Cross-cultural equivalence in depression assessment: Japan-Europe-North American study.

OBJECTIVE: Worldwide use of the Hamilton Rating Scale for Depression (HRSD) presupposes that depression symptomatology can be measured the same way across countries but no empirical study has yet examined this issue. We therefore examined cross-cultural consistency of factor structure of HRSD. METHOD: A 17-item HRSD data were sought for 5,185 individuals diagnosed with major depression in Japan, Europe and North America. Candidate factor structures were obtained with simultaneous component analysis (SCA) across the three cultures. They were then submitted to multiple-group confirmatory factor analysis (CFA). RESULTS: According to SCA, 3-, 4- or 5-factor solutions were found to optimally and adequately summarize the variables for all the three populations. When submitted to CFA, the 5-factor solution was the best fitting and the most parsimonious: they were 'anhedonia/retardation,''guilt/agitation,''bodily symptoms,''insomnia' and 'appetite.' CONCLUSION: Common underlying factors exist for HRSD among Japanese, European and American patients with major depression.

Identification and characterization of the human serotonin-4 receptor gene promoter.

The human serotonin-4 (5-HT(4)) receptor gene expression is highly regulated in various tissues. We isolated the human 5-HT(4) receptor gene containing the 5'-flanking region and characterized its promoter. By 5'-RACE (5'-rapid amplification of the cDNA ends) and inverse PCR, multiple transcription initiation sites were identified. The most 5' one (assigned to +1) was 5135 bp upstream to the translation start site. The 500-bp 5'-flanking region contained potential binding sites for transcription factor Sp-1, AP-2, AP-4, and GATA. However, this region lacked TATA- and CAAT-boxes. Transient transfection analyses in human choriocarcinoma T3M-3 (5-HT(4) receptor-positive) and HepG2 (5-HT(4) receptor-negative) cells revealed that the region (-210 to -105) is necessary for the basic and cell-type specific 5-HT(4) receptor gene expression. In addition, untranslated exon 1 contained negative (+112 to +182) as well as positive (+1 to +111) modulators, indicating that exon 1 plays a regulatory role in the 5-HT(4) receptor gene expression.

Effects of long-term treatment with desipramine on microtubule proteins in rat cerebral cortex.

The molecular mechanism of the action of antidepressants beyond the receptor level has not yet been elucidated. We have investigated the effects of long-term treatment with desipramine on the phosphorylation state of microtubule-associated protein 2 (MAP2) and microtubule assembly in the rat cerebral cortex. Phosphorylation of MAP2 was detected by immunoblotting after immunoprecipitation of MAP2 in the soluble fraction. The degree of phosphorylation of serine residues of MAP2 was significantly increased after chronic administration of desipramine without changes in the total concentration of MAP2. Microtubule assembly in crude brain extracts was monitored in terms of changes in turbidity measured at 350 nm using a spectrophotometer. Chronic but not acute treatment with desipramine inhibited microtubule assembly, assayed in the presence of a phosphatase inhibitor, calyculin A, whereas the inhibition was completely nullified in the absence of calyculin A. Desipramine had no direct effect on microtubule assembly in vitro. These results raise the possibility that the changes in the degree of phosphorylation of MAP2 and microtubule assembly represent intracellular modifications involved in functional changes elicited by long-term treatment with desipramine.

The effect of age on plasma level of setiptiline maleate in depressed patients.

1. Setiptiline maleate (SPT) was administered orally to 45 subjects aged 22-86 years and steady state plasma levels were determined by mass fragment chromatography (GC-MF) to examine the effect of aging on those values. 2. There was a significant correlation between the plasma levels and daily dose. However, there was a wide interindividual variability. 3. Dose-corrected plasma level (DC-PL), or values corrected by dividing the plasma level by daily dose/body weight, was used as the systemic drug clearance parameter. 4. DC-PL was compared among 7 age groups of the subjects distributed in 10-year-intervals. DC-PL showed no difference among groups of subjects between the > 29 years bracket to the 70 years bracket, but showed significantly higher values in those in the > 80 bracket compared to all age groups and subjects in the < 79 bracket. 5. There was a significant correlation between the age of patients and DC-PL according to polynomial response curve analysis. Regression analysis yielded the equation y = -52.72 + 7.05 x -0.17 x2 + 0.01 x3 (n = 45, r = 0.49, p < 0.01).

[Efficacy and safety of electroshock therapy without convulsions under general anesthesia in senile depression].

We examined the efficacy and safety of electroshock therapy (EST) under general anesthesia in 26 depressed patients (9 males, 17 females, age range 55-79). The scores of the Hamilton Psychiatric Rating Scale for depression were significantly decreased after EST and clinical symptoms such as depressive mood. psychomotor retardation, anxiety, agitation, suicidal tendencies, hypochondria and sleeplessness improved in all of the patients. Complications included amnesia (16/26), delirium (3/26) and transient arrhythmia (1/26) after EST, but neither lethal nor lasting complications were observed. In summary, EST was an effective and convenient method of treatment for senile depression.

Effects of bromocriptine in Huntington chorea. Case report.

1. The effects of bromocriptine (BC) on choreiform movement were compared with those of bromperidol (BP) and fluphenazine (FLZ) in a patient with Huntington disease. The patient (male, 42 years old) was treated with BP (15 mg/day, 4 weeks), FLZ (3 mg/day, 4 weeks), low dose of BC (5 mg/day, 4 weeks) and relatively high dose of BC (10 mg/day, 8 weeks). The CSF content of homovanilic acid (HVA) was assayed at last day of the each drug trial. The efficacy of the drugs was evaluated by electromyography. 2. Although BP and FLZ did not succeed to ameliorate the choreiform movement, both low dose and high dose BC showed rapid improvement of the involuntary movement. The CSF HVA concentration was 35.0 ng/ml before beginning treatment. Whereas FLZ and high dose of BC substantially increased the levels of HVA after the dosage (49.3 and 53.1 ng/ml, respectively), moderate increase of HVA (41.5 ng/ml) was observed when the low dose of BC was administered. These observations suggest that increase of CSF HVA might be necessary for clinical improvement of choreiform movement but not correlate with the degree of improvement and dopamine agonists could be useful drug for the treatment of choreiform movement which is refractory to the administration of neuroleptics.

Intraventricular infusion of leupeptin decreases Bmax of the D2 receptor in the striatum of young rats.

Intraventricular infusion of a thiol protease inhibitor, leupeptin, was previously shown to induce several morphological and immunochemical manifestations of normal and pathological aging in rat brain. The present study attempted to elucidate whether this treatment also perturbs another brain function which declines in aging, dopamine D2 receptor binding in striatum. Intraventricular infusion of leupeptin (0.6 mg per day) for two weeks caused a significant (about 20%) reduction in the binding maximum (Bmax) of dopamine D2 receptors (as examined by [3H] spiperone binding) in the striatum of young male Fischer-344 rats in comparison to (saline-infused) control rats. The apparent Kd values did not differ significantly between the control and leupeptin-treated rat groups. The results suggest that decreased protein turnover may be a factor in the decline in Bmax of D2 receptors during aging.

[Depression in late life].

Depression is the most common psychiatric condition encountered in elderly people. The present paper intended to first review past epidemiological studies on depression in late life and secondly to investigate the symptomatological characteristics of depression in the elderly. The author also report significant results of a therapeutic approach to late-life depression, including antidepressant drug treatment and non-convulsive electric shock therapy. Previous epidemiological studies on prevalence rate of late life depression can be divided into two distinct groups according to their different methodologies including subjective and objective evaluations. Approximately 30% subjectively evaluated and 3% objectively evaluated in elderly people older than 65 years of age were depressed with depressed women outnumbering men approximately 2 to 1. Comparisons of the symptomatological characteristics were made in an extremely wide series of 104 depressed in-patients. Depressed patients with hypochodriacal complaints, pseudo-dementia, delusion and suicidal urges increased with aging. Depressed patients with a genetic factor decreased with aging, suggesting that the depressed patients in late life seems to have multiple etiological factors. We intended to correlate the plasma levels of various antidepressant drugs to the age of the depressed patients. There were significant positive correlations between the plasma levels and the age in patients with tricyclic antidepressant (amoxapine, dothiepin) treatment while on the other hand, no significant correlation was found between the two values in the patients with non-tricyclic antidepressant (setiptiline) treatment. These results suggest that non-tricyclic antidepressant drug should be selected for the treatment of depression in the elderly.(ABSTRACT TRUNCATED AT 250 WORDS)

Redistribution of haloperidol after electroshock: experimental evidence.

We have previously reported that plasma and red blood cell levels of haloperidol, a neuroleptic agent, significantly increased immediately after electroconvulsive shock therapy (ECT) in schizophrenic patients on long term haloperidol treatment. To elucidate the mechanism of this increase, we attempted to reproduce this phenomenon in female Wistar rats. After 4 successive days of ip administration of haloperidol (10 mg/kg body weight, once daily), rats were given ECT through corneal electrodes on the fifth day (a.c. 50 Herz, 55 mA, 2.0 sec). Haloperidol levels were determined in plasma and other major tissues using a radioreceptor assay for haloperidol distribution before and after ECT at appropriate time intervals. Plasma haloperidol level was significantly increased 1 min after ECT but tended to return to the control level (without ECT) after 5 min. A significant decrease in haloperidol concentration in tissues was not observed in any of the tissues examined including frontal cerebrum, striatum, and muscle tissues (gluteal muscles). However, the relatively high haloperidol level and the large volume of muscle tissues suggested that the muscle could be the source of the transient increase in haloperidol levels in plasma. This conclusion was also supported by the data showing no significant rise of plasma haloperidol level after ETC in rats previously given a muscle relaxant, succamethonium chloride.

Plasma neuroleptic levels in the elderly patients on propericiazine therapy--possible role of morbidity.

Plasma neuroleptic levels of 31 elderly psychiatric patients (8 males and 23 females, age 80.1 +/- 8.95 years) on chronic propericiazine therapy and with multimorbidity were measured by means of radioreceptor assay. There was no significant correlation between the daily dose and the plasma neuroleptic level. Nor was there any significant correlation between the patients' age and the ratio of plasma neuroleptic level to the daily dose. On the other hand, the immobility score of patients (GBS scale) had a high correlation with the ratio of the plasma neuroleptic level to the daily dose. Furthermore, patients with positive C-reactive protein (CRP) had an average ratio value 3-fold higher than the CRP negative group. The results suggest that the plasma neuroleptic level of propericiazine in elderly patients is raised by morbidity and immobility rather than chronological age per se.

Absence of age effect on plasma haloperidol neuroleptic levels in psychiatric patients.

Plasma neuroleptic levels in 41 patients (21 men, 20 women, aged 18 to 74) on haloperidol therapy were examined in relation to their age by means of radioreceptor assay. There was no significant difference among three age groups (below 45 years, 46 to 60 years, over 60 years) in the ratio of the plasma neuroleptic level to daily dose (nM/mg/kg), but a significant difference in the plasma neuroleptic level was found between the average values in parkinsonian (19.1 +/- 8.5 nM, M +/- SD) and nonparkinsonian (5.5 +/- 3.0 nM, M +/- SD) patients. There was, however, no significant difference in the incidence of parkinsonian symptoms between the young (below 60 years) and the old (over 60 years) age groups. These results suggest that in contrast to the previously reported study with chlorpromazine, the plasma neuroleptic level of haloperidol is not altered with aging and that parkinsonian symptoms induced by haloperidol occur simply in a plasma-neuroleptic-level-dependent manner.

Electric convulsive therapy (ECT) increases plasma and red blood cell haloperidol neuroleptic activities.

In nine schizophrenic patients (five males and four females) on haloperidol treatment, plasma and red blood cell (RBC) haloperidol neuroleptic activities were measured before and after ECT by radioreceptor assay. Five patients randomly selected from these patients also served as controls on another occasion and neuroleptic activities in plasma and RBC were examined before and after the premedication only. All patients given ECT showed a considerable increase in plasma and RBC haloperidol neuroleptic activities after ECT (% increase in plasma neuroleptic activity, 28-409%; mean + SD, 136 +/- 155%, P less than 0.005, Wilcoxon test; % increase in RBC neuroleptic activity, 11-121%; mean + SD, 59 +/- 40%, P less than 0.005). However, no significant increase was observed for either plasma or RBC haloperidol neuroleptic activity, when patients were examined after premedication only. It was suggested that ECT induced a transient redistribution of haloperidol. It remains to be studied whether this phenomenon is causally related to the previous observation that the combination therapy of ECT and neuroleptics is more effective in the treatment of schizophrenia than ECT alone.

Neuroleptic, antimuscarinic, and antiadrenergic activity of chlorpromazine, thioridazine, and their metabolites.

Chlorpromazine and thioridazine are widely used antipsychotic agents that are extensively metabolized. Parent compounds and metabolites have diverse pharmacologic activities, and differences in patterns of metabolism may explain differences in therapeutic and side effects from individual to individual. Radioreceptor assays were used to determine the neuroleptic, antimuscarinic, and anti-alpha-noradrenergic potency of chlorpromazine, thioridazine, and their metabolites. The results indicate that these metabolites show a wide range of potencies. The spectrum of activity of a metabolite may be quite different from that of its parent compound. The clinical relevance of these findings to individual differences in drug response is discussed. The combined use of radioreceptor assays and chemical assays in future clinical research is proposed.