-related PGSs were calculated using PRS-CS. Univariable analyses were conducted to compare sociodemographic and clinical variables of MDD cases with (IR+) and without (IR-) lifetime insulin resistance-related conditions. Multiple regressions were performed to identify factors, including insulin resistance-related PGSs, potentially associated with treatment outcomes, adjusting for confounders. RESULTS: Among 30 919 MDD cases, 51.95% were IR+. These had more antidepressant prescriptions and classes utilisation and longer treatment duration than patients without insulin resistance-related conditions (P < 0.001). IR+ participants showed distinctive depressive profiles, characterised by concentration issues, loneliness and inadequacy feelings, which varied according to the timing of MDD diagnosis relative to insulin resistance-related conditions. After adjusting for confounders, insulin resistance-related conditions (i.e. cardiovascular diseases, hypertension, non-alcoholic fatty liver disease, obesity/overweight, prediabetes and type 2 diabetes mellitus) were associated with antidepressant non-response/resistance and longer treatment duration, particularly when MDD preceded insulin resistance-related conditions. No significant PGS associations were found with antidepressant treatment outcomes. CONCLUSIONS: Our findings support an integrated treatment approach, prioritising both psychiatric and metabolic health, and public health strategies aimed at early intervention and prevention of insulin resistance in MDD.
AD - Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.; Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.; Department of Cognitive Neuroscience, Radboud University Medical Center, Nijmegen, The Netherlands.; Department of Psychiatry, University of Campania 'Luigi Vanvitelli', Naples, Italy.; Department of Neuroscience and Rehabilitation, University of Ferrara, Ferrara, Italy.; Department of Medicine and Surgery, Kore University of Enna, Enna, Italy.; Oasi Research Institute-IRCCS, Troina, Italy.
AN - 40548411
BT - Br J Psychiatry
C5 - Healthcare Disparities
DA - Jun 23
DO - 10.1192/bjp.2025.82
DP - NLM
ET - 20250623
JF - Br J Psychiatry
LA - eng
N2 - BACKGROUND: Major depressive disorder (MDD) and insulin resistance-related conditions are major contributors to global disability. Their co-occurrence complicates clinical outcomes, increasing mortality and symptom severity. AIMS: In this study, we investigated the association of insulin resistance-related conditions and related polygenic scores (PGSs) with MDD clinical profile and treatment outcomes, using primary care records from UK Biobank. METHOD: We identified MDD cases and insulin resistance-related conditions, as well as measures of depression treatment outcomes (e.g. resistance) from the records. Clinical-demographic variables were derived from self-reports, and insulin resistance-related PGSs were calculated using PRS-CS. Univariable analyses were conducted to compare sociodemographic and clinical variables of MDD cases with (IR+) and without (IR-) lifetime insulin resistance-related conditions. Multiple regressions were performed to identify factors, including insulin resistance-related PGSs, potentially associated with treatment outcomes, adjusting for confounders. RESULTS: Among 30 919 MDD cases, 51.95% were IR+. These had more antidepressant prescriptions and classes utilisation and longer treatment duration than patients without insulin resistance-related conditions (P < 0.001). IR+ participants showed distinctive depressive profiles, characterised by concentration issues, loneliness and inadequacy feelings, which varied according to the timing of MDD diagnosis relative to insulin resistance-related conditions. After adjusting for confounders, insulin resistance-related conditions (i.e. cardiovascular diseases, hypertension, non-alcoholic fatty liver disease, obesity/overweight, prediabetes and type 2 diabetes mellitus) were associated with antidepressant non-response/resistance and longer treatment duration, particularly when MDD preceded insulin resistance-related conditions. No significant PGS associations were found with antidepressant treatment outcomes. CONCLUSIONS: Our findings support an integrated treatment approach, prioritising both psychiatric and metabolic health, and public health strategies aimed at early intervention and prevention of insulin resistance in MDD.
PY - 2025
SN - 0007-1250
SP - 1
EP - 10+
ST - Insulin resistance and poorer treatment outcomes in depression: evidence from UK Biobank primary care data
T1 - Insulin resistance and poorer treatment outcomes in depression: evidence from UK Biobank primary care data
T2 - Br J Psychiatry
TI - Insulin resistance and poorer treatment outcomes in depression: evidence from UK Biobank primary care data
U1 - Healthcare Disparities
U3 - 10.1192/bjp.2025.82
VO - 0007-1250
Y1 - 2025
ER -