Biomedical subjects

Francisco A Moreno

Publications and source records attributed to Francisco A Moreno.

8 recordsLinked to original sources

PubMed2006

Number of risk genotypes is a risk factor for major depressive disorder: a case control study.

BACKGROUND: The objective of the study was to determine the genetic basis of Major Depressive Disorder, and the capacity to respond to antidepressant treatment. An association study of 21 candidate polymorphisms relevant to monoamine function and the mechanism of antidepressant response was conducted in 3 phenotypically distinct samples: a group with chronic or recurrent depression unable to respond to antidepressants (non-responders) (n = 58), a group capable of symptomatic improvement with or without treatment (responders) (n = 39), and volunteer controls (n = 85). The responders and non-responders constituted a larger group of depressed subjects. METHODS: A candidate gene approach was employed to asses the genetics basis of Major Depressive Disorder. The genotypic frequencies of selected polymorphisms were compared between the controls and depressed subjects. To asses the genetics basis of the capacity to respond to antidepressant treatment, the responders were compared to the non-responders. Candidate genes were chosen based on functional studies and proximity to whole genome linkage findings in the literature. Risk genotypes were identified by previous functional studies and association studies. RESULTS: A statistically significant difference in genotype frequency for the SLC6A4 intron 2 VNTR was detected between the subjects with a history of depression and controls (p = 0.004). Surprisingly, a statistically significant difference was detected between responders and non-responders for the DRD4 exon III VNTR genotype frequencies (p = 0.009). Furthermore, a difference between the controls and depressed subjects as well as between the controls and non-responders was detected for the number and distribution of risk genotypes in each group. CONCLUSION: An association between several monoamine-related genes and Major Depressive Disorder is supported. The data suggest that the two depressive phenotypes are genetically different, inferring that the genetic basis for the capacity to respond to standard antidepressant treatment, and the genetic susceptibility to Major Depressive Disorder may be independent. In addition, a proof of concept is provided demonstrating that the number of risk genotypes may be an indication of susceptibility of major depressive disorder and the severity of the disorder.

Journal Article↗

PubMed2006

Sex differences in depressive response during monoamine depletions in remitted depressive subjects.

OBJECTIVE: Although sex differences in the prevalence of depression are well known, the effects of sex on the underlying mechanisms of illness and on antidepressant action remain less clear. Tryptophan depletion and catecholamine depletion (via alpha-methylparatyrosine [AMPT] administration) are broadly utilized methods for studying the effects of the safe and transient reduction of serotonin and catecholamine neuro-transmission, respectively. The present study assessed the effects of sex on the mood response during acute monoamine depletion. METHOD: Data on Hamilton Rating Scale for Depression (HAM-D) scores during depletion tests were analyzed retrospectively in 59 subjects (41 women, 18 men) who underwent tryptophan depletion and 39 subjects (25 women, 14 men) who underwent catecholamine depletion. All subjects were in remission from a DSM-IV-defined major depressive episode. Data reviewed included subjects enrolled between November 1993 and November 1997. RESULTS: Significant increases in HAM-D scores were observed in response to both depletion procedures, with a similar magnitude of change. Analysis of variance with repeated measures of HAM-D scores revealed a significant main effect of time for tryptophan depletion (F = 7.31, df = 3, p < .01) and for catecholamine depletion (F = 9.61, df = 4, p < .01). Time-by-sex interaction was significant for tryptophan depletion (F = 4.04, df = 3, p = .01), but not for catecholamine depletion (F = 0.75, df = 4, p = .57). Depressive symptoms were significantly greater in women during tryptophan depletion (t test p < .01), while no significant sex differences were found during catecholamine depletion. CONCLUSIONS: These findings suggest that the effect of sex in depressive vulnerability may be related to differential sex effects in monoaminergic function.

Adult↗

PubMed2006

Acupuncture for depression: a randomized controlled trial.

OBJECTIVE: To assess the efficacy of acupuncture as an intervention for major depressive disorder (MDD). METHOD: Acupuncture was examined in 151 patients with MDD (DSM-IV) who were randomly assigned to 1 of 3 groups in a double-blind randomized controlled trial. The specific intervention involved Traditional Chinese Medicine (TCM)-style acupuncture with manual stimulation for depression; the control conditions consisted of (1) a nonspecific intervention using a comparable number of legitimate acupuncture points not specifically targeted to depressive symptoms and (2) a waitlist condition, which involved waiting without intervention for 8 weeks. After 8 weeks, all patients received the depression-specific acupuncture. Each 8-week intervention regimen consisted of 12 acupuncture sessions delivered in an acupuncturist's office in the community. The primary outcome measure was the 17-item Hamilton Rating Scale for Depression. The study was conducted from February 1998 to April 2002. RESULTS: Twenty patients terminated treatment before the completion of the 8-week intervention (13%) but not differentially by study group. Random regression models of the intent-to-treat sample revealed that although patients receiving acupuncture improved more than those awaiting intervention, no evidence of differential efficacy of the depression-specific over nonspecific intervention was found. Response rates in acupuncture-treated patients were relatively low after 8 weeks (22% and 39% for specific and nonspecific intervention groups, respectively), with the response rate after the entire 16-week trial reaching 50%. CONCLUSION: Although TCM manual acupuncture is a well-tolerated intervention, results fail to support its efficacy as a monotherapy for MDD. It can't be ruled out that factors unique to the implementation of acupuncture in this research study may have limited the efficacy of interventions compared to those provided in naturalistic settings. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier NCT00010517.

Acupuncture↗

PubMed2006

Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder.

BACKGROUND: Anecdotal reports suggest that psychedelic agents may relieve symptoms of obsessive-compulsive disorder (OCD). This modified double-blind study investigated the safety, tolerability, and clinical effects of psilocybin, a potent 5-HT(1A) and 5-HT(2A/2C) agonist, in patients with OCD. METHOD: Nine subjects with DSM-IV-defined OCD and no other current major psychiatric disorder participated in up to 4 single-dose exposures to psilocybin in doses ranging from sub-hallucinogenic to frankly hallucinogenic. Low (100 microg/kg), medium (200 microg/kg), and high (300 microg/kg) doses were assigned in that order, and a very low dose (25 microg/kg) was inserted randomly and in double-blind fashion at any time after the first dose. Testing days were separated by at least 1 week. Each session was conducted over an 8-hour period in a controlled environment in an outpatient clinic; subjects were then transferred to a psychiatric inpatient unit for overnight observation. The Yale-Brown Obsessive Compulsive Scale (YBOCS) and a visual analog scale measuring overall obsessive-compulsive symptom severity were administered at 0, 4, 8, and 24 hours post-ingestion. The Hallucinogen Rating Scale was administered at 8 hours, and vital signs were recorded at 0, 1, 4, 8, and 24 hours after ingestion. The study was conducted from November 2001 to November 2004. RESULTS: Nine subjects were administered a total of 29 psilocybin doses. One subject experienced transient hypertension without relation to anxiety or somatic symptoms, but no other significant adverse effects were observed. Marked decreases in OCD symptoms of variable degrees were observed in all subjects during 1 or more of the testing sessions (23%-100% decrease in YBOCS score). Repeated-measures analysis of variance for all YBOCS values revealed a significant main effect of time on Wilks lambda (F = 9.86, df = 3,3; p = .046), but no significant effect of dose (F = 2.25, df = 3,3; p = .261) or interaction of time and dose (F = 0.923, df = 9,45; p = .515). Improvement generally lasted past the 24-hour timepoint. CONCLUSIONS: In a controlled clinical environment, psilocybin was safely used in subjects with OCD and was associated with acute reductions in core OCD symptoms in several subjects.

Adult↗

PubMed2005

Carnitine levels in valproic acid-treated psychiatric patients: a cross-sectional study.

BACKGROUND: Carnitine facilitates the transport of long-chain fatty acids across the mitochondria for beta oxidation, and the removal of potentially toxic acylcoenzyme-A metabolites from the inner aspect of mitochondrion as acylcarnitines. Previous studies suggest a significant decrease in carnitine concentrations and changes in the ratio of acylcarnitine to free carnitine in seizure-disoriented patients treated with valproic acid (VPA), which may lead to clinical manifestations of carnitine deficiency. This study sought to explore whether the same decrease in plasma free carnitine and increase in acylcarnitines are seen when VPA is used in the treatment of patients with psychiatric disease. METHOD: Thirty psychiatric patients treated with VPA for at least six months were selected for the study and granted informed consent for participation. Exclusion criteria included liver disorder or pancreatitis, metabolic defects known to affect plasma carnitine levels, or noncompliance with VPA regimen. Plasma free carnitine, total carnitine, VPA, and amylase levels were determined, and liver function tests (LFTs) were performed. Pearson correlations were conducted between VPA levels, levels and ratios of carnitines, as well as LFTs and amylase levels. RESULTS: Plasma free and total carnitine levels were lower than the reported normal range for the laboratory performing the assay, and the ratio of acylcarnitine to free carnitine was increased. There was a significant positive correlation of VPA levels and acylcarnitine-free carnitine ratio, a trend toward significance between VPA levels and acylcarnitine levels, and a marginal negative correlation between VPA levels and free carnitine levels. VPA levels correlated also with several LFTs and acylcarnitine levels. Octanoyl carnitine and acylcarnitine levels, as well as acylcarnitine-free carnitine and octanoyl-free carnitine ratios, correlated significantly with amylase levels. CONCLUSION: Although the study was limited by a cross-sectional design without direct control comparison, the findings suggest that patients with various psychiatric conditions treated with polypharmacy that includes VPA may have lower plasma carnitine levels than would be expected in healthy controls.

Adult↗

PubMed2004

Effect of vagus nerve stimulation on cerebrospinal fluid monoamine metabolites, norepinephrine, and gamma-aminobutyric acid concentrations in depressed patients.

BACKGROUND: Vagus nerve stimulation (VNS) has shown promising antidepressant effects in treatment-resistant depression, but the mechanisms of action are not known. Cerebrospinal fluid (CSF) studies in epilepsy patients show that VNS alters concentrations of monamines and gamma-aminobutyric acid (GABA), neurotransmitter systems possibly involved in the pathogenesis of depression. METHODS: Twenty-one adults with treatment-resistant, recurrent, or chronic major depression underwent standardized lumbar puncture for collection of 12 mL CSF on three separate but identical procedure days during participation in the VNS D-02 clinical trial. All subjects remained on stable regimens of mood medications. Collections were made at baseline (2 weeks after surgical implantation but before device activation), week 12 (end of the acute-phase study), and week 24. Cerebrospinal fluid concentrations of norepinephrine (NE), 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) were determined with high-performance liquid chromatography. Concentrations of GABA were assayed with mass spectrometry. RESULTS: Comparison of sham versus active VNS revealed a significant (mean 21%) VNS-associated increase in CSF HVA. Mean CSF concentrations of NE, 5-HIAA, MHPG, and GABA did not change significantly. Higher baseline HVA/5-HIAA ratio predicted worse clinical outcome. CONCLUSIONS: Although several of the CSF neurochemical effects we observed in this VNS study were similar to those described in the literature for antidepressants and electroconvulsive therapy, the results do not suggest a putative antidepressant mechanism of action for VNS.

Adult↗

PubMed2002

Sequential catecholamine and serotonin depletion in mirtazapine-treated depressed patients.

This study was aimed at determining whether patient- or antidepressant-related variables are most important to the mood response to serotonin (5-HT) or catecholamine depletion. Depressed patients treated with open-label mirtazapine (>or=6 wk) received two depletion tests (5-HT and catecholamine depletion) 1 wk apart. Both 5-HT and catecholamine depletion led to a partial return of depression in most patients. Antidepressant response to mirtazapine is dependent on its dual actions on norepinephrine and 5-HT neurotransmission. Mood response to tryptophan or catecholamine depletion is dependent on the pharmacological properties of the antidepressant being taken during depletion.

Adrenergic Uptake Inhibitors↗

PubMed2002

Emotional blunting associated with SSRI-induced sexual dysfunction. Do SSRIs inhibit emotional responses?

Anecdotal and published case reports suggest that some patients taking selective serotonin reuptake inhibitors (SSRI) experience diminution in emotional responsiveness. This study aims to define the individual components of emotion disturbed in these patients. Fifteen patients reporting SSRI-induced sexual dysfunction completed the Laukes Emotional Intensity Scale (LEIS), a questionnaire about various emotions. Compared to controls, patients reported significantly (p<0.05) less ability to cry, irritation, care about others' feelings, sadness, erotic dreaming, creativity, surprise, anger, expression of their feelings, worry over things or situations, sexual pleasure, and interest in sex. Total score on the LEIS did not correlate with total score on the Hamilton Depression Rating Scale. In our sample, 80% of patients with SSRI-induced sexual dysfunction also describe clinically significant blunting of several emotions. Emotional blunting may be an under-appreciated side-effect of SSRIs that may contribute to treatment non-compliance and/or reduced quality of life.

Adult↗