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A putative right anterior insula metabolism biomarker predictive of treatment outcomes was retrospectively applied to 30 depressed psychotherapy--or escitalopram-treated nonremitters who entered combination treatment. Patients whose added treatment matched the biomarker-indicated treatment remitted more often than biomarker-mismatched patients.

Major depressive disorder is one of the most common psychiatric disorders, with a worldwide lifetime prevalence rate of 10%-20% in women and a slightly lower rate in men. While many patients are successfully treated using established therapeutic strategies, a significant percentage of patients fail to respond. This report describes the successful recovery of a previously treatment-resistant patient following right unilateral deep brain stimulation of Brodmann's area 25. Current therapeutic approaches to treatment-resistant patients are reviewed in the context of this case with an emphasis on the role of the right and left hemispheres in mediating disease pathogenesis and clinical recovery.

A working model of depression implicating failure of the coordinated interactions of a distributed network of limbic-cortical pathways is proposed. Resting state patterns of regional glucose metabolism in idiopathic depressed patients, changes in metabolism with antidepressant treatment, and blood flow changes with induced sadness in healthy subjects were used to test and refine this hypothesis. Dorsal neocortical decreases and ventral paralimbic increases characterize both healthy sadness and depressive illness; concurrent inhibition of overactive paralimbic regions and normalization of hypofunctioning dorsal cortical sites characterize disease remission. Normal functioning of the rostral anterior cingulate, with its direct connections to these dorsal and ventral areas, is postulated to be additionally required for the observed reciprocal compensatory changes, since pretreatment metabolism in this region uniquely predicts antidepressant treatment response. This model is offered as an adaptable framework to facilitate continued integration of clinical imaging findings with complementary neuroanatomical, neurochemical, and electrophysiological studies in the investigation of the pathogenesis of affective disorders.

Depression is common in patients with neurological disease, particularly with diseases involving the basal ganglia. Although the mechanisms of mood disorders in these patients are poorly understood, selective neural pathways affected directly and indirectly by basal ganglia injury provide a strategy for examining these patients with functional imaging techniques. Studies of regional cerebral glucose metabolism by use of positron-emission tomography are reviewed. These studies demonstrate bilateral hypometabolism of orbital-inferior prefrontal cortex and anterior temporal cortex in depressed subjects, independent of disease etiology. This pattern is similar to that seen in patients with primary unipolar depression. These findings suggest that disruption of paralimbic pathways linking frontal cortex, temporal cortex, and striatum may contribute to both primary depression and depression associated with basal ganglia disease. The findings support the evolving concept of a neuroanatomical locus for mood regulation.

Cortical serotonin receptor binding was measured with positron-emission tomography (PET) in uninjured regions of cortex in 26 stroke patients. Cognitive function was assessed with the Mini-Mental State Exam (MMSE) and a neuropsychological test battery. Left frontal cortex serotonin binding was correlated positively with MMSE total score (r = 0.50, P = 0.01) and with the MMSE concentration, writing, and copying tasks (r = 0.42, 0.56, 0.53, respectively; P < 0.05). Tests of orientation and repetition of difficult phrases were significantly correlated with serotonin binding (r = 0.53 and 0.52, respectively; P < 0.05). These findings suggest that cognitive performance after stroke may be influenced by alterations in the serotonergic system.

The authors examined a consecutive series of 50 patients for the presence of apathy, depression, anxiety, and neuropsychological deficits using a neuropsychological battery that included a recently designed apathy scale. This scale was found to be reliable and valid in the diagnosis of apathy in patients with PD. Of patients in the study, 12% showed apathy as their primary psychiatric problem, and 30% were both apathetic and depressed. Patients with apathy (with or without depression), showed significantly more deficits in both tasks of verbal memory and time-dependent tasks. Results suggest that apathy is a frequent finding in PD, is significantly associated with specific cognitive impairments, and may have a different mechanism than depression.

A patient with post-stroke depression following infarction of the left basal ganglia is described. The patient's depression remitted during a 6-week double-blind treatment trial while receiving placebo medication. Cortical S2-receptor binding that was measured using 11C-N methyl spiperone and positron emission tomography (PET), increased in the left temporal cortex by more than 25% during the treatment trial. The change in serotonin receptor binding and its relationship to the improvement in mood observed in this patient are consistent with previously published data demonstrating a correlation between serotonin receptor binding in the left temporal cortex and severity of symptoms of depression.