Neural correlates of stress-reactive rumination in depression - The role of childhood trauma and social anxiety

Abstract

Recent work showed an association of prefrontal dysfunctions in patients with Major Depressive Disorder (MDD) and social stress induced rumination. However, up to date it is unclear which etiological features of MDD might cause prefrontal dysfunctions. In the study at hand, we aimed to replicate recent findings, that showed prefrontal activation alterations during the Trier Social Stress Test (TSST) and subsequently increased stress-reactive rumination in MDD compared to healthy controls. Moreover, we aimed to explore the role of adverse childhood experiences and other clinical variables in this relationship. N = 55 patients currently suffering from MDD and n = 42 healthy controls (HC) underwent the TSST, while cortical activity in areas of the Cognitive Control Network (CCN) was measured via functional near-infrared spectroscopy (fNIRS). The TSST successfully induced a stress reaction (physiologically, as well as indicated by subjective stress ratings) and state rumination in all subjects with moderate to large effect sizes. In comparison to HC, MDD patients showed elevated levels of state rumination with large effect sizes, as well as a typical pattern of reduced cortical oxygenation during stress in the CCN with moderate effect sizes. Self-reported emotional abuse and social anxiety were moderately positively associated with increased stress-reactive rumination. Within the MDD sample, emotional abuse was negatively and social anxiety positively associated with cortical oxygenation within the CCN with moderate to large effect sizes. In conclusion, our results replicate previous findings on MDD-associated prefrontal hypoactivity during stress and extends the research toward specific subtypes of depression.

Keywords: CCN; Childhood trauma; Cognitive control network; DLPFC; Emotional abuse; Functional near-infrared spectroscopy; Perseverative thinking; Repetitive negative thinking; Rumination; Social anxiety; Stress; Trier social stress test; fNIRS.

Fig. 1

Experimental time course of the study. BDI-II = Beck Depression Inventory II, fNIRS = functional near-infrared spectroscopy, ECG = electrocardiography, RRS = Ruminative Response Scale, CTQ = Childhood Trauma Questionnaire, SRSRQ = Stress-Reactive State Rumination Questionnaire, PANAS = Positive and Negative Affect Schedule. Please note that while subjective stress ratings were assessed every 15 min post TSST (0 min, 15 min, 30 min, 45 min, 60 min), salivary cortisol was only assessed at 0 min, 15 min, 30 min, 60 min. Tube icon: Flaticon.com.

Fig. 2

Subjective stress ratings in percent dependent on group. MDD = Major Depressive Disorder, HC = Healthy controls. Error bars show 1 standard error of the mean.

Fig. 3

Mean cortisol levels dependent on group. MDD = Major Depressive Disorder, HC = Healthy controls. The x-axis represents the time relative to TSST completion: 0 min represents the end of the TSST, −45 min the first saliva collection. Error bars show 1 standard error of the mean.

Fig. 4

Mean heart rate in beats per minute (bpm) dependent on group. MDD = Major Depressive Disorder, HC = Healthy controls, rest1 = resting-state measurement 1, ctl1 = control task 1 (reading numbers), ctl2 = control task 2 (mental arithmetic without time or social stress), anti = anticipation phase of the job interview (preparation, taking notes), inter = job interview of the TSST, arit = arithmetic task of the TSST, rest2 = resting-state measurement 2. Error bars show 1 standard error of the mean.

Fig. 5

State rumination ratings dependent on group. MDD = Major Depressive Disorder, HC = Healthy controls. Error bars show 1 standard error of the mean.

Fig. 6

Differences between MDD and HC in mean cortical oxygenation during control task 1 (ctl1, reading numbers), control task 2 (ctl2, mental arithmetic without time or social stress) and the arithmetic task of the TSST (TSST, mental arithmetic under time or social stress). Cool colors indicate reduced HbO2 levels in the MDD group as compared to the HC group; warm colors vice versa. Differences are depicted in Cohen’s d. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Fig. 7

Differences in HbO2 reactivity (TSST arithmetic task vs. control task 1) between MDD with and without history of abuse and anxiety and HC. Shown is the mean CCN reactivity over all ROIs. All tests are FDR corrected. **p < 0.01. Error bars show 1 standard error of the mean.