Reduced lateral orbitofrontal cortex volume and suicide behavior in youth with bipolar disorder

Abstract

Suicide in individuals with bipolar disorder (BD) is a significant concern, as 15%-20% of patients with BD die by suicide and up to 50% report at least one suicide attempt during their lifetime. 1 Suicidal behavior often emerges during adolescence in BD, and has varying degrees of severity which may include ideation, planning, or attempts. 2 Suicidal behavior frequently begins with the development Objectives: Structural abnormalities in cortical and subcortical regions, including the orbitofrontal cortex (OFC), are altered during brain development in adolescents with bipolar disorder (BD), which may increase risk for suicide. Few studies have examined the neural substrates of suicidal behavior in BD youth. The aim of the present study was to investigate the relationship between suicide behavior and the OFC in youth with BD.Methods: Thirty-seven participants with BD and 26 non-psychiatric controls, ages 13-21 years, completed a diagnostic interview and mood rating scales. Lifetime symptoms of suicide ideation and behavior were examined using the Columbia Suicide Severity Rating Scale. Participants underwent magnetic resonance imaging on a 3T Siemens Verio scanner. Morphometric analysis of brain images was performed using FreeSurfer.Results: Eighteen participants with BD had a history of suicide attempt (SA). Bipolar youth with a history of SA showed reduced left lateral OFC volumes compared to controls, but there was no difference between BD attempters and non-attempters.Controls and BD non-attempters had significantly greater OFC cortical thickness than BD attempters. Additionally, there was a significant negative correlation between OFC volumes and suicide lethality, demonstrating that as suicide lethality increased, OFC volume in BD youth was reduced. Conclusions:The OFC is involved in decision-making, impulsivity, and reward circuitry which have shown to be impaired in BD. Reduced OFC volume and its association with lethality of suicide suggest that suicide behavior in BD may be related to the emerging neuroanatomical substrates of the disorder, particularly abnormalities of the OFC. K E Y W O R D S bipolar disorder, cortical thickness, orbitofrontal cortex, suicide attempt, suicide lethality, youth

<p><em>CACNA1C</em> Risk Variant and Mood Stabilizers Effects in the Prefrontal Cortical Thickness of Mexican Patients with Bipolar Disorder</p>

“…In BD patients, the CT of the orbitofrontal cortex is associated with executive functions 40 and suicide attempts. 38 Hence, the conservation of the analyzed region is crucial for patient's clinical outcomes. The findings in our study contribute to a better understanding of the effect of CACNA1C risk allele rs1006737 and mood stabilizers over the structure of PFC.…”

“…The orbitofrontal cortex is implicated in decision making and impulsivity, 4 in BD patients orbitofrontal CT is related to executive functioning 40 and cortical thinning of this area was associated with suicide attempts in young subjects. 38 In light of the previously mentioned, the preservation of the orbitofrontal cortex may play a role in lithium effects on suicidal behavior. 39 The findings that we present regarding a lithiumrelated cortical thickening are in agreement with previous works on the effects of lithium and valproate in GM.…”

Gray matter volume alterations associated with suicidal ideation and suicide attempts in patients with mood disorders

“…However, a previous study showed that GMVs in the DLPFC and orbitofrontal cortex (OFC) in patients with MDD with higher-lethality SAs were larger than those in patients with MDD with lower-lethality SAs and non-SAs [17]. For BD patients, the GMVs in the OFC, hippocampus, and cerebellum were reduced in the suicide attempters group when compared with the non-suicide attempters group [18,19]. Prefrontal cortex gray matter volume was lower in patients with than without SAs in patients with BD and past psychiatric hospitalization, and prefrontal cortex gray matter volume was higher in patients with than without SAs in those BD cases without hospitalization [20].…”

Discriminating Suicide Attempters and Predicting Suicide Risk Using Altered Frontolimbic Resting-State Functional Connectivity in Patients With Bipolar II Disorder

“…Patients with damages in the OFC and amygdala often exhibit impulsive patterns of behavior (46). Previous MRI studies have confirmed abnormal structural changes, including decreased OFC volume and increased amygdala volume in SA patients (35,48). Also, decreased white matter volume in the OFC in bipolar disorder patients with suicidality (49) and lower anisotropy between the left orbitofrontal area and the left anterior-limbic system have been reported.…”