In this study, depression severity in patients groups was higher than health control group. There may be deeply related with the disease of MDD itself. However, our results suggested that the depression severity was not significantly different between two patients groups, which is consistent with the another study of brain structures in suicidal and nonsuicidal female patients with MDD [
24]. In our study, we reported that changes in amygdala–precuneus/cuneus rsFC in female patients with first-episode MDD with suicidal ideation were different from female patients with first-episode MDD without suicidal ideation and HC group. However, there were not significant differences in amygdala–precuneus/cuneus rsFC between patients with first-episode MDD without suicidal ideation and the HC group. These findings also suggest that the mechanism underlying suicidal ideation may be related to an abnormality in amygdala–precuneus/cuneus neural circuitry in female patients with first-episode MDD.
Interestingly, two key brain regions underlying suicidal ideation, the amygdala and precuneus, have been strongly implicated in female patients with first-episode MDD. As stated in preface, the amygdala may be a brain region related to the mechanisms of suicidal behavior with MDD. The previous study reported that impulsivity in patients with MDD with a history of suicide attempts was associated with an altered paralimbic (precuneus) encoding of value differences during intertemporal choice [
9]. A study of the structural brain found that, among suicide attempters with psychotic disorders, a history of high-lethality attempts was associated with significantly smaller volumes of gray matter in the right cuneus [
39]. Studies of fMRI showed that past suicidal behavior in people with the early course psychotic MDD was associated with lower activity in midline parietal regions, including the cuneus and precuneus, when performing cognitive control tasks [
40], and the correlation between BOLD signal and relief was greater in nonsuicidal, self-injury patients in areas associated with reward or pain and addiction, including the anterior precuneus [
41]. Why precuneus/cuneus may be related to suicide due to its own functions. The previous fMRI studies showed that the precuneus may be related significantly to emotion processing [
42‐
45]. For example, one study of neural correlates of intentional and incidental self-processing suggested that self-processing involves distinct processes and can occur in areas, including the left precuneus, previously implicated in self-awareness [
42]. The same regions including the precuneus constitute a functional network of reflective self-awareness that is thought to be a core function of consciousness [
43]. The precuneus is associated with mentalizing, self-reference, and autobiographic information [
44]. A review of the precuneus functional anatomy and behavioral correlates showed that recent functional imaging findings in healthy subjects suggest a central role for the precuneus in a wide spectrum of highly integrated tasks, including visuospatial imagery, episodic memory retrieval, and self-processing operations—namely, first-person perspective taking and an experience of agency [
45]. Therefore, we hypothesize that the precuneus/cuneus may be also associated with the patients with MDD with suicidal behavior.
The circuit of the amygdala–precuneus has been highlighted in MDD, because a recent study reported that adolescents with MDD had positive rsFC between the amygdala and precuneus in contrast to healthy adolescents who showed negative rsFC in this circuit [
28], whether this circuit is related to suicide is unclear in this study. From the above studies, those findings do confirm our results that an abnormality in the neural circuitry of the amygdala–precuneus/cuneus may be an important mechanism in suicidal ideation in patients with first-episode MDD. We speculated that the functional connectivity between the amygdala and precuneus could be very important to MDD with suicidal behavior. Thus far, no detailed studies of gender differences have been conducted in amygdala–precuneus/cuneus functional connectivity in MDD with suicidal behavior. Therefore, our results need to be proved by future research. The present study provided evidence that the abnormalities in amygdala–precuneus/cuneus functional connectivity might present the trait feature for female in MDD with suicidal ideation. Moreover, they may indicate potential differentiating markers may improve the early prevention in female in MDD with suicidal ideation. In addition, the clinicians could treat patients in MDD with suicidal ideation using physical therapy-related brain regions. The first limitation in this study is that the assessments of Axis I disorders were performed according to the DSM-IV, not the DSM-V, which could affect the accuracy of the diagnoses. Then, we only investigated the abnormalities of neural circuitry in females with MDD, and did not study males with MDD. Another limitation is the small sample size of the MDD with suicidal ideation group.