Depression is an important public health problem affecting about 15% of the general population; however, little is known about possible changes in the brain that might underlie the disorder. Neuroimaging has been a powerful tool to map actual changes in the brain structure of depressed patients that might be directly related to their symptoms of depression. Some imaging studies of brain structure have shown smaller hippocampal volume with the chronicity of depression correlating to a reduction in volume. Although the meaning of these findings is unclear, other studies have shown increased amygdala volume. Studies have found reductions in volume of the frontal cortex, with some studies showing specific reductions in subregions of the frontal cortex, including the orbitofrontal cortex. Findings of an increase in white matter lesions in elderly patients with depression have been replicated and correlated with late-onset depression, as well as impairments in social and cognitive function. These findings point to alterations in a circuit of brain regions hypothesized to include the frontal cortex, hippocampus, amygdala, striatum, and thalamus, that underlie symptoms of depression.

Depression and reduced heart rate variability (HRV) are predictors of coronary artery disease (CAD), and highly correlated with each other. However, little is known to what extend this correlation can be explained by common genetic components. We examined 198 middle-aged male twins (121 monozygotic and 77 dizygotic) from the Vietnam Era Twin Registry. Current depressive symptoms were assessed using the Beck Depression Inventory-II and HRV was assessed on 24-hour electrocardiographic Holter recordings. Five frequency domain variables were used, including ultra low frequency (ULF), very low frequency (VLF), low frequency (LF), high frequency (HF) and total power (TPow). Structural equation modeling was used to estimate shared genetic effects for depressive symptoms and the HRV frequency domains. Both depressive symptoms (h2=.5) and all measurements of HRV showed high heritability (h2=.43-.63). A significant inverse correlation was found between depressive symptoms and all HRV indices except LF and HF, with the highest coefficient (r) for TPow (r = −.24, P = .01) and ULF (r = −.24, P = .01). Bivariate genetic modeling revealed significant genetic correlations between depressive symptoms and TPow (rA = −.21, P = .04), as well as ULF (rA = −.23, P = .02). Of the total covariance between depressive symptoms and these two HRV indices, over 80% was due to the same genetic factors. In conclusion, depressive symptoms are associated with decreased HRV and this association is due, in large part, to a shared genetic effect. These results suggest that a common neurobiological dysfunction links depression and autonomic dysregulation.

Background. In the conditioned fear paradigm, repeated pairing of an aversive unconditioned stimulus (US) (e.g. electric shock) with a neutral conditioned stimulus (CS) (e.g. bright light) results in a conditioned fear response to the light alone. Animal studies have shown that the amygdala plays a critical role in acquisition of conditioned fear responses, while the medial prefrontal cortex (including anterior cingulate), through inhibition of amygdala responsiveness, has been hypothesized to play a role in extinction of fear responses. No studies have examined neural correlates of fear conditioning and extinction in patients with post-traumatic stress disorder (PTSD).

Method. Women with early childhood sexual-abuse-related PTSD (n=8) and women without abuse or PTSD (n=11) underwent measurement of psychophysiological (skin conductance) responding as well as positron emission tomographic (PET) measurement of cerebral blood flow during habituation, acquisition and extinction conditions. During habituation subjects were repeatedly exposed to a blue square on a screen. During acquisition, exposure to the blue square (CS) was paired with an electric shock to the forearm (US). With extinction, subjects were again exposed to the blue squares without shock. On a different day subjects went through the same procedure with electric shocks administered randomly in the absence of the blue square.

Results. Skin conductance responding to the CS was consistent with the development of conditioned responses with this paradigm. PTSD patients had increased left amygdala activation with fear acquisition, and decreased anterior cingulate function during extinction, relative to controls.

Conclusions. These findings implicate amygdala and anterior cingulate in the acquisition and extinction of fear responses, respectively, in PTSD.

Childhood abuse is an important public health problem; however, little is known about the effects of abuse on the brain and neurobiological development. This article reviews the behavioral and biological consequences of childhood abuse and places them in a developmental context. Animal studies show that both positive and negative events early in life can influence neurobiological development in unique ways. Early stressors such as maternal separation result in lasting effects on stress-responsive neurobiological systems, including the hypothalamic–pituitary–adrenal (HPA) axis and noradrenergic systems. These studies also implicate a brain area involved in learning and memory, the hippocampus, in the long-term consequences of early stress. Clinical studies of patients with a history of abuse also implicate dysfunction in the HPA axis and the noradrenergic and hippocampal systems; however, there are multiple questions related to chronicity of stress, developmental epoch at the time of the stressor, presence of stress-related psychiatric disorders including posttraumatic stress disorder and depression, and psychological factors mediating the response to trauma that need to be addressed in this field of research. Understanding the effects of abuse on the development of the brain and neurobiology will nevertheless have important treatment and policy implications.

Studies in animals showing hippocampal atrophy and associated memory deficits in stress and aging have implications for stress and aging in humans. Clinical studies in traumatized human populations with posttraumatic stress disorder (PTSD) have replicated studies in animals, showing reduction in volume of the hippocampus measured with magnetic resonance imaging and associated memory deficits. Trauma at different stages of development (early childhood abuse versus trauma in later life due to combat) may influence the nature of memory deficits and hippocampal atrophy. Studies in aging human subjects are consistent with animal studies, although future research is needed in this area. The similarities between biological findings related to cortisol and the hippocampus in stress and aging in both animal and human studies raises the question of whether PTSD can be seen as a form of accelerated aging. Evidence that stress affects the hippocampus and the capacity for learning has broad implications for public health policy, underlying the need for additional resources in this important area and a reexamination of our understanding of factors influencing academic achievement.