Toward the Application of Functional Neuroimaging to Individualized Treatment for Anxiety and Depression

Abstract

Functional neuroimaging has led to significant gains in understanding the biological bases of anxiety and depressive disorders. However, the ability of functional neuroimaging to directly impact clinical practice is unclear. One important method by which neuroimaging could impact clinical care is to generate single patient level predictions that can guide clinical decision-making. The present review summarizes published functional neuroimaging studies of predictors of medication or psychotherapy outcome in major depressive disorder, obsessive-compulsive disorder (OCD), posttraumatic stress disorder, generalized anxiety disorder, panic disorder, and social anxiety disorder. In major depressive disorder and OCD, there is converging evidence of specific brain circuitry that has both been implicated in the disordered state itself, and where pretreatment activation levels have been predictive of treatment response. Specifically, in major depressive disorder, greater pretreatment ventral and pregenual anterior cingulate cortex (ACC) activation may predict better antidepressant medication outcome but poorer psychotherapy outcome. In OCD, activation in the ACC and orbitofrontal cortex has been inversely associated with pharmacological treatment response. In other anxiety disorders, research in this area is just beginning, with the ACC potentially implicated. However, the question of whether these results can directly translate to clinical practice remains open. In order to achieve the goal of single patient level prediction and individualized treatment, future research should strive to establish replicable models with good predictive performance and clear incremental validity.

Prefrontal Reactivity to Social Signals of Threat as a Predictor of Treatment Response in Anxious Youth

“…Although anxious youths exhibit heightened amygdala reactivity to threat (Killgore and Yurgelun-Todd, 2005;McClure et al, 2007b;Thomas et al, 2001), and one previous study demonstrated that greater amygdala predicted better treatment response in a small sample of anxious youth (McClure et al, 2007a), we did not find evidence that amygdala activation predicted treatment response. Prior studies using data-driven approaches have also failed to find amygdala activation as a significant predictor of response to treatment (Ball et al, 2014a), suggesting that pathophysiology, as reflected by abnormal patterns of brain reactivity, may not necessarily serve as predictors of treatment response.…”

“…For example, anterior cingulate cortex (ACC) reactivity measured by functional magnetic resonance imaging (fMRI) has been shown to predict responses to pharmacological and psychotherapy treatment in depression (Ball et al, 2014a;Fu et al, 2013). In contrast, the existing literature on predictors of response to treatment in anxiety disorders is much smaller (Ball et al, 2014a).…”

Basolateral amygdala–ventromedial prefrontal cortex connectivity predicts cognitive behavioural therapy outcome in adults with obsessive–compulsive disorder

“…Functional neuroimaging measures may help achieve this goal. 1 For example, greater activity at baseline in the anterior insula or anterior cingulate cortex (ACC), measured with 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET), has been associated with a positive outcome from antidepressant medication in patients with major depressive disorder. 2,3 In the present study we tested whether resting-state functional connectivity (rs-fc) between the basolateral amygdala (BLA) and ventromedial prefrontal cortex (vmPFC) could predict outcome from cognitive behavioural therapy (CBT) in patients with obsessive-compulsive disorder (OCD).…”

“…4 There have been several attempts to correlate functional neuro imaging measures and CBT outcomes in patients with OCD. 1,5 Initial studies focused on cortico-striato-thalamo-cortical regions believed to be involved in the pathophysiology of OCD, such as the orbitofrontal cortex (OFC). Indeed, findings from studies using FDG-PET or single-photon emission computed tomography (SPECT) suggest that greater baseline OFC activity in patients with OCD is associated with a positive outcome from CBT.…”

“…However, findings from functional MRI (fMRI) studies do not consistently show that pretreatment frontal or striatal activation is associated with CBT outcome. 1 Newer conceptualizations emphasize the contribution of the amygdala and vmPFC in OCD pathophysiology and treatment. 6 Both regions are involved in fear processing and regulation, and both play a role in extinction learning, a likely mech anism of action in CBT for fearrelated disorders, including OCD.…”