Hostname: page-component-848d4c4894-sjtt6 Total loading time: 0 Render date: 2024-06-23T05:41:23.311Z Has data issue: false hasContentIssue false

Cannabidiol attenuates insular activity during motivational salience processing in patients with early psychosis

Published online by Cambridge University Press:  01 July 2022

Brandon Gunasekera
Affiliation:
Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK
Robin Wilson
Affiliation:
Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK
Aisling O'Neill
Affiliation:
Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK
Grace Blest-Hopley
Affiliation:
Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK
Owen O'Daly
Affiliation:
Department of Neuroimaging, Centre for Neuroimaging Sciences, King's College London, UK
Sagnik Bhattacharyya*
Affiliation:
Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK
*
Author for correspondence: Sagnik Bhattacharyya, E-mail: sagnik.2.bhattacharyya@kcl.ac.uk

Abstract

Background

The mechanisms underlying the antipsychotic potential of cannabidiol (CBD) remain unclear but growing evidence indicates that dysfunction in the insula, a key brain region involved in the processing of motivationally salient stimuli, may have a role in the pathophysiology of psychosis. Here, we investigate whether the antipsychotic mechanisms of CBD are underpinned by their effects on insular activation, known to be involved in salience processing.

Methods

A within-subject, crossover, double-blind, placebo-controlled investigation of 19 healthy controls and 15 participants with early psychosis was conducted. Administration of a single dose of CBD was compared with placebo in psychosis participants while performing the monetary incentive delay task, an fMRI paradigm. Anticipation of reward and loss were used to contrast motivationally salient stimuli against a neutral control condition.

Results

No group differences in brain activation between psychosis patients compared with healthy controls were observed. Attenuation of insula activation was observed following CBD, compared to placebo. Sensitivity analyses controlling for current cannabis use history did not affect the main results.

Conclusion

Our findings are in accordance with existing evidence suggesting that CBD modulates brain regions involved in salience processing. Whether such effects underlie the putative antipsychotic effects of CBD remains to be investigated.

Type
Original Article
Copyright
Copyright © The Author(s), 2022. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Berridge, K. C. (2012). From prediction error to incentive salience: Mesolimbic computation of reward motivation. European Journal of Neuroscience, 35(7), 11241143. https://doi.org/10.1111/j.1460-9568.2012.07990.xCrossRefGoogle ScholarPubMed
Bhattacharyya, S., Morrison, P. D., Fusar-Poli, P., Martin-Santos, R., Borgwardt, S., Winton-Brown, T., … McGuire, P. K. (2010). Opposite effects of δ-9-tetrahydrocannabinol and cannabidiol on human brain function and psychopathology. Neuropsychopharmacology, 35(3), 764774. https://doi.org/10.1038/npp.2009.184CrossRefGoogle ScholarPubMed
Bhattacharyya, S., Wilson, R., Appiah-Kusi, E., O'Neill, A., Brammer, M., Perez, J., … McGuire, P. (2018). Effect of cannabidiol on medial temporal, midbrain, and striatal dysfunction in people at clinical high risk of psychosis: A randomized clinical trial. JAMA Psychiatry, 75(11), 11071117. https://doi.org/10.1001/jamapsychiatry.2018.2309CrossRefGoogle ScholarPubMed
Bisogno, T., Hanuš, L., De Petrocellis, L., Tchilibon, S., Ponde, D. E., Brandi, I., … Di Marzo, V. (2001). Molecular targets for cannabidiol and its synthetic analogues: Effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide. British Journal of Pharmacology, 134(4), 845852. https://doi.org/10.1038/sj.bjp.0704327CrossRefGoogle ScholarPubMed
Boggs, D. L., Surti, T., Gupta, A., Gupta, S., Niciu, M., Pittman, B., … Ranganathan, M. (2018). The effects of cannabidiol (CBD) on cognition and symptoms in outpatients with chronic schizophrenia a randomized placebo controlled trial. Psychopharmacology, 235(7), 19231932. https://doi.org/10.1007/s00213-018-4885-9CrossRefGoogle ScholarPubMed
Bonaccorso, S., Ricciardi, A., Zangani, C., Chiappini, S., & Schifano, F. (2019). Cannabidiol (CBD) use in psychiatric disorders: A systematic review. NeuroToxicology, 74, 282298. https://doi.org/10.1016/j.neuro.2019.08.002CrossRefGoogle Scholar
Borgwardt, S. J., Riecher-Rössler, A., Dazzan, P., Chitnis, X., Aston, J., Drewe, M., … McGuire, P. K. (2007). Regional gray matter volume abnormalities in the at risk mental state. Biological Psychiatry, 61(10), 11481156. https://doi.org/10.1016/j.biopsych.2006.08.009CrossRefGoogle ScholarPubMed
Brosnan, K. C., Hayes, K., & Harrison, A. J. (2017). Effects of false-start disqualification rules on response-times of elite-standard sprinters. Journal of Sports Sciences, 35(10), 929935. https://doi.org/10.1080/02640414.2016.1201213CrossRefGoogle ScholarPubMed
Ceccarini, J., De Hert, M., Van Winkel, R., Peuskens, J., Bormans, G., Kranaster, L., … Van Laere, K. (2013). Increased ventral striatal CB1 receptor binding is related to negative symptoms in drug-free patients with schizophrenia. NeuroImage, 79, 304312. https://doi.org/10.1016/j.neuroimage.2013.04.052CrossRefGoogle ScholarPubMed
Chan, R. C. K., Di, X., McAlonan, G. M., & Gong, Q. Y. (2011). Brain anatomical abnormalities in high-risk individuals, first-episode, and chronic schizophrenia: An activation likelihood estimation meta-analysis of illness progression. Schizophrenia Bulletin, 37(1), 177188. https://doi.org/10.1093/schbul/sbp073CrossRefGoogle ScholarPubMed
Chapman, J. (1966). The early symptoms of schizophrenia. The British Journal of Psychiatry: The Journal of Mental Science, 112(484), 225251. https://doi.org/10.1192/bjp.112.484.225CrossRefGoogle ScholarPubMed
Chesney, E., Oliver, D., Green, A., Sovi, S., Wilson, J., Englund, A., … McGuire, P. (2020). Adverse effects of cannabidiol: A systematic review and meta-analysis of randomized clinical trials. Neuropsychopharmacology, 45(11), 17991806. https://doi.org/10.1038/s41386-020-0667-2CrossRefGoogle ScholarPubMed
Davies, C., & Bhattacharyya, S. (2019). Cannabidiol as a potential treatment for psychosis. Therapeutic Advances in Psychopharmacology, 9, 204512531988191. https://doi.org/10.1177/2045125319881916CrossRefGoogle ScholarPubMed
Davies, C., Wilson, R., Appiah-Kusi, E., Blest-Hopley, G., Brammer, M., Perez, J., … Bhattacharyya, S. (2020). A single dose of cannabidiol modulates medial temporal and striatal function during fear processing in people at clinical high risk for psychosis. Translational Psychiatry, 10(1), 112. https://doi.org/10.1038/s41398-020-0862-2CrossRefGoogle ScholarPubMed
Ellison-Wright, I., Glahn, D. C., Laird, A. R., Thelen, S. M., & Bullmore, E. (2008). The anatomy of first-episode and chronic schizophrenia: An anatomical likelihood estimation meta-analysis. American Journal of Psychiatry, 165(8), 10151023. https://doi.org/10.1176/appi.ajp.2008.07101562CrossRefGoogle ScholarPubMed
Englund, A., Morrison, P. D., Nottage, J., Hague, D., Kane, F., Bonaccorso, S., … Kapur, S. (2013). Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment. Journal of Psychopharmacology, 27(1), 1927. https://doi.org/10.1177/0269881112460109CrossRefGoogle ScholarPubMed
Ferguson, L. M., Ahrens, A. M., Longyear, L. G., & Aldridge, W. (2020). Neurons of the ventral tegmental area encode individual differences in motivational ⇜wanting⇝ for reward cues. Journal of Neuroscience, 40(46), 89518963. https://doi.org/10.1523/JNEUROSCI.2947-19.2020CrossRefGoogle ScholarPubMed
Goodkind, M., Eickhoff, S. B., Oathes, D. J., Jiang, Y., Chang, A., Jones-Hagata, L. B., … Etkin, A. (2015). Identification of a common neurobiological substrate for mental illness. JAMA Psychiatry, 72(4), 305315. https://doi.org/10.1001/jamapsychiatry.2014.2206CrossRefGoogle ScholarPubMed
Gunasekera, B., Davies, C., Martin-Santos, R., & Bhattacharyya, S. (2021). The Yin and Yang of Cannabis: A systematic review of human neuroimaging evidence of the differential effects of Δ9-tetrahydrocannabinol and cannabidiol. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 6(6), 636645. https://doi.org/10.1016/j.bpsc.2020.10.007Google ScholarPubMed
Gunasekera, B., Diederen, K., & Bhattacharyya, S. (2022). Cannabinoids, reward processing, and psychosis. Psychopharmacology, 239(5), 11571177.10.1007/s00213-021-05801-2CrossRefGoogle ScholarPubMed
Howes, O. D., Kambeitz, J., Kim, E., Stahl, D., Slifstein, M., Abi-Dargham, A., & Kapur, S. (2012). The nature of dopamine dysfunction in schizophrenia and what this means for treatment: Meta-analysis of imaging studies. Archives of General Psychiatry, 69(8), 776786. https://doi.org/10.1001/archgenpsychiatry.2012.169CrossRefGoogle Scholar
Jauhar, S., Fortea, L., Solanes, A., Albajes-Eizagirre, A., McKenna, P. J., & Radua, J. (2021). Brain activations associated with anticipation and delivery of monetary reward: A systematic review and meta-analysis of fMRI studies. PLOS ONE, 16(8), e0255292. https://doi.org/10.1371/JOURNAL.PONE.0255292CrossRefGoogle ScholarPubMed
Kapur, S. (2003). Psychosis as a state of aberrant salience: A framework linking biology, phenomenology, and pharmacology in schizophrenia. American Journal of Psychiatry, 160, 1323. https://doi.org/10.1176/appi.ajp.160.1.13CrossRefGoogle ScholarPubMed
Kay, S. R., Fiszbein, A., & Opler, L. A. (1987). The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophrenia Bulletin, 13(2), 261276. https://doi.org/10.1093/schbul/13.2.261CrossRefGoogle ScholarPubMed
Knutson, B., Westdorp, A., Kaiser, E., & Hommer, D. (2000). fMRI visualization of brain activity during a monetary incentive delay task. NeuroImage, 12(1), 2027. https://doi.org/10.1006/nimg.2000.0593CrossRefGoogle Scholar
Landy, G. L., & Kripalani, M. (2015). False positive phencyclidine result on urine drug testing: A little known cause. BJPsych Bulletin, 39(1), 5050. https://doi.org/10.1192/pb.39.1.50CrossRefGoogle Scholar
Laprairie, R. B., Bagher, A. M., Kelly, M. E. M., & Denovan-Wright, E. M. (2015). Cannabidiol is a negative allosteric modulator of the cannabinoid CB1 receptor. British Journal of Pharmacology, 172(20), 47904805. https://doi.org/10.1111/bph.13250CrossRefGoogle ScholarPubMed
Lee, S. H., Niznikiewicz, M., Asami, T., Otsuka, T., Salisbury, D. F., Shenton, M. E., & McCarley, R. W. (2016). Initial and progressive gray matter abnormalities in insular gyrus and temporal pole in first-episode schizophrenia contrasted with first-episode affective psychosis. Schizophrenia Bulletin, 42(3), 790801. https://doi.org/10.1093/schbul/sbv177CrossRefGoogle ScholarPubMed
Leweke, F. M., Piomelli, D., Pahlisch, F., Muhl, D., Gerth, C. W., Hoyer, C., … Koethe, D. (2012). Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Translational Psychiatry, 2(3), e94e94. https://doi.org/10.1038/tp.2012.15CrossRefGoogle ScholarPubMed
Li, X. B., Wang, L. B., Xiong, Y. B., Bo, Q. J., He, F., Li, F., … Wang, C. Y. (2019). Altered resting-state functional connectivity of the insula in individuals with clinical high-risk and patients with first-episode schizophrenia. Psychiatry Research, 282, 17. https://doi.org/10.1016/j.psychres.2019.112608.CrossRefGoogle ScholarPubMed
Malla, A., Joober, R., Iyer, S., Norman, R., Schmitz, N., Brown, T., … Abadi, S. (2017). Comparing three-year extension of early intervention service to regular care following two years of early intervention service in first-episode psychosis: A randomized single blind clinical trial. World Psychiatry, 16(3), 278286. https://doi.org/10.1002/WPS.20456CrossRefGoogle ScholarPubMed
McGhiee, A., & Chapman, J. (1961). Disorders of attention and perception in early schizophrenia. British Journal of Medical Psychology, 34(2), 103116. https://doi.org/10.1111/j.2044-8341.1961.tb00936.xCrossRefGoogle Scholar
McGuire, P., Robson, P., Cubala, W. J., Vasile, D., Morrison, P. D., Barron, R., … Wright, S. (2018). Cannabidiol (CBD) as an adjunctive therapy in schizophrenia: A multicenter randomized controlled trial. American Journal of Psychiatry, 175(3), 225231. https://doi.org/10.1176/appi.ajp.2017.17030325CrossRefGoogle ScholarPubMed
Miller, R. (1976). Schizophrenic psychology, associative learning and the role of forebrain dopamine. Medical Hypotheses, 2(5), 203211. https://doi.org/10.1016/0306-9877(76)90040-2CrossRefGoogle ScholarPubMed
Mir, P., Trender-Gerhard, I., Edwards, M. J., Schneider, S. A., Bhatia, K. P., & Jahanshahi, M. (2011). Motivation and movement: The effect of monetary incentive on performance speed. Experimental Brain Research, 209(4), 551559. https://doi.org/10.1007/s00221-011-2583-5CrossRefGoogle ScholarPubMed
Moran, L. V., Tagamets, M. A., Sampath, H., O'Donnell, A., Stein, E. A., Kochunov, P., & Hong, L. E. (2013). Disruption of anterior insula modulation of large-scale brain networks in schizophrenia. Biological Psychiatry, 74(6), 467474. https://doi.org/10.1016/j.biopsych.2013.02.029CrossRefGoogle ScholarPubMed
Nielsen, M. Ø., Rostrup, E., Wulff, S., Bak, N., Broberg, B. V., Lublin, H., … Glenthoj, B. (2012a). Improvement of brain reward abnormalities by antipsychotic monotherapy in schizophrenia. Archives of General Psychiatry, 69(12), 11951204. https://doi.org/10.1001/archgenpsychiatry.2012.847CrossRefGoogle ScholarPubMed
Nielsen, M. Ø., Rostrup, E., Wulff, S., Bak, N., Lublin, H., Kapur, S., & Glenthøj, B. (2012b). Alterations of the brain reward system in antipsychotic nave schizophrenia patients. Biological Psychiatry, 71(10), 898905. https://doi.org/10.1016/j.biopsych.2012.02.007CrossRefGoogle Scholar
Oldham, S., Murawski, C., Fornito, A., Youssef, G., Yücel, M., & Lorenzetti, V. (2018). The anticipation and outcome phases of reward and loss processing: A neuroimaging meta-analysis of the monetary incentive delay task. Human Brain Mapping, 39(8), 33983418. https://doi.org/10.1002/HBM.24184CrossRefGoogle ScholarPubMed
O'Neill, A., Annibale, L., Blest-Hopley, G., Wilson, R., Giampietro, V., & Bhattacharyya, S. (2021a). Cannabidiol modulation of hippocampal glutamate in early psychosis. Journal of Psychopharmacology, 35(7), 814822. https://doi.org/10.1177/02698811211001107CrossRefGoogle ScholarPubMed
O'Neill, A., Mechelli, A., & Bhattacharyya, S. (2019). Dysconnectivity of large-scale functional networks in early psychosis: A meta-analysis. Schizophrenia Bulletin, 45(3), 579590. https://doi.org/10.1093/schbul/sby094CrossRefGoogle ScholarPubMed
O'Neill, A., Wilson, R., Blest-Hopley, G., Annibale, L., Colizzi, M., Brammer, M., … Bhattacharyya, S. (2021b). Normalization of mediotemporal and prefrontal activity, and mediotemporal-striatal connectivity, may underlie antipsychotic effects of cannabidiol in psychosis. Psychological Medicine, 51(4), 596606. https://doi.org/10.1017/S0033291719003519CrossRefGoogle ScholarPubMed
Palaniyappan, L., & Liddle, P. F. (2012). Does the salience network play a cardinal role in psychosis? An emerging hypothesis of insular dysfunction. Journal of Psychiatry and Neuroscience, 37, 1727. https://doi.org/10.1503/jpn.100176CrossRefGoogle Scholar
Palaniyappan, L., Simmonite, M., White, T. P., Liddle, E. B., & Liddle, P. F. (2013). Neural primacy of the salience processing system in schizophrenia. Neuron, 79(4), 814828. https://doi.org/10.1016/j.neuron.2013.06.027CrossRefGoogle ScholarPubMed
Python Software Foundation (2016). Welcome to Python.org. Retrieved January 26, 2021, from https://www.python.org/about/.Google Scholar
Radua, J., Borgwardt, S., Crescini, A., Mataix-Cols, D., Meyer-Lindenberg, A., McGuire, P. K., & Fusar-Poli, P. (2012). Multimodal meta-analysis of structural and functional brain changes in first episode psychosis and the effects of antipsychotic medication. Neuroscience and Biobehavioral Reviews, 36, 23252333. https://doi.org/10.1016/j.neubiorev.2012.07.012CrossRefGoogle ScholarPubMed
Radua, J., Schmidt, A., Borgwardt, S., Heinz, A., Schlagenhauf, F., McGuire, P., & Fusar-Poli, P. (2015). Ventral striatal activation during reward processing in psychosis a neurofunctional meta-analysis. JAMA Psychiatry, 72(12), 12431251. https://doi.org/10.1001/jamapsychiatry.2015.2196CrossRefGoogle ScholarPubMed
Raij, T. T., Mäntylä, T., Mantere, O., Kieseppä, T., & Suvisaari, J. (2016). Cortical salience network activation precedes the development of delusion severity. Psychological Medicine, 46(13), 27412748. https://doi.org/10.1017/S0033291716001057CrossRefGoogle ScholarPubMed
Ranganathan, M., Cortes-Briones, J., Radhakrishnan, R., Thurnauer, H., Planeta, B., Skosnik, P., … D'Souza, D. C. (2016). Reduced brain cannabinoid receptor availability in schizophrenia. Biological Psychiatry, 79(12), 9971005. https://doi.org/10.1016/j.biopsych.2015.08.021CrossRefGoogle ScholarPubMed
Sartim, A. G., Guimarães, F. S., & Joca, S. R. L. (2016). Antidepressant-like effect of cannabidiol injection into the ventral medial prefrontal cortex-possible involvement of 5-HT1A and CB1 receptors. Behavioural Brain Research, 303, 218227. https://doi.org/10.1016/j.bbr.2016.01.033CrossRefGoogle ScholarPubMed
Schmidt, A., Palaniyappan, L., Smieskova, R., Simon, A., Riecher-Rössler, A., Lang, U. E., … Borgwardt, S. J. (2016). Dysfunctional insular connectivity during reward prediction in patients with first-episode psychosis. Journal of Psychiatry & Neuroscience: JPN, 41(6), 367. https://doi.org/10.1503/JPN.150234CrossRefGoogle ScholarPubMed
Seeley, W. W. (2019). The salience network: A neural system for perceiving and responding to homeostatic demands. Journal of Neuroscience, 39(50), 98789882. https://doi.org/10.1523/JNEUROSCI.1138-17.2019CrossRefGoogle ScholarPubMed
Seeley, W. W., Menon, V., Schatzberg, A. F., Keller, J., Glover, G. H., Kenna, H., … Greicius, M. D. (2007). Dissociable intrinsic connectivity networks for salience processing and executive control. Journal of Neuroscience, 27(9), 23492356. https://doi.org/10.1523/JNEUROSCI.5587-06.2007CrossRefGoogle ScholarPubMed
Sheffield, J. M., Huang, A. S., Rogers, B. P., Blackford, J. U., Heckers, S., & Woodward, N. D. (2021). Insula sub-regions across the psychosis spectrum: Morphology and clinical correlates. Translational Psychiatry, 11(1), 113. https://doi.org/10.1038/s41398-021-01461-0CrossRefGoogle ScholarPubMed
Sheffield, J. M., Rogers, B. P., Blackford, J. U., Heckers, S., & Woodward, N. D. (2020). Insula functional connectivity in schizophrenia. Schizophrenia Research, 220, 6977. https://doi.org/10.1016/j.schres.2020.03.068CrossRefGoogle ScholarPubMed
Shepherd, A. M., Matheson, S. L., Laurens, K. R., Carr, V. J., & Green, M. J. (2012). Systematic meta-analysis of insula volume in schizophrenia. Biological Psychiatry, 72(9), 775784. https://doi.org/10.1016/j.biopsych.2012.04.020CrossRefGoogle ScholarPubMed
Smieskova, R., Roiser, J. P., Chaddock, C. A., Schmidt, A., Harrisberger, F., Bendfeldt, K., … Borgwardt, S. (2014). Modulation of motivational salience processing during the early stages of psychosis. Schizophrenia Research, 166(1–3), 1723. https://doi.org/10.1016/j.schres.2015.04.036CrossRefGoogle Scholar
Takahashi, T., Wood, S. J., Soulsby, B., McGorry, P. D., Tanino, R., Suzuki, M., … Pantelis, C. (2009a). Follow-up MRI study of the insular cortex in first-episode psychosis and chronic schizophrenia. Schizophrenia Research, 108(1–3), 4956. https://doi.org/10.1016/j.schres.2008.12.029CrossRefGoogle ScholarPubMed
Takahashi, T., Wood, S. J., Yung, A. R., Phillips, L. J., Soulsby, B., McGorry, P. D., … Pantelis, C. (2009b). Insular cortex gray matter changes in individuals at ultra-high-risk of developing psychosis. Schizophrenia Research, 111(1–3), 94102. https://doi.org/10.1016/j.schres.2009.03.024CrossRefGoogle ScholarPubMed
Thomas, A., Baillie, G. L., Phillips, A. M., Razdan, R. K., Ross, R. A., & Pertwee, R. G. (2007). Cannabidiol displays unexpectedly high potency as an antagonist of CB 1 and CB 2 receptor agonists in vitro. British Journal of Pharmacology, 150(5), 613623. https://doi.org/10.1038/sj.bjp.0707133CrossRefGoogle Scholar
Thusius, N., Romanowicz, M., Mlynek, K., & Sola, C. (2018). Prolonged psychosis associated with left insular stroke: Talking to god in the walls. Psychosomatics, 59(6), 618621. https://doi.org/10.1016/j.psym.2018.03.006CrossRefGoogle ScholarPubMed
Tian, Y., Zalesky, A., Bousman, C., Everall, I., & Pantelis, C. (2019). Insula functional connectivity in schizophrenia: Subregions, gradients, and symptoms. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 4(4), 399408. https://doi.org/10.1016/j.bpsc.2018.12.003Google ScholarPubMed
Tuplin, E. W., & Holahan, M. R. (2017). Aripiprazole, a drug that displays partial agonism and functional selectivity. Current Neuropharmacology, 15(8), 1192. https://doi.org/10.2174/1570159x15666170413115754CrossRefGoogle ScholarPubMed
Uddin, L. Q. (2015). Salience processing and insular cortical function and dysfunction. Nature Reviews Neuroscience, 16, 5561. https://doi.org/10.1038/nrn3857CrossRefGoogle ScholarPubMed
Uddin, L. Q., Nomi, J. S., Hébert-Seropian, B., Ghaziri, J., & Boucher, O. (2017). Structure and function of the human insula. Journal of Clinical Neurophysiology, 34, 300306. https://doi.org/10.1097/WNP.0000000000000377CrossRefGoogle ScholarPubMed
Velayudhan, L., Diepen, E., Marudkar, M., Hands, O., Suribhatla, S., Prettyman, R., … Bhattacharyya, S. (2014). Therapeutic potential of cannabinoids in neurodegenerative disorders: A selective review. Current Pharmaceutical Design, 20(13), 22182230. https://doi.org/10.2174/13816128113199990434CrossRefGoogle ScholarPubMed
Velayudhan, L., McGoohan, K., & Bhattacharyya, S. (2021). Safety and tolerability of natural and synthetic cannabinoids in adults aged over 50 years: A systematic review and meta-analysis. PLoS Medicine, 18, 142. https://doi.org/10.1371/JOURNAL.PMED.1003524CrossRefGoogle Scholar
Walter, A., Suenderhauf, C., Smieskova, R., Lenz, C., Harrisberger, F., Schmidt, A., … Borgwardt, S. (2016). Altered insular function during aberrant salience processing in relation to the severity of psychotic symptoms. Frontiers in Psychiatry, 7(NOV), 110. https://doi.org/10.3389/fpsyt.2016.00189CrossRefGoogle Scholar
Wang, C., Ji, F., Hong, Z., Poh, J. S., Krishnan, R., Lee, J., … Zhou, J. (2016). Disrupted salience network functional connectivity and white-matter microstructure in persons at risk for psychosis: Findings from the LYRIKS study. Psychological Medicine, 46(13), 27712783. https://doi.org/10.1017/S0033291716001410CrossRefGoogle ScholarPubMed
Wilson, R., Bossong, M. G., Appiah-Kusi, E., Petros, N., Brammer, M., Perez, J., … Bhattacharyya, S. (2019). Cannabidiol attenuates insular dysfunction during motivational salience processing in subjects at clinical high risk for psychosis. Translational Psychiatry, 9(1), 203. https://doi.org/10.1038/s41398-019-0534-2CrossRefGoogle ScholarPubMed
Wilson, R., Colizzi, M., Bossong, M. G., Allen, P., Kempton, M., Abe, N., … Bhattacharyya, S. (2018). The neural substrate of reward anticipation in health: A meta-analysis of fMRI findings in the monetary incentive delay task. Neuropsychology Review, 28(4), 496506. https://doi.org/10.1007/s11065-018-9385-5CrossRefGoogle ScholarPubMed
Wotruba, D., Michels, L., Buechler, R., Metzler, S., Theodoridou, A., Gerstenberg, M., … Heekeren, K. (2014). Aberrant coupling within and across the default mode, task-positive, and salience network in subjects at risk for psychosis. Schizophrenia Bulletin, 40(5), 10951104. https://doi.org/10.1093/schbul/sbt161CrossRefGoogle ScholarPubMed
Wylie, K. P., & Tregellas, J. R. (2010). The role of the insula in schizophrenia. Schizophrenia Research, 123, 93104. https://doi.org/10.1016/j.schres.2010.08.027CrossRefGoogle ScholarPubMed
Supplementary material: Image

Gunasekera et al. supplementary material

Gunasekera et al. supplementary material 1

Download Gunasekera et al. supplementary material(Image)
Image 57.1 KB
Supplementary material: File

Gunasekera et al. supplementary material

Gunasekera et al. supplementary material 2

Download Gunasekera et al. supplementary material(File)
File 41.4 KB