Differential judgement of static facial expressions of emotions in three cultures.

Judging facial expressions of emotions has important clinical value in the assessment of psychiatric patients. Judging facial emotional expressions in foreign patients however, is not always easy. Controversy has existed in previous reports on cultural differences in identifying static facial expressions of emotions. While it has been argued that emotional expressions on the face are universally recognized, experimental data obtained were not necessarily totally supportive. Using the data reported in the literature, our previous pilot study showed that the Japanese interpreted many emotional expressions differently from USA viewers of the same emotions. In order to explore such discrepancies further, we conducted the same experiments on Chinese subjects residing in Beijing. The data showed that, similar to the Japanese viewers, Chinese viewers also judged many static facial emotional expressions differently from USA viewers. The combined results of the Chinese and the Japanese experiments suggest a major cross-cultural difference between American and Asian viewers in identifying some static facial emotional expressions, particularly when the posed emotion has negative connotations. The results have important implications for cross-cultural communications when facial emotional expressions are presented as static images.

Effect of venlafaxine on imipramine metabolism.

The present study was designed to determine the effect of venlafaxine on imipramine metabolism in an attempt to elucidate the potential for cytochrome P450 drug-drug interactions with venlafaxine. We examined the metabolism of a single 100-mg dose of imipramine before and after treatment with venlafaxine, 50 mg three times a day. Eight male subjects were phenotyped for CYP2D6 activity. Two subjects were poor metabolizers of dextromethophan, and data from the remaining six subjects (mean age=45.3+/-15) were analyzed. Venlafaxine increased imipramine C(max) and elevated AUC by 40%. Desipramine clearance and volume of distribution were reduced by 20% and 25%, respectively. These findings are consistent with a statistically significant, but clinically modest impact of venlafaxine on CYP2D6-metabolized substrates.

Dopamine D4 receptors.

Initial investigations on dopamine D4 receptors generated much interest in the role of this receptor in schizophrenia and other aspects of human behavior, as well as new opportunities for novel therapeutics. However, attempts to treat patients suffering from schizophrenia with dopamine D4 agents have failed to yield satisfactory results so far. An examination of the dopamine D4 literature shows that contrasting and conflicting data seemed to be the norm in this field of research. This paper reviews the literature on the dopamine D4 receptor and discusses many of the associated methodological problems that might have contributed to the paradoxical findings.

Digital psychiatry.

The American managed care movement has been viewed as a big experiment and is being watched closely by the rest of the world. In the meanwhile, computer-based information technology (IT) is changing the practice of medicine, much more rapidly than managed care. A New World of digitized knowledge and information has been created. Although literature on IT in psychiatry is largely absent in peer-reviewed psychiatric journals, IT is finding its way into all aspects of medicine, particularly psychiatry. Telepsychiatry programs are becoming very popular. At the same time, medical information sites are flourishing and evolving into a new health-care industry. Patient-physician information asymmetry is decreasing as patients are gaining easy access to medical information hitherto only available to professionals. Thus, psychiatry is facing another paradigm shift, at a time when most attention has been focused on managed care. In this new digital world, knowledge and information are no longer the sole property of professionals. Value will migrate from traditional in-person office-based therapy to digital clinical products, from in-person library search and classroom didactic instruction to interactive on-line searches and distance learning. In this time of value migration, psychiatrists have to determine what their 'distinctive competence' is and where best to add value in the health-care delivery value chain. The authors assess the impact of IT on clinical psychiatry and review how clinical practice, education and research in psychiatry are expected to change in this emerging digital world.

Binding of [3H]U-101958 to sigma1 receptor-like sites in human cerebellum and neuroblastoma cells.

1-Benzyl-4-[N-(3-isopropoxy-2-pyridinyl)-N-methyl]-amino-piperidine ([3H]U-101958), a dopamine D4 receptor ligand, was found to bind to a large sigma1 receptor-like component in human cerebellum and SK-N-MC neuroblastoma cells with high affinity (2-4 nM Kd). By contrast, binding to dopamine D4 receptors represented 10% or less of the sigma1 receptor-like site. Considering that U-101958 has been characterized as either a dopamine D4 receptor agonist or antagonist, depending on the system under study, the observation that U-101958 also binds to sigma1 receptor-like sites is important for accurate interpretation of the pharmacological actions of this compound. [3H]U-101958 may be a useful radioligand for sigma1 rather than dopamine D4 receptor sites.

Misinterpretation of facial expression: a cross-cultural study.

Accurately recognizing facial emotional expressions is important in psychiatrist-versus-patient interactions. This might be difficult when the physician and patients are from different cultures. More than two decades of research on facial expressions have documented the universality of the emotions of anger, contempt, disgust, fear, happiness, sadness, and surprise. In contrast, some research data supported the concept that there are significant cultural differences in the judgment of emotion. In this pilot study, the recognition of emotional facial expressions in 123 Japanese subjects was evaluated using the Japanese and Caucasian Facial Expression of Emotion (JACFEE) photos. The results indicated that Japanese subjects experienced difficulties in recognizing some emotional facial expressions and misunderstood others as depicted by the posers, when compared to previous studies using American subjects. Interestingly, the sex and cultural background of the poser did not appear to influence the accuracy of recognition. The data suggest that in this young Japanese sample, judgment of certain emotional facial expressions was significantly different from the Americans. Further exploration in this area is warranted due to its importance in cross-cultural clinician-patient interactions.

Cultural difference in recognition of facial emotional expression: contrast between Japanese and American raters.

Using the Japanese and Caucasian Facial Expressions of Emotion (JACFEE) photo set, the relationship between recognition and intensity ratings of universal facial expressions of emotions in 123 Japanese undergraduate students was examined and compared with data reported by American raters. In Japanese raters, although the intensity was rated as high for some of the poses, their correctness scores were poor, suggesting a serious misjudgment of the intended emotions as defined in the JACFEE photo set. Only in Japanese raters were significant relationships between the intensity scores and the percentage correctness scores for sadness detected (r = 0.97, P < 0.0001), but no significant relationship was observed for other emotions. The robust correlation suggests the possibility that Japanese raters might be more responsive to certain emotional expressions when they are fully or intensely expressed. It is proposed that the facial emotional expression paradigm cannot be applied to the psychiatric setting without first refining for cultural differences.

The role of calcium in the etiology of the affective disorders.

Calcium abnormalities are some of the more consistent findings in platelets of affective disorder patients. While medication status does not correlate with this finding, antidepressants do modulate intracellular calcium. This, in combination with reports that calcium channel inhibitors may have antidepressant potential, suggests that calcium may play an important role in this disorder. This paper reviews the specificity of calcium abnormalities for the affective disorders and also discusses possible mechanisms of action.

Inhibition of platelet serotonin uptake by cytochrome P450 inhibitors miconazole and econazole.

Serotonin uptake in human platelets was inhibited by cytochrome P450 inhibitors such as miconazole and econazole but not clotrimazole. There was a correlation between inhibition of serotonin uptake and inhibition of imipramine binding, suggesting that these P450 inhibitors may inhibit serotonin uptake via direct binding to the transporter. P450 inhibitor effects on serotonin uptake did not seem to be related to the effects of these compounds on intracellular calcium mobilization. Additionally, nitric oxide pathway stimulation does not appear to be involved.

Differential labeling of dopamine and sigma sites by [3H]nemonapride and [3H]raclopride in postmortem human brains.

The difference between the binding of [3H]nemonapride and [3H]raclopride has been used to quantify dopamine D4 receptors in postmortem schizophrenic brain studies. Recent work, however, has suggested that at least part of the differential between [3H]nemonapride and [3H]raclopride binding may represent sigma rather than D4 receptor sites. We applied the nemonapride-raclopride subtraction method to postmortem, non-schizophrenic human striatum to examine the variation in dopaminergic receptor binding labeled by these ligands. Variation in sigma receptor binding labeled by [3H]nemonapride was studied in frontal cortex, striatum and cerebellum. Specific binding was defined by sulpiride (dopamine receptor ligand), PPAP (sigma receptor ligand) and haloperidol (mixed dopaminergic/sigma agent), respectively. Haloperidol defined a combination of sites, which were approximately the sum of the dopaminergic and sigma components defined by sulpiride and PPAP, respectively. Significant inter-individual variation in the amount of specific binding for dopaminergic and sigma receptor sites was observed. However, no significant nor consistent observation of striatal dopamine D4 receptors or D4-like binding sites was observed in the striatum even though two independent sets of tissues, with different dissections were used. The inconsistencies in some previous postmortem studies appear to be at least partially explained by the inclusion of both sigma and dopaminergic components in [3H]nemonapride binding and the inherent high inter-individual variability of the different components.

Multiple [3H]-nemonapride binding sites in calf brain.

[3H]-Nemonapride has been the ligand of choice to label D4 dopamine receptors. Its specificity was questioned when it was discovered that sigma (sigma) sites were also labeled by [3H]-nemonapride. To further characterize the binding of [3H]-nemonapride, three areas of calf brain (striatum, frontal cortex and cerebellum) were examined. In all three areas, [3H]-nemonapride labeled multiple sites. Dopaminergic and sigma sites were the most prominent. The sigma binding profile was sigma-1 like with a Ki binding profile as follows (in order of decreasing potency): haloperidol, PPAP, pentazocine, DTG, U-50488, R(+)-3-PPP. Experiments using sulpiride and pentazocine to block striatal dopaminergic and sigma sites, respectively, revealed additional, not previously characterized binding sites for [3H]-nemonapride. One component which was present in striatum but not in frontal cortex or cerebellum, had affinity for some neuroleptics and WB-4101, but not for typical serotonergic agents. Thus, [3H]-nemonapride has no selectivity for dopamine receptors unless stringent experimental conditions are met.

Rapid determination of venlafaxine and O-desmethylvenlafaxine in human plasma by high-performance liquid chromatography with fluorimetric detection.

A rapid and sensitive high-performance liquid chromatographic technique for simultaneous measurement of plasma venlafaxine (VEN) and its active metabolite O-desmethylvenlafaxine (ODV) is described. The process begins with the extraction of VEN and ODV, with maprotiline (MAP) as internal standard, from human plasma into an intermediate organic mixture of hexane-isoamyl alcohol and finally into an aqueous solution of 0.05% phosphoric acid. Isocratic separation of VEN, ODV and MAP is carried out by utilizing a reversed-phase butyl-bonded column (C4/E) with mobile phase consisting of acetonitrile and 40 mM phosphate buffer, pH 6.8 (50:50, v/v). Detection of VEN, ODV and MAP is done by mean of fluorimetry with excitation and emission wavelengths set at 276 and 598 nm, respectively. As low as 1.0 ng/ml VEN is detectable; while the limit of detection for ODV is 5 ng/ml. C.V. (%) of intra-day samples for both VEN and ODV are less than 10% at three concentrations tested (10.0, 50.0, 100.0 ng/ml). Similarly, over the same nominal concentrations, the precision of inter-day (5 days) samples also results in C.V. (%) smaller than 10% for both compounds, except for ODV measured at 10 ng/ml (C.V.<15%). Approximately, 100% VEN can be extracted from plasma; whereas, for ODV the recovery rate is nearly 70%. This present method is rapid, sensitive, accurate and simple for routine clinical monitoring of plasma VEN and its major metabolite ODV.

Decrease in sigma but no increase in striatal dopamine D4 sites in schizophrenic brains.

[3H]Nemonapride differentially defines sigma and dopamine receptor sites depending upon assay conditions. In post-mortem schizophrenic brain tissues, [3H]nemonapride-labeled sigma receptor binding is decreased compared to match normal controls. No striatal dopamine D4/D4-like receptor differential was observed between the schizophrenic or control tissues, using the [3H]nemonapride minus [3H]raclopride subtraction method.

Brain sigma receptors labelled by [3H]nemonapride.

Binding of [3H]nemonapride and [3H]raclopride was examined in the brain areas of three species (rat, cow and human). The results indicated that [3H]nemonapride binding is inhibited by selective sigma receptor ligands in frontal cortex, striatum and cerebellum. Only the striatum showed significant dopaminergic sites as defined by sulpiride. Use of the subtraction method of [3H]nemonapride minus [3H]raclopride binding as a measure of D4 dopamine receptor binding may, therefore, also include a sigma receptor component.

Serotonin indices and impulsivity in normal volunteers.

Hormonal responses to oral paroxetine were examined in a group of healthy subjects. The calcium response to serotonin (5-hydroxytryptamine, 5HT), mediated by platelet 5HT2A, was also measured. Paroxetine elicited a cortisol response that was directly correlated with the magnitude of platelet calcium response. The cortisol response was also correlated with the trait of impulsivity. These results suggest that paroxetine may be a useful probe in studies of serotonergic systems.

Paroxetine shifts imipramine metabolism.

The combination of selective serotonin reuptake inhibitors with tricyclic antidepressants has proven useful in treatment-resistant depression but has the potential for adverse drug-drug interactions. In the present study, the metabolism of a single dose of imipramine was studied before and after treatment with paroxetine. Paroxetine induced significant elevations of approximately 50% in half-life, area under the curve, and Cmax of imipramine and decreased clearance twofold. The effects on desipramine pharmacokinetics were even more pronounced. These findings indicate a significant interaction of paroxetine with the CYP2D6 isoenzyme.

Serotonin-stimulated intracellular calcium mobilization in platelets from alcoholic men.

Numerous lines of evidence have suggested a key role for serotonin (5-hydroxytryptamine, 5HT) pathways in the regulation of alcohol consumption. To explore the functioning of the 5HT2 receptor in alcoholism, 5HT-stimulated intracellular calcium response was measured in platelets from abstinent alcoholic patients and normal comparison subjects. No difference in resting or stimulated calcium levels was observed. This finding suggests that 5HT2 receptor function is unaffected in non-drinking alcoholic subjects. The previously reported 5HT inhibition in actively drinking alcoholic subjects is likely to be a state rather than trait marker of alcoholism.

Tyrosine kinase inhibitors regulate serotonin uptake in platelets.

Uptake of tritiated serotonin into human platelets was found to be rapidly inhibited by the tyrosine kinase inhibitors, genistein and methyl 2,5-dihydroxycinnamate. Binding studies indicated that uptake inhibition did not correlate with direct binding of these inhibitors to the transporter. Chelation of mobilizable intracellular Ca2+ did not inhibit the effects of genistein on uptake. These results suggest a more direct, non-Ca2+ mediated effect of tyrosine kinase inhibitors on uptake.

Serotonin uptake inhibitors modulate intracellular Ca2+ mobilization in platelets.

The serotonin uptake inhibitors sertraline, paroxetine and fluoxetine were compared with imipramine and the calmodulin antagonists N-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide (W-7) and calmidazolium, for their effects on intracellular Ca2+ mobilization in human platelets. All serotonin uptake inhibitors and calmodulin antagonists augmented thrombin-mediated increases in intracellular Ca2+. Sertraline, calmidazolium and W-7 also caused large dose-dependent increases in baseline levels of intracellular Ca2+. There was a rough correlation between the ability to elevate intracellular Ca2+ and potencies for inhibition of calmodulin. Neomycin, an inhibitor of inositol trisphosphate (IP3) generation, significantly inhibited the effects of sertaline. This is consistent with a role of IP3 and calmodulin in the effects of these drugs.

Kinase inhibitors compete with imipramine for binding and inhibition of serotonin transport.

Effects of kinase inhibitors and activators on the binding of tritiated imipramine and inhibition of serotonin uptake were tested in platelets. The majority of compounds inhibited specific [3H]imipramine binding and serotonin uptake with affinities similar to those reported for their action on protein kinases themselves. Many of these compounds are derivatives with modified naphthalenesulfonamide or isoquinolinesulfonamide structures, which appear to compete directly with imipramine for binding to the serotonin transporter. This is of great importance for studies involving kinase regulation since at these concentrations, the inhibitors and activators were previously thought to interact virtually exclusively with protein kinases.