Serotonin function in panic disorder: intravenous administration of meta-chlorophenylpiperazine.

A placebo-controlled study of the direct serotonin receptor agonist meta-chlorophenylpiperazine (MCPP), intravenously infused over 90 s in a 0.06 mg/kg dose, was conducted in 10 patients with panic disorder and 9 normal control subjects. Cortisol, MCPP serum levels, and behavioral responses in both groups. Differences between intravenous and oral administration of MCPP are discussed, and the present findings are related to the serotonergic hypothesis of panic disorder.

Event-related potentials in schizotypal personality disorder.

This study examined whether abnormalities in event-related potentials (ERPs), reported in schizophrenia, extend to patients with schizotypal personality disorder (SPD). Auditory ERPs in an oddball paradigm were obtained in 19 SPD patients, 17 schizophrenic patients, and 20 normal control subjects (NCs). Schizophrenic patients had lower P300 amplitude than NCs; the P300 amplitude of SPD patients was intermediate, showing a linear trend but not a significant group difference. P200 amplitudes showed a similar trend. SPD patients had N100 and N200 amplitudes intermediate to schizophrenic patients and NCs, without significant group differences. Results suggest diminished P300 amplitude may not be as prominent in SPD as in schizophrenia. Studies with larger sample sizes, multiple lead assessment strategies, and more demanding tasks may further characterize ERP deficits in schizophrenia-spectrum disorders such as SPD.

The boundaries of schizophrenia.

Evidence from a variety of domains including the phenomenologic, genetic, psychological, neuropsychological, psychophysiologic, neurochemical, imaging, outcome, and treatment response suggests that schizotypal personality disorder is related closely to chronic schizophrenia and that this disorder may be part of a continuum of schizophrenia-related disorders. Questions remain as to how the boundaries of schizophrenia should be defined. The commonalities across the schizophrenia spectrum as well as the differences between disorders on the spectrum need to be clarified further. A multidimensional approach to the pathogenesis of the schizophrenia-related disorders offers a beginning opportunity for such a clarification. The study of patients with schizotypal personality disorder suggest that a dimension of deficit-like or "negative" symptoms of asociality and interpersonal impairment may be associated with neuropsychological and psychophysiologic correlates of altered cortical, particularly frontal, function and raise the possibility in structural changes as reflected in increased ventricular size in frontal and third ventricle areas. On the other hand, the psychotic-like or "positive" symptoms seem to be more related to increases in dopaminergic activity that may be partially responsive to neuroleptic treatment. It is conceivable that these two dimensions may represent partially distinct but potentially interactive pathophysiologic processes that may converge and interact to result in chronic schizophrenia. In this way, the study of the boundaries of schizophrenia and the milder schizophrenia-related personality disorders may provide important clues as to the genetic and pathophysiology of chronic schizophrenia itself, as well as to illuminate a set of disorders that are clinically underrecognized but probably more prevalent than more severe forms of schizophrenia.

A dose-response study of intravenous m-chlorophenylpiperazine in normal subjects.

A placebo-controlled dose-response study of the direct serotonin receptor agonist m-chlorophenylpiperazine (MCPP), intravenously infused over 90 s in 0.06 and 0.08 mg/kg doses, was conducted in nine normal male subjects. Cortisol, prolactin, MCPP serum levels and behavioral responses were measured over a 210-min period. Both doses caused significant cortisol and prolactin release and were associated with significantly greater behavioral effects as compared to placebo. Though the two doses were associated with different MCPP serum levels, they did not significantly differ in their hormonal and behavioral effects.

Plasma homovanillic acid in schizotypal personality disorder.

Schizotypal patients were found to have a significantly higher mean plasma HVA concentration than normal comparison subjects. Furthermore, plasma HVA concentration positively correlated with "psychotic-like" schizotypal symptoms. These results implicate dopaminergic mechanisms modulating the psychotic-like symptoms of schizotypal personality disorder.

Desipramine treatment in panic disorder.

Apart from imipramine (IMI), the efficacy of tricyclic antidepressants in panic disorder (PD) has received surprisingly little investigation. The authors report on a 6 week open trial of desipramine (DMI) preceded by a 10 day placebo lead-in, in 15 patients with PD. By week 6, 80% of the patients were globally rated as much or very much improved on a mean dose of 198 mg. Much of the improvement resulted from a reduction in non-panic attack symptomatology (i.e., psychic, somatic and phobic anxiety). Longer duration of illness, male gender and residual psychic anxiety were associated with poorer response in a subgroup of patients. DMI caused minimal intolerable side effects, suggesting possible compliance advantages in comparison to IMI. Beyond supporting the efficacy of DMI in PD, the results of the study point to a significant medication responsive non-panic illness component and caution against over-relying on panic attacks in assessing both illness severity and treatment response.

Effects of serotonin antagonists on m-chlorophenylpiperazine-mediated responses in normal subjects.

The serotonin (5HT) agonist, m-chlorophenylpiperazine (MCPP), has been used as a challenge agent to assess central 5HT receptor sensitivity in normal subjects and patients with panic disorder, obsessive-compulsive disorder, and major depression. Adrenocorticotropin, cortisol, and prolactin responses to MCPP were among the variables measured. MCPP's usefulness as a probe of 5HT receptors, however, hinges on its 5HT selectivity. To address MCPP's selectivity for 5HT, this study tested whether two different 5HT antagonists, methysergide (4 mg p.o.) and metergoline (4 mg p.o.), could block the hormonal and behavioral effects of MCPP (0.5 mg/kg p.o.) in 10 normal male subjects in comparison to placebo. Both 5HT antagonists abolished the prolactin release to MCPP. Metergoline, the antagonist with the more potent 5HT binding affinity, significantly blocked MCPP's effect on cortisol release as compared to placebo, and methysergide showed a nonsignificant trend to that effect. MCPP alone did not have a significant effect on behavioral variables, perhaps explaining why neither 5HT antagonist affected these measures. The findings from this study suggest that both MCPP-induced prolactin release and cortisol release are indeed 5HT-mediated effects.