Although imbalanced functional integration has been increasingly reported in major depressive disorder (MDD), there still lacks a general framework to characterize common characteristic and origin shared by the integrative disturbances. Here we examined spatial selectivity, temporal uniqueness, metabolic basis, and therapeutic response of altered functional connectivity (FC) in MDD by analyzing both cross-sectional and longitudinal multimodal functional magnetic resonance imaging data from 35 patients and 34 demographically matched healthy controls. First, based on a voxel-wise, data-driven, graph-based degree centrality approach, the bilateral anterior cingulate gyri, middle frontal gyri and superior frontal gyri, and the right parahippocampal gyrus were robustly identified to show decreased FC in MDD. Further spatiotemporal analyses revealed that these regions exhibited hub-like features and were selectively located in limbic and default mode networks spatially and, relative to other areas in the brain, exhibited unique, frequency-dependent oscillation power (stronger within 0.01-0.027 Hz and weaker within 0.027-0.073 Hz) and less dynamical variability of whole-brain FC profiles temporally. Moreover, a cross-modality fusion analysis showed that all MDD-related FC impairments were associated with reduced cerebral blood flow (CBF); however, there existed multiple regions that showed reduced CBF but had intact FC in the patients, which resulted in a decreased FC-CBF coupling and implied an earlier emergence of reduced CBF than impaired FC in MDD. Finally, the disrupted FC in MDD gradually recovered over the course of drug treatment (2 and 12 weeks). Altogether, these findings could help establish a general framework to provide mechanistic insights into integrative dysfunctions in MDD.

BackgroundBipolar disorder types I (BD I) and II (BD II) behave differently in clinical manifestations, normal personality traits, responses to pharmacotherapies, biochemical backgrounds and neuroimaging activations. How the varied emotional states of BD I and II are related to the comorbid personality disorders remains to be settled.MethodsWe therefore administered the Plutchick – van Praag Depression Inventory (PVP), the Mood Disorder Questionnaire (MDQ), the Hypomanic Checklist-32 (HCL-32), and the Parker Personality Measure (PERM) in 37 patients with BD I, 34 BD II, and in 76 healthy volunteers.ResultsCompared to the healthy volunteers, patients with BD I and II scored higher on some PERM styles, PVP, MDQ and HCL-32 scales. In BD I, the PERM Borderline style predicted the PVP scale; and Antisocial predicted HCL-32. In BD II, Borderline, Dependant, Paranoid (-) and Schizoid (-) predicted PVP; Borderline predicted MDQ; Passive-Aggressive and Schizoid (-) predicted HCL-32. In controls, Borderline and Narcissistic (-) predicted PVP; Borderline and Dependant (-) predicted MDQ.ConclusionBesides confirming the different predictability of the 11 functioning styles of personality disorder to BD I and II, we found that the prediction was more common in BD II, which might underlie its higher risk of suicide and poorer treatment outcome.

Aberrant production of nitric oxide following inducible nitric oxide synthase (iNOS) expression has been implicated in cell death and contributes to ischemic brain injury. Tetrahydrobiopterin (BH4) is an essential cofactor of NOS activity. Herein, we evaluated antiapoptotic and anti-inflammatory effects of diamino-6-hydroxypyrimidine (DAHP), a guanosine 5′-triphosphate cyclohydrolase 1 (GTPCH1) inhibitor on focal cerebral ischemia-reperfusion injury by middle cerebral artery occlusion and reperfusion (MCAO) and investigated the underlying mechanism. Sprague-Dawley rats were divided into five groups. Experimental groups were subjected to 1.5 h transient MCAO. T2-weighted imaging was performed to evaluate brain edema lesions in the stroke rats. Infarct volume was estimated by 2,3,5-triphenyltetrazolium chloride (TTC) staining after 24 h reperfusion. Western blotting and immunohistochemistry were performed to detect iNOS, caspase-3, Bcl-2, COX-2, and TNF-α protein expressions. Apoptosis was determined by TUNEL staining. T2 hyperintensity changes were observed in primary ischemic region. DAHP pretreatment significantly suppressed iNOS overexpression, caspase-3, and TNF-α. There was also attenuation of neuronal apoptosis with decrement in proteins Bcl-2 and COX-2 expressions. On the basis of our results, we hypothesize DAHP to have a neuroprotective function against focal cerebral ischemia and might attenuate brain injury by decreasing reactive oxygen species (ROS) production, subsequently inhibiting apoptosis.