Faculty Bibliography

BACKGROUND: The goal of this study was to investigate the co-occurrence of depressive disorders in obsessive-compulsive disorder (OCD) and the effect of these disorders on combined pharmacologic and behavioral treatment for OCD. METHOD: A retrospective chart analysis was performed on baseline ratings of 120 OCD patients and posttreatment ratings of 72 of these patients. For depressive symptoms, the Montgomery-Asberg Depression Rating Scale and the Self-Rating Depression Scale were applied; for obsessive-compulsive symptoms, the Yale-Brown Obsessive Compulsive Scale and the Maudsley Obsessive Compulsive Inventory were used; and for general anxiety symptoms, the Self-Rating Anxiety Scale, the Clinical Anxiety Scale, and the State-Trait Anxiety Inventory were given. RESULTS: One third of the OCD patients in our sample were found to be depressed. Symptom severity on OCD symptoms at baseline did not differ between depressed and nondepressed OCD patients; on general anxiety symptoms, the comorbid group was more severely affected. Both depressed and nondepressed OCD patients responded well to treatment, as reflected in assessments for depressive, obsessive-compulsive, and general anxiety symptoms. However, comorbid depression had a negative effect on treatment: depressed OCD patients showed less improvement than nondepressed OCD patients on most scales. CONCLUSION: Depression frequently accompanies OCD and appears to affect treatment outcome negatively. While both groups of patients improved with combination treatment, the OCD-alone group had more improvement than the group that had comorbid depression.

BACKGROUND: Functional neuroimaging studies have implicated dysfunction of orbitofrontal cortex in the symptoms of depression, and a recent postmortem study of depressed patients found reduced density of neurons and glia in this area. The purpose of this study was to measure volume of orbitofrontal cortex and other frontal cortical subregions in patients with major depression. METHODS: Magnetic resonance imaging was used to measure volume of the orbitofrontal cortex and other frontal cortical regions in patients with major depression in remission (n = 15) and comparison subjects (n = 20). RESULTS: Patients with depression had a statistically significant 32% smaller medial orbitofrontal (gyrus rectus) cortical volume, without smaller volumes of other frontal regions including anterior cingulate Brodmann's area 24 (subgenual gyrus), anterior cingulate Brodmann's area 32, subcallosal gyrus (Brodmann's area 25), or whole brain volume. The findings were significant after statistically controlling for brain size. CONCLUSIONS: These findings are consistent with smaller orbitofrontal cortical volume in depression.

This paper follows the preclinical work on the effects of stress on neurobiological and neuroendocrine systems and provides a comprehensive working model for understanding the pathophysiology of posttraumatic stress disorder (PTSD). Studies of the neurobiology of PTSD in clinical populations are reviewed. Specific brain areas that play an important role in a variety of types of memory are also preferentially affected by stress, including hippocampus, amygdala, medial prefrontal cortex, and cingulate. This review indicates the involvement of these brain systems in the stress response, and in learning and memory. Affected systems in the neural circuitry of PTSD are reviewed (hypothalamic-pituitary-adrenal axis (HPA-axis), catecholaminergic and serotonergic systems, endogenous benzodiazepines, neuropeptides, hypothalamic-pituitary-thyroid axis (HPT-axis), and neuro-immunological alterations) as well as changes found with structural and functional neuroimaging methods. Converging evidence has emphasized the role of early-life trauma in the development of PTSD and other trauma-related disorders. Current and new targets for systems that play a role in the neural circuitry of PTSD are discussed. This material provides a basis for understanding the psychopathology of stress-related disorders, in particular PTSD.

This paper reviews the preclinical literature related to the effects of stress on neurobiological and neuroendocrine systems. Preclinical studies of stress provide a comprehensive model for understanding neurobiological alterations in post-traumatic stress disorder (PTSD). The pathophysiology of stress reflects long-standing changes in biological stress response systems and in systems involved in stress responsivity, learning, and memory. The neural circuitry involved includes systems mediating hypothalamic-pituitary-adrenal (HPA) axis, norepinephrine (locus coeruleus), and benzodiazepine, serotonergic, dopaminergic, neuropeptide, and central amino acid systems. These systems interact with brain structures involved in memory, including hippocampus, amygdala, and prefrontal cortex. Stress responses are of vital importance in living organisms; however excessive and/or repeated stress can lead to long-lasting alterations in these circuits and systems involved in stress responsiveness. Intensity and duration of the stressor, and timing of the stressor in life, have strong impact in this respect.