Preliminary evidence for medication effects on functional abnormalities in the amygdala and anterior cingulate in bipolar disorder.

RATIONALE: Abnormal amygdala and frontocortical responses to emotional stimuli are implicated in bipolar disorder (BD) and have been proposed as potential treatment targets. OBJECTIVES: The aim of this study was to investigate amygdala and frontocortical responses to emotional face stimuli in BD and the influences of mood-stabilizing medications on these responses. METHODS: Functional magnetic resonance imaging was performed while 17 BD participants (5 unmedicated) and 17 healthy comparison (HC) participants viewed faces with happy, sad, fearful, or neutral expressions. RESULTS: The group by stimulus-condition interaction was significant (p<0.01) for amygdala activation, with the greatest effects in the happy face condition. Relative to HC, amygdala increases were greater in unmedicated BD, but lower in medicated BD. Rostral anterior cingulate (rAC) activation was decreased in unmedicated BD compared to HC; however, BD participants taking medication demonstrated rAC activation similar to HC participants. CONCLUSIONS: Although the sample sizes were small, these preliminary results suggest that BD is associated with increased amygdala and decreased rAC response to emotional faces. The findings also provide preliminary evidence that mood-stabilizing medications may reverse abnormalities in BD in the response of an amygdala-frontal neural system to emotional stimuli.

Amygdala hyperreactivity in borderline personality disorder: implications for emotional dysregulation.

BACKGROUND: Disturbed interpersonal relations and emotional dysregulation are fundamental aspects of borderline personality disorder (BPD). The amygdala plays important roles in modulating vigilance and generating negative emotional states and is often abnormally reactive in disorders of mood and emotion. The aim of this study was to assess amygdala reactivity in BPD patients relative to normal control subjects. We hypothesized that amygdala hyperreactivity contributes to hypervigilance, emotional dysregulation, and disturbed interpersonal relations in BPD. METHODS: Using functional magnetic resonance imaging, we examined neural responses to 20-sec blocks of neutral, happy, sad, and fearful facial expression (or a fixation point) in 15 BPD and 15 normal control subjects. The DSM IV-diagnosed BPD patients and the normal control subjects were assessed by a clinical research team in a medical school psychiatry department. RESULTS: Borderline patients showed significantly greater left amygdala activation to the facial expressions of emotion (vs. a fixation point) compared with normal control subjects. Post-scan debriefing revealed that some borderline patients had difficulty disambiguating neutral faces or found them threatening. CONCLUSIONS: Pictures of human emotional expressions elicit robust differences in amygdala activation levels in borderline patients, compared with normal control subjects, and can be used as probes to study the neuropathophysiologic basis of borderline personality disorder.

Deficits in language-mediated mental operations in patients with schizophrenia.

We found previously that a subgroup of schizophrenic patients who passed screening tests of attentional competence showed memory deficits on word memory tasks, but were comparable with controls on tone memory tasks. To better understand the nature of language-specific memory deficits in this subgroup of patients, the present experiment was designed to bypass early perceptual processing of verbal material and determine if patients continue to show impaired performance on verbal memory tasks. Patients who passed the screening tests ('discriminator' patients; DSz) received four serial position tasks. In two, familiar sounds or line drawings were presented and subjects were required to remember the word associated with each stimulus item. In the other two, subjects received hard-to-label auditory and visual stimuli (birdsongs or snowflakes).DSz patients showed large memory deficits compared with controls when required to remember words associated with the familiar sounds or drawings, providing clear evidence of deficits in verbal memory processes independent of sensory processing of verbal stimuli. The interaction between diagnosis and labeling was highly significant, confirming that these patients have particular difficulty with verbal as opposed to non-verbal memory. This was particularly striking on the auditory tests where two patients out-performed all controls on the birdsong test, but were below all controls on the easy-to-label sounds test. The verbal memory tests were easier than the non-verbal memory tests for controls, thus deconfounding task difficulty and deficit specificity.