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Altered resting-state functional connectivity in lung cancer patients with comorbid depressive symptoms
Huixia Zhou1,2, Wei Tang3, Hengqin Ren1,2
1State Key Laboratory of Cognitive Science and Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.
Background:
It is quite common clinically for cancer patients (including those with lung cancer) to have comorbid depressive symptoms. Numerous studies have shown that patients with depression often have altered resting-state functional connectivity (RS-FC). However, only a few studies have reported abnormal RS-FC in cancer patients with comorbid depressive symptoms. This exploratory and cross-sectional study examined a heterogeneously treated Chinese lung cancer population. Data on psychotropic medication, cancer-related symptoms, and detailed treatment histories were not systematically collected. The main objective was to observe the relationship between comorbid depressive symptoms and RS-FC in this population, which has not been reported yet.
Methods:
We calculated whole-brain RS-FC in 33 lung cancer patients with comorbid depressive symptoms and 42 age- and sex-matched lung cancer patients without comorbid depressive symptoms. The Patient Health Questionnaire-9 (PHQ-9) was used to assess depressive symptoms in lung cancer patients.
Results:
Compared to lung cancer patients without depressive symptoms, those with comorbid depressive symptoms showed altered RS-FC across eight brain region pairs: (1) left calcarine cortex-right cerebellar lobules IV-V, (2) left medial frontal gyrus-left anterior cingulate gyrus, (3) left insular-left middle temporal gyrus, (4) left precentral gyrus-left cerebellar lobule Ⅲ, (5) left thalamus-vermis Ⅰ and Ⅱ, (6) right olfactory cortex-right fusiform gyrus, (7) right rectus gyrus-right cerebellar lobule Ⅶ b, and (8) right cerebellar lobule Ⅶ b and right olfactory. Furthermore, total depressive symptom scores were negatively correlated with RS-FC between multiple brain regions, including the left superior frontal gyrus and right middle temporal gyrus (r = -0.72, p < 0.001), left superior frontal gyrus and left temporal pole middle temporal gyrus (r = -0.69, p < 0.001), left triangular inferior frontal gyrus and left temporal pole middle temporal gyrus (r = -0.65, p < 0.001), left medial superior frontal gyrus and right middle temporal gyrus (r = -0.65, p < 0.001), left insula and right cerebellar crus II (r = -0.6, p < 0.001), and right superior temporal gyrus and right cerebellar crus II (r = -0.67, p < 0.001).
Conclusions:
Our findings suggest preliminary associations between depressive symptoms and altered RS-FC in lung cancer patients, with connectivity changes correlating with symptom severity. However, because data on psychotropic medication use, cancer-related symptoms (e.g., pain, fatigue), and treatment details were not systematically collected, these findings should be considered preliminary and hypothesis-generating rather than definitive markers of comorbid depression. Future longitudinal studies with systematic assessment of medication, treatment, and multidimensional symptom burden are needed to determine whether these connectivity patterns specifically reflect depressive symptoms or broader cancer-related sequelae.
