Research paperAltered resting-state fMRI signals and network topological properties of bipolar depression patients with anxiety symptoms
Introduction
Bipolar disorder (BD) is characterized as a severe mental disorder with mood fluctuation (Lau et al., 2018) and a high rate of comorbidity (Krishnan, 2005). Meanwhile, anxiety disorders top the list of comorbidities in BD (Krishnan, 2005). Suffering from anxiety symptoms or disorders (Ellard et al., 2017) could always lead to higher morbidity and mortality of BD, especially the suicide rate (Goes, 2015). In addition, anxiety symptoms may imply an increased risk of BD onset as a preceding appearance (Goes, 2015). Adolescent time anxiety disorders can even predict the occurrence of later life BD (Johnson et al., 2000).
Heretofore, the underlying neurobiology of BD patients with anxiety symptoms has merely been explained through a few neuroimaging studies. Larger gray matter volume (GMV) was found to be correlated with lower trait anxiety in a study with 27 BD type I (BD-I) patients. Furthermore, a remarkable group by trait anxiety by gender interaction was discovered in the left posteromedial rectal gyrus (Almeida et al., 2009). Another structural neuroimaging study reported that the anxiety scores were negatively associated with the total hippocampal volume (Simeonova et al., 2009). With respect to resting-state functional magnetic resonance imaging (rs-fMRI), previous research showed a marked association between posterior cingulate cortex−angular gyrus (ANG) connectivity and anxiety symptoms in euthymic female BD patients (Syan et al., 2017). More robust connectivity was related to higher levels of anxiety between the right laterobasal amygdala and the right hippocampus in BD-I youth (Singh et al., 2015). In a group of bipolar depression (BDP) patients, the resting-state functional connectivity (FC) values between the posterior insula and right lateral postcentral gyrus were positively correlated with the anxiety scores (Yin et al., 2018). Nevertheless, no significant relationship was explored between disrupted brain regions and anxiety scores in other studies mentioned about anxiety symptoms in BD patients (Hagele et al., 2016, 2015; Rey et al., 2016).
There is hardly any literature mainly probing into BD patients with anxiety symptoms. Moreover, the related results were all presented as secondary outcomes. These facts highlight the necessity of concentrating on this subgroup of patients. The majority of the episode time in BD is depression (Judd et al., 2003), which results in a worse prognosis. In addition, rs-fMRI has been widely used to investigate the neuropathphysiology of mental disorders because of its high temporal, spatial resolution, and homogeneity. Without a task, rs-fMRI trials are easier to conduct and compare with other studies.
Thus, we hypothesized that bipolar depression patients with anxiety symptoms (BDP-A) might have more severe and complex impairments in rs-fMRI characteristics comparing to those without anxiety bipolar depression patients (BDP-NA). This study was aimed to present (1) the differences of rs-fMRI signals, FCs, and topological network properties between BDP-A patients and other control groups; (2) the correlation between the neuroimaging indexes and anxiety/depression characteristics in patient groups.
Section snippets
Participants
Seventy-four BDP patients and fifty-one healthy controls (HC) were involved in the current study. The present study was approved by the Ethics Committee of the Shanghai Mental Health Center. In addition, written informed consents in line with the Helsinki Declaration of 1975 (and as revised in 1983) following a thorough description of the measurement were acquired from all the participants. The patients all signed the written informed consent that included permission to publish the case details
Demographics and clinical measures
Finally, 45 BDP-A patients, 22 BDP-NA patients, and 48 HC were involved (6 BDP-A patients, 1 BDP-NA patient, and 3 HC were eliminated because of the poor neuroimaging data quality). The demographic and clinical characteristics of these three groups are summarized in Table 1. There were no significant differences among the three groups in age or gender. Years of education in the BDP-A group were significantly lower than those in HC (P = 0.042, see Table 1). Interestingly, though the patient
4. Discussion
To the best of our knowledge, this is the first study focus on functional neuroimaging changes of BDP-A patients. The findings of our study revealed that BDP-A patients have different brain signals and network properties when compared to BDP-NA and HC, respectively.
Conclusions
In conclusion, the data-driven analysis suggests that BDP-A patients have altered BOLD signals, FC, and network properties in rs-fMRI. Given that the significant regions of dysfunctional BOLD signals are located at DAN, DMN, and fronto-limbic systems, the findings of our study might reveal disturbed top-down emotion regulation, dysfunction of inner- and inter- networks in BDP-A patients indirectly.
Conflict of interest
The authors of the paper do not have any commercial association that might pose a conflict of interest in connection with this manuscript.
Contributors
Jun Chen, Yi-Ru Fang, and Xiao Lin designed the study. All authors were involved in the participants’ recruitment. All the authors agreed to be responsible for the work.
Role of the funding sources
This work was supported by the National Key R&D Program of China (2016YFC1307100), Clinical Research Plan of Shanghai Hospital Development Center (16CR2027B), National Natural Science Foundation of China (81930033, 81771465, 81761128032), Key Area Research and Development Program of Guangdong Province (2018B030334001), and the Sanming Project of Medicine in Shenzhen (SZSM201612006).
Acknowledgments
We sincerely appreciate Xiao-Xia Lei, Jian-Ye Zhang, for the help in the analysis of neuroimaging data.
References (60)
- et al.
Reduced gray matter volume in ventral prefrontal cortex but not amygdala in bipolar disorder: significant effects of gender and trait anxiety
Psychiatry Res.
(2009) - et al.
Transdiagnostic treatment of bipolar disorder and comorbid anxiety using the Unified Protocol for Emotional Disorders: a pilot feasibility and acceptability trial
J. Affect. Disord.
(2017) - et al.
Resting-state functional connectivity in major depression: abnormally increased contributions from subgenual cingulate cortex and thalamus
Biol. Psychiatry
(2007) - et al.
Affective responses across psychiatric disorders—a dimensional approach
Neurosci. Lett.
(2016) - et al.
Default mode network alterations in individuals with high-trait-anxiety: an EEG functional connectivity study
J. Affect. Disord.
(2019) - et al.
Differential engagement of cognitive control regions and subgenual cingulate based upon presence or absence of comorbid anxiety with depression
J. Affect. Disord.
(2018) - et al.
Neural basis of distorted self-face recognition in social anxiety disorder
Neuroimage Clin.
(2016) - et al.
Electroconvulsive therapy changes the regional resting state function measured by regional homogeneity (ReHo) and amplitude of low frequency fluctuations (ALFF) in elderly major depressive disorder patients: an exploratory study
Psychiatry Res. Neuroimaging
(2017) - et al.
Family environment and psychopathology in offspring of parents with bipolar disorder
J. Affect. Disord.
(2018) - et al.
Disrupted brain network topology in chronic insomnia disorder: a resting-state fMRI study
Neuroimage Clin.
(2018)
Selective aberrant functional connectivity of resting state networks in social anxiety disorder
Neuroimage
Altered gray matter morphometry and resting-state functional and structural connectivity in social anxiety disorder
Brain Res.
Risk factors associated with cognitions for late-onset depression based on anterior and posterior default mode sub-networks
J. Affect. Disord.
Prefrontal activation in response to emotional words in patients with bipolar disorder and major depressive disorder
Neuroimage
Working memory dysfunction associated with brain functional deficits and cellular metabolic changes in patients with generalized anxiety disorder
Psychiatry Res. Neuroimaging
Emotion regulation in mood and anxiety disorders: a meta-analysis of fMRI cognitive reappraisal studies
Prog. Neuropsychopharmacol. Biol. Psychiatry
Resting-state functional connectivity of emotion regulation networks in euthymic and non-euthymic bipolar disorder patients
Eur. Psychiatry
Subcortical volumetric correlates of anxiety in familial pediatric bipolar disorder: a preliminary investigation
Psychiatry Res.
Reward processing in adolescents with bipolar I disorder
J. Am. Acad. Child Adolesc. Psychiatry
Intrinsic amygdala functional connectivity in youth with bipolar I disorder
J. Am. Acad. Child Adolesc. Psychiatry
Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain
Neuroimage
Successful antidepressant chronotherapeutics enhance fronto-limbic neural responses and connectivity in bipolar depression
Psychiatry Res.
Aberrant regional neural fluctuations and functional connectivity in generalized anxiety disorder revealed by resting-state functional magnetic resonance imaging
Brain Struct. Funct.
A quantitative meta-analysis of fMRI studies investigating emotional processing in excessive worriers: application of activation likelihood estimation analysis
J. Affect. Disord.
Altered default mode network activity in patient with anxiety disorders: an fMRI study
Eur. J. Radiol.
Effect of acute tryptophan depletion on pre-frontal engagement
Psychopharmacol. Berl.
The neuropsychology and neuroanatomy of bipolar affective disorder: a critical review
Bipolar Disord.
Positive and negative modulation of word learning by reward anticipation
Hum. Brain Mapp.
Modes of large-scale brain network organization during threat processing and posttraumatic stress disorder symptom reduction during TF-CBT among adolescent girls
PLoS ONE
Control of goal-directed and stimulus-driven attention in the brain
Nat. Rev. Neurosci.
Cited by (11)
Depression circuit adaptation in post-stroke depression
2023, Journal of Affective DisordersImmediate modulatory effects of transcutaneous auricular vagus nerve stimulation on the resting state of major depressive disorder
2023, Journal of Affective DisordersResting-state fMRI in depressive and (hypo)manic mood states in bipolar disorders: A systematic review
2022, Progress in Neuro-Psychopharmacology and Biological PsychiatryCitation Excerpt :Further, elevated ReHo was reported in the middle occipital cortex in two unmedicated groups of up to 100 people with bipolar depression (Liang et al., 2013; Qiu et al., 2019). Studies in both medicated and unmedicated samples demonstrated increased ReHo in the inferior parietal lobe (Liang et al., 2013; Liu et al., 2012b) and in the precentral cortex (Lin et al., 2020; Qiu et al., 2019). In contrast, decreased ReHo was found in medial temporal regions such as the parahippocampus (Gao et al., 2014; Liu et al., 2013) and the pericentral cortex (Liang et al., 2013; Russo et al., 2020).
Diurnal mood variation symptoms in major depressive disorder associated with evening chronotype: Evidence from a neuroimaging study
2022, Journal of Affective DisordersCitation Excerpt :In particular, ALFF can be used to select the “seed” voxels for subsequent functional connectivity (FC) analyses (Yan et al., 2019), which can complement the findings from the ALFF analysis and be applied to elucidate the neurobiological changes underlying DMV symptoms in patients with MDD. ALFF combined with FC has been widely used in the study of mental disorders, including the elucidation of brain functional abnormalities in different states of bipolar disorder (Zhang et al., 2020), detection of potential changes in remote connectivity with the insula in adolescents and young adults with MDD (Hu et al., 2019), and assessment of bipolar disorder patients with anxiety symptoms (Lin et al., 2020). Although this method has not been reported in the study of MDD with DMV symptoms, it has been applied in other subtypes of depression, such as anxious depression (Zhao et al., 2019) or somatic depression (Yan et al., 2019).