Higher brain blood flow at amygdala and lower frontal cortex blood flow in PTSD patients with comorbid cocaine and alcohol abuse compared with normals.

Posttraumatic stress disorder (PTSD) patients with histories of cocaine and alcohol abuse (CA-PTSD) were compared with normal volunteers. Positron emission tomography (PET) scans with 15O-butanol were used to compare regional cerebral blood flow (rCBF) between the groups during rest and during an auditory continuous performance task (ACPT). CA-PTSD patients had significantly higher rCBF in right amygdala and left parahippocampal gyrus than normals during the ACPT. Normals had higher rCBF at frontal cortex during the resting scan and during the ACPT. The role of the amygdala in attention and fear conditioning suggests that increased amygdala rCBF may be related to clinical features of PTSD. Cocaine use may be associated with increased amygdala rCBF in PTSD patients. Amygdala and frontal cortex attention system components may be reciprocally related and their relative contributions to processing of neutral stimuli perturbed in CA-PTSD.

Nefazodone therapy in patients with treatment-resistant or treatment-intolerant depression and high psychiatric comorbidity.

Given the potentially severe functional impairment, morbidity, and high costs associated with refractory depression, it is important to explore all treatment options that may benefit patients with this disorder. This is a retrospective, uncontrolled analysis of our experience with nefazodone therapy in treatment-resistant and treatment-intolerant depression. Potential candidates for nefazodone therapy were referred by their treating psychiatrist. Documentation of failure to respond to previous antidepressant therapy, a diagnosis of clinical depression according to criteria in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and completion of a Beck Depression Inventory (BDI) were required before initiation of nefazodone. A follow-up BDI was obtained after > or =4 weeks of nefazodone therapy. A Clinical Global Inventory (CGI) score was obtained retrospectively based on documentation of target symptoms in the clinical record of the last clinic visit. The study group consisted of 20 patients with treatment-resistant or treatment-intolerant major depression who received nefazodone therapy. The mean (+/- SD) age of the group was 48.1+/-9.4 years. The mean number of previously failed antidepressant trials was 1.9+/-0.6. Psychiatric comorbidity in this group was substantial, with posttraumatic stress disorder (PTSD) found in 11 (55%) patients, substance abuse in 3 (15%) patients, and personality disorder found in 2 (10%) patients. After treatment with nefazodone, 11 of 20 patients (55%) were rated on the CGI as much or very much improved. In addition, 9 patients (45%) had >20% improvement on BDI, 3 patients (15%) had 10% to 20% improvement, and 6 patients (30%) had <10% change. Two patients (10%) discontinued nefazodone therapy due to adverse effects. Analysis of our experience with nefazodone therapy in a population with treatment-resistant depression and a high degree of psychiatric comorbidity suggests that approximately 50% of patients may have substantial response to treatment, with a smaller proportion having a more modest clinical response. While receiving nefazodone therapy, most patients continued to take concurrently prescribed psychotropic medications, primarily anxiolytics or other antidepressants. Of interest was the positive drug response among a subgroup of individuals with depression and chronic, severe PTSD. Larger, controlled studies are needed to determine whether these preliminary observations are confirmed.

Intestinal satiety in rats.

Infusion of liquid food into the duodenum inhibited sham feeding. The inhibition of sham feeding reflected satiety because the duodenal infusion elicited the complete behavioral sequence characteristic of satiety. The chemical and/or colligative load that the infusion imposed on the intestine appeared to be the adequate stimulus for satiety. Duodenal infusions that inhibit sham feeding and elicit satiety are not aversive because they will not function as the unconditioned stimulus for the formation of a conditioned taste aversion for saccharin. We call the satiety elicited by the infusion of food into the duodenum "intestinal satiety." This emphasizes our belief that satiety is a reflex that can be elicited by the activation of receptors in the wall of the intestine. It is known that the activation of some intestinal receptors releases the hormone cholecystokinin (CCK). Since CCK mimics a duodenal infusion by inhibiting sham feeding and eliciting the complete behavioral sequence of satiety, we suggest, but do not prove, that CCK mediates intestinal satiety in the rat.