Family and twin studies suggest that early-onset and later-onset major
depressive disorder (MDD) may have distinct etiologies and correlates. In
a prospective study of a birth cohort followed until age 26 years, Jaffee et al (SEE ARTICLE) found that those whose MDD onset
was in childhood (before age 15 years) experienced higher levels of early
childhood psychosocial risks compared with those whose MDD onset was in adulthood
(ages 18-26 years), including perinatal insults and motor skills deficits,
caretaker instability, and psychopathology in their family of origin, and
behavioral and socioemotional problems. Those with adult-onset MDD experienced
similarly low levels of risk as the never-depressed group (with the exception
of elevated childhood sexual abuse).
A commentary by Myrna M. Weissman (SEE ARTICLE) is included.
Fergusson and Woodward (SEE ARTICLE) used data gathered over the course of a 21-year longitudinal study to examine
the continuities and consequences of adolescent (ages 14-16 years) depression.
Results suggested the presence of 2 major pathways linking early depression
to later outcomes. First, there was a direct linkage between early depression
and increased risks of later depression or anxiety disorders. Second, the
associations between early depression and other outcomes (substance dependence,
educational underachievement, suicide attempts, unemployment, and early parenthood)
were explained by confounding social, family, and individual factors.
Thase et al (SEE ARTICLE) studied the
utility of a switch across antidepressant classes in 168 chronically depressed
patients who had not responded to 12 weeks of double-blind therapy with imipramine
hydrochloride or sertraline hydrochloride. Results indicated a significant
tolerability advantage for the selective serotonin reuptake inhibitor, but
the drugs had comparable efficacy after taking attrition rates into account.
The stress-diathesis model predicts that the magnitude of stress at
illness onset should be inversely proportional to the level of underlying
diathesis. Kendler et al (SEE ARTICLE) were
unable to confirm 3 predictions of the stress-diathesis model for phobias
in more than 7500 epidemiologically sampled twins. No relationship was found
between the severity of trauma at onset of phobias (a measure of stress) and
2 indices of the diathesis: risk of phobias in co-twin or level of the personality
trait of neuroticism. These results are more consistent with nonassociative
models of phobia acquisition than with traditional etiologic theories involving
conditioning or social transmission.
Serotonin reuptake inhibitor (SRI) medications are effective for both
major depressive disorder (MDD) and obsessive-compulsive disorder (OCD), but
there has been scant evidence as to whether they had the same or different
effects on brain function in these 2 disorders. Saxena et
al (SEE ARTICLE) found that pretreatment to posttreatment
changes in brain glucose metabolism differed significantly between 3 groups
of subjects (OCD alone, MDD alone, and concurrent OCD + MDD) that were treated
with the same dose of the SRI, paroxetine, and between responders and nonresponders.
These findings suggest that the effects of SRIs on brain activity are both
disorder specific and response specific.
Improving the discovery and evaluation of psychotropic
drugs would have enormous scientific, economic, and public health implications. Klein et al (SEE ARTICLE) present many technical
recommendations that could be currently effected by institutional leaders.
However, some substantive suggestions require increased resources, both scientific
and clinical, as well as federal initiatives to establish a proactive, pharmacological
development agency.
Commentaries by Paul Leber (SEE ARTICLE) and Alan J. Gelenberg (SEE ARTICLE) are included.
Carpenter (SEE ARTICLE) describes
the growing concern with commercialism in the creation and dissemination of
therapeutic knowledge. He specifies sources of relatively unbiased appraisal
of clinical trials and notes a discordance in this information and industry-sponsored
education regarding pharmacotherapy of schizophrenia. Carpenter provides specific
suggestions for addressing potential commercial bias in psychopharmacology
research and education.
