Resting-state neural mechanisms of capability for suicide and their interaction with pain - A CAN-BIND-05 Study.

BACKGROUND

Suicidal ideation is highly prevalent in Major Depressive Disorder (MDD). However, the factors determining who will transition from ideation to attempt are not established. Emerging research points to suicide capability (SC), which reflects fearlessness of death and increased pain tolerance, as a construct mediating this transition. This Canadian Biomarker Integration Network in Depression study (CANBIND-5) aimed to identify the neural basis of SC and its interaction with pain as a marker of suicide attempt.

METHODS

MDD patients (n = 20) with suicide risk and healthy controls (n = 21) completed a self-report SC scale and a cold pressor task measuring pain threshold, tolerance, endurance, and intensity at threshold and tolerance. All participants underwent a resting-state brain scan and functional connectivity was examined for 4 regions: anterior insula (aIC), posterior insula (pIC), anterior mid-cingulate cortex (aMCC) and subgenual anterior cingulate cortex (sgACC).

RESULTS

In MDD, SC correlated positively with pain endurance and negatively with threshold intensity. Furthermore, SC correlated with the connectivity of aIC to the supramarginal gyrus, pIC to the paracingulate gyrus, aMCC to the paracingulate gyrus, and sgACC to the dorsolateral prefrontal cortex. These correlations were stronger in MDD compared to controls. Only threshold intensity mediated the correlation between SC and connectivity strength.

LIMITATIONS

Resting-state scans provided an indirect assessment of SC and the pain network.

CONCLUSIONS

These findings highlight point to a neural network underlying SC that is associated with pain processing. This supports the potential clinical utility of pain response measurement as a method to investigate markers of suicide risk.

Informations de copyright

Copyright © 2023 Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of interest Dr. Sidney H. Kennedy has received research funding or honoraria from Abbott, Alkermes, Allergan, Boehringer Ingelheim, Brain Canada, Canadian Institutes for Health Research (CIHR), Janssen, Lundbeck, Lundbeck Institute, Ontario Brain Institute, Ontario Research Fund (ORF), Otsuka, Pfizer, Servier, Sunovion and Xian-Janssen. He also has received stock options from Field Trip Health. Over the past 3 years, Dr. Shane J. McInerney has received research funding from The National Office of Suicide Prevention (NOSP) in Ireland. Over the past 3 years, Dr. Diego A. Pizzagalli has received consulting fees from BlackThorn Therapeutics, Boehringer Ingelheim, Compass Pathway, Concert Pharmaceuticals, Engrail Therapeutics, Neurocrine Biosciences, Neuroscience Software, Otsuka Pharmaceuticals, and Takeda Pharmaceuticals; one honorarium from Alkermes, and research funding from NIMH, Dana Foundation, Brain and Behavior Research Foundation, Millennium Pharmaceuticals. In addition, he has received stock options from BlackThorn Therapeutics and Compass Pathways. All views expressed are solely those of the authors. All other authors report no financial relationships with commercial interest. DAP was also partially supported by R37 2R37MH068376 and P50 MH119467 from the National Institute of Mental Health. Dr. Mark Sinyor receives funding through Academic Scholar Awards from the Departments of Psychiatry at Sunnybrook Health Sciences Centre and the University of Toronto. Dr. Sakina J. Rizvi has received research funding or honoraria from Pfizer Canada, Quintiles, Janssen, Neurocrine Inc., Allergan, and Takeda. Ms. Shijing Wang, Ms. Amanda K. Ceniti, Dr. Yvonne Bergmans, Dr. Tim V. Salomons, Dr. Gustavo Turecki, Dr. Norman Farb, Dr. Nathan Churchill, and Dr. Tom A. Schweizer declare no conflict of interest.