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Objective: Inhibition mediated by [gamma]-aminobutyric acid at the axon initial segment of pyramidal neurons appears to be altered in the prefrontal cortex in schizophrenia. This study examined the densities and laminar distribution of axon initial segments labeled with an antibody against the [serotonin.sub.1A] (5-H[T.sub.1A]) receptor, which also mediates inhibitory regulation of pyramidal neurons, in subjects with schizophrenia. Method: The densities and laminar distribution of axon initial segments with 5-H[T.sub.1A]-like immunoreactivity were assessed in postmortem tissue from the prefrontal cortex (Brodmann's area 46) of 14 matched triads of subjects with schizophrenia, subjects with major depressive disorder, and comparison subjects with no psychiatric disorder. Results: The relative densities of the labeled axon initial segment in both the superficial and the deep cortical layers did not differ across the three subject groups. Conclusions: The findings do not support a role for altered serotonin transmission by means of the 5-HT1A receptor in dysfunction of prefrontal cortex pyramidal neurons in schizophrenia.

There are approximately 30 different chemical substances which transmit messages between brain cells (neurons). Each of these neurotransmitters has a specific effect. The neurotransmitter serotonin (also called 5-HT), unlike amphetamine anorectics (agents which decrease appetite), does not have a stimulatory effect and lacks the potential for abuse. D-fenfluramine is a drug that enhances serotonin transmission by releasing serotonin and then blocking its uptake at receptor sites. When uptake is blocked, more active serotonin is free to circulate in the brain. A chemical breakdown product of D-fenfluramine is D-norfenfluramine, which is extremely active in reducing food intake. D-fenfluramine was the first drug of its class used to treat obesity. With other indirect serotonin anorectics (e.g., fluoxetine) that do not release serotonin, but function by blocking its uptake, the mechanisms inhibiting food intake are less clear. Fluoxetine is now available for clinical use and is primarily prescribed as an antidepressant. While traditional antidepressants tend to increase appetite and cause weight gain, fluoxetine has the opposite effect; it has been shown to relieve symptoms of bulimia, an eating disorder characterized by binging and purging. (Consumer Summary produced by Reliance Medical Information, Inc.)

A review of the research linking brain serotonin (also called 5-HT) function to obsessive-compulsive disorder (OCD) is presented. Clomipramine is an antidepressant drug that prevents the re-uptake of serotonin, with the result that more serotonin remains active. In the early 1980s, several studies found clomipramine to be more effective than other drugs of its type in reducing symptoms of OCD. Later studies found a relationship between improvement in OCD symptoms and reductions in concentrations of the serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA), in cerebrospinal fluid (the fluid that bathes the brain and spinal cord). Reduced cerebrospinal levels of 5-HIAA imply a reduction in the re-uptake of serotonin. Studies evaluating the appropriate duration of treatment for OCD found that patients who improved after 5 to 27 months of clomipramine treatment, and were subsequently withdrawn from the drug, experienced a return of OCD symptoms within seven weeks. New, selective serotonin uptake inhibitors that have proven to be effective antidepressants (e.g., fluvoxamine) have also been tested and found to be highly effective in reducing OCD symptoms. Inducing serotonin activity by other means does not always improve OCD symptoms. For example, when OCD patients were administered m-chlorophenylpiperazine (m-CPP), which initiates serotonin activity, they became anxious and depressed, and their OCD symptoms increased. However, when m-CPP was administered to patients treated with clomipramine for several months, the depression, anxiety and OCD symptoms did not significantly increase. These paradoxical findings suggest that there may be a brain abnormality in OCD involving alterations and possible interactions of serotonin and related substances. (Consumer Summary produced by Reliance Medical Information, Inc.)

To the Editor: The serotonin syndrome is a well-described drug-induced disorder characterized by alterations in mental status, neuromuscular activity, and autonomic nervous system function.[1-3] It is solely produced by drugs [...]

American scientists have discovered how methylphenidate (Ritalin), which is often given to calm children with attention deficit hyperactivity disorder (ADHD), works in an animal model of the condition. Their work […]

The search for a rapid-acting antidepressant has been a subject of intense research interest for several decades. The article by Lucas and colleagues in this issue of Neuron provides compelling evidence from preclinical animal models that drugs acting at the serotonin 5-HT(4) receptor could finally achieve this goal. However, caution is warranted, as results from animal studies are not always predictive of therapeutic actions in humans.

Nimodipine, a dihydropyridine calcium entry blocker, has been shown to protect from neuronal damage due to ischemia by providing for increased postischemic perfusion. Further, it has also been demonstrated to have antiepileptic properties. These two properties--calcium channel blockade and anticonvulsant benefits have been applied with success to mood disorder treatment. Although found helpful nearly a decade ago for uncomplicated mania, nimodipine may have particular benefits for those diagnostic subclasses of bipolar disorder most resistant to therapy, e.g., ultra-rapid-cycling bipolars and brief recurrent depressions.