Daiga M. Helmeste

Influence of exercise on serum brain-derived neurotrophic factor concentrations in healthy human subjects.

The effect of short-term exercise (15 min step-exercise) on serum brain-derived neurotrophic factor (BDNF) levels was evaluated in healthy human subjects. Results showed a short-term, significant increase in serum BDNF levels after exercise. Intra-individual differences in serum BDNF levels were remarkably small on the rest day and also when compared to rest values on the day of the exercise test. Inter-individual differences, on the other hand, were larger by comparison. The result of this study supports the need for larger sample size in studies on BDNF changes in psychiatric disorders or psychiatric drug effects.

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.

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.

Amphetamine-induced hypolocomotion in mice with more brain D2 dopamine receptors

The relationship between brain D2 dopamine receptors and locomotor response to amphetamine was investigated in eight strains of mice. The D2 receptor is defined as that dopaminergic site with high affinity (nanomolar) for neuroleptics and low affinity (micromolar) for agonists. D2 receptors were measured in the striatum and olfactory tubercle using [3H]spiperone and 10 microM sulpiride to define specific binding. Four inbred strains of mice (CBA/J; C57BL/6J; DBA/2J; SEC/1ReJ) had low receptor densities of about 380 and 160 fmoles/mg protein in the striatum and olfactory tubercle, respectively; all these mice were essentially nonresponsive (i.e., locomotion) to low doses of amphetamine (0.5 and 1.0 mg/kg i.p.) or showed hyperlocomotion to high doses (5 mg/kg). Three other mouse strains (BALB/cJ; A/J; C3H/HeJ) had higher densities of about 600 and 230 fmoles/mg protein in the striatum and olfactory tubercle, respectively, and these mice all responded with hypolocomotion to the low doses and hyperlocomotion to the high dose of amphetamine. The two genetically different populations, one of which responded to amphetamine with hypolocomotion while the other did not, are analogous to hyperactive children, only 70% of whom respond to amphetamine-like drugs. Thus, the mice with high receptor density may serve as a model for studying the hyperactivity syndrome which may be associated with dopaminergic dysfunction.

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.

Decrease in σ but no increase in striatal dopamine D4 sites in schizophrenic brains

Abstract [3H]Nemonapride differentially defines σ and dopamine receptor sites depending upon assay conditions. In post-mortem schizophrenic brain tissues, [3H]nemonapride-labeled σ receptor binding is decreased compared to matched normal controls. No striatal dopamine D 4 D 4 - like receptor differential was observed between the schizophrenic or control tissues, using the [3H]nemonapride minus [3H]raclopride subtraction method.

Modulation of the suppressive effect of corticosterone on adult rat hippocampal cell proliferation by paroxetine.

ObjectiveThe literature has shown that cognitive and emotional changes may occur after chronic treatment with glucocorticoids. This might be caused by the suppressive effect of glucocorticoids on hippocampal neurogenesis and cell proliferation. Paroxetine, a selective serotonin reuptake transporter, is a commonly used antidepressant for alleviation of signs and symptoms of clinical depression. It was discovered to promote hippocampal neurogenesis in the past few years and we wanted to investigate its interaction with glucocorticoid in this study.MethodsAdult rats were given vehicle, corticosterone, paroxetine, or both corticosterone and paroxetine for 14 d. Cell proliferation in the dentate gyrus was quantified using 5-bromo-2-deoxyuridine (BrdU) immunohistochemistry.ResultsThe corticosterone treatment suppressed while paroxetine treatment increased hippocampal cell proliferation. More importantly, paroxetine treatment could reverse the suppressive effect of corticosterone on hippocampal cell proliferation.ConclusionThis may have clinic application in preventing hippocampal damage after glucocorticoid treatment.

Unusual acute effects of antidepressants and neuroleptics on S2-serotonergic receptors

The antidepressants mianserin and amoxapine, and the neuroleptic loxapine caused significant decreases in the number of rat frontal cortex S2-serotonergic receptors after a single acute injection. The affinity of serotonin for this site was also decreased after acute mianserin. Daily injections of loxapine and amoxapine for 2, 7 or 28 days resulted in decreased receptor density but no change in Kd. Down-regulation of S2 sites by mianserin was not dependent on endogenous serotonin stores or occupation of the S2 recognition site since chronic PCPA or acute ketanserin preadministration did not affect the mianserin-induced decreases. The results suggest that mianserin may be acting on other sites which it does not share in common with other S2-antagonists such as ketanserin.

Is neurogenesis relevant in depression and in the mechanism of antidepressant drug action? A critical review.

Abstract Objectives. Major depression is a complex disorder that involves genetic, epigenetic and environmental factors in its aetiology. Recent research has suggested that hippocampal neurogenesis may play a role in antidepressant action. However, careful examination of the literature suggests that the complex biological and psychological changes associated with depression cannot be attributed to disturbance in hippocampal neurogenesis alone. While antidepressants may induce hippocampal neurogenesis in non-human primates, there is a paucity of evidence that such effects are sufficient for full therapeutic action in humans. Methods. This review examines the literature on neurogenesis and discusses the stress-induced cortisol neurotoxicity and antidepressant-induced neurogenesis rescue model of depression. The disparity between a simple antidepressant-induced neurogenesis rescue model in the hippocampus and the complexity of clinical depression is analyzed through critical evaluation of recent research data. Results and conclusions. Major depression is a complex brain disorder with multiple symptoms and disturbances reflecting dysfunction in more than one single brain area. Initial research suggesting a model of hippocampal degeneration as basis of depression, and reversal by antidepressants through neurogenesis seems to be over-simplified given the emergence of new data. Synaptogenesis and re-organization or re-integration of new neurons rather than simple addition of new neurons may underlie the role of antidepressant drugs in the reversal of some but not all symptoms in depression. The importance of the neurogenesis hypothesis of depression and antidepressant action lies in stimulating further research into the possible roles played by the new neurons and synapses generated.