Inter-amygdala-FC emerged as a robust, cross-dimensional correlate of BD risk, linking subsyndromal risk to syndromal BD, whereas vlPFC-dlPFC-FC was specific to mania risk, which support a multidimensional, circuit-based model of BD risk supporting early identification and prevention.
Abstract
Background
Identifying reproducible neural markers of bipolar disorder(BD) risk is critical for early detection and differentiation from unipolar/major depression. We previously demonstrated that inter-amygdala functional connectivity(FC) and bilateral-ventrolateral-right-dorsolateral-prefrontal-cortex(vlPFC-dlPFC)-FC were positively associated with both mania/hypomania and depression risk and mania/hypomania risk, respectively, as measured by the Mood Spectrum Self-Report(MOODS-SR) 'mood' subdomains, replicated in three independent samples. We tested whether these neural markers also generalized to the MOODS-SR 'cognition' and 'energy' subdomains and whether they are elevated in individuals with BD versus those at-risk.
Methods
Three independent young adult samples without BD(n=299/ages 18-30) completed an fMRI approach emotion-processing task(Discovery n=114/age=21.60±1.91; Test sample-1 n=103/21.57±2.09; Test sample-2 n=82/23.43±2.86), and a fourth sample with BD(n=32/25.11±3.73) completed the same protocol. Poisson loglinear models tested whether previously identified neural markers of MOODS-SR mood subdomains were also associated with manic and depressive cognition and energy subdomains. One-way ANOVAs compared neural variables showing significant relationships with subdomain scores between low-risk, high-risk, and BD groups.
Results
Across all risk samples, inter-amygdala-FC was positively associated with manic and depressive mood and cognition subdomains(qFDRs<0.001-0.01); vlPFC-dlPFC-FC was positively associated with manic mood and cognition subdomains(qFDRs<0.001-0.048). Inter-amygdala-FC differed significantly across groups(F2,328=3.56, P=0.03) and was higher in BD versus low-risk and in high-risk versus low-risk groups(Ps=0.033).
Conclusions
Inter-amygdala-FC emerged as a robust, cross-dimensional correlate of BD risk, linking subsyndromal risk to syndromal BD, whereas vlPFC-dlPFC-FC was specific to mania risk. Findings support a multidimensional, circuit-based model of BD risk supporting early identification and prevention.
Associations between patterns of brain connectivity and brain structural features have transdiagnostic relevance to psychopathology. There is considerable evidence for disruptions to the hippocampus and temporoparietal brain systems in psychotic disorders. The present study examines structure–function relationships—specifically, the relation of hippocampal volume with patterns of temporoparietal effective connectivity—in youth at clinical high-risk for psychosis (CHR-P) and healthy controls (HCs). Participants at CHR-P and HCs completed clinical symptom measures and magnetic resonance imaging at baseline (n = 388, 42.5% female, age = 19.8 ± 4.2) in the second cohort of the North American Prodrome Longitudinal Study. Group Iterative Multiple Model Estimation established a common functional network of temporoparietal effective connectivity in the full sample. Next, supervised (assuming the CHR-P and HC groups represent classes) and unsupervised (data-driven) clustering procedures interrogated effective connectivity parameters relevant to subsamples. Mean difference tests by unsupervised cluster membership determined whether clusters formed based on temporoparietal effective connectivity differed in hippocampal volume. Clusters were also compared on representation of CHR-P and positive and negative symptom totals to determine whether unsupervised clustering recovered clinical features. Unsupervised clustering generated two clusters that differed significantly in right hippocampal volume and attenuated positive and negative symptoms with small-to-medium effect sizes. The cluster demonstrating reduced right hippocampal volume reported greater symptoms. Unsupervised clustering did not recover diagnostic groups. Findings are consistent with literature indicating the transdiagnostic relevance of hippocampal volume to organizational properties of brain functional networks and patterns of temporoparietal connectivity.
K. Aberizk, B. Ku, Hengyi Cao et al.· Brain Structure and Function· 0 citations
BACKGROUND
Major depressive disorder (MDD) is highly prevalent and often complicated by anxiety symptoms, yet the neurobiological features associated with anxious depression remain incompletely characterized. The amygdala-prefrontal cortex (PFC) circuit, central to affect regulation, has been implicated in anxious depressive symptoms.
METHODS
We recruited 40 MDD patients and 69 healthy controls (HCs) from Tianjin Anding Hospital. All participants underwent resting-state functional magnetic resonance imaging(fMRI) and clinical assessments. Seed-based functional connectivity (FC) analyses were performed using the bilateral amygdala based on the Automated Anatomical Labeling (AAL) atlas. Group comparisons, partial correlations, and regression analyses tested associations between amygdala-based FC and HDRS-17 symptom dimensions, with subgroup analyses distinguishing MDD patients with and without anxiety.
RESULTS
Compared with HCs, MDD patients exhibited reduced FC between the right amygdala and prefrontal cortex, including the right middle frontal gyrus (MFG) and the left inferior frontal gyrus, triangular part (IFGtri) (GRF: voxel-level p < 0.001, cluster-level p < 0.05). Within the MDD group, higher right amygdala-MFG FC values were associated with HDRS-17 symptoms, including total scores and depressive and somatic symptom dimensions (r = 0.393, p = 0.020; r = 0.360, p = 0.033; r = 0.351, p = 0.039, uncorrected p). In exploratory subgroup analyses, right amygdala-MFG FC showed a positive association with HDRS-17 scores in MDD patients with anxiety (R2 = 0.280, F = 8.957, p = 0.006, Beta = 0.529, t = 2.993, p = 0.006); however, the FC × anxiety subgroup interaction did not reach statistical significance.
CONCLUSION
Our findings identify disrupted right amygdala-MFG connectivity as a potential neural correlate of symptom heterogeneity in MDD, particularly in patients with anxiety symptoms.
Chuhao Zhang, Li-Jun Wang, Wen-Jie Sun et al.· Neuroscience Letters· 0 citations
Understanding functional connectivity alterations across manic, depressive, and remitted states of bipolar disorder (BD) remains an important challenge. In this cross-sectional study, we collected resting-state functional magnetic resonance imaging data from 117 BD patients, including manic BD patients (BipM: n = 38), depressive BD patients (BipD: n = 42), remitted BD patients (rBD: n = 37), and 35 healthy controls. We aimed to identify functional connectivity patterns associated with different BD episode states and shared alterations across groups, and to examine their normative reliability, heritability, and spatial correspondence with molecular and cellular brain maps. We identified shared altered connectivity patterns mainly involving ventral attention network-related regions, together with candidate state-associated patterns involving default-mode-related regions in BipM, frontoparietal/somatomotor/visual regions in BipD, and limbic-related regions in rBD. Using Human Connectome Project data, we further found that subsets of these selected connections showed normative test-retest reliability and heritability in healthy adults. Exploratory machine-learning analyses suggested that these patterns contained information related to BD episode-state classification and symptom variation, although the results require independent external validation. Spatial annotation analyses showed that the regional distribution of these connectivity patterns corresponded with normative neurotransmitter receptor, cell-type, and BD-related gene-expression maps. These findings suggest that BD episode states are associated with partially distinct and partially shared functional connectivity alterations. However, because the study was cross-sectional and single-center, and because the molecular analyses were based on normative spatial maps, the findings should be interpreted as exploratory state-associated network observations rather than causal mechanisms or validated clinical biomarkers.
Xiaobo Liu, Zhenqi Liu, Bin Wan et al.· Journal of Affective Disorde...· 0 citations
Major depressive disorder (MDD) exhibits substantial clinical and neurobiological heterogeneity, along with marked variability in treatment response, underscoring the need for objective neuroimaging markers to inform personalized interventions.
Twenty-two patients with MDD and twenty-one age- and sex-matched healthy controls (HCs) were enrolled. Depressive symptoms were assessed using the 17-item Hamilton Rating Scale for Depression (HAMD17), and the Hamilton Rating Scale for Anxiety (HAMA), while cognitive function was evaluated with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Structural magnetic resonance imaging (sMRI) was performed to assess cortical features in MDD patients and HCs. Cortical morphological features [fractal dimension (FD), gyrification index (GI), sulcus depth (SD), and cortical thickness (CT)] were quantified using the automated Computational Anatomy Toolbox (CAT12). Multiple regression analyses were conducted to identify cortical regions in which baseline morphology was associated with subsequent depressive and cognitive changes, controlling for age and sex (voxel-wise
p
< 0.001, family wise error corrected cluster-level
p
< 0.05). To further assess the stability and potential out-of-sample consistency of these associations, exploratory leave-one-out cross-validation (LOOCV) analyses with permutation testing were performed.
Baseline FD in the left superior frontal cortex (SFC), left cuneus, right rostral middle frontal cortex and right lateral occipital cortex (LOC), GI in the left LOC, and CT in the bilateral insula and pericalcarine cortex were significantly associated with greater improvement in depressive symptoms following antidepressant treatment. In addition, lower baseline SD in the left LOC was associated with greater improvement in delayed memory. Single-ROI models (adjusted for age and sex) revealed that baseline left cuneus FD and left SFC FD was significantly correlated with changes in HAMD17 and HAMA, respectively, and the baseline left LOC/lingual SD showed a moderate cross-validated correlation with delayed memory change. These associations were supported by permutation testing, whereas the model for memory improvement showed only exploratory, non-significant cross-validated performance.
Baseline cortical morphometric features were associated with clinical and cognitive changes following antidepressant treatment in MDD. Single-ROI LOOCV models based on left cuneus and left SFC FD showed cross-validated associations with symptom improvement. These findings are preliminary and should be interpreted with caution, pending replication in independent cohorts.
BACKGROUND
Older adults with bipolar disorder (BD) are at high risk for severe mood symptoms, cognitive difficulties, and early mortality; however, underlying brain alterations have received little study. Gray matter decreases in ventral prefrontal cortex (VPFC) seen in younger persons with BD, and additionally in dorsal PFC (DPFC), are implicated. Here, cortical thickness was examined in an international sample.
METHODS
Cortical thickness in 34 regions was measured from structural magnetic resonance imaging data using enhancing neuroImaging genetics through meta-analysis pipelines for individuals with BD (n = 308) and non-psychiatric comparison participants (n = 287), ages 40-70y, from six Global Aging and Geriatric Experiments in BD (GAGE-BD) consortium sites. Group differences were assessed for VPFC, DPFC and remaining cortical regions, covarying for scanner, age and sex. Results were considered significant corrected for false discovery fate (FDR) at pFDR < 0.05. Relationships with demographic and clinical factors were explored.
RESULTS
Cortical thickness was significantly lower among BD in VPFC and DPFC, and additional distributed regions (pFDR < 0.05) and negatively associated with age (p < 0.05); group and age did not interact significantly. Relationships with BD subtype and medications were observed; lithium was associated with higher frontal pole and anterior cingulate thickness (pFDR < 0.05).
CONCLUSIONS
In this international middle and older aged adult BD sample, lower VPFC cortical thickness was observed, suggesting these deficits persist from younger age. DPFC and additional regions of reduced cortical thickness could contribute to the older adult BD phenotype. Cortical thinning was more pronounced among older individuals regardless of diagnosis. Lithium may lessen cortical thinning.
Rebecca B. Marks, A. Sankar, L. Colic et al.· Bipolar Disorders· 0 citations
BACKGROUND
Bipolar disorder (BD) is associated with facial emotion recognition (FER) deficits. Among these, impairments in recognizing moral emotions may be especially relevant to social dysfunction, but their relationship with brain structure remains poorly defined.
METHODS
In this cross-sectional case-control study, 48 euthymic adults with BD (BD-I, n = 20; BD-II, n = 28) and 45 sex- and age-matched healthy controls completed a computerized FER task and 3T T1-weighted MRI scan. FER efficiency (accuracy/response time) for facial moral (anger and disgust) emotion expressions and gray-matter volume (GMV) from 9 bilateral a priori fronto-limbic/salience regions were compared between groups. Group-specific psychometric networks (regularized partial-correlation, i.e. Gaussian graphical models; LASSO/EBIC) integrating FER and GMV nodes were estimated and compared using the Network Comparison Test.
RESULTS
Relative to BD-II and controls, BD-I showed lower FER efficiency, with poorer decoding of moral but not neutral facial expressions. Network structure differed between BD-II and controls, whereas global network strength was comparable across all pairwise group comparisons. Exploratory centrality analyses suggested a more frontally weighted configuration in BD-I, with the superior frontal gyrus among the more central nodes.
CONCLUSION
In BD-I, persistently reduced ability to decode morally salient facial cues co-occurred with subtype-related differences in fronto-limbic structural covariance.
Marialaura Lussignoli, G. Cattarinussi, Alessandro Miola et al.· European Archives of Psychia...· 0 citations
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