ro-16-0154 and Psychotic-Disorders

Topics: Adolescent; Adult; Brain Mapping; Dissociative Disorders; Double-Blind Method; Dronabinol; Electroencephalography; Event-Related Potentials, P300; Flumazenil; gamma-Aminobutyric Acid; Humans; Male; Pain Measurement; Psychiatric Status Rating Scales; Psychotic Disorders; Psychotropic Drugs; Young Adult

Some schizophrenia patients are more sensitive to amphetamine (AMPH)-induced exacerbations in psychosis-an effect that correlates with higher striatal dopamine release. This enhanced vulnerability may be related to gamma-aminobutyric acid (GABA) deficits observed in schizophrenia. We hypothesized that a pharmacologically induced GABA deficit would create vulnerability to the psychotomimetic effects to the 'subthreshold' dose of AMPH in healthy subjects, which by itself would not induce clinically significant increase in positive symptoms. To test this hypothesis, a GABA deficit was induced by intravenous infusion of iomazenil (IOM; 3.7 μg/kg), an antagonist and partial inverse agonist of benzodiazepine receptor. A subthreshold dose of AMPH (0.1 mg/kg) was administered by intravenous infusion. Healthy subjects received placebo IOM followed by placebo AMPH, active IOM followed by placebo AMPH, placebo IOM followed by active AMPH, and active IOM followed by active AMPH in a randomized, double-blind crossover design over 4 test days. Twelve healthy subjects who had a subclinical response to active AMPH alone were included in the analysis. Psychotomimetic effects (Positive and Negative Syndrome Scale (PANSS)), perceptual alterations (Clinician Administered Dissociative Symptoms Scale (CADSS)), and subjective effects (visual analog scale) were captured before and after the administration of drugs. IOM significantly augmented AMPH-induced peak changes in PANSS positive symptom subscale and both subjective and objective CADSS scores. There were no pharmacokinetic interactions. In conclusion, GABA deficits increased vulnerability to amphetamine-induced psychosis-relevant effects in healthy subjects, suggesting that pre-existing GABA deficits may explain why a subgroup of schizophrenia patients are vulnerable to AMPH.

Topics: Adolescent; Adult; Amphetamine; Cross-Over Studies; Double-Blind Method; Drug Administration Schedule; Flumazenil; gamma-Aminobutyric Acid; Hallucinogens; Healthy Volunteers; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Psychotic Disorders; Time Factors; Visual Analog Scale; Young Adult

An 11-year-old girl who had been given antiepileptic drugs (AEDs) for occipital lobe epilepsy was hospitalized with alternative psychosis and dysgraphia accompanied by forced normalization of the EEG. Her epileptic seizures and psychosis disappeared after administration of carbamazepine. She developed dysgraphia for Kanji words (Japanese morphograms). The EEG showed sporadic spikes predominantly in the left occipital region, and [123I]iomazenil single-photon-emission computed tomography (IMZ-SPECT) imaging revealed an area of hypoperfusion in the left occipital lobe. Interestingly, the left posterior inferior temporal area is known to play an important role in writing Kanji words. It is assumed that abnormal discharges in the left occipital lobe were projected into the left posterior inferior temporal area and that a functional disorder in that area led to dysgraphia; however, further exploration is needed.

Topics: Agraphia; Anticonvulsants; Carbamazepine; Child; Electroencephalography; Epilepsies, Partial; Female; Flumazenil; Humans; Psychotic Disorders; Tomography, Emission-Computed, Single-Photon