Differential effects of venlafaxine in the treatment of major depressive disorder according to baseline severity.

In this meta-analysis, we compare the relative efficacy of venlafaxine to selective serotonin reuptake inhibitors (SSRIs) in patients with major depressive disorder classified according to baseline disease severity. Data from 31 double-blind randomised clinical trials comparing venlafaxine and SSRIs (intent-to-treat n = 6,492) were pooled. For this secondary analysis, patients were stratified into groups based on baseline HAM-D(17) total score (>or=30, <30, >or=25, and <25). Remission rates (HAM-D(17) < 8) were analyzed for each subgroup using Fisher's exact test to compare treatment effects between venlafaxine and SSRIs; last observation carried forward (LOCF) and observed cases (OC) data were analyzed. The number needed to treat (NNT) to benefit was determined for each analysis. Statistically significant remission rate differences, favoring venlafaxine, were seen in LOCF and OC analyses for each subgroup. In patients with baseline HAM-D(17) < 25 (n = 3,928) the differences were (LOCF) 7.3 [P < 0.001; NNT = 14] and (OC) 6.2 [P = 0.003; NNT = 16], and in patients with baseline HAM-D(17) >or= 25 (n = 2,564) were (LOCF) 5.7 [P = 0.002; NNT = 17] and (OC) 6.7 [P = 0.009; NNT = 15]. In patients with baseline HAM-D(17) < 30 (n = 5,836) the differences were (LOCF) 6.4 [P < 0.001; NNT = 16] and (OC) 5.5 [P = 0.001; NNT = 18], and in patients with baseline HAM-D(17) >or= 30 (n = 656) were (LOCF) 8.9 [P = 0.015; NNT = 11] and (OC) 14.8 [P = 0.003; NNT = 7]. In conclusion, these analyses demonstrate that venlafaxine may be superior to SSRIs in achieving remission in both mild/moderate and severely depressed patients. The greater difference in remission rates among patients with baseline HAM-D(17) >or= 30 suggests a more pronounced clinical benefit that may be achieved with venlafaxine in severely depressed patients.

Regulation of stearoyl-CoA desaturase-1 after central and peripheral nerve lesions.

BACKGROUND: Interruption of mature axons activates a cascade of events in neuronal cell bodies which leads to various outcomes from functional regeneration in the PNS to the failure of any significant regeneration in the CNS. One factor which seems to play an important role in the molecular programs after axotomy is the stearoyl Coenzyme A-desaturase-1 (SCD-1). This enzyme is needed for the conversion of stearate into oleate. Beside its role in membrane synthesis, oleate could act as a neurotrophic factor, involved in signal transduction pathways via activation of protein kinases C. RESULTS: In situ hybridization and immunohistochemistry demonstrated a strong up-regulation of SCD at mRNA and protein level in regenerating neurons of the rat facial nucleus whereas non-regenerating Clarke's and Red nucleus neurons did not show an induction of this gene. CONCLUSION: This differential expression points to a functionally significant role for the SCD-1 in the process of regeneration.

Retrograde reactions of Clarke's nucleus neurons after human spinal cord injury.

Successful axon regeneration depends on the expression of regeneration-associated genes by axotomized neurons. Here, we demonstrate, for the first time to our knowledge, the expression of regeneration-associated genes by axotomized human CNS neurons. In situ hybridization and immunohistochemistry showed a transient induction of GAP-43 and c-jun in Clarke's nucleus neurons caudal to traumatic human spinal cord injury. These results support experimental data that nonregenerating central nervous system neurons can temporarily upregulate regeneration-associated genes, reflecting a transient regenerative capacity that fails over time.

Identification of regeneration-associated genes after central and peripheral nerve injury in the adult rat.

BACKGROUND: It is well known that neurons of the peripheral nervous system have the capacity to regenerate a severed axon leading to functional recovery, whereas neurons of the central nervous system do not regenerate successfully after injury. The underlying molecular programs initiated by axotomized peripheral and central nervous system neurons are not yet fully understood. RESULTS: To gain insight into the molecular mechanisms underlying the process of regeneration in the nervous system, differential display polymerase chain reaction has been used to identify differentially expressed genes following axotomy of peripheral and central nerve fibers. For this purpose, axotomy induced changes of regenerating facial nucleus neurons, and non-regenerating red nucleus and Clarke's nucleus neurons have been analyzed in an intra-animal side-to-side comparison. One hundred and thirty five gene fragments have been isolated, of which 69 correspond to known genes encoding for a number of different functional classes of proteins such as transcription factors, signaling molecules, homeobox-genes, receptors and proteins involved in metabolism. Sixty gene fragments correspond to genomic mouse sequences without known function. In situ-hybridization has been used to confirm differential expression and to analyze the cellular localization of these gene fragments. Twenty one genes (approximately 15%) have been demonstrated to be differentially expressed. CONCLUSIONS: The detailed analysis of differentially expressed genes in different lesion paradigms provides new insights into the molecular mechanisms underlying the process of regeneration and may lead to the identification of genes which play key roles in functional repair of central nervous tissues.