Metabolic mediators of anxious depression? Researchers investigated metabolic correlates of overweight/obesity in patients with MDD.
“Ms Hat” is a 21-year-old Caucasian female who was newly diagnosed with major depressive disorder (MDD), single episode, severe, without psychotic features. She also has significant symptoms of anxiety. She does not smoke, drink alcohol, or use illicit drugs. She meets criteria for obesity, with a current body mass index (BMI) of 32.
At her initial outpatient clinic visit, her blood pressure is elevated at 137/90. Routine laboratory studies, including thyroid function tests (TSH and free T4) and a lipid panel are all within normal limits. She had a good clinical response to the combination of a selective-serotonin reuptake inhibitor and cognitive behavioral therapy.
Overweight and obesity are associated with the severity of MDD and antidepressant treatment outcomes.1 The mechanisms underlying these associations are complex and multifactorial, and may include stress, dysfunctional eating behaviors, and neuroendocrine abnormalities.1
There is evidence that patients with MDD and comorbid anxiety have differences in neurobiology2 and treatment response3 compared to patients without this comorbidity. Thyroid hormones may link weight problems and anxiety in MDD.4 However, previous studies have not comprehensively evaluated these associations in patients with MDD.
The Current Study
Luo and colleagues5 hypothesized that abnormal thyroid hormones would explain part of the relationship between overweight and obesity and anxiety in patients with MDD. The authors investigated these associations in a large cohort of Han Chinese outpatients with first-episode, drug-naïve MDD.
The inclusion criteria were age 18 to 60 years, DSM-IV diagnosis of MDD, first episode of depression without prior antidepressant or antipsychotic treatment, 17-item Hamilton Rating Scale for Depression (HAMD) ≥ 24, and Han ethnicity. Exclusion criteria were other Axis I disorders, substance use disorders (except nicotine), serious physical conditions, and pregnancy or breastfeeding.
The authors assessed depressive symptoms with the HAMD and anxiety symptoms with the 14-item Hamilton Anxiety Inventory (HAMA). Anthropomorphic measures included height and weight for calculation of BMI, and blood pressure was also obtained.
Overweight was defined as BMI ≥ 24 and < 28. Obesity was defined as BMI ≥ 28. A fasting blood sample was collected for glucose, lipids, thyroid function (thyroid peroxidase antibody [TPOAb], thyroglobulin antibody [HgAb], thyroid stimulating hormone [TSH], free thyroxine [FT4], and free triiodothyronine [FT3]).
TSH was dichotomized as normal (0.27-4.20 mIU/L) and abnormal (>4.20 mIU/L). Multinomial logistic models were used to assess the association between anxiety and overweight and obesity and the potential mediation effect of clinical and physiological measures.
Of the 1718 patients, 218 (13%) had severe anxiety. Patients with severe anxiety were older and had longer untreated duration, greater HAMD scores, and a history of suicide attempt. They also had higher levels of thyroid hormones, glucose, lipids, and blood pressure.
The prevalence of overweight was higher in patients with versus without anxiety (63% versus 55%), which was driven by female sex. In the baseline (unadjusted) model, severe anxiety was associated with a 47% higher likelihood of being overweight and a 110% higher likelihood of obesity. However, in adjusted models, the associations with overweight and obesity were attenuated, primarily by thyroid hormones (TSH and FT4) and blood pressure, and no longer significant.
The authors concluded that their study was the first to examine associations between severe anxiety and overweight/obesity in first-episode, drug-naïve MDD. The primary finding was that severe anxiety symptoms in MDD were associated with overweight/obesity, and these associations were explained by thyroid hormones and metabolic parameters.
Study strengths include the large cumulative sample size and drug-naïve status of participants, which minimizes residual confounding due to psychotropic medications. Study limitations include the cross-sectional design, which delimits the ability to make causal inferences, and possible effects of depression itself on thyroid function. Findings are relevant to increased understanding of the pathophysiology of these comorbidities.
The Bottom Line
Patients with MDD and severe anxiety, especially females, were more likely to be overweight and obese, and thyroid hormones and metabolic parameters help explain these associations.
Dr Miller is a professor in the Department of Psychiatry and Health Behavior at Augusta University in Augusta, Georgia. He is on the Editorial Board and serves as the schizophrenia section chief for Psychiatric Times®. The author reports that he receives research support from Augusta University, the National Institute of Mental Health, and the Stanley Medical Research Institute.
1. Hidese S, Asano S, Saito K, et al. Association of depression with body mass index classification, metabolic disease, and lifestyle: a web-based survey involving 11,876 Japanese people. J Psychiatr Res. 2018;102:23-28.
2. Cameron OG. Anxious-depressive comorbidity: effects on HPA axis and CNS noradrenergic functions. Essent Psychopharmacol. 2006;7(1):24-34.
3. Wu Z, Chen J, Yuan C, et al. Difference in remission in a Chinese population with anxious versus nonanxious treatment-resistant depression: a report of OPERATION study. J Affect Disord. 2013;150(3):834-839.
4. Medici M, Direk N, Visser WE, et al. Thyroid function within the normal range and the risk of depression: a population-based cohort study. J Clin Endocrinol Metab. 2014;99(4):1213-1219.
5. Luo G, Li Y, Yao C, et al. Prevalence of overweight and obesity in patients with major depressive disorder with anxiety: mediating role of thyroid hormones and metabolic parameters. J Affect Disord. 2023;335:298-304.