Generalized anxiety disorder versus panic disorder: participation in controlled efficacy trials.

Seventy-one patients with panic disorder (PD) and 46 patients with generalized anxiety disorder (GAD) were studied in relation to their behavior before, during, and after participation in two contemporaneous and procedurally similar double-blind drug efficacy trials. The two groups were administered a battery of assessments aimed at comparing them on the nature and intensity of various symptom domains, social and work-related disability, personality, life events, and previous treatments. The results yielded few significant differences that were not due to definitional factors, most notably a more prevalent history of depression and treatment for depression in the GAD group and a higher rate of pharmacological treatment in the PD group. On the other hand, the two groups behaved in a comparable way in the screening, experimental, and postexperimental phases of the trials. The findings are in support of more similarities than differences between the groups. In addition, the comparable behavior of the two groups throughout the three phases of the trial suggests that differential pretreatment attrition and compliance with placebo-controlled trials may not present major confounding problems in comparative treatment effectiveness studies between GAD and PD diagnostic groups.

Recovery of choline acetyltransferase activity without sprouting of the residual acetylcholine innervation in adult rat cerebral cortex after lesion of the nucleus basalis.

In view of the divergent literature concerning the long-term effects of ibotenic acid lesions of the nucleus basalis of Meynert (NBM) on the choline acetyltransferase (ChAT) activity in adult rat cerebral cortex, we have critically reassessed the issue of an eventual recovery of this enzymatic activity by sprouting of the residual acetylcholine (ACh) innervation. At short (1 week) and long survival time (3 months) after unilateral ibotenic acid lesion, ChAT activity was biochemically measured in the ipsi and contralateral fronto-parietal cortex of several rats in which the extent of ACh neuronal loss in NBM was also estimated by counts of ChAT-immunostained cell bodies on the lesioned vs. non-lesioned side. In other lesioned rats, particular attention was paid to the distribution of the residual cortical ACh (ChAT-immunostained) innervation, and that of immunostained vasoactive intestinal polypeptide (VIP) axon terminals known to belong in part to intrinsic cortical ACh neurons which co-localize this peptide. One week after NBM lesion, profound decreases of ipsilateral cortical ChAT activity were tightly correlated with the extent of ACh cell body loss in the nucleus. A significant recovery of cortical ChAT activity could be documented after 3 months, despite persistence of NBM cell body losses as severe as after 1 week. At both survival times, the number of ChAT-immunostained axons was markedly reduced throughout the ipsilateral fronto-parietal cortex, demonstrating that most ACh fibers of extrinsic origin had been permanently removed. This result also indicated that the long-term recovery of ChAT activity had occurred without sprouting of the residual ACh innervation. The laminar distribution and number of VIP-immunostained terminals remained the same on the lesioned and intact side and comparable to normal, ruling out an extensive sprouting of intrinsic ACh/VIP or VIP alone fibers. The return to a near normal cortical ChAT activity in severely ACh-denervated cortex suggested that the intrinsic ACh innervation was primarily responsible for this recovery.