Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Nov 18;54(15):1-12.
doi: 10.1017/S0033291724001685. Online ahead of print.

Regional neural functional efficiency across schizophrenia, bipolar disorder, and major depressive disorder: a transdiagnostic resting-state fMRI study

Jun Yang  1 , Zhening Liu  1 , Yunzhi Pan  1 , Zebin Fan  1 , Yixin Cheng  1 , Feiwen Wang  1 , Fuping Sun  1 , Guowei Wu  1 , Xuan Ouyang  1 , Haojuan Tao  1 , Jie Yang  1 , Lena Palaniyappan  2   3   4
Affiliations

Regional neural functional efficiency across schizophrenia, bipolar disorder, and major depressive disorder: a transdiagnostic resting-state fMRI study

Jun Yang et al. Psychol Med. .

Abstract

Background: Major psychiatric disorders (MPDs) are delineated by distinct clinical features. However, overlapping symptoms and transdiagnostic effectiveness of medications have challenged the traditional diagnostic categorisation. We investigate if there are shared and illness-specific disruptions in the regional functional efficiency (RFE) of the brain across these disorders.

Methods: We included 364 participants (118 schizophrenia [SCZ], 80 bipolar disorder [BD], 91 major depressive disorder [MDD], and 75 healthy controls [HCs]). Resting-state fMRI was used to caclulate the RFE based on the static amplitude of low-frequency fluctuation, regional homogeneity, and degree centrality and corresponding dynamic measures indicating variability over time. We used principal component analysis to obtain static and dynamic RFE values. We conducted functional and genetic annotation and enrichment analysis based on abnormal RFE profiles.

Results: SCZ showed higher static RFE in the cortico-striatal regions and excessive variability in the cortico-limbic regions. SCZ and MDD shared lower static RFE with higher dynamic RFE in sensorimotor regions than BD and HCs. We observed association between static RFE abnormalities with reward and sensorimotor functions and dynamic RFE abnormalities with sensorimotor functions. Differential spatial expression of genes related to glutamatergic synapse and calcium/cAMP signaling was more likely in the regions with aberrant RFE.

Conclusions: SCZ shares more regions with disrupted functional integrity, especially in sensorimotor regions, with MDD rather than BD. The neural patterns of these transdiagnostic changes appear to be potentially driven by gene expression variations relating to glutamatergic synapses and calcium/cAMP signaling. The aberrant sensorimotor, cortico-striatal, and cortico-limbic integrity may collectively underlie neurobiological mechanisms of MPDs.

Keywords: activity; calcium; connectivity; dynamic; glutamate; potassium; static; variability.

PubMed Disclaimer

Conflict of interest statement

LP reports personal fees for serving as chief editor from the Canadian Medical Association Journals, speaker/consultant fee from Janssen Canada and Otsuka Canada, SPMM Course Limited, UK, Canadian Psychiatric Association; book royalties from Oxford University Press; investigator-initiated educational grants from Janssen Canada, Sunovion and Otsuka Canada outside the submitted work. All other authors report no potential conflicts.

Figures

Figure 1.
Figure 1.
Significant differences in static and dynamic RFE among all groups. Brain maps depict the clusters with omnibus differences in static and dynamic RFE, and violin plots show the results in post hoc comparisons. SCZ, schizophrenia; BD, bipolar disorder; MDD, major depressive disorder patients; HCs, healthy controls; L, left; R, right; IPL, inferior parietal lobule; IFG, inferior frontal gyrus; MFG, middle frontal gyrus; PoCG, postcentral gyrus; STG, superior temporal gyrus; PreCG, precentral gyrus; LING, lingual gyrus; MCC, middle cingulate cortex; SFG, superior frontal gyrus; CAU, caudate; PI, posterior insula; PHG, parahippocampal gyrus; ITG, inferior temporal gyrus. * pFDR < 0.05; ** pFDR < 0.01; *** pFDR < 0.001.
Figure 2.
Figure 2.
Functional correlation of transdiagnostic static and dynamic RFE abnormalities. Heat maps (a and c) depict the correlation between clusters with omnibus differences in static and dynamic RFE and clinical and cognitive characteristics respectively. Word cloud maps (b and d) show the functional terms related to overall static and dynamic RFE via Neurosynth respectively. Note: PANSS was only used in SCZ; YMRS and HAMD were used in BD and MDD. PANSS-P, N, and G, positive, negative, and general psychopathology subscale in Positive and Negative Syndrome Scale; BPRS, Brief Psychiatric Rating Scale; YMRS, Young Mania Rating Scale; HAMD, Hamilton Depression Rating Scale; L, left; R, right; CAU, caudate; PoCG, postcentral gyrus; IFG, inferior frontal gyrus; IPL, inferior parietal lobule; STG, superior temporal gyrus; MCC, middle cingulate cortex; MFG, middle frontal gyrus; LING, lingual gyrus; PreCG, precentral gyrus; SFG, superior frontal gyrus; PI, posterior insula; PHG, parahippocampal gyrus; ITG, inferior temporal gyrus.* p < 0.05; ** p < 0.01; *** p < 0.001.
Figure 3.
Figure 3.
Genetic correlation of static and dynamic RFE abnormalities. The enrichment results are arranged by GO terms (a and c) and KEGG pathways (b and d). BP, biological process; CC, cellular component; MF, molecular function.
See this image and copyright information in PMC

References

    1. Alam, K. A., Svalastoga, P., Martinez, A., Glennon, J. C., & Haavik, J. (2023). Potassium channels in behavioral brain disorders. Molecular mechanisms and therapeutic potential: A narrative review. Neuroscience & Biobehavioral Reviews, 152, 105301. doi: 10.1016/j.neubiorev.2023.105301 - DOI - PubMed
    1. Aminoff, S. R., Onyeka, I. N., Ødegaard, M., Simonsen, C., Lagerberg, T. V., Andreassen, O. A., … Melle, I. (2022). Lifetime and point prevalence of psychotic symptoms in adults with bipolar disorders: A systematic review and meta-analysis. Psychological Medicine, 52(13), 2413–2425. doi: 10.1017/S003329172200201X - DOI - PMC - PubMed
    1. Baker, J. T., Dillon, D. G., Patrick, L. M., Roffman, J. L., Brady, Jr. R. O., Pizzagalli, D. A., … Holmes, A. J. (2019). Functional connectomics of affective and psychotic pathology. Proceedings of the National Academy of Sciences of the United States of America, 116(18), 9050–9059. doi: 10.1073/pnas.1820780116 - DOI - PMC - PubMed
    1. Berman, R. A., Gotts, S. J., McAdams, H. M., Greenstein, D., Lalonde, F., Clasen, L., … Rapoport, J. (2016). Disrupted sensorimotor and social-cognitive networks underlie symptoms in childhood-onset schizophrenia. Brain, 139(Pt 1), 276–291. doi: 10.1093/brain/awv306 - DOI - PMC - PubMed
    1. Brosch, K., Stein, F., Schmitt, S., Pfarr, J. K., Ringwald, K. G., Thomas-Odenthal, F., … Kircher, T. (2022). Reduced hippocampal gray matter volume is a common feature of patients with major depression, bipolar disorder, and schizophrenia spectrum disorders. Molecular Psychiatry, 27(10), 4234–4243. doi: 10.1038/s41380-022-01687-4 - DOI - PMC - PubMed

LinkOut - more resources