Generic placeholder image

CNS & Neurological Disorders - Drug Targets


ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

Research Article

Effective Connectivity Between the Orbitofrontal Cortex and the Precuneus Differentiates Major Psychiatric Disorders: Results from a Transdiagnostic Spectral DCM Study

Author(s): Sevdalina Kandilarova, Drozdstoy Stoyanov*, Katrin Aryutova, Rossitsa Paunova, Mladen Mantarkov, Ivo Mitrev, Anna Todeva-Radneva and Karsten Specht

Volume 22, Issue 2, 2023

Published on: 24 November, 2021

Page: [180 - 190] Pages: 11

DOI: 10.2174/1871527320666210917142815

Price: $65


Background & Objective: We have previously identified aberrant connectivity of the left precuneus, ventrolateral prefrontal cortex, anterior cingulate cortex, and anterior insula in patients with either a paranoid (schizophrenia), or a depressive syndrome (both unipolar and bipolar). In the current study, we attempted to replicate and expand these findings by including a healthy control sample and separating the patients in a depressive episode into two groups: unipolar and bipolar depression. We hypothesized that the connections between those major nodes of the resting state networks would demonstrate different patterns in the three patient groups compared to the healthy subjects.

Methods: Resting-state functional MRI was performed on a sample of 101 participants, of which 26 patients with schizophrenia (current psychotic episodes), 24 subjects with Bipolar Disorder (BD), 33 with Major Depressive Disorder (MDD) (both BD and MDD patients were in a current depressive episode), and 21 healthy controls. Spectral Dynamic Causal Modeling was used to calculate the coupling values between eight regions of interest, including the anterior precuneus (PRC), anterior hippocampus, anterior insula, angular gyrus, lateral Orbitofrontal Cortex (OFC), middle frontal gyrus, planum temporale, and anterior thalamus.

Results & Conclusion: We identified disturbed effective connectivity from the left lateral orbitofrontal cortex to the left anterior precuneus that differed significantly between unipolar depression, where the influence was inhibitory, and bipolar depression, where the effect was excitatory. A logistic regression analysis correctly classified 75% of patients with unipolar and bipolar depression based solely on the coupling values of this connection. In addition, patients with schizophrenia demonstrated negative effective connectivity from the anterior PRC to the lateral OFC, which distinguished them from healthy controls and patients with major depression. Future studies with unmedicated patients will be needed to establish the replicability of our findings.

Keywords: Effective connectivity, transdiagnostic, schizophrenia, bipolar disorder, major depression, resting state MRI, spectral Dynamic Causal Modeling, precuneus, orbitofrontal cortex.

Semahegn A, Torpey K, Manu A, Assefa N, Tesfaye G, Ankomah A. Psychotropic medication non-adherence and its associated factors among patients with major psychiatric disorders: a systematic review and meta-analysis. Syst Rev 2020; 9(1): 17.
[] [PMID: 31948489]
Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med 2006; 3(11): e442.
[] [PMID: 17132052]
Boyer L, Lançon C, Baumstarck K, Parola N, Berbis J, Auquier P. Evaluating the impact of a quality of life assessment with feedback to clinicians in patients with schizophrenia: randomised controlled trial. Br J Psychiatry 2013; 202: 447-53.
[] [PMID: 23661768]
Charlson FJ, Ferrari AJ, Flaxman AD, Whiteford HA. The epidemiological modelling of dysthymia: application for the Global Burden of Disease Study 2010. J Affect Disord 2013; 151(1): 111-20.
[] [PMID: 23806588]
García-Gutiérrez MS, Navarrete F, Sala F, Gasparyan A, Austrich-Olivares A, Manzanares J. Biomarkers in Psychiatry: Concept, Definition, Types and Relevance to the Clinical Reality. Front Psychiatry 2020; 11: 432.
[] [PMID: 32499729]
Swartz MS, Stroup TS, McEvoy JP, et al. What CATIE found: results from the schizophrenia trial. Psychiatr Serv 2008; 59(5): 500-6.
[] [PMID: 18451005]
Sinyor M, Schaffer A, Levitt A. The sequenced treatment alternatives to relieve depression (STAR*D) trial: a review. Can J Psychiatry 2010; 55(3): 126-35.
[] [PMID: 20370962]
Pincus HA, Tew JD, First MB. Psychiatric comorbidity: is more less? World Psychiatry 2004; 3(1): 18-23.
[PMID: 16633444]
Buckley PF, Miller BJ, Lehrer DS, Castle DJ. Psychiatric comorbidities and schizophrenia. Schizophr Bull 2009; 35(2): 383-402.
[] [PMID: 19011234]
Stoyanov DS. Key Developments in Translational Neuroscience: an Update. Balkan Med J 2017; 34(6): 485-6.
[] [PMID: 29215334]
Helm K, Viol K, Weiger TM, et al. Neuronal connectivity in major depressive disorder: a systematic review. Neuropsychiatr Dis Treat 2018; 14: 2715-37.
[] [PMID: 30425491]
Menon V. Large-scale brain networks and psychopathology: a unifying triple network model. Trends Cogn Sci 2011; 15(10): 483-506.
[] [PMID: 21908230]
Fornito A, Bullmore ET. Connectomics: a new paradigm for understanding brain disease. Eur Neuropsychopharmacol 2015; 25(5): 733-48.
[] [PMID: 24726580]
Supekar K, Cai W, Krishnadas R, Palaniyappan L, Menon V. Dysregulated Brain Dynamics in a Triple-Network Saliency Model of Schizophrenia and Its Relation to Psychosis. Biol Psychiatry 2019; 85(1): 60-9.
[] [PMID: 30177256]
Friston KJ. Functional and effective connectivity: a review. Brain Connect 2011; 1(1): 13-36.
[] [PMID: 22432952]
Friston KJ, Kahan J, Biswal B, Razi A. A DCM for resting state fMRI. Neuroimage 2014; 94: 396-407.
[] [PMID: 24345387]
Friston KJ, Harrison L, Penny W. Dynamic causal modelling. Neuroimage 2003; 19(4): 1273-302.
[] [PMID: 12948688]
Razi A, Kahan J, Rees G, Friston KJ. Construct validation of a DCM for resting state fMRI. Neuroimage 2015; 106: 1-14.
[] [PMID: 25463471]
Goya-Maldonado R, Brodmann K, Keil M, Trost S, Dechent P, Gruber O. Differentiating unipolar and bipolar depression by alterations in large-scale brain networks. Hum Brain Mapp 2016; 37(2): 808-18.
[] [PMID: 26611711]
Fateh AA, Long Z, Duan X, et al. Hippocampal functional connectivity-based discrimination between bipolar and major depressive disorders. Psychiatry Res Neuroimaging 2019; 284: 53-60.
[] [PMID: 30684896]
Wei Y, Chang M, Womer FY, et al. Local functional connectivity alterations in schizophrenia, bipolar disorder, and major depressive disorder. J Affect Disord 2018; 236: 266-73.
[] [PMID: 29751242]
Sheehan DV, Lecrubier Y, Sheehan KH, et al. The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 1998; 59 (Suppl. 20): 22-33.
[PMID: 9881538]
Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry 1979; 134(4): 382-9.
[] [PMID: 444788]
Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 1987; 13(2): 261-76.
[] [PMID: 3616518]
Jackowski AP, Araújo Filho GM, Almeida AG, et al. The involvement of the orbitofrontal cortex in psychiatric disorders: an update of neuroimaging findings. Br J Psychiatry 2012; 34(2): 207-12.
[] [PMID: 22729418]
Fjellvang M, Grøning L, Haukvik UK. Imaging violence in schizophrenia: a systematic review and critical discussion of the MRI literature. Front Psychiatry 2018; 9: 333.
[] [PMID: 30083111]
Takayanagi Y, Takahashi T, Orikabe L, et al. Volume reduction and altered sulco-gyral pattern of the orbitofrontal cortex in first-episode schizophrenia. Schizophr Res 2010; 121(1-3): 55-65.
[] [PMID: 20605415]
Hoptman MJ, Volavka J, Weiss EM, et al. Quantitative MRI measures of orbitofrontal cortex in patients with chronic schizophrenia or schizoaffective disorder. Psychiatry Res 2005; 140(2): 133-45.
[] [PMID: 16253482]
Wagner G, Koch K, Schachtzabel C, Reichenbach JR, Sauer H, Schlösser Md RG. Enhanced rostral anterior cingulate cortex activation during cognitive control is related to orbitofrontal volume reduction in unipolar depression. J Psychiatry Neurosci 2008; 33(3): 199-208.
[PMID: 18592043]
Arnone D, McIntosh AM, Ebmeier KP, Munafò MR, Anderson IM. Magnetic resonance imaging studies in unipolar depression: systematic review and meta-regression analyses. Eur Neuropsychopharmacol 2012; 22(1): 1-16.
[] [PMID: 21723712]
Nery FG, Chen H-H, Hatch JP, et al. Orbitofrontal cortex gray matter volumes in bipolar disorder patients: a region-of-interest MRI study. Bipolar Disord 2009; 11(2): 145-53.
[] [PMID: 19267697]
Kringelbach ML, Rolls ET. The functional neuroanatomy of the human orbitofrontal cortex: evidence from neuroimaging and neuropsychology. Prog Neurobiol 2004; 72(5): 341-72.
[] [PMID: 15157726]
Rolls ET, Cheng W, Feng J. The orbitofrontal cortex: reward, emotion and depression. Brain Commun 2020; 2(2): fcaa196.
Cheng W, Rolls ET, Qiu J, et al. Medial reward and lateral non-reward orbitofrontal cortex circuits change in opposite directions in depression. Brain 2016; 139(Pt 12): 3296-309.
[] [PMID: 27742666]
Li C-T, Yang K-C, Lin W-C. Glutamatergic dysfunction and glutamatergic compounds for major psychiatric disorders: evidence from clinical neuroimaging studies. Front Psychiatry 2019; 9: 767.
[] [PMID: 30733690]
Gigante AD, Bond DJ, Lafer B, Lam RW, Young LT, Yatham LN. Brain glutamate levels measured by magnetic resonance spectroscopy in patients with bipolar disorder: a meta-analysis. Bipolar Disord 2012; 14(5): 478-87.
[] [PMID: 22834460]
Chitty KM, Lagopoulos J, Lee RSC, Hickie IB, Hermens DF. A systematic review and meta-analysis of proton magnetic resonance spectroscopy and mismatch negativity in bipolar disorder. Eur Neuropsychopharmacol J Eur Coll Neuropsychopharmacol 2013; 23(11): 1348-63.
[] [PMID: 23968965]
Arnone D, Mumuni AN, Jauhar S, Condon B, Cavanagh J. Indirect evidence of selective glial involvement in glutamate-based mechanisms of mood regulation in depression: meta-analysis of absolute prefrontal neuro-metabolic concentrations. Eur Neuropsychopharmacol J Eur Coll Neuropsychopharmacol 2015; 25(8): 1109-17.
[] [PMID: 26028038]
Cavanna AE, Trimble MR. The precuneus: a review of its functional anatomy and behavioural correlates. Brain 2006; 129(Pt 3): 564-83.
[] [PMID: 16399806]
Pardoen D, Bauwens F, Tracy A, Martin F, Mendlewicz J. Self-esteem in recovered bipolar and unipolar out-patients. Br J Psychiatry 1993; 163(6): 755-62.
[] [PMID: 8306117]
Knowles R, Tai S, Jones SH, Highfield J, Morriss R, Bentall RP. Stability of self-esteem in bipolar disorder: comparisons among remitted bipolar patients, remitted unipolar patients and healthy controls. Bipolar Disord 2007; 9(5): 490-5.
[] [PMID: 17680919]
Fransson P, Marrelec G. The precuneus/posterior cingulate cortex plays a pivotal role in the default mode network: evidence from a partial correlation network analysis. Neuroimage 2008; 42(3): 1178-84.
[] [PMID: 18598773]
Buckner RL, Andrews-Hanna JR, Schacter DL. The brain’s default network: anatomy, function, and relevance to disease. 2008.
Whitfield-Gabrieli S, Ford JM. Default mode network activity and connectivity in psychopathology. Annu Rev Clin Psychol 2012; 8: 49-76.
[] [PMID: 22224834]
Schilbach L, Hoffstaedter F, Müller V, et al. Transdiagnostic commonalities and differences in resting state functional connectivity of the default mode network in schizophrenia and major depression. Neuroimage Clin 2015; 10: 326-35.
[] [PMID: 26904405]
Bastos-Leite AJ, Ridgway GR, Silveira C, Norton A, Reis S, Friston KJ. Dysconnectivity within the default mode in first-episode schizophrenia: a stochastic dynamic causal modeling study with functional magnetic resonance imaging. Schizophr Bull 2015; 41(1): 144-53.
[] [PMID: 24939881]
Gong X, Lu W, Kendrick KM, et al. A brain-wide association study of DISC1 genetic variants reveals a relationship with the structure and functional connectivity of the precuneus in schizophrenia. Hum Brain Mapp 2014; 35(11): 5414-30.
[] [PMID: 24909300]
Stephan KE, Friston KJ, Frith CD. Dysconnection in schizophrenia: from abnormal synaptic plasticity to failures of self-monitoring. Schizophr Bull 2009; 35(3): 509-27.
[] [PMID: 19155345]
Stephan KE, Baldeweg T, Friston KJ. Synaptic plasticity and dysconnection in schizophrenia. Biol Psychiatry 2006; 59(10): 929-39.
[] [PMID: 16427028]
Anticevic A, Van Snellenberg JX, Cohen RE, Repovs G, Dowd EC, Barch DM. Amygdala recruitment in schizophrenia in response to aversive emotional material: a meta-analysis of neuroimaging studies. Schizophr Bull 2012; 38(3): 608-21.
[] [PMID: 21123853]
Kitis O, Ozalay O, Zengin EB, et al. Reduced left uncinate fasciculus fractional anisotropy in deficit schizophrenia but not in non-deficit schizophrenia. Psychiatry Clin Neurosci 2012; 66(1): 34-43.
[] [PMID: 22250608]
Gradin VB, Waiter G, O’Connor A, et al. Salience network-midbrain dysconnectivity and blunted reward signals in schizophrenia. Psychiatry Res Neuroimaging 2013; 211(2): 104-11.
[] [PMID: 23146249]
Koch K, Schachtzabel C, Wagner G, et al. Altered activation in association with reward-related trial-and-error learning in patients with schizophrenia. Neuroimage 2010; 50(1): 223-32.
[] [PMID: 20006717]
Corlett PR, Murray GK, Honey GD, et al. Disrupted prediction-error signal in psychosis: evidence for an associative account of delusions. Brain 2007; 130(Pt 9): 2387-400.
[] [PMID: 17690132]
Williamson P. Are anticorrelated networks in the brain relevant to schizophrenia? Schizophr Bull 2007; 33(4): 994-1003.
[] [PMID: 17493957]
Javitt DC. Glutamate and schizophrenia: phencyclidine, N-methyl-D-aspartate receptors, and dopamine-glutamate interactions. Int Rev Neurobiol 2007; 78: 69-108.
[] [PMID: 17349858]
Gao W-J, Yang S-S, Mack NR, Chamberlin LA. Aberrant maturation and connectivity of prefrontal cortex in schizophrenia-contribution of NMDA receptor development and hypofunction. Mol Psychiatry 2021; 1-13.
[PMID: 34163013]
Sen B, Mueller B, Klimes-Dougan B, Cullen K, Parhi KK. Classification of major depressive disorder from resting-state fMRI. 2019 41st Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC). 3511-4.
Li M, Das T, Deng W, et al. Clinical utility of a short resting-state MRI scan in differentiating bipolar from unipolar depression. Acta Psychiatr Scand 2017; 136(3): 288-99.
[] [PMID: 28504840]
Wang L, Xia M, Li K, et al. The effects of antidepressant treatment on resting-state functional brain networks in patients with major depressive disorder. Hum Brain Mapp 2015; 36(2): 768-78.
[] [PMID: 25332057]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy