The relation of worry to prefrontal cortex volume in older adults with and without generalized anxiety disorder

Abstract

Despite the widespread prevalence of generalized anxiety disorder (GAD) in later life, almost nothing is known about the neural aspects of worry in adults over the age of 60. Given the ongoing rapid increase in the older adult population, the relatively poor response rates to current interventions for late life GAD, and the effects of age-related changes to the brain, additional research on worry neurobiology is needed. The study group comprised 15 older GAD patients and 15 matched controls who were compared on clinical measures and brain volumes. It was expected that prefrontal cortex (PFC) volumes [medial orbital cortex (mOFC), dorsolateral cortex (DLPFC)] would show positive relations to worry scores, and weaker relations to more general measures of anxiety and depression. Negative relations were expected between amygdala volumes and worry scores. As expected, mOFC volumes were positively related to worry scores; however, DLPFC and amygdala volumes were not. The mOFC is involved in emotional decision-making under uncertain conditions and has the ability to suppress the amygdala, both of which are hypothesized functions of worry. Results are partly consistent with GAD theory and suggest that worry may involve neural areas that are also involved in the successful control of anxiety.

Brain structural changes in late-life generalized anxiety disorder

“…Although the results did not survive multiple comparison correction, the effect sizes suggest a large effect regarding decreased cortical thickness in the OFC, rostral ACC and inferior frontal gyrus in late-life GAD. Some of our results confirm previous reports regarding the role of OFC in late-life GAD (Mohlman et al, 2009). The results also indicate a moderate effect of worry severity, although these results also did not survive FDR correction.…”

“…The second peak of GAD incidence later in life may be related to the age-related reconfiguration of the structural and functional architecture of the brain (Andrews-Hanna et al, 2007). Late-life GAD is relatively understudied, and in particular, the underlying structural and functional neuroanatomy has received little attention (Andreescu et al, 2011; Mohlman et al, 2009). …”

“…The only published study that explored the structural neuroanatomy of late-life GAD described a positive correlation between orbitofrontal cortex volume (OFC) correlated and worry severity, a finding pointing toward the role of OFC in emotional decision-making under uncertain conditions (Mohlman et al, 2009). …”

Emotion Reactivity and Cerebrovascular Burden in Late-Life GAD: A Neuroimaging Study

“…Late-life GAD is relatively understudied, and the underlying structural and functional neuroanatomy has received little attention (9, 10). This is a particularly unfortunate gap in our knowledge given the mediocre treatment response in late-life GAD (8), (11, 12) .…”

Experiencing, Psychopathology, and the Tripartite Mind

“…Hyperactivity in the dmPFC has also recently been associated with anxiety arising from a sense of social threat [98]. Finally, it has been found that there is a positive association between left mOFC volume and worry scores in a cohort of older adults with Generalized Anxiety Disorder (GAD) [99], supporting a model of GAD as rooted in maladaptive, frontal over-control of limbic activity. In GAD, this may occur largely through the use of worry, putatively associated with medial OFC activity, as a maladaptive means of down-regulating the CNA (via the BLA).…”