Molecular basis underlying default mode network functional abnormalities in postpartum depression with and without...

Area of Science:

• Neuroscience
• Psychiatry
• Molecular Biology

Background:

• Postpartum depression (PPD) and PPD with anxiety (PPD-A) are characterized by brain functional disruptions.
• Quantitative delineation of brain functional system irregularity and the molecular basis of these conditions remain unclear.

Purpose of the Study:

• To quantitatively investigate brain functional system irregularity and functional connectivity abnormalities in PPD and PPD-A.
• To establish the molecular basis of functional abnormalities in PPD and PPD-A using transcriptomic and neurotransmitter data.

Main Methods:

• Utilized brain sample entropy (SampEn), resting-state functional connectivity (RSFC), transcriptomic, and neurotransmitter density data.
• Analyzed SampEn and RSFC in medial prefrontal cortex (MPFC) and posterior cingulate cortex (PPC) in PPD, PPD-A, and healthy postnatal women (HPW).
• Performed spatial association analyses between functional changes and molecular data.

Main Results:

• PPD-A showed higher SampEn in MPFC and PPC compared to HPW and PPD.
• PPD exhibited lower SampEn in PPC than HPW and PPD-A, and decreased functional connectivity in the default mode network (DMN).
• Functional changes correlated with estrogen levels, clinical symptoms, and were associated with synaptic signaling, neurotransmitter regulation (5-HT, dopamine, norepinephrine, glutamate), and cAMP signaling.

Conclusions:

• Abnormal brain entropy and functional connectivities, primarily within the DMN, are identified in PPD and PPD-A.
• Established the molecular basis for PPD and PPD-A by linking functional changes to specific molecular pathways and neurotransmitters.
• Highlighted the significant role of the DMN in the neuropathology of PPD and PPD-A.