From evidence that unanesthetized rats given long-term lithium chloride
demonstrated reduced turnover of arachidonic acid (n-6 polyunsaturated fatty
acid [PUFA] but not docosahexaenoic acid (n-3 PUFA) in brain phospholipids,
and reduced conversion of arachidonate to prostaglandin E2 by cyclooxygenase
2, Rapoport and Bosetti (SEE ARTICLE) hypothesize that lithium and antimanic anticonvulsants act by inhibiting brain
arachidonate metabolism. If arachidonate metabolism were functionally hyperactive
in mania, a cyclooxygenase 2 inhibitor might help in its treatment. Their
hypothesis is consistent with evidence that n-3 PUFAs, which can inhibit brain
arachidonate metabolism, may be effective in bipolar disorder.
Elliott et al (SEE ARTICLE) used functional
brain imaging to study depressed patients and controls during performance
of a simple cognitive task. Specific regions of the prefrontal cortex responded
differently depending on the emotional tone of stimuli, reflecting the cognitive
biases reported in previous studies. These findings suggest a crucial role
for prefrontal regions in mediating the interaction between mood, cognition,
and neurobiology in depression.
Beekman et al (SEE ARTICLE) characterized
the natural history of depression in a large prospective study of elderly
individuals (>55 years of age) in the Netherlands. In the depressed cohort,
the average symptom severity remained above the 85th percentile for the population
for 6 years. In only 14% were the symptoms short-lived, whereas 32% exhibited
a chronic course. The remainder experienced a fluctuating course.
Neumeister et al (SEE ARTICLE) evaluated
the behavioral responses to tryptophan depletion in a group of healthy women
with and without a first-degree family history of major depression and examined
the relationship to the serotonin transporter gene promotor polymorphism (5HTTLPR). The short allele of the 5HTTLPR and a positive family history of depression were shown to be additive
risk factors for developing depressive symptoms during tryptophan depletion.
In contrast, subjects homozygous for the long allele did not develop depressive
symptoms during tryptophan depletion, irrespective of their family history.
New et al (SEE ARTICLE) used positron
emission tomography to examine the regional metabolic activity in response
to a serotonergic stimulus, meta-chlorophenylpiperazine (m-CPP), in impulsive-aggressive
and normal subjects. Unlike normal subjects, impulsive-aggressive patients
did not show activation specifically in the left anteromedial orbital cortex
or the anterior cingulate gyrus in response to m-CPP. The decreased activation
of inhibitory regions in patients with impulsive aggression in response to
a serotonergic stimulus may contribute to their difficulty in modulating aggressive
impulses.
Hemby et al (SEE ARTICLE) present
the first single-cell expression analysis of schizophrenia. Using macroarrays,
they show that the abundances of various mRNAs differ in cortical layer II/III
stellate neurons between control and schizophrenic subjects. Because of the
cellular heterogeneity of the central nervous system, the interconnectivity
of various neuronal systems, and the relative abundances of mRNAs in different
cell types, these data suggest that both whole-tissue and single-cell analysis
complement each other in providing a more complete picture of the molecular
consequences of schizophrenia.
Abnormal spread of activation through neural networks controlling semantic
associations has been proposed as a cause of symptoms in schizophrenia. Four
hundred milliseconds after a semantic stimulus, a negative wave (N400) can
be recorded by electroencephalogram. Mathalon et al (SEE ARTICLE) show that subjects with schizophrenia exhibited smaller
N400 waves than controls, although the response was normalized when they were
provided with a contextual stimulus prior to the semantic stimulus.
Currently there is no consensus on the best therapeutic approach to
chronic tic disorders and comorbid attention-deficit/hyperactivity disorder
(ADHD). Spencer et al (SEE ARTICLE) report
findings from a controlled trial of desipramine in children and adolescents
with chronic tic disorders and ADHD. Desipramine treatment was well tolerated
and associated with robust reductions in both tic and ADHD symptoms.
Kupfer et al (SEE ARTICLE) have identified
special challenges to the recruitment and retention of the next generation
of physician researchers in mental health and clinical neuroscience. These
challenges include the need to interest undergraduate and medical researchers
to compete successfully for National Institutes of Health career development
(K) awards, to provide bridge support between postdoctoral fellowship training,
and successful receipt of pay for mentoring.
