Plasma Apo-E mediated corticospinal tract abnormalities and suicidality in patients with major depressive disorder.

This study aims to explore the link between Apo-E, brain white matter, and suicide in patients with major depressive disorder (MDD) to investigate the potential neuroimmune mechanisms of Apo-E that may lead to suicide. Thirty-nine patients with MDD (22 patients with suicidality) and 57 age, gender, and education-matched healthy controls participated in this study, provided plasma Apo-E samples, and underwent diffusion tensor imaging scans. Plasma Apo-E levels and white matter microstructure were analyzed among the MDD with suicidality, MDD without suicidality, and HC groups using analysis of variance with post hoc Bonferroni correction and tract-based spatial statistics (TBSS) with threshold-free cluster enhancement correction. Mediation analysis investigated the relationship between Apo-E, brain white matter, and suicidality in MDD. The MDD with suicidality subgroup had higher depressive and suicide scores, longer disease course, and lower plasma Apo-E levels than MDD without suicidality. TBSS revealed that the MDD non-suicide subgroup showed significantly increased mean diffusivity in the left corticospinal tract and body of the left corpus callosum, as well as increased axial diffusivity in the left anterior corona radiata and the right posterior thalamic radiation compared to the suicidal MDD group. The main finding was that the increased MD of the left corticospinal tract contributed to the elevated suicide score, with Apo-E mediating the effect. Preliminary result that Apo-E's mediating role between the left corticospinal tract and the suicide factor suggests the neuroimmune mechanism of suicide in MDD. The study was registered on ClinicalTrials.gov (NCT03790085).

Association of anhedonia with brain-derived neurotrophic factor and interleukin-10 in major depressive disorder.

BACKGROUND: Anhedonia, a core symptom of major depressive disorder (MDD), manifests in two forms: anticipatory and consummatory, reflecting a diminished capacity to anticipate or enjoy pleasurable activities. Prior studies suggest that brain-derived neurotrophic factor (BDNF) and interleukin-10 (IL-10) may play key roles in the emergence of anhedonia in MDD. The specific relationships between these biomarkers and the two forms of anhedonia remain unclear. This study investigated the potential links between BDNF, IL-10, and both forms of anhedonia in MDD patients. METHODS: This study included 43 participants diagnosed with MDD and 58 healthy controls. It involved detailed assessments of depression and anxiety levels, anticipatory and consummatory pleasure, cognitive functions, and a broad spectrum of plasma biomarkers, such as C-reactive protein, various interleukins, and BDNF. Using partial correlation, variables related to pleasant experiences were identified. Stepwise multiple linear regression analysis was applied to pinpoint the independent predictors of anhedonia in the MDD group. RESULTS: Demographically, both groups were comparable in terms of age, sex, body mass index, educational year, and marital status. Individuals with MDD displayed markedly reduced levels of anticipatory and consummatory pleasure, higher anxiety, and depression scores compared to healthy controls. Additionally, cognitive performance was notably poorer in the MDD group. These patients also had lower plasma diamine oxidase levels. Analysis linked anhedonia to impaired delayed memory. Regression results identified IL-10 and BDNF as independent predictors of anticipatory and consummatory anhedonia, respectively. CONCLUSION: These findings demonstrate that anticipatory and consummatory anhedonia are influenced by independent factors, thereby providing critical insights into the distinct neuroimmunological mechanisms that underlie various forms of anhedonia. Clinicl Trial Registration Number: NCT03790085.

Aberrant patterns of spontaneous brain activity in schizophrenia: A resting-state fMRI study and classification analysis.

BACKGROUND: Schizophrenia is a prevalent mental disorder, leading to severe disability. Currently, the absence of objective biomarkers hinders effective diagnosis. This study was conducted to explore the aberrant spontaneous brain activity and investigate the potential of abnormal brain indices as diagnostic biomarkers employing machine learning methods. METHODS: A total of sixty-one schizophrenia patients and seventy demographically matched healthy controls were enrolled in this study. The static indices of resting-state functional magnetic resonance imaging (rs-fMRI) including amplitude of low frequency fluctuations (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo), and degree centrality (DC) were calculated to evaluate spontaneous brain activity. Subsequently, a sliding-window method was then used to conduct temporal dynamic analysis. The comparison of static and dynamic rs-fMRI indices between the patient and control groups was conducted using a two-sample t-test. Finally, the machine learning analysis was applied to estimate the diagnostic value of abnormal indices of brain activity. RESULTS: Schizophrenia patients exhibited a significant increase ALFF value in inferior frontal gyrus, alongside significant decreases in fALFF values observed in left postcentral gyrus and right cerebellum posterior lobe. Pervasive aberrations in ReHo indices were observed among schizophrenia patients, particularly in frontal lobe and cerebellum. A noteworthy reduction in voxel-wise concordance of dynamic indices was observed across gray matter regions encompassing the bilateral frontal, parietal, occipital, temporal, and insular cortices. The classification analysis achieved the highest values for area under curve at 0.87 and accuracy at 81.28% when applying linear support vector machine and leveraging a combination of abnormal static and dynamic indices in the specified brain regions as features. CONCLUSIONS: The static and dynamic indices of brain activity exhibited as potential neuroimaging biomarkers for the diagnosis of schizophrenia.

Comparison of brain network between schizophrenia and bipolar disorder: A multimodal MRI analysis of comparative studies.

OBJECTIVE: Cognitive impairment is a shared symptom of Schizophrenia (SCZ) and bipolar disorder (BP), but the underlying neural mechanisms for both remain unclear. We aimed to identify abnormalities in the structural and functional brain network of patients with SCZ and BP. METHODS: The study included 69 patients with SCZ, 40 with BP, and 63 healthy controls (HC). After neurocognitive function assessment, resting-state functional magnetic resonance imaging and diffusion tensor imaging were acquired respectively. We compared the network of structural connectivity (SC) and functional connectivity (FC) among the three groups and performed graph theoretical analyses. The SC-FC coupling was calculated, and the correlations between the cognitive function scores and network properties were ascertained. RESULTS: The BP group showed significantly higher indicators in subnetworks and graph theory analysis than SCZ and HC. Several brain regions, such as the inferior parietal lobe, exhibited differences among all pairwise comparisons and showed significant correlations with cognitive scores in both SCZ and BP. SC-FC coupling did not significantly differ between the three groups but showed close associations with clinical performance. Interestingly, the direction of correlations between the network properties and cognition tends to present the opposite between SCZ and BP, especially regarding the working memory, attention, and language sections. CONCLUSIONS: The FC and SC network of the SCZ group appeared more inefficient and disconnected than BP. The network demonstrated to be closely but differently associated with cognitive function at both local and global levels, indicating the potentially separated pathologies of cognition deficits in SCZ and BP.

Increased cortical structural covariance correlates with anhedonia in schizophrenia.

Anhedonia is a common symptom in schizophrenia and is closely related to poor functional outcomes. Several lines of evidence reveal that the orbitofrontal cortex plays an important role in anhedonia. In the present study, we aimed to investigate abnormalities in structural covariance within the orbitofrontal subregions, and to further study their role in anticipatory and consummatory anhedonia in schizophrenia. T1 images of 35 schizophrenia patients and 45 healthy controls were obtained. The cortical thickness of 68 cerebral regions parcellated by the Desikan-Killiany (DK) atlas was calculated. The structural covariance within the orbitofrontal subregions was calculated in both schizophrenia and healthy control groups. Stepwise linear regression was performed to examine the relationship between structural covariance and anhedonia in schizophrenia patients. Patients with schizophrenia exhibited higher structural covariance between the left and right medial orbitofrontal thickness, the left lateral orbitofrontal thickness and left pars orbitalis thickness compared to healthy controls (p < 0.05, FDR corrected). This results imply that the increased structural covariance in orbitofrontal thickness may be involved in the process of developing anhedonia in schizophrenia. The result indicated that the increased structural covariance between the left and right medial orbitofrontal thickness might be a protective factor for anticipatory pleasure (B' = 0.420, p = 0.012).

Abnormal functional connectivity of the anterior cingulate cortex subregions mediates the association between anhedonia and sleep quality in major depressive disorder.

BACKGROUND: The anterior cingulate cortex (ACC) is a crucial region in the pathophysiology of major depressive disorder (MDD). However, the relationship between functional alterations of the ACC subregions, anhedonia and sleep quality remains unclear in MDD patients. METHODS: The resting-state functional connectivity (rsFC) of ACC subregions was measured in 41 first-episode medication-naïve MDD patients and 63 healthy controls who underwent functional magnetic resonance imaging. Between-group differences were examined using two-sample t-test. Furthermore, correlation and mediation analyses were carried out to investigate the relationships between the aberrant rsFC of ACC subregions, anhedonia and sleep quality in the patients and controls. RESULTS: Compared to healthy controls, the MDD patients exhibited increased rsFC of ACC subregions to areas of the anterior default mode network (DMN) and showed decreased rsFC of the right subgenual ACC to left precuneus (PCUN), which belongs to the posterior DMN. In MDD group, the sleep quality and consummatory anhedonia are correlated with some rsFC, which involves the angular gyrus (ANG) and superior frontal gyrus (SFG). More importantly, the rsFC between the right perigenual ACC and left SPG mediates the association between anhedonia and sleep quality in MDD. LIMITATIONS: The cross-sectional design and the subjective questionaries for assessment. CONCLUSION: These findings confirm the functional alterations of the ACC subregions and reveal the mediating role of ACC subregions in sleep and reward dysfunction in MDD.

Gender Differences of Schizophrenia Patients With and Without Depressive Symptoms in Clinical Characteristics.

Objectives: To investigate the differences in psychotic symptoms and cognitive function in schizophrenics with and without depression and to compare gender differences in the correlation between depressive symptoms and clinical characteristics in those patients. Methods: A total of 190 schizophrenia patients and 200 healthy controls were recruited in the study. We used the Positive and Negative Symptom Scale (PANSS), the Calgary Depression Scale for Schizophrenia (CDSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) to evaluate the psychiatric symptoms, depressive symptoms and cognitive function, respectively. Patients with CDSS score ≥7 were divided into depression group, and CDSS < 7 was viewed as without depression. Results: Patients with schizophrenia had lower total scores of RBANS and five subscale (immediate memory, visual span, verbal function, attention, and delayed memory) scores compared to healthy controls. In the case group, patients who concomitant with depression had higher PANSS scores (Ps < 0.001) and lower RBANS (Ps < 0.05) scores than those without depression. After gender stratification, PANSS total scores and subscale scores were significantly different between schizophrenics with and without depressive symptoms in both male and female groups (Ps < 0.001). For cognitive function, there were significant differences in RBANS total score and subscale scores except attention between female patients with and without schizophrenia but not in male schizophrenia patients. Furthermore, the correlation analysis showed that the total CDSS score was positively correlated with PANSS score (P < 0.001) and RBANS score in male and female groups (male: P = 0.010, female: P = 0.001). Conclusion: Our findings provided evidence supporting the gender differences in psychiatric symptoms and cognitive function between schizophrenia patients with and without depressive symptoms.