Personality correlates of platelet monoamine oxidase activity and red cell lithium transport

Platelet monoamine oxidase (MAO) activity and the ratio of red cell to plasma lithium concentrations (Li ratio) may be important in the pathophysiology of, and genetic vulnerability to, some psychiatric disorders. By using the Clinical Analysis Questionnaire, we assessed personality correlates of MAO activity and the Li ratio in vitro in a sample of psychiatrically normal adult women. We found that there were correlates of each variable, and a unique constellation of personality traits when the two variables were considered simultaneously.     

Low platelet monoamine oxidase activity: A possible biochemical correlate of borderline schizophrenia

Platelet monoamine oxidase (MAO) activity, psychiatric disorders, and family history of psychopathology were studied in 115 nonhospitalized, previously undiagnosed college student volunteers. Subjects were classified into two extreme groups: those with platelet MAO activity two standard deviations below the mean (“low-MAO” probands) and those with platelet MAO activity two standard deviations above the mean (“high”-MAO probands). Low-MAO probands were found to have a significant increase in the incidence of borderline schizophrenia and other psychiatric disorders compared to high-MAO probands. First-degree relatives of low-MAO probands were more often affected with psychiatric disorders and borderline schizophrenia than relatives of high-MAO probands. The data suggest that reduced platelet MAO activity is associated with psychiatric vulnerability and that the spectrum of schizophrenia may be more closely related to this vulnerability than other psychiatric disorders.     

Morbidity risk for psychiatric disorders in families of probands with affective disorders divided according to levels of platelet MAO activity

In a series comprising 166 subjects with affective disorders, the lowest and highest quartiles in the male and female platelet monoamine oxidase (MAO) distribution, respectively, were included. The morbidity risk in the first-degree relatives (parents and siblings) of these low and high platelet MAO subjects was determined. First-degree relatives of low platelet MAO probands were found to have an increased morbidity risk for neurotic-reactive depressions and for alcoholism. The results seem to be in line with the biological high-risk paradigm, indicating that platelet MAO could be a biological marker for increased vulnerability. First-degree relatives of high platelet MAO probands were found to have an increased morbidity risk for bipolar affective disorders.     

Life events and biological vulnerability: a study of life events and platelet MAO activity in depressed patients

The present study investigated the possible relationship between platelet monoamine oxidase (MAO) activity and life events. From the general hypothesis that the impact of life events should be seen against the background of an individual's vulnerability, it was assumed that low platelet MAO patients would need fewer life events to develop a psychopathological condition and that they would experience more negatively those events that occurred. Patients (n = 127) of both sexes suffering from various kinds of depressive disorders participated in the study. There were 39 unipolar patients, 11 bipolar patients, 43 patients suffering from neurotic-reactive disorder, and 34 patients suffering from an unspecified depressive disorder. No statistically significant differences in MAO activity were found in this series among the diagnostic subgroups. Younger patients predominated among those with the lowest MAO values. As expected, low MAO patients reported a lower number of life events than patients in the highest MAO quartile, and had experienced those events more negatively.     

注意缺陷多动障碍血小板单胺氧化酶活性测定的初步研究

本文测定了注意缺陷多动障碍（ＡＤＨＤ）患者血小板单胺氧化酶活性，结果显示ＡＤＨＤ时该酶活性明显低于对照组，而在经哌醋甲酯治疗后无明显改变，与Ｃｏｎｎｅｒｓ量表也未显示出明显相关。文中还对单胺氧化酶与治疗的关系进行了讨论。     

Low B12 levels related to high activity of platelet MAO in patients with dementia disorders. A retrospective study

In 35 patients with Alzheimer's presenile disease (AD), 56 patients with senile dementia of the Alzheimer type (SDAT), 54 patients with vascular dementia (VD) and 10 patients with confusional states, age, vitamin B12 in serum, P-folate, B-folate and B-Hb were investigated. Platelet monoamine oxidase (MAO) and cerebrospinal fluid (CSF) levels of homovanillic acid (HVA), 5-hydroxyin-doleacetic acid and 3-methoxy-4-hydroxyphenylglycol were measured. Group differences showed that vitamin B12 levels were reduced in the group of patients with confusional states and SDAT. Five out of ten and 13 out of 56 (respectively) had vitamin B12 concentrations below the lower limit of the reference value (130 pmol/l). A negative correlation was found between B12 levels and platelet MAO activity. The findings indicate that there is a subgroup of patients with late-onset dementia that has low vitamin B12 blood concentrations. HVA levels in CSF, usually found to be reduced in AD patients, were normal in this subgroup.     

Prevalence and correlates of depression in late life: a population based study from a rural Greek town

BACKGROUND: Depression in late life is common and has serious consequences on function, medical co-morbidity, quality of life, and use of medical services. OBJECTIVE: To estimate the age- and gender-specific prevalence of depression among people over 60 years of age, and to examine correlates of depression, in particular the relationship between depression and cognitive impairment. METHOD: From a total of 965 inhabitants, aged over 60 years, in Velestino, a rural town in central Greece, 608 were accessible and constituted the target population. During a five-month period in 2000, a trained health visitor interviewed all study participants. The interview covered socio-demographic characteristics, medical history, and administration of the 15-question Geriatric Depression Scale (GDS-15) and the Mini Mental Scale Examination instrument (MMSE). RESULTS: The prevalence of mild or more severe depression (GDS> or =7) was 27%, while the prevalence of moderate to severe depression (GDS> or =11) was 12%. Increasing age, female gender, lower education, and being currently unmarried were associated with higher risk of depression in univariate regression models, but these associations disappeared after controlling for cognitive function, except for the association with marital status. Cognitive impairment was strongly associated with increased risk for depression. The co-morbid presence of digestive, neurological and heart conditions was also associated with increased risk for depression, while cancer was not. CONCLUSION: In a rural Greek area, the prevalence of depression in late life is high. Depression was more common among unmarried individuals, those with significant cognitive impairment, and in association with specific medical conditions.     

807C/T polymorphism of platelet glycoprotein Ia gene is associated with cerebral hemorrhage in a Chinese population

Platelet glycoprotein (GP) mediated the role of platelet in coagulation. Platelet GP Ia 807C/T is the only GP polymorphism associated with the expression levels of GP Ia/IIa (the platelet collagen receptor). Recently, the GP Ia 807C/T polymorphism has been reported to have no association with cerebral hemorrhage (CH) in two studies pertained to Caucasian populations. The purpose of this study is to evaluate the association between platelet GP Ia 807C/T polymorphism and CH in a Han Chinese population. We performed genotype analysis for platelet GP Ia 807C/T polymorphism in a case-control study involving 195 patients with CH and 116 age- and sex-matched controls. In contrast to previous reports, we found that the frequencies of GP Ia 807C/T T allele, CT and TT genotype were much higher in CH patients than in controls (33.9% vs. 22.8%, p = 0.004; 45.5% and 11.1% vs. 40.4% and 2.6%, p = 0.022). Logistic regression analysis revealed that the presence of GP Ia 807C/T C allele and CC genotype were both associated with a decreased risk of CH compared with T allele, CT and TT genotypes, respectively (adjusted odds ratio [OR] = 0.565, 95% CI: 0.384–0.887, p = 0.005; adjusted OR = 0.172, 95% CI: 0.043–0.639, p = 0.009; adjusted OR = 0.254, 95% CI: 0.085–0.961, p = 0.041, respectively). These findings indicated that platelet GP Ia 807C/T polymorphism could be a protective factor of CH in the Chinese population.     

Effect of monoamine oxidase inhibition on amphetamine-evoked changes in dopamine receptor availability in the living pig: a dual tracer PET study with [11C]harmine and [11C]raclopride

The activity of both isozymes of monoamine oxidase (MAO) is reduced by 50% in the brain of human smokers. We hypothesized that this is not an epiphenomenon, but should bring about potentiation of the action of psychostimulant drugs. To test this hypothesis, we carried out serial positron emission tomography (PET) studies in G?ttingen miniature pigs to measure the binding of the MAO-A ligand [11C]harmine and to measure the changes in [11C]raclopride binding evoked by a low dose of amphetamine (0.7 mg/kg as free base, i.v.), first in a baseline condition, and, one month later, after acute treatment with pargyline (2 x 3 mg/kg as free base, i.m.). In the baseline, the distribution volume of [11C]harmine relative to the arterial input (V(d), ml g(-1)) ranged from 74 ml g(-1) in cerebellum to 139 ml g(-1) in the medial hypothalamus. Pargyline treatment reduced the magnitude of V(d) globally to 34-54 ml g(-1). Nearly complete displacement of [11C]harmine binding was detected in neocortex and striatum, but there was evidence for pargyline-resistant binding in the pituitary gland and diencephalon. In the baseline condition, the low dose of amphetamine evoked a 14% decline in the binding potential (BP) (pB) of [11C]raclopride in striatum (P = 0.026). After pargyline treatment, the amphetamine effect was of similar magnitude (-11%), although not statistically significant (P = 0.054). However, the second amphetamine challenge evoked a 24% reduction in [11C]raclopride pB relative to the original baseline condition (P = 0.018). Present results do not strongly support our hypothesis that MAO inhibition should potentiate the amphetamine-evoked dopamine release as measured in the [11C]raclopride competition paradigm.     

Antithrombotic activity of Z4A5, a new platelet glycoprotein IIb/IIIa receptor antagonist evaluated in a rabbit arteriovenous shunt thrombosis model

Introduction

The antithrombotic effect of the glycopreotein IIb/IIIa (GP IIb/IIIa) receptor antagonist Z4A5, exert alone or combination with heparin, and/or aspirin, was examined in a rabbit arteriovenous shunt thrombosis model.

Materials and Methods

Thrombosis was induced by the insertion of a silk thread (thrombogenic substrate) into an extracorporeal shunt. Before and after drug administration (0, 5, and 15 min), ex vivo adenosine diphosphate (ADP)-induced platelet aggregation and coagulation parameters (prothrombin time (PT) and activated partial thromboplastin time (APTT)) were determined in platelet-rich plasma (PRP) and platelet poor-plasma (PPP), respectively.

Results

Our data demonstrated that, compared to the control, Z4A5 decreased the thrombus weight (31-65%) in a dose-dependent manner and inhibited ADP-induced platelet aggregation (47-98%) 5 min after Z4A5 administration (25-100 mg/kg). However, PT and APTT remained stable, even at the highest dose (100 mg/kg). Heparin (100 U/kg) and aspirin (15 mg/kg) also significantly reduced thrombus mass, but this effect was accompanied by an increase of APTT by heparin. Furthermore, the combination of heparin (100 U/kg) and a low dose of Z4A5 (25 mg/kg) failed to produce an additional benefit beyond that provided by heparin or Z4A5 alone, whereas Z4A5 (25 mg/kg) plus aspirin (15 mg/kg) potentiated the antithrombotic effects of both compounds without further increasing the values of coagulation.

Conclusions

Our results indicate that Z4A5 is an effective antithrombotic agent with no significant effects on values of coagulation. Furthermore, Z4A5 can potentiate these antithrombotic effects when prescribed with aspirin.     

The effect of lamotrigine on platelet monoamine oxidase type B activity in patients with bipolar depression

Lamotrigine is an anticonvulsant drug effective in the treatment of epilepsy and bipolar depression. Preclinical data showed that lamotrigine inhibited monoamine oxidase (MAO) activity in vitro. The aim of the study was to determine the effects of 6-weeks lamotrigine treatment on platelet MAO type B (MAO-B) activity in patient with bipolar depression. The study included 26 female patients with bipolar I disorder in depressive episode (DSM-IV criteria, Hamilton Depression Rating Scale (HAMD) and Young Mania Rating Scale). Platelet MAO-B activity was determined spectrofluorimetrically before and after 6 weeks of the treatment with a relatively low dose of lamotrigine (100 mg/day). Six weeks of treatment with lamotrigine significantly decreased platelet MAO-B activity in bipolar depressed patients. This inhibitory effect was not related to smoking status and was independent of the treatment combinations (lamotrigine alone or in combination with either lithium or antipsychotics). Lamotrigine treatment induced a decrease in total HAMD scores in bipolar depressed patients, which was not significantly correlated with reduction of platelet MAO-B activity. These findings provide in vivo insight of lamotrigine effect on platelet MAO-B activity in patients with bipolar depression. Its in vivo MAO-B inhibiting effect might have contributed in part to its antidepressant activity.     

Effect of feeding on Fos protein expression in sheep hypothalamus with special reference to the supraoptic and paraventricular nuclei: an immunohistochemical study

The hypothalamus plays an important role in the control of food intake in different species, but there is little relevant information for ruminants like sheep. In order to study the putative role of several hypothalamic nuclei in food intake in sheep, Fos expression, a marker of cellular activity, was compared by immunohistochemistry between fed and unfed ewes. The expression of Fos protein was stimulated in the supraoptic nucleus of fed ewes, whereas it was increased in the paraventricular nucleus of unfed animals. In the latter nucleus, Fos immunoreactivity was mainly localized close to the third ventricle, an area corresponding to the parvocellular system of the nucleus, but never in the magnocellular system. In the paraventricular nucleus, the number of corticotrophin releasing factor-immunoreactive neurons and the number of Fos/corticotrophin releasing factor double-labelled neurons were not affected by feeding or lack of feeding. The number of Fos-immunoreactive neurons was higher in the lateral septum, the infundibular, the ventromedial and in the dorsomedial nuclei of unfed ewes than in those of fed ewes. Our results show for the first time that the dorsomedial and ventromedial nuclei are involved in the control of feeding in sheep as in rodents. The supraoptic nucleus of sheep is activated by the same conditions as in rodents but, conversely, the paraventricular nucleus is activated in unfed sheep, whereas in rodents and primates, this nucleus is activated by satiety as well as by fasting. In sheep, unlike in rodents, corticotrophin releasing factor did not appear to be involved in short-term regulation of food intake.     

Quantitative mapping of cytovhrome oxidase activity in the central auditory system of the gerbil: a study with calibrated activity standards and metal-intensified histochemistry

The objective was to obtain detailed topographic determinations of cytochrome oxidase activity in the gerbil central auditory system at the light microscopic level. Quantitative techniques were developed using (1) tissue standards calibrated to express histochemical measures as actual enzyme activity units, (2) densitometry and image analysis of histochemical reaction product formation, (3) spectrophotometry of cytochrome oxidase activity, and (4) a cobalt-intensified staining procedure compatible with autoradiography and other techniques requiring fresh-frozen brains without perfusion-fixation. Linear relationships between incubation time, section thickness, and activity of dissected brain regions, with their reaction product measured densitometrically were determined. Auditory structures with the high activities showed about 8 times the labeling intensity of the white matter or control sections inhibited with cyanide, glutaraldehyde, or heat. This indicated the high sensitivity of the method without loss of specificity. Specific activity for each of the 18 auditory structures measured were all above the units measured for whole brain homogenates, supporting the notion that basal levels of oxidative metabolism are greater for the auditory system. There was a progressive decrement in activity from brain stem to forebrain auditory structures. The more peripheral nuclei also showed a higher proportion of somatic as compared to neuropil reactivity. In contrast, auditory midbrain and thalamocortical regions were characterized primarily by neuropil reactivity. Comparison of intrinsic patterns of activity with morphological schemes to subdivide nuclei, showed a good correspondence with classical subdivisions derived from Golgi studies. The reported activities may provide a base of normative data in the gerbil for subsequent studies of central auditory functions. The method presented fulfilled established quantitative criteria and provided a more sensitive approach for regional mapping studies of brain cytochrome oxidase activity.     

Influence of a low dose of amphetamine on vesicular monoamine transporter binding: A PET (+)[11C]DTBZ study in humans

We previously reported increased binding of (+)[¹¹C]DTBZ (dihydrotetrabenazine), the vesicular monoamine transporter (VMAT2) positron emission tomography (PET) radioligand, in striatum of some methamphetamine users. This finding might be explained by stimulant‐induced vesicular DA depletion resulting in decreased DA (+)[¹¹C]DTBZ competition at VMAT2. In a prospective PET study, we now find that administration of an acute oral dose of amphetamine (0.4 mg/kg) to humans does not cause increased striatal (+)[¹¹C]DTBZ binding but a slight 5% decrease. Our data suggest that a low amphetamine dose is unlikely to cause sufficient DA depletion to detect increased (+)[¹¹C]DTBZ binding and that a higher dose might be required. Synapse 64:417–420, 2010. © 2010 Wiley‐Liss, Inc.     

In vivo quantification of monoamine oxidase A in baboon brain: a PET study using [11C]befloxatone and the multi-injection approach

[¹¹C]befloxatone is a high-affinity, reversible, and selective radioligand for the in vivo visualization of the monoamine oxidase A (MAO-A) binding sites using positron emission tomography (PET). The multi-injection approach was used to study in baboons the interactions between the MAO-A binding sites and [¹¹C]befloxatone. The model included four compartments and seven parameters. The arterial plasma concentration, corrected for metabolites, was used as input function. The experimental protocol—three injections of labeled and/or unlabeled befloxatone—allowed the evaluation of all the model parameters from a single PET experiment. In particular, the brain regional concentrations of the MAO-A binding sites (B′_max) and the apparent in vivo befloxatone affinity (K_d) were estimated in vivo for the first time. A high binding site density was found in almost all the brain structures (170±39 and 194±26 pmol/mL in the frontal cortex and striata, respectively, n=5). The cerebellum presented the lowest binding site density (66±13 pmol/mL). Apparent affinity was found to be similar in all structures (K_dV_R=6.4±1.5 nmol/L). This study is the first PET-based estimation of the B_max of an enzyme.     

Effect of music care on depression and behavioral problems in elderly people with dementia in Taiwan: a quasi-experimental,longitudinal study

Objectives: The purpose was to examine the effectiveness of music care on cognitive function, depression, and behavioral problems among elderly people with dementia in long-term care facilities in Taiwan.

Methods: The study had a quasi-experimental, longitudinal research design and used two groups of subjects. Subjects were not randomly assigned to experimental group (n = 90) or comparison group (n = 56). Based on Bandura's social cognition theory, subjects in the experimental group received Kagayashiki music care (KMC) twice per week for 24 weeks. Subjects in the comparison group were provided with activities as usual.

Results: Results found, using the control score of the Clifton Assessment Procedures for the Elderly Behavior Rating Scale (baseline) and time of attending KMC activities as a covariate, the two groups of subjects had statistically significant differences in the mini-mental state examination (MMSE). Results also showed that, using the control score of the Cornell Scale for Depression in Dementia (baseline) and MMSE (baseline) as a covariate, the two groups of subjects had statistically significant differences in the Clifton Assessment Procedures for the Elderly Behavior Rating Scale.

Conclusion: These findings provide information for staff caregivers in long-term care facilities to develop a non-invasive care model for elderly people with dementia to deal with depression, anxiety, and behavioral problems.     

Acute effects of cigarette smoking on cerebral oxygenation and hemodynamics: a combined study with near-infrared spectroscopy and transcranial Doppler sonography

Cigarette smoking has been shown to increase cerebral blood flow velocity (CBFV) and reduce vasomotor reactivity temporarily. The aim of our study was to clarify whether this results from dilation of resistance vessels alone with subsequent increase in regional cerebral blood flow (rCBF), or an additional constriction of basal cerebral arteries. In 24 healthy smokers (mean age+/-S.D., 32.7+/-10.5 years), cerebral oxygenation and hemodynamics were monitored by transcranial Doppler sonography and near-infrared spectroscopy before, during, and after smoking a cigarette (nicotine 0.9 mg). We simultaneously recorded CBFV of both middle cerebral arteries, mean arterial blood pressure, skin blood flow, end-tidal CO(2), changes in concentration of cerebral oxyhemoglobin, deoxyhemoglobin, and total hemoglobin (micromol/l), and a cerebral tissue oxygenation index. Smoking increased CBFV (p<0.01), oxyhemoglobin (p<0.01), and total hemoglobin (p<0.01). After smoking, the increase in CBFV and total hemoglobin persisted (p<0.01), while oxyhemoglobin returned to baseline. Deoxyhemoglobin and cerebral tissue oxygenation index did not change during the whole procedure. During, but not after smoking, CBFV increase was correlated to ipsilateral changes in oxyhemoglobin and total hemoglobin (p<0.05).The increase in oxyhemoglobin only during smoking and the lack of changes in deoxyhemoglobin and cerebral tissue oxygenation index indicate that smoking did not substantially increase rCBF. The smoking-induced elevation in CBFV might therefore be due to an additional constriction of the middle cerebral artery. The combined effects of smoking on basal cerebral arteries and arterioles might contribute to the increased stroke risk in smokers.     

Effect of smoking habits and concomitant valproic acid use on relapse in patients with treatment-resistant schizophrenia receiving clozapine: A 1-year retrospective cohort study

Introduction

No study has investigated the impact of smoking habits and concomitant valproic acid (VPA) use on clinical outcomes in maintenance treatment with clozapine. Thus, we aimed to examine the effect of smoking habits and concomitant VPA use on relapse during the first year after discharge in patients with treatment-resistant schizophrenia (TRS) receiving clozapine.

Methods

This retrospective cohort study included patients with TRS who were initiated on clozapine during hospitalization and discharged between April 2012 and January 2021 in two tertiary psychiatric hospitals in Japan. Relapse was defined as rehospitalization due to psychiatric exacerbation during the first year after discharge. A multivariable Cox proportional hazards regression analysis was performed to analyze the effect of smoking habits and concomitant VPA use on relapse. Subgroup analyses were also conducted to examine potential interactions between smoking habits and concomitant VPA use.

Results

Among the included 192 patients, 69 (35.9%) met the criteria of relapse. While smoking habits (adjusted hazard ratio [aHR], 2.27; 95% confidence interval [CI], 1.28–4.01; p < 0.01) independently increased the risk of relapse, a significant interaction for relapse risk was found between smoking habits and concomitant VPA use (p-interaction = 0.015). Concomitant VPA use may be an effective modifier of the increased relapse risk associated with smoking habits. Among patients who smoked, those using VPA concomitantly exhibited a higher risk of relapse (aHR, 5.32; 95% CI, 1.68–16.9; p < 0.01) than those not using VPA (aHR, 1.41; 95% CI, 0.73–2.70; p = 0.30).

Conclusion

The findings suggest that the combination of smoking habits and concomitant VPA use may increase the risk of relapse after discharge. Future studies are required to elucidate the mechanisms underlying these findings, such as a decrease in clozapine blood levels.     

Impact of frequency of nightmares comorbid with insomnia on depression in Japanese rural community residents: a cross-sectional study

ObjectiveNightmares and insomnia are known to be associated with the development and aggravation of depression. Our community-based study was conducted to clarify the relation between the impacts of nightmares and insomnia on depression.MethodsA cross-sectional questionnaire-based survey was administered to residents of a rural community in Japan. In all, 2822 participants responded to questions assessing personal characteristics, the Pittsburgh Sleep Quality Index (PSQI) for assessing insomnia, and a 12-item version of the Center for Epidemiological Studies Depression scale (CES-D) for evaluating depression. Nightmare frequency was assessed using an item for nightmares on the PSQI.ResultsNightmares more frequently occurred in participants with insomnia than those without (P < .01). Multiple regression analysis revealed that the scores of both nightmares and insomnia were significantly associated with the increase in depression score (nightmares (β = 0.09, P < .01); insomnia (β = 0.39, P < .01)). Participants with coexisting nightmares and insomnia showed higher depression scores than participants with insomnia alone or those with nightmares who did not have insomnia (P < .01).ConclusionsInsomnia and nightmares independently and additively impact the aggravation of depression.