Nobukatsu Kato

Effect of L-5-hydroxytryptophan on brain monoamine metabolism and evaluation of its clinical effect in depressed patients

SEVERAL modes of observation suggest that there may be deficient brain serotonin metabolism in the depressed patients. This serotonin hypothesis has initially been supported by a study on the brains of depressive suicides, indicative of a decrease in brainstem concentration of serotonin or its major metabolite, 5-hydroxyindoleacetic acid (5-HIAA),’ followed by a series of reports on decreases in cerebrospinal fluid (CSF) concentrations of 5-HIAA in the depressed patients. 2 -8 Clinical attempts to treat the depressed patients with L-tryptophan and 5-hydroxytryptophan (5-HTP), the major amino acid precursors of serotonin, were also carried out and they appeared to be a relatively effective antidepressant. -11 When large doses of L-tryptophan were administered to the depressed patients, no increase in the reduced levels of CSF 5-HIAA was initially reported. This result was interpreted for evidence suggesting that some depressed patients may have a deficiency in their capacity to form serotonin from tryptophan. 12 A decrease in the accumulation of 5-HIAA in the CSF following the administration of probenecid is regarded to be good evidence of the reduced rate of brain serotonin synthesis in the depressed patients.4*51*3 However, some recent data do not agree with this hypothesis.**l4,15 On the other hand, data implicating the depletion of brain dopamine and norepinephrine have given support to the “catecholamine hypothesis” in depression. For example in the CSF studies, baseline levels of homovanillic acid (HVA), the major metabolite of dopamine, have been found to be lower in the depressed patients than in control subjects,6*15 -18 and the initial reduction of HVA was followed by a relative increase after treatment.6 Levels of 3-methoxy-4-hydroxyphenylethylene glycol (MHPG), the major metabolite of norepinephrine, were also significantly lower in the depressed patients than in control subjects, while observed to be markedly elevated in the manic patients with a decrease to normal values during successful treatment with lithium carbonate.l6,19,*0 Exploring these two lines of “amine hypothesis” in depression, some authors, already aware of the physiological interaction between CNS serotonin and catecholamines, deem

Biorhythm of arginine-vasopressin in the paraventricular, supraoptic and suprachiasmatic nuclei of rats

The diurnal variations in content of arginine-vasopressin in the supraoptic nucleus, the paraventricular nucleus and the suprachiasmatic nucleus of rats were determined using radioimmunoassay. In the supraoptic nucleus and the paraventricular nucleus the arginine-vasopressin level was relatively constant during the light phase (the inactive phase). When it became dark, the level of arginine-vasopressin lowered during the early and middle dark phase and then increased to the highest level during the late dark phase. In the suprachiasmatic nucleus the level was stable during the light phase, while in the early and the late dark phase it was significantly higher than that in the middle dark phase.

A comparison of the CNV in young and old subjects: Its relation to memory and personality

Abstract Memory and personality of 16 healthy old subjects (8 preseniles and 8 seniles) were assessed by the CLTR of selective reminding (Buschke and Fuld 1974) and the Maudsley Personality Inventory (MPI), respectively, and were correlated with the CNVs recorded in the serial conditions of habituation—reinforcement—motor extinction (free attention)—reinforcement—motor extinction (forced attention), and compared with those in 8 young subjects. The mean CNV amplitude under the reinforcement condition decreased prominently at ages over 65 years. The mean reaction time (RT) was prolonged with aging and correlated with the CNV amplitude. The mean CNV amplitude under the motor extinction (free attention) condition decreased from the young to the presenile and senile ages. The mean CNV amplitudes under the habituation and motor extinction (forced attention) conditions did not show any definite changes among the groups. The CNV amplitude in the reinforcement had significant correlations with the CLTR value, extraversion and neuroticism scores of the MPI, while the RT had a significant correlation with the neuroticism score. Resistance against the motor extinction was enhanced with a decrease of the CLTR value and the extraversion score. We concluded that the CNV in the old people was more influenced by senile changes in memory and personality than by chronological age.

A Lithium and Carbamazepine Combination in the Treatment of Bipolar Disorder–A Preliminary Report

Abstract: A lithium and carbamazepine combination was reported in five patients with bipolar disorder (DSM‐III), who had not received benefits from conventional treatments. Patients 1, 2 and 4 showed favorable antimanic responses to carbamazepine used in combination with lithium carbonate. Patient 3 did not respond well to either lithium or carbamazepine alone, but improved dramatically on the simultaneous administration of the two drugs. The prophylactic benefit was observed in two patients. These clinical results suggest that a lithium and carbamazepine combination may be more efficacious in the treatment of acute manic episode and the prevention of affective recurrences than each drug alone.

Visual evoked potential characteristics and subtypes of schizophrenia.

Visual evoked potentials (VEPs) were recorded from the midoccipital area of 72 schizophrenic patients. The amplitude of wave IV (100− to 115-millisecond latency) was reduced after the addition test for 15 minutes. It recovered to the pretest level later, and four types of recovery curves were found; marked reduction in amplitude occurred in A1 (A1 type), in A3 with fast recovery (A3f type), in A3 with slow recovery (A3s type), and in A5 (A5 type) (A1, A3, A5: averaged potentials evoked by 1-Hz flashes which started 1 minute, 3 minutes, and 5 minutes after the end of the test). Each type closely corresponded to paranoid, atypical hebephrenic, typical hebephrenic, and simple schizophrenia, respectively.

Effect of DL-erythro-dihydroxyphenylserine on the locomotor activity of the mouse

Effect of dihydroxyphenylserine (DOPS) on the locomotor activity of mice pretreated with beta-phenylisopropylhydrazine was studied using an Animex activity meter. An intraperitoneal injection of DL-erythro-DOPS (200 mg/kg) suppressed significantly the locomotor stimulation by the MAO inhibitor, while DL-threo-DOPS (200 mg/kg) had no effect. Only slight suppression was observed after the administration of 100 mg/kg of DL-erythro-DOPS. Effect of DOPS on the concentrations of brain catecholamines and serotonin of mice pretreated with the MAO inhibitor was also analysed. The administration of DL-erythro-DOPS significantly increased the concentration of noradrenaline, while DL-threo-DOPS did not affect the contents of brain amines in the experimental condition. The suppressive effect of DL-erythro-DOPS on the locomotor stimulation by the MAO inhibitor was confirmed by a simultaneous administration of the amino acid and d-phenylisopropylmethylamine to mice. Based on these findings, the neural mechanisms of the locomotor activity and a clinical application of DL-erythro-DOPS to the manic syndrome were discussed.

Changes in visual evoked potentials of schizophrenics after addition test.

Visual evoked potentials were obtained for schizophrenics, neurotics and patients with affective disorders, and comparison between those before and after an addition test for 15 min was made. Reduction in amplitude and prolongation of latency of the potential were observed in schizophrenics after the test, while there was no change after that in neurotics and patients with affective psychosis. In schizophrenics, 4 types of changes in amplitude of the potential could be seen after the test. Namely, marked reduction occurred in A1 (A1 type), in A3 with fast recovery (A3f type), in A3 with slow recovery (A3s type), and in A5 (A5 type). (A1, A3, A5: Averaged potentials evoked by 1c/sec flashes which started 1 min, 3 min and 5 min after the end of the test.) Each type closely corresponded to paranoid schizophrenia, atypical hebephrenia, typical hebephrenia and simple schizophrenia, respectively.

The effect of motor-response-deprivation on contingent negative variation (CNV). II. Information of the warning stimulus.

1) Using a single click as the warning stimulus (S1), a yellow‐colored light as the imperative stimulus (S2) and a button‐press as the motor‐response (MR), conventional (paradigm of S1‐S2‐MR) and motor‐response‐deprived (S1‐S2) CNVs were recorded in 16 normal subjects.

A schizophrenic subgroup: type A5.

This report concerns a group of schizophrenics whose visual evoked potential reduced in amplitude most markedly in A5 (averaged potential evoked by 1 Hz flashes which started 5 min after the addition test for 15 min). These patients in general had poor productive symptoms and progressed very slowly. Most of them were simple schizophrenics.

The Effect of Motor-Response-Deprivation on Contingent Negative Variation (CNV) III: Relation with Maudsley Personality Inventory (MPI)

The contingent negative variation (CNV) was correlated with Maudsley Personality Inventory (MPI) in 43 healthy adults as follows: