Plasma Catecholamine Metabolites Research Articles

A CASE OF PHEOCROMOCYTOMA ARISING FROM HETEROTOPIC ADRENAL GLAND IN CHILDREN

Pheochromocytoma is a rare tumor in children. We present the case of a 9-year-old female child with heterotopic retroperitoneal localized pheochromocytoma, clinically manifesting hypertension, tachycardia and headache. The diagnosis was based on abdominal ultrasound, CT and contrast-enhanced MRI, confirmed by evaluation of free plasma catecholamine metabolites and testing of fractionated urinary metanephrines. This case is of interest due to an atypical position and vascularization of the pheochromoctioma, located retroperitoneally on the right, casuistical described in the literature, which created some diagnostic confusions. The use of the transperitoneal approach, in this case, allowed an excellent exposure and radical removal of the tumor without injuring the kidney and ureter attached to the tumor.

Comparison of plasma catecholamine metabolites in melancholic and non-melancholic depression

Major depressive disorder (MDD) manifests either with or without melancholic features. Differences in catecholamine dynamics between these two types of MDD are yet to be clarified definitively. We compared and investigated serum catecholamine metabolite levels in patients presenting with MDD for the first time who had never received treatment. We enrolled 78 patients (male/female: 35/43; melancholic/non-melancholic: 30/48) at the Neuropsychiatry Branch of the University Hospital of University of Occupational and Environmental Health, Kitakyushu, Japan. The patients were screened for axis I psychiatric disorders using the Japanese version of the Mini-International Neuropsychiatric Interview, and blood sampling was performed on the first day of hospital visit. Major depressive episodes were diagnosed using the Diagnostic and Statistical Manual of Mental Disorders IV, Text Revision , and severity of depression was evaluated using the 17-item Hamilton Depression Rating Scale. We observed no significant differences in serum 3-methoxy-4-hydroxyphenylglycol or homovanillic acid levels between healthy controls and untreated patients with either melancholic or non-melancholic MDD. These findings offer evidence suggesting that MDD cannot be simply classified into melancholic and non-melancholic subtypes, but is rather a highly heterogenous disorder with symptoms that extend seamlessly from the grief reactions experienced by healthy individuals. • Serum MHPG levels nor serum HVA levels did not differ among the the three group. • Catechoalminergic activity might not differ among the three group. • MDD is not a disease that can simply be classified into mechancholic and non-melancholic subtypes; rather it is highly heterogenous.

Diagnostic algorithm of the subclinical forms of adrenal neoplasms

The possibility of modifying the existing diagnostic algorithm of latent forms of hormone-active and potentially malignant formations in the adrenal glands using modern methods of laboratory diagnostics and radiation imaging is substantiated. In the clinic of a faculty of surgery and on its clinical base, experience in the examination and treatment of 1457 patients with various formations of the adrenal glands has been accumulated. Among them, 270 (14.9%) patients were selected, in whom precursor hormones of steroidogenesis and metabolites of catecholamines in the blood plasma were specially studied by high-performance liquid chromatography, tumor marker measurement, and three-phase computed tomography with intravenous contrast enhancement. Determination of steroidogenesis precursor hormones and catecholamine metabolites in the blood plasma by high-performance liquid chromatography in combination with traditional methods of laboratory diagnostics, use of computed tomography with intravenous contrast enhancement, construction of multiplanar reconstructions, and postprocessor image processing are the basis of a modified algorithm for verification of latent forms of hormone-active and potentially malignant tumors of the adrenal glands. The implementation of the diagnostic algorithm developed in the clinic made early diagnosis of the subclinical forms of NP neoplasms possible, as well as ensure the implementation of minimally invasive surgical interventions before the development of endocrine and metabolic disorders and consequently prevent the development of intraoperative and postoperative complications, which thereby reduce the duration of rehabilitation and disability of patients with good long-term treatment results and high quality of life.

Re-evaluating the prevalence and factors characteristic of catecholamine secreting head and neck paragangliomas.

IntroductionWe sought to characterize the prevalence and factors characteristic of head and neck paragangliomas (HNPGLs) that secrete catecholamines to inform best practices for diagnosis and management.MethodsThis was a retrospective cohort study from 2000 to 2020 at a single‐institution tertiary centre. One‐hundred fifty‐two patients (182 tumours) with HNPGLs with at least one measurement of urine or plasma catecholamines and/or catecholamine metabolite levels prior to treatment were included. We differentiated and characterized those patients with increased level(s) of any nature and those with ‘clinically significant’ versus ‘clinically insignificant’ catecholamine production.ResultsThirty‐one (20.4%) patients had increased catecholamine and/or catecholamine metabolite levels. In most patients, these levels were ≤5‐fold above the upper limit of the reference range. Four of these 31 patients with increased levels were ultimately found to have an additional catecholamine secreting mediastinal paraganglioma or pheochromocytoma. Fourteen of 31 patients with HNPGL were deemed clinically significant secretors of catecholamines based on hyper‐adrenergic symptoms and/or profound levels of normetanephrines. This cohort was enriched for patients with paragangliomas of the carotid body or cervical sympathetic chain and those with SDHB genetic mutations. Ultimately, the prevalence of clinically significant catecholamine secreting Hangs was determined to be 9.2% and 7.7% based on a per‐patient and per‐tumour basis, respectively.ConclusionsThe rate of catecholamine excess in the current cohort of patients with HNPGLs was higher than previously reported. Neuroendocrine tumours of any anatomic subsite may secrete catecholamines, although not all increased laboratory level(s) are indicative of clinically significant catecholamine secretion causing symptoms or warranting adrenergic blockade.

ДИАГНОСТИКА И ЛЕЧЕНИЕ БОЛЬНЫХ СУБКЛИНИЧЕСКИМИ ФОРМАМИ ГОРМОНАЛЬНО-АКТИВНЫХ ОПУХОЛЕЙ НАДПОЧЕЧНИКОВ

The increased incidence of accidental revealing adrenal tumors in radiation studies requires further improvement of laboratory diagnostic methods for the timely detection of their latent hormonal activity and malignancy potential, as well as the determination of strategic therapeutic approaches. The aim of the work was to evaluate the capabilities of modern laboratory diagnostics in verification of latent forms of hormone-active adrenal tumors to determine further treatment tactics. The study included 207 (14.9%) of 1390 patients in whom the hormones precursors of steroidogenesis and catecholamine metabolites were studied in blood plasma by liquid chromatography, as well as tumor markers. These patients were divided into a group of subclinical forms of hormone-active NP tumors (n = 173) and a group of truly hormone-inactive formations (n=34). It has been established that pre-aldosteroma is characterized with an increase of corticosterone (8.1±3.4 ng/ml), 11-deoxycorticosterone (12.3±3.0 ng/ml), 18-hydroxycorticosterone (5.4±1,4 ng/ml) in blood. For pre-corticosteroma: increased cortisol (119.2±16.1 ng/ml), 11-deoxycortisol (11.5±1.9 ng/ml), 11-deoxycorticosterone (12.8±2.1 ng/ml), the ratio of cortisol/cortisone (9.1±1.6 ng/ml) in blood. The presence of «silent» pheochromocytoma was confirmed by an increase of blood free methanephrine (105.0±27.1 ng/ml) and normetanephrine (196.0±43.6 ng/ml), as well as chromogranin A (223.3±15.3 pg/ml). The latent forms of adrenocortical cancer were characterized by an increase in blood dehydroepiandrosterone sulfate (45.2±3.9 μmol/L), cancer embryo antigen (9.8±1.2 ng/ml), vascular endothelial growth factor (1122.0±24.5 ng/ml), IL-6 (95.4±1.8 pg/ml), 11-deoxycortisol (21.8±4.5 ng/ml), 11-deoxycorticosterone (4.2±3.2 ng/ml). All 173 patients with hormone-active NP tumors, as well as 30 (88.2%) with large (6.5±2.0 cm) hormone-inactive formations with the presence of compression syndrome, underwent adrenalectomy. Determination of the precursors of steroidogenesis and catecholamine metabolites in blood plasma by liquid chromatography can reliably identify the functional activity of adrenal tumors and determine their malignant potential, as well as substantiate indications for timely surgical treatment.

Plasma levels of IL-6 in patients with untreated major depressive disorder: comparison with catecholamine metabolites.

ObjectiveIL-6 and catecholamines play roles in the pathophysiology of major depressive disorder (MDD).AimThe present study investigated associations between plasma IL-6 and plasma catecholamine metabolites in patients with MDD.Participants and methodsA total of 148 patients (male/female 65/83, age 49.5±12.1 years) who met the criteria for MDD based on the Diagnostic and Statistical Manual of Mental Disorders IV and 40 participants as healthy controls (HC; male/female 23/17, age 44.0±10.5 years) were enrolled in the present study. Plasma levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) and homovanillic acid (HVA) were analyzed using high-performance liquid chromatography, and plasma IL-6 levels were measured using ELISA.ResultsNo correlations were observed among plasma IL-6 levels, MHPG levels, and HVA levels in patients with MDD. Plasma IL-6 levels in patients with MDD were significantly higher than in the HC. A positive correlation was found between plasma IL-6 levels and Hamilton Rating Scale for Depression-17 scores.ConclusionNo correlations existed between plasma IL-6 levels and plasma catecholamine metabolite levels in patients with MDD, and the severity of depressive state was related to plasma IL-6 levels in MDD.

Antidopaminergic medication in healthy subjects provokes subjective and objective mental impairments tightly correlated with perturbation of biogenic monoamine metabolism and prolactin secretion.

ObjectivesOff-label prescription of antipsychotics to patients without psychotic symptoms has become a routine matter for many psychiatrists and also some general practitioners. Nonetheless, little is known about the possibly detrimental effects of antidopaminergic medications on general psychopathology, subjective mental state, or a possible association with physiological parameters in nonpsychotic individuals.MethodsIn this randomized, single-blinded study, groups of healthy volunteers (n=18) received low doses of reserpine, aripiprazole, haloperidol, or placebo on 7 successive days. Relevant physiological parameters (plasma prolactin, concentrations of catecholamine metabolites in plasma, and 24-hour urine) and each subject’s mental state (Positive and Negative Syndrome Scale, Hamilton Rating Scale for Depression, visual analogue scale, Beck Depression Inventory II) were assessed at the start and end of the trial.ResultsOf the three active treatments, only reserpine caused a significant increase in some plasma- and urine-catecholamine metabolites, but all three medications evoked objective and subjective changes in general psychopathology scores, which correlated with individual increases in plasma homovanillic acid concentrations. Both objective and subjective impairments were significantly more pronounced in the subgroup with greatest increase of plasma prolactin. Subjects experiencing the most pronounced side effects under haloperidol, which compelled them to drop out, showed significantly higher prolactin concentration increases than those who tolerated haloperidol well.ConclusionWe found consistent associations between altered markers of dopamine transmission and several objective and subjective mental impairments in healthy volunteers after 1 week’s treatment with antidopaminergic medications. These findings should draw attention to a more intensive risk–benefit evaluation in cases of off-label prescription of antipsychotic medications.

Serum Brain-Derived Neurotrophic Factor, and Plasma Catecholamine Metabolites in People with Major Depression: Preliminary Cross-Sectional Study.

There are complicated interactions between catecholaminergic neurons and brain-derived neurotrophic factor (BDNF) in the brain. However, no reports have addressed the relationship among 3-methoxy-4-hydroxyphenylglycol (MHPG), homovanillic acid (HVA), and BDNF in the blood. This paper sought to investigate correlations between serum BDNF and plasma levels of MHPG and HVA in people with major depression (MD). A total of 148 patients (male/female 65/83, age 49.5 ± 12.1 years old) who satisfied criteria for MD based on the Diagnostic and Statistical Manual of Mental Disorders IV were enrolled in the present study. Plasma levels of MHPG and HVA were analyzed using high-performance liquid chromatography, and serum BDNF was measured using ELISA. No interactions were observed between plasma HVA levels (mean ± SD = 4.5 ± 1.5 ng/mL) and age, sex, HAMD scores, or serum BDNF levels (mean ± SD = 9.8 ± 2.9 ng/mL). No correlations were not also observed between plasma MHPG levels (mean ± SD = 5.9 ± 2.1 ng/mL) and age, sex, the HAMD17 scores (mean ± SD = 22.2 ± 2.9 ng/mL), or serum BDNF levels. Serum BDNF levels were negatively associated with HAMD17 scores. The results suggest that there are no significant correlations between catecholamine metabolites and BDNF in the blood for MDD patients.

Blood Biomarkers Predict the Cognitive Effects of Aripiprazole in Patients with Acute Schizophrenia.

Aripiprazole has been reported to exert variable effects on cognitive function in patients with schizophrenia. Therefore, in the present study, we evaluated biological markers, clinical data, and psychiatric symptoms in order to identify factors that influence cognitive function in patients with schizophrenia undergoing aripiprazole treatment. We evaluated cognitive function in 51 patients with schizophrenia using Brief Assessment of Cognition in Schizophrenia (BACS), as well as background information, psychiatric symptoms, plasma catecholamine metabolites—homovanillic acid (HVA), 3-methoxy-4-hydroxyphenylglycol (MHPG)—, and serum brain-derived neurotrophic factor (BDNF). Multivariate analyses were performed in order to identify factors independently associated with cognitive function. Brain-derived neurotrophic factor levels, number of hospitalizations, and MHPG levels were associated with verbal memory and learning. Total hospitalization period and MHPG levels were associated with working memory. Age at first hospitalization and education were associated with motor speed. The number of hospital admissions, Positive and Negative Syndrome Scale negative subscale scores (PANSS-N), MHPG levels, BDNF levels, and Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) scores were associated with verbal fluency. Homovanillic acid and MHPG levels, duration of illness, and PANSS-N scores were associated with attention and processing speed. Brain-derived neurotrophic factor and MHPG levels were associated with executive function. These results suggest that treatment of psychiatric symptoms and cognitive dysfunction may be improved in patients treated with aripiprazole by controlling for these contributing factors.

COMT haplotypes, catecholamine metabolites in plasma and clinical response in schizophrenic and bipolar patients.

We examined the association of COMT haplotypes and plasma metabolites of catecholamines in relation to the clinical response to antipsychotics in schizophrenic and bipolar patients. We studied 165 patients before and after four weeks of treatment, and 163 healthy controls. We assessed four COMT haplotypes and the plasma concentrations of HVA, DOPAC and MHPG. Bipolar patients: haplotypes are associated with age at onset and clinical evolution. In schizophrenic patients, an haplotype previously associated with increased risk, is related to better response of negative symptoms. Haplotypes would be good indicators of the clinical status and the treatment response in bipolar and schizophrenic patients. Larger studies are required to elucidate the clinical usefulness of these findings.

Catechol-O-methyltransferase Val158Met genotype and the clinical responses to duloxetine treatment or plasma levels of 3-methoxy-4-hydroxyphenylglycol and homovanillic acid in Japanese patients with major depressive disorder.

PurposeThis study investigated the relationships among the plasma levels of catecholamine metabolites, the clinical response to duloxetine treatment, and Val158Met polymorphism of the catechol-O-methyltransferase (COMT) gene.Subjects and methodsSixty-four patients and 30 healthy control subjects were recruited. Major depressive episodes were diagnosed using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria. The severity of depression was evaluated using the 17-item Hamilton Rating Scale for Depression (HAMD17). Patients whose HAMD17 scores were 15 or greater were enrolled in the study. Blood sampling and clinical evaluation were performed at week 0 and week 8. The levels of plasma catecholamine metabolites were measured using high-performance liquid chromatography with electrochemical detection. Genotyping was performed using direct sequencing.ResultsThirty of 45 patients (67%) responded to duloxetine treatment during the 8 weeks of treatment. The baseline plasma levels of 3-methoxy-4-hydroxyphenylglycol (MHPG), but not homovanillic acid (HVA), were lower in patients with major depressive disorder (MDD) who had the Val/Val genotype than in patients who were Met-carriers. Patients with MDD and the Val/Val genotype, but not Met carriers, had increased plasma levels of MHPG after 8 weeks of duloxetine treatment. The baseline plasma MHPG levels in healthy control subjects with the Val/Val genotype were significantly higher than those in patients with MDD. Among the subjects in the MDD group with the Val/Val genotype, the plasma MHPG levels increased to the same degree as in the healthy control subjects with the Val/Val genotype after 8 weeks of duloxetine treatment.ConclusionThe relationship among the COMT Val158Met polymorphism, plasma levels of catecholamine metabolites, and responses to duloxetine is complex. Nevertheless, our results suggest that patients with MDD and the Val/Val genotype are more sensitive to the influence of noradrenergic neurons by duloxetine treatment.

P.2.f.011 Serum levels of BDNF, BDNF gene Val66Met polymorphism, or plasma catecholamine metabolites, and response to mirtazapine (MRT) with major depressive disorder (MDD)

P.2.f.011 Serum levels of BDNF, BDNF gene Val66Met polymorphism, or plasma catecholamine metabolites, and response to mirtazapine (MRT) with major depressive disorder (MDD)

Norepinephrine and impulsivity: effects of acute yohimbine

Rapid-response impulsivity, characterized by inability to withhold response to a stimulus until it is adequately appraised, is associated with risky behavior and may be increased in a state-dependent manner by norepinephrine. We assessed effects of yohimbine, which increases norepinephrine release by blocking alpha-2 noradrenergic receptors, on plasma catecholamine metabolites, blood pressure, subjective symptoms, and laboratory-measured rapid-response impulsivity. Subjects were 23 healthy controls recruited from the community, with normal physical examination and ECG, and negative history for hypertension, cardiovascular illness, and axis I or II disorder. Blood pressure, pulse, and behavioral measures were obtained before and periodically after 0.4mg/kg oral yohimbine or placebo in a randomized, counterbalanced design. Metabolites of norepinephrine [3-methoxy-4-hydroxyphenylglycol (MHPG) and vanillylmandelic acid (VMA)] and dopamine [homovanillic acid (HVA)] were measured by high-pressure liquid chromatography with electrochemical detection. Rapid-response impulsivity was measured by commission errors and reaction times on the immediate memory task (IMT), a continuous performance test designed to measure impulsivity and attention. Yohimbine increased plasma MHPG and VMA but not HVA. Yohimbine increased systolic and diastolic blood pressure and pulse rate. On the IMT, yohimbine increased impulsive errors and impulsive response bias and accelerated reaction times. Yohimbine-associated increase in plasma MHPG correlated with increased impulsive response rates. Time courses varied; effects on blood pressure generally preceded those on metabolites and test performance. These effects are consistent with increased rapid-response impulsivity after pharmacological noradrenergic stimulation in healthy controls. Labile noradrenergic responses, or increased sensitivity to norepinephrine, may increase risk for impulsive behavior.

Plasma catecholamine metabolite levels and the activities of psychiatric symptoms in systemic lupus erythematosus

Neuropsychiatric systemic lupus erythematosus (NPSLE) is accompanied by neurological or psychiatric symptoms that can be severe. We hypothesized plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) and homovanillic acid (HVA) levels were the biological marker that reflected the severity of the NPSLE psychiatric symptoms, and we examined MHPG and HVA levels in systemic lupus erythematosus (SLE) patients. The participants were 42 healthy volunteers and 41 SLE patients. SLE patients were divided into the three groups: NPSLE with psychiatric symptoms (NP group), NPSLE without psychiatric symptoms (NN group), and SLE without neuropsychiatric symptoms (S group). All blood samples were drawn before (T0) and after 4 weeks of treatment (T4) in all SLE patients, and once in the healthy volunteers. Plasma levels of MHPG and HVA were analyzed using high-performance liquid chromatography. Plasma MHPG levels at T0 were significantly increased in the SLE compared to those in healthy volunteers. The NN group had the greatest increase compared with other SLE patient groups. There were no significant differences in plasma HVA levels at T0 between the four groups, and there was also no difference in MHPG and HVA plasma levels between T0 and T4. Hyperactivity of noradrenergic neurons and/or sympathetic nerves might be involved in SLE pathophysiology.

Serum levels of brain-derived neurotrophic factor (BDNF), BDNF gene Val66Met polymorphism, or plasma catecholamine metabolites, and response to mirtazapine in Japanese patients with major depressive disorder (MDD)

We investigated an association between the polymorphism of brain-derived neurotrophic factor (BDNF) gene Val66Met and the response to mirtazapine in Japanese patients with major depressive disorder (MDD). We also examined mirtazapine's effects on the serum BDNF and plasma levels of catecholamine metabolites in these patients. Eighty-four patients who met the DSM-IV-TR criteria for MDD were treated with only mirtazapine for 4 weeks. The BDNF Val66Met polymorphism was detected by direct sequencing in the region, and serum BDNF levels and plasma levels of catecholamine metabolites were measured by ELISA and HPLC-ECD, respectively. Mirtazapine treatment for 4 weeks significantly increased serum BDNF levels in the responders, whereas nonresponders showed significant decreases. No association was found between either of the two genotypes (Val/Val vs. Met-carriers) and the response to mirtazapine at T4 or the serum BDNF levels at T0. Mirtazapine did not alter the plasma levels of homovanillic acid (HVA) or 3-methoxy-4-hydroxyphenylglycol (MHPG). Discussion The dynamics of serum BDNF levels, but not plasma levels of HVA and MHPG, reflect the response to mirtazapine treatment; the BDNF Val66Met polymorphism in patients with depression is, however, associated with neither a particular response to mirtazapine treatment nor baseline serum BDNF levels. Serum BDNF levels, but not plasma levels of HVA or MHPG, and BDNF Val66Met polymorphism are related to the mirtazapine response in MDD.

Aripiprazole altered plasma levels of brain‐derived neurotrophic factor and catecholamine metabolites in first‐episode untreated Japanese schizophrenia patients

We investigated the effects of aripiprazole on plasma levels of brain-derived neurotrophic factor (BDNF) and catecholamine metabolites in first-episode untreated schizophrenia patients. The subjects were 50 Japanese first-episode untreated schizophrenia patients who met the Diagnostic and Statistical Manual of Mental Disorders Text Revision criteria and were treated with aripiprazole monotherapy. Twenty-nine were males, and 21 were females. The age ranged from 21 to 42 years (mean ± SD; 30.8 ± 5.3 years). Plasma BDNF and catecholamine metabolites were measured by ELISA and HPLC, respectively. Psychiatric symptoms were evaluated using by Positive and Negative Syndrome Scale. Treatment with aripiprazole for 8 weeks significantly increased plasma BDNF levels. It also changed plasma levels of homovanillic acid and 3-methoxy-4-hydroxyphenylglycol. A negative correlation was also observed between duration of psychosis and plasma BDNF levels. No correlation was observed however between plasma BDNF levels and the dose of aripiprazole. To the best of our knowledge, this is the first report showing that aripiprazole increases plasma BDNF levels in first-episode untreated schizophrenia patients. Furthermore, the BDNF Val66Met polymorphism was independent of the response to aripiprazole.

Catechol O-methyltransferase and monoamine oxidase A genotypes, and plasma catecholamine metabolites in bipolar and schizophrenic patients

Metabolites of dopamine and norepinephrine measured in the plasma have long been associated with symptomatic severity and response to treatment in schizophrenic, bipolar and other psychiatric patients. Plasma concentrations of catecholamine metabolites are genetically regulated. The genes encoding enzymes that are involved in the synthesis and degradation of these monoamines are candidate targets for this genetic regulation. We have studied the relationship between the Val158Met polymorphism in catechol O-methyltransferase gene, variable tandem repeat polymorphisms in the monoamine oxidase A gene promoter, and plasma concentrations of 3-methoxy-4-hydroxyphenylglycol, 3,4-dihydroxyphenylacetic acid and homovanillic acid in healthy control subjects as well as in untreated schizophrenic and bipolar patients. We found that the Val158Met substitution in catechol O-methyltransferase gene influences the plasma concentrations of homovanillic and 3,4-dihydroxyphenylacetic acids. Although higher concentrations of plasma homovanillic acid were found in the high-activity ValVal genotype, this mutation did not affect the plasma concentration of 3-methoxy-4-hydroxyphenylglycol. 3,4-dihydroxyphenylacetic acid concentrations were higher in the low-activity MetMet genotype. Interestingly, plasma values 3-methoxy-4-hydroxyphenylglycol were greater in schizophrenic patients and in bipolar patients than in healthy controls. Our results are compatible with the previously reported effect of the Val158Met polymorphism on catechol O-methyltransferase enzymatic activity. Thus, our results suggest that this polymorphism, alone or associated with other polymorphisms, could have an important role in the genetic control of monoamine concentration and its metabolites.

Predictive factors for responding to sertraline treatment: views from plasma catecholamine metabolites and serotonin transporter polymorphism

In the present study, we investigated the effects of sertraline on plasma levels of 3-methoxy-4-hydroxyphenylglycol (MHPG), homovanillic acid (HVA), and serum brain-derived neurotrophic factor (BDNF) levels in 59 depressed patients treated with sertraline. We also examined the relationship between the dynamics of the catecholamine metabolites, BDNF, serotonin transporter-linked polymorphic region (5-HTTLPR) gene polymorphism (long and short alleles), and the clinical response to sertraline. The extent of clinical improvement was evaluated using the 17-item Hamilton Rating Scale for Depression (Ham-D) before and 8 weeks after treatment with sertraline. Responders were defined as showing at least a 50% decrease in the Ham-D score. Baseline plasma HVA levels of responders to sertraline treatment were significantly lower than those of non-responders (p = 0.02). In addition, a positive correlation was identified between changes in plasma HVA levels and the rate of response to sertraline treatment (p = 0.001). A trend toward higher baseline serum BDNF levels was found in responders compared with non-responders (p = 0.095). In addition, serum BDNF levels were slightly increased (not significant) in responders (p = 0.058), but not in non-responders. Responders had a higher short-allele genotype frequency in the 5-HTTLPR for the promoter region than did non-responders (p = 0.037). These results suggest that pre-treatment plasma HVA levels and the 5-HTTLPR genotype for the promoter might be associated with a response to sertraline.

Adjuvant bupivacaine scalp block facilitates stabilization of hemodynamics in patients undergoing craniotomy with general anesthesia: a preliminary report

Study ObjectiveTo evaluate the effect of 0.25% bupivacaine scalp block on alterations in hemodynamics and plasma catecholamine metabolites during general anesthesia in patients undergoing frontotemporal craniotomy. DesignProspective, clinical study. SettingOperating room of a university hospital. Patients16 ASA physical status II and III patients who were scheduled for frontotemporal craniotomy. InterventionsPatients were prospectively randomized to receive a saline control (C group) or bupivacaine scalp block (SB group) as an adjuvant to general anesthesia using isoflurane in 50% N2O-O2. MeasurementsRoutine monitoring of electrocardiogram, heart rate (HR), and mean arterial blood pressure (MAP) were recorded at two-minute intervals from the beginning of anesthesia until 10 minutes after incision, followed by 5-minute intervals throughout the remaining course of the surgery. By prospective design, increases in MAP or HR by 20% above the mean baseline values were treated with 2.5 mg/kg of thiopental combined with 2 μg/kg of fentanyl. Arterial blood was sampled at 5 minutes before and after skin incision and at the start of dural opening for measuring serum catecholamine metabolites by high-performance liquid chromatography. Main ResultsOnly two patients in the SB group needed additional anesthetics for stabilizing their hemodynamics during the course of anesthesia. In contrast, all C group patients required supplemental anesthesia for controlling the abrupt rise in hemodynamic parameters. In addition, absolute MAP and HR values were significantly higher in the C group than in the SB group during the surgical period between incision and dural opening. The differences in hemodynamics observed between the two groups were, however, not accompanied with a significant change in plasma catecholamine metabolites at each predetermined time interval measured. ConclusionsPretreatment with 0.25% bupivacaine scalp block appeared to be an effective adjuvant treatment for maintaining stable hemodynamics for patients undergoing craniotomy during general anesthesia especially at the time of skin incision and dural opening. This study design was unable to discern any correlation between elevation in hemodynamic parameters and a rise in serum catecholamine levels.

Effect of risperidone on plasma catecholamine metabolites and brain‐derived neurotrophic factor in patients with bipolar disorders

A combination treatment with a mood stabilizer and an antipsychotic drug is often used in as many as 90% of subjects with acute mania. Recently, augmentation therapy with atypical antipsychotics has been investigated in both the acute and long-term treatment of bipolar disorder with or without psychosis. In the present study, the authors investigated the efficacy of risperidone treatment for both acute manic and depressive episodes in bipolar disorder. Eighteen patients (M/F: 8/10, age: 34 +/- 15 yr) who met the DSM-IV criteria for bipolar I disorder (12 cases of manic episodes, 6 cases of depressive episodes) with risperidone treatment were evaluated regarding their clinical improvement using the Young Mania rating Scale (YMRS) and the Hamilton rating Scale for Depression (Ham-D). Plasma concentrations of HVA and MHPG were analyzed by HPLC-ECD and plasma brain-derived neurotrophic factor (BDNF) levels were detected by sandwich ELISA. The mean scores of the YMRS were 22, 18, 12, 8, and 5 at time points before and 1, 2, 3, and 4 weeks after the risperidone administration, respectively. The mean scores of the Ham-D were 24, 25, 21, 21, and 19 at time points before and 1, 2, 3, and 4 weeks after the risperidone administration, respectively. The plasma levels of HVA and 3-methoxy-4-hydroxyphenylglycol (MHPG) were observed to have decreased 4 weeks after risperidone administration in manic patients. The levels did not change in depressive patients. The plasma levels of BDNF were decreased in depressive patients compared with manic patients or healthy controls. However, the administration of risperidone did not alter plasma BDNF levels.