An increased hypothermic response to buspirone in patients with major depression.
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Adult↗
Biomedical subjects
Cristóbal Gastó
Publications and source records attributed to Cristóbal Gastó.
Cognitive remediation therapy for outpatients with chronic schizophrenia: a controlled and randomized study.
Cognitive Remediation Therapy (CRT) is a novel rehabilitation approach designed to improve neurocognitive abilities such as attention, memory and executive functioning. The aim of the present study is to evaluate the effect of CRT on neurocognition, and secondarily on symptomatology and psychosocial functioning. Cognitive Behavioural Therapy (CBT) was used as a control condition because it aims to improve emotional problems and positive symptoms, focusing on modification of maladaptive beliefs and schemas, but neurocognition is not targeted. A total of 40 chronic patients with DSM-IV schizophrenia disorder were randomly assigned for 4 months to one of two treatment groups: CRT or CBT. Repeated assessments were conducted before and after the treatments and at the end of a follow-up period of 6 months. Additionally, a method to establish reliable change was calculated from a separate sample of 20 schizophrenic patients who were under standard medication without any kind of psychological treatment. Results showed that CRT produced an overall improvement on neurocognition (Mean effect size=0.5), particularly in verbal and nonverbal memory, and executive function. CBT showed the expected treatment effect on general psychopathology (anxiety and depression) but produced only a slight non-specific improvement in neurocognition (Working Memory). Furthermore, patients receiving CRT showed improvement in social functioning, demonstrating that cognitive improvements are clinically meaningful. These gains were still present at the 6 month follow-up.
Adult↗
[Maintenance electroconvulsive therapy in elderly psychotic unipolar depression].
BACKGROUND AND OBJECTIVE: This study was designed to assess the safety and efficacy of continuation/maintenance electroconvulsive therapy (ECT) in elderly psychotic major depressed patients after ECT remission. PATIENTS AND METHOD: Using a longitudinal randomized single-blind design, we compared the two-year outcome of two subgroups of psychotic unipolar depressed elderly patients who were ECT remitters: one treated with a maintenance nortriptyline regimen (n = 13) and one treated with combined maintenance ECT plus nortriptyline (n = 6). RESULTS: During 2 years of maintenance treatment in elderly psychotic unipolar depressed ECT remitters, relapse/recurrence rates were significantly higher in the nortriptyline subgroup than in the combined ECT plus nortriptyline subgroup. The tolerability of both treatments was similar. CONCLUSIONS: This study supports the use of combined maintenance ECT and antidepressant treatment in elderly psychotic unipolar depressed patients who are ECT remitters.
Aged↗
Analysis of COMT gene (Val 158 Met polymorphism) in the clinical response to SSRIs in depressive patients of European origin.
INTRODUCTION AND OBJECTIVES: There is convincing evidence of interactions between serotonergic and dopaminergic systems and it seems that an increase of dopamine concentration in the whole brain could be a limiting factor for the antidepressant like effect of antidepressants. The COMT gene might be a good candidate for explaining some aspects of the pharmacological response to SSRIs. METHODS: The aim of our study was to analyse the Val 158 Met functional polymorphism on COMT gene and clinical response (4 weeks) and clinical remission (6/8 and 12 weeks) in two samples of depressive patients (DSM-IV) treated with SSRIs of Italian and Spanish origin. Clinical outcome was measured using 21 items Hamilton scale, weekly in the Italian sample (along 6 weeks) and monthly in the Spanish one (along 12 weeks). RESULTS: No overall effect of genotype or genotypextime interaction was detected. However, we observed a genotypextime interaction on HDRS decrease for citalopram treatment (F((4.6,317.5)) = 3.38, P = 0.007) in the Spanish sample. No clear effect was observed in the Italian sample. The three samples were pooled in order to test if carrying the Met/Met genotype confers an increased risk for non-remission at 6-8 weeks. The results showed that Met/Met carriers have an odds ratio of 2.21 (95% CI [1.20-4.12]) for non-remission (chi(2) = 7.43, df = 2, P = 0.006). The Met/Met effect was not observed in response at 4th week (for all SSRI treatments) or in remission at 12th week (citalopram treatment). CONCLUSIONS: COMT gene could have a small and indirect effect of clinical response to SSRIs by slowing-down the antidepressant action along the follow-up, basically in citalopram treatment.
Antidepressive Agents, Second-Generation↗
Executive function and nonverbal memory in obsessive-compulsive disorder.
It has been suggested that memory impairments found in obsessive-compulsive disorder (OCD) are mediated by organizational problems in encoding that are caused by primary executive dysfunction. Performance on different nonverbal memory and executive skills was tested in 68 subjects (35 non-depressed OCD sufferers and 33 healthy controls). Multiple regression models were performed to analyze the role of different cognitive variables, especially organizational encoding strategies in nonverbal memory. OCD patients performed significantly worse than controls in immediate nonverbal memory [Rey-Osterrieth Complex Figure Test (RCFT)] and on all the executive functions such as interference control (Stroop test), mental set shifting (Trail-Making Test), and organizational strategies (copy organization). As no differences were found in the memory of faces, where organizational strategies are minimal, it is possible to speculate that immediate nonverbal memory problems in OCD appear only when organizational strategies mediate the recalling process. Thus, memory deficits appear to have less to do with memory, per se, and more to do with the degree of organization necessary to effectively complete the task. Statistical analyses of mediation models showed the highest explanatory power for the organizational approach and demonstrated the mediation effect of organizational strategies in nonverbal impairment.
Adult↗
Neuropsychological prediction of recovery in late-onset major depression.
OBJECTIVES: To assess antidepressant response in late-onset major depression in relation to neuropsychological domains: attention, memory and planning. METHODS: A neuropsychological battery was administered in 30 medication-free patients with late-onset major depression, who were then included in a 12-week antidepressant treatment regimen within a 12-month follow-up period. Logistic regression was used to define a predictive model of recovery. RESULTS: Eighteen patients were classed as remitters and seven as non-remitters. The 'indexrem' refers to the results of a logistic regression from verbal learning and planning and had a global predictive power of 84%. CONCLUSIONS: Our study suggests that the balance between verbal learning (memory) and planning (executive function)-both related to the dorsolateral prefrontal cortex-could predicts recovery.
Age of Onset↗
Evidence for a combined genetic effect of the 5-HT(1A) receptor and serotonin transporter genes in the clinical outcome of major depressive patients treated with citalopram.
In the context of a long-term follow-up study, we analysed the possible implication of the 5-HT(1A) receptor gene (HTR1A) -1018C/G polymorphism in the clinical outcome of major depressive patients treated with citalopram. We had previously reported an association between variation on the SERT gene (SLC6A4) and clinical remission after citalopram treatment. In the present 12-week follow-up study, the combined effect of HTR1A and SLC6A4 genes in clinical outcome and response to citalopram was also evaluated. The sample consisted of 130 patients, all of Spanish origin, who were diagnosed as having a current major depressive episode according to DSM-IV criteria. A 21-item Hamilton Depression Rating Scale was used to assess severity of symptoms at the beginning and during the follow-up to determine the outcome and remission status at week 12. Patients were genotyped for HTR1A gene and, in addition, for two polymorphisms at the CYP2C19 gene, which together account for the 87% of the Caucasian poor metabolizer phenotype. Data were analysed adjusting for the effect of poor metabolizers in clinical response. No independent effect was found for the 5-HT(1A) receptor gene in relation to clinical outcome or remission after citalopram treatment. However, a combined genetic effect of HTR1A and SLC6A4 genes was found to influence the clinical outcome of patients [F(4,102) = 2.89, p= 0.02]. When considering the remission status, an increase of patients carrying the risk genotype combination (S/S-G/G) was found among those subjects who did not reach remission (Fisher's exact test = 0.009). Our results suggest that the combined effect of the serotonin transporter and the 5-HT(1A) receptor genes could be related to the clinical outcome of depressive patients treated with citalopram.
Adult↗
Clinical value of 99mTc-HMPAO SPECT in depressed bipolar I patients.
Regional cerebral blood flow was studied in 17 bipolar I depressed patients (DSM-IV criteria) with single photon emission computed tomography (SPECT). Visual analysis of images revealed no abnormality in eight patients and abnormal findings in nine patients. In the nine patients with abnormal findings, all showed regional decreases of the uptake of (99m)Tc-D,L-hexamethylpropylene amine oxime (HMPAO, four in the frontal region, two in the basal ganglia, and three in both the frontal region and the basal ganglia). The patients with visible SPECT abnormalities had significantly higher scores on the Hamilton Rating Scale for Depression (HDRS).
Adult↗
Decrease of the platelet 5-HT2A receptor function by long-term imipramine treatment in endogenous depression.
BACKGROUND: Animal studies have found that many antidepressants induce decreases in both the density and the functional activity of the serotonin 2A (5-HT2A) receptor subtype. However, the extrapolation of findings to humans has been inconclusive. A physiological platelet response mediated by this receptor, the serotonin-amplified platelet aggregation, was measured to study whether long-term antidepressant treatment induces changes in 5-HT2A receptor functioning in endogenous depressed patients. METHOD: The percentage of serotonin-amplified platelet aggregation to adenosine diphosphate (ADP) was studied in 15 untreated patients with major depressive disorder (DSM-IV) with endogenous features (Newcastle scale). This index was used as an indirect measurement of the functional status of platelet 5-HT2A receptors. Aggregation studies were repeated once remission of the symptoms was achieved during treatment with imipramine (150-300 mg/day). A group of 15 concurrent normal subjects was used as a control. RESULTS: A statistically significant decrease (p = 0.038) in the percentage of serotonin-amplified platelet aggregation to ADP was observed when remission was achieved (after 145 +/- 27 days). CONCLUSIONS: The results showed a decrease in a platelet functional response mediated by 5-HT2A receptors following effective imipramine treatment, suggesting that desensitization or down-regulation of the 5-HT2A receptor function could be linked to the therapeutic effect of some antidepressants. The data also support the use of platelet aggregometry as a surrogate measurement of antidepressant action, particularly in intra-subject designs.
Adult↗
Psychometric study of quality of life instruments used during hospitalization for stem cell transplantation.
OBJECTIVE: To test the psychometric properties of four patient-rated quality of life (QoL) instruments devised by the authors: three single-item instruments measuring (1) overall physical status, (2) overall emotional status, and (3) energy level, and one eight-item instrument measuring systemic symptoms. METHOD: In a prospective inpatient study conducted from July 1994 to August 1997, 220 patients aged 16-65 years received hematopoietic stem cell transplantation (SCT) for hematologic cancer at a single institution. Patients were assessed at hospital admission and then on a weekly basis during hospitalization until discharge or death. RESULTS: Internal consistency reliability and test-retest reliability of the tested scales were adequate. Convergent, divergent, criterion, and predictive validities as well as responsiveness to change of our scales were demonstrated by significant associations with their tested constructs. CONCLUSION: Our data indicate that the four QoL instruments are reliable and valid for use during hospitalization for SCT.
Adolescent↗
Association analysis between a functional polymorphism in the monoamine oxidase A gene promoter and severe mood disorders.
Monoamine oxidase A (MAOA) has been suggested to be involved in human behaviour and physiology due to its key role in the metabolism of several different biological amines including the neurotransmitters serotonin, norepinephrin and dopamine.Recently, a 30 bp repeat in the MAOA gene promoter (uMAOA) has been demonstrated to be polymorphic and to affect transcriptional activity. In the context of an association case-control study design, we analysed the uMAOA polymorphism in 389 unrelated patients affected by severe mood disorders (88 bipolar subjects and 301 major depressive individuals) and in 156 controls. No association was found between the uMAOA locus and bipolar disorder or major depression. However, an increase of high-activity uMAOA alleles was found in major depression female patients presenting a seasonal pattern (chi2=3.013, P=0.05) or psychotic symptoms in their episodes (chi2=2.679, P=0.07). In female bipolar disorder patients, long alleles were associated with longest times of admission (F=4.604, P=0.037). A trend for association with seasonal pattern was also defined in this group (data not corrected for multiple testing). Our results suggest that MAOA gene variation may modulate the expression of some clinical aspects of severe mood disorders, especially in females, and support the existence of a genetic and aetiologic heterogeneity underlying the diagnoses of bipolar disorder and major depression.
Adult↗
Prognostic value of frontal functional neuroimaging in late-onset severe major depression.
BACKGROUND: There is growing evidence of a relationship between frontal neuroimaging and neuropsychological abnormalities and the physiopathology and course of late-onset major depression. AIMS: To assess acute antidepressant response in late-onset major depression in relation to baseline frontal perfusion ratios. METHOD: A 99mTc HMPAO single photon emission computed tomographic brain scan was performed in medication-free patients with late-onset major depression, who were then included in a 12-week antidepressant treatment regimen. Logistic regression was used to define a predictive model of non-remission. RESULTS: A total of 47 patients completed the study, 34 of whom were classed as remitters and 13 as non-remitters. The variable left anterior fronto-cerebellar perfusion ratio had a global predictive power of 87%. Analysing this variable together with the baseline variables age of onset and duration of index episode, the predictive power of the model rose to 94%. CONCLUSIONS: Our study suggests that a specific frontal functioning could predict the acute antidepressant response in late-onset severe major depression.
Age of Onset↗
Frontal cerebral perfusion after antidepressant drug treatment versus ECT in elderly patients with major depression: a 12-month follow-up control study.
BACKGROUND: Little is known about the evolution of brain perfusion alterations in patients with major depression, and still less about the changes in functional neuroimage produced by different antidepressant biological treatments. METHOD: Between January 2001 and December 2003, long-term follow-up frontal brain perfusion was compared in 2 subgroups of elderly patients (>or= 60 years) treated for severe unipolar major depression (DSM-IV): one subgroup of 16 patients administered electroconvulsive therapy, and another of 26 patients receiving pharmacologic treatment. All patients were remitters. A medication-free brain single photon emission computed tomography was performed in baseline conditions and after a minimum period of 12 months of euthymia. Twenty-eight age- and sex-matched healthy controls were also assessed. RESULTS: No significant differences were found between the 2 subgroups in frontal uptake ratios after a 12-month follow-up period of euthymia. During the acute episode, patients presented significant anterior hypofrontality; 12 months later the hypofrontality had disappeared. CONCLUSION: The long-term evolution of frontal perfusion in elderly major depressives who respond to antidepressant biological treatment is essentially the same in those who receive electroconvulsive therapy and in those who receive medication.
Aged↗
Single-blind comparison of venlafaxine and nortriptyline in elderly major depression.
The objective of this single-blind study was to compare the efficacy and safety of venlafaxine extended-release and nortriptyline in elderly patients with moderate to severe major depression. In- and out-patients (N=68) with unipolar major depression were randomized to receive 6-month treatment with either nortriptyline or venlafaxine. Outcomes of the two groups were compared using measures including the Hamilton Depression Rating Scale (HDRS) and the Newcastle Scale. Side effects were assessed with the UKU side-effect rating scale. Of the 34 venlafaxine-treated patients, 22 were remitters, 7 were nonremitters, and 5 dropped out. The intent-to-treat remission rate was 71% (22 of 31). Of the 34 who received nortriptyline, 21 were remitters, 7 were nonremitters, and 6 dropped out. The intent-to-treat remission rate was 70% (21 of 30). These results suggest that the remission rate with a therapeutic plasma level of nortriptyline is similar to the remission rate with a standard dose of venlafaxine in this group of elderly major depressed patients. No significant differences were observed between dropout rates in the two groups, but autonomic side-effects were significantly more frequent for nortriptyline than for venlafaxine. These results confirm the efficacy and safety of venlafaxine extended-release for treating elderly major depression.
Aged↗
5-HTTLPR polymorphism of the serotonin transporter gene predicts non-remission in major depression patients treated with citalopram in a 12-weeks follow up study.
In the context of a long term follow-up study, we analysed the possible implication of the 5-HTTLPR polymorphism at the serotonin transporter gene in clinical response and remission of major depressive patients treated with citalopram. The sample consisted of 131 patients, all of Spanish origin, diagnosed according to DSM-IV criteria. A 21-item Hamilton Depression Rating Scale (HDRS) was used to evaluate severity of the symptoms during the follow-up and to determine clinical response and remission condition of the patients at 4th and 12th week, respectively. Our results showed that S/S genotype of the 5-HTTLPR polymorphism was associated with the non-Remission condition at 12th week (chi2 = 8.7, P = 0.013). Moreover, homozygous for the allele S presented three times more risk for non reaching remission of depressive episode after citalopram treatment than patients with any other 5-HTTLPR genotype combination (chi2: 7.29, P = 0.006; OR = 3.23 [95%CI: 1.24-8.5]). In conclusion, our results show that genetic variation of serotonin transporter is involved in clinical remission of major depressive episodes after twelve weeks of citalopram treatment.
Adult↗
Psychiatric morbidity and impact on hospital length of stay among hematologic cancer patients receiving stem-cell transplantation.
PURPOSE: To determine the prevalence of psychiatric disorders during hospitalization for hematopoietic stem-cell transplantation (SCT) and to estimate their impact on hospital length of stay (LOS). PATIENTS AND METHODS: In a prospective inpatient study conducted from July 1994 to August 1997, 220 patients aged 16 to 65 years received SCT for hematologic cancer at a single institution. Patients received a psychiatric assessment at hospital admission and weekly during hospitalization until discharge or death, yielding a total of 1,062 psychiatric interviews performed. Psychiatric disorders were determined on the basis of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Univariate and multivariate linear regression analyses were used to identify variables associated with LOS. RESULTS: Overall psychiatric disorder prevalence was 44.1%; an adjustment disorder was diagnosed in 22.7% of patients, a mood disorder in 14.1%, an anxiety disorder in 8.2%, and delirium in 7.3%. After adjusting for admission and in-hospital risk factors, diagnosis of any mood, anxiety, or adjustment disorder (P =.022), chronic myelogenous leukemia (P =.003), Karnofsky performance score less than 90 at hospital admission (P =.025), and higher regimen-related toxicity (P <.001) were associated with a longer LOS. Acute lymphoblastic leukemia (P =.009), non-Hodgkin's lymphoma (P =.04), use of peripheral-blood stem cells (P <.001), second year of study (P <.001), and third year of study (P <.001) were associated with a shorter LOS. CONCLUSION: Our data indicate high psychiatric morbidity and an association with longer LOS, underscoring the need for early recognition and effective treatment.
Adjustment Disorders↗
Platelet 5-HT2A-receptor-mediated induction of aggregation is not altered in major depression.
BACKGROUND: Studies of the 5-HT(2A) receptor subtype in major depression have focused on the density of these receptors in neuronal cells and platelets, showing an up-regulation secondary to a deficit in serotonergic activity in major depression. However, their functional state has often been disregarded. The aim of the study was to investigate whether depressed patients show abnormalities in the function of the 5-HT(2A) receptor pathway in platelets. METHOD: The percentage of serotonin-amplified platelet aggregation to adenosine diphosphate (ADP) was assessed in 30 untreated patients with major depressive disorder and in 15 controls. Since 5-HT(2A) platelet receptors mediate the serotonin-induced platelet aggregation response, this index was used as a measure of the functional status of the platelet 5-HT(2A) receptor pathway. RESULTS: There was no significant difference in the percentage of serotonin-amplified platelet aggregation to ADP between depressed patients and controls. No correlation with the severity of depression, as assessed by the Hamilton scale, was found. CONCLUSION: The results showed no consistent changes in the platelet aggregating responses to serotonin in the depressed patients. Therefore this study does not support the hypothesis of an alteration of the functional status of platelet 5-HT(2A) receptors in major depression.
Adenosine Diphosphate↗
Normalization of frontal cerebral perfusion in remitted elderly major depression: a 12-month follow-up SPECT study.
We examined global and regional cerebral blood flow abnormalities in a group of unmedicated nondemented elderly late-onset unipolar major depressed patients in acute depression and in remission (after a 12-month follow-up period). 35 somatic treatment remitter patients over the age of 60 years and 20 sex-, age-, and vascular risk factor-matched healthy controls were imaged with single photon emission computed tomography, using technetium-99m hexamethylpropylene amine oxime as a tracer. In depression, the depressed group had significantly lower uptake in the left anterior frontal region than the control group. In remission, the left frontal cerebral perfusion abnormalities disappeared, and there were no significant differences in uptake between controls and patients. No significant correlations were found between baseline clinical characteristics of patients and their regional cerebral perfusion at baseline or after a 12-month follow-up. These findings are consistent with the hypothesis that certain neuroanatomic regions of the central nervous system may be functionally and reversibly involved in unipolar major depression, particularly in the late-onset subgroup.
Aged↗