Frontal Pole Abnormalities and Increased Suicidality in Medication-Naive Young Adults

While suicide rates among young people continue to rise, we do not yet have validated strategies for reliably identifying those at greatest risk for suicide. Given that neuroimaging and autopsy studies have revealed structural abnormalities in the brains of individuals experiencing suicidal thoughts and behaviors, researchers have speculated that neuroimaging techniques may be able to identify those at high risk for suicide.

More specifically, abnormalities in the medial prefrontal cortex (mPFC) have been observed in suicidal individuals; however, it is difficult to determine if these structural differences reflect vulnerability to suicide, or if these structural abnormalities are the downstream effects of confounding factors, such as treatment with antidepressants and/or exposure to recurrent or chronic psychiatric illness.  In a recent study, Gwang-Won Kim, PhD, Daphne Holt MD, PhD and colleagues from the A. A. Martinos Center for Biomedical Imaging and the Depression Clinical and Research Program at Mass General examined suicidality and the size and connectivity of the medial prefrontal cortex in a group of young adults who have received no treatment with psychotropic medications.

Decreased Frontal Pole Size and Connectivity in Individuals with High Suicidality

For this study, a cohort of college students (n = 102) was recruited from a survey-based study of depression and other psychological symptoms conducted at four Boston-area universities.  The participants enrolled in the current study had no history of neurological or psychiatric disorders (mean age 19.6 ± 1.3; 74 female, 28 male).  Suicidality was evaluated using the Suicide Behaviors Questionnaire-Revised (SBQ-R).  Magnetic resonance imaging (MRI) focused on four regions of interest within the medial prefrontal cortex: the superior frontal cortex, frontal pole, anterior cingulate cortex, and medial orbitofrontal cortex. 

Comparing individuals with high suicidality (HS; SBQ-R score > 7; n = 20) to those with low suicidality (LS; SBQ-R score = 3, n = 37), they observed that the high suicidality group had a significantly lower surface area of the right frontal pole (p < 0.05) than individuals with low suicidality.  In the female (but not the male) participants, they observed that right frontal pole surface area decreased as suicidality (SBQ-R scores) increased.

In addition, the researchers also examined functional connectivity of the medial prefrontal cortex using resting-state functional MRI data.  The group reporting high suicidality had significantly lower functional connectivity of the right frontal pole with the bilateral inferior frontal cortex (p < 0.001).

Can Neuroimaging Be Used to Identify Individuals at High Risk for Suicide?

While abnormalities of the mPFC have been observed in suicidal individuals in prior studies, these earlier studies typically have included patients with high levels of psychiatric comorbidity who are undergoing treatment, often with multiple medications.  This study is unique in that it examines a group of medication-free young adults, indicating that a smaller right frontal pole and reduced functional connectivity of the right frontal pole with the bilateral inferior frontal cortex may be linked to elevated levels of suicidality.

The authors speculate that decreased frontal pole size may be associated with impairments in higher-order cognitive functions, such as decision-making and response inhibition, imagining future events, and emotional regulation, all of which are risk factors for suicidal behaviors.  Previous studies have reported structural and functional abnormalities in the frontal pole of suicidal patients with MDD, bipolar disorder, and schizophrenia, suggesting that frontal pole abnormalities, cognitive impairment and suicidality may be linked and present across different psychiatric disorders. Furthermore, the current study provides evidence that frontal pole abnormalities are likely present early in the trajectory of illness.  

Being able to identify changes in brain structure or function that are associated with suicidal behavior before the emergence of significant psychiatric symptoms may be particularly useful for future clinical applications.  Such findings could be used to generate quantitative algorithms predicting suicidal behavior in adolescents and young adults.  

Kim GW, Farabaugh AH, Vetterman R, Holmes A, Nyer M, Nasiriavanaki Z, Fava M, Holt DJ. Diminished frontal pole size and functional connectivity in young adults with high suicidality. J Affect Disord. 2022 Aug 1; 310:484-492.