Biomedical subjects

Enrico Smeraldi

Publications and source records attributed to Enrico Smeraldi.

At least 19 recordsLinked to original sources

PubMed2007

Actimetric evidence that CLOCK 3111 T/C SNP influences sleep and activity patterns in patients affected by bipolar depression.

Depressive insomnia and diurnal fluctuations of mood and activity are core clinical features of mood disorders. Here we studied the effect of CLOCK 3111 T/C SNP (rs1801260) on the actimetric recorded diurnal activity and nocturnal sleep of 39 bipolar depressed inpatients. Compared to T/T homozygotes, carriers of the C allele had a similar degree of severity of depression, but showed higher activity levels in the evening, a delayed sleep onset (mean 79 min later), and a reduced amount of sleep during the night (mean 75 min less). Ongoing lithium treatment significantly interacted with rs1801260 by enhancing activity levels in the evening and reducing the differences among genotype groups. Individual characteristics of the molecular clock can influence sleep symptoms in mood disorders.

Adult↗

PubMed2006

Serotonin transporter gene influences the time course of improvement of "core" depressive and somatic anxiety symptoms during treatment with SSRIs for recurrent mood disorders.

The short variant of the serotonin transporter gene (SERTPR) has been consistently associated with a poorer response to treatment with various selective serotonin reuptake inhibitors (SSRIs). Antidepressant response is not a unitary phenomenon, however, and we here hypothesized that the SERTPR effect could be specific to some types of symptomatology. The sample comprised 281 inpatients affected by mood disorders and treated for major depression with SSRIs. The total depressive scores for all patients were analyzed in previous reports, but symptomatologic clusters were not examined previously. The 21-item Hamilton Rating Scale for Depression (HAM-D) was administered to evaluate depressive symptoms at baseline and weekly over 6 weeks of treatment. All patients were genotyped for the SERTPR polymorphism. Compared with patients with the SERTPR l/l and l/s polymorphisms, s/s patients showed a selective and slower improvement of depressive "core" and somatic anxiety symptoms, but they did not differ from other patients regarding other symptomatologic clusters such as insomnia and motor retardation. These findings support the view that response to SSRIs is not a unitary phenomenon and that improvement of symptomatologic clusters as, at least in part, genetically driven. SERTPR may be hypothesized as concurrently participating to the activity of anatomic brain regions differentially involved in depression and somatic symptoms of anxiety; however, further studies are required to examine these complex interactions.

Adult↗

PubMed2006

Pooling pharmacogenetic studies on the serotonin transporter: a mega-analysis.

Pharmacogenetic studies on antidepressants have reported an association between the promoter of the serotonin transporter gene (SERTPR) and response to antidepressant treatment. In the present study, individual subject data from three pharmacogenetic studies on SERTPR were pooled ('mega-analysis') to investigate the role of this gene in the antidepressant activity of selective serotonin reuptake inhibitors (SSRIs). A group of 548 patients who were treated with different SSRIs in a double blind design were included; the severity of depressive symptoms was weekly assessed with the Hamilton Rating Scale for Depression. SERPR allelic variants were determined in each subject using a PCR-based technique. In the whole sample, subjects with SERPR() l/l variants showed a significantly better response to treatment, and this effect was independent from analyzed demographic and clinical variables but was not uniform across samples. This result supports the involvement of the SERTPR gene in response to antidepressant treatments.

Adult↗

PubMed2006

A neural network model for combining clinical predictors of antidepressant response in mood disorders.

Artificial neural networks (ANN) represent a promising tool for combining multiple predictors in complex diseases. Antidepressant response in mood disorders is a typical complex phenomenon were a number of predictors influence outcome under non-linear interactions. In the present study we tested a neural network strategy for antidepressant outcome in subjects affected by major depression. One hundred and forty-five never reported depressed inpatients were included in this study (major depressives/bipolars: 111/34). A multi layer perceptron network composed of 1 hidden layer with 13 nodes was chosen. The network was performed on the sample of 145 cases divided as follows: train 73+verify 36+test 36. Correlation of predicted versus observed response was 0.46 in the test (independent) sample that corresponds to 21% of variance explained. Number of episodes, side effects, delusional features, baseline HAM-D, length of current episode, lithium augmentation, current medical condition and personality disorders were the main factors identified by the model. Sex, age at onset, polarity, plasma level and baseline VAS score were part of the model but with a lower rank. Overall, our findings suggest that neural networks could be a valid technique for the analysis of psychopharmacology studies. The complex interactions modelled through ANN may be eventually applied at the clinical level for the individualized therapy.

Antipsychotic Agents↗

PubMed2006

The effect of verbalization strategy on Wisconsin Card Sorting Test performance in schizophrenic patients receiving classical or atypical antipsychotics.

BACKGROUND: A number of reports showed en encouraging remediation in some patients' executive deficits thanks to the use of 'information processing strategies'. Moreover the impact of antipsychotics on cognitive functions of the schizophrenics is an important issue, especially if an integrated psychosocial treatment is needed. The aim of this paper is to evaluate different executive performance and response to verbalization, a strategy of the Wisconsin Card Sorting Test (WCST) remediation, in subjects on classical vs atypical antipsychotic (AP) treatment. METHODS: Sixty-three schizophrenic subjects undertook the WCST under standard and modified (verbalization) administration. Subjects were stratified by the kind of WCST response (i.e. good, poor and remediable) and AP treatment (i.e. atypical vs. classical). RESULTS: Subjects on atypical APs showed a better performance than those on classical ones. More poor performers who did not remediate were seen in the sample with classical Aps while subjects who remediated the performance were seen in the subgroup with atypical APs only. An increase of perseverative and total errors was seen in poor performers subjects on classical APs. CONCLUSION: Subjects on atypicals showed a better cognitive pattern in terms of WCST performance. Since the naturalistic assignment of medication we cannot draw conclusions about its effect on cognitive performance and its interaction with cognitive remediation potential. However the data lead us to hypothesize that subjects with potential room for remediation did so with the atypical APs.

Adult↗

PubMed2006

Relapse during a 6-month continuation treatment with fluvoxamine in an Italian population: the role of clinical, psychosocial and genetic variables.

The efficacy of SSRIs in relapse prevention in major depression has been extensively demonstrated. Considering published data, the relapse rate during a psychopharmacological continuation treatment ranges from 10% to 30%. Since the reasons of depressive relapses could be heterogeneous, we have tested the effect of clinical, psychosocial and genetic variables in sustained remission from an index depressive episode during continuation treatment with fluvoxamine over a 6-month follow-up period. 101 patients maintained the same full dosage treatment after remission from a depressive episode efficaciously treated with fluvoxamine. During the follow-up period, they were clinical assessed monthly by an experienced psychiatrist and SASS was administered, to assess their psychosocial adjustment. From a genetical point of view, SERTPR and CLOCK polymorphisms were analyzed for each patients, using PCR-based techniques. At the end of follow-up period, the 57.4% of the patients maintained remission during fluvoxamine continuation treatment; the 8.9% relapsed within the first 2 months of continuation; the 7.9% switched and the 25.8% dropped-out for poor compliance. Relapsed subjects presented a significantly longer mean duration of the index depressive episode than non-relapsed subjects and a subjective poor social adjustment than non-relapsed also in the euthymia period. None of the analyzed polymorphisms significantly appear to influence the outcome of the whole sample. The present data confirm that patients with severe depression and a long duration of the episode have a major risk of psychosocial disability. These patients could need a different psychopharmacological strategies and peculiar psychological intervention.

Adult↗

PubMed2006

Serotonin transporter gene-linked polymorphic region: possible pharmacogenetic implications of rare variants.

A functional insertion/deletion (*l/*s) repeat polymorphism within the promoter region of the serotonin transporter (5-HTTLPR) has been described. An association between *l variant and a better and faster response to serotonin selective reuptake inhibitors in depressed patients was reported in Caucasians. The value of the explained variance due to the 5-HTTLPR, however, was 7% only, and different *l and *s variants were reported according to the nucleotide sequence of repeats. In this study, we investigated the antidepressant response to fluvoxamine in individuals carrying different *l and *s variants according to the Nakamura findings. Two hundred and twenty-eight patients affected by bipolar disorder and major depression were administered a daily dose of fluvoxamine up to 300 mg and evaluated at baseline and weekly thereafter until week 7, using the 21-item Hamilton Rating Scale for Depression. We found a marginally significant difference in genotype and allele (P=0.04, data not shown) distribution (*l and *s traditional variants) according to diagnosis (bipolar disorder vs. major depression). We confirmed a better and faster response in our depressed patients bearing the *l variant, but we also found significant differences in response among *l carriers according to the type of *l allele. In fact, 16F *l carriers showed only a partial response, while 16D *l carriers showed a marginally significantly better response than 16A *l allele carriers. These results, although very preliminary, can represent a further step toward a better understanding of the molecular genetics of antidepressant response.

Adult↗

PubMed2006

Catechol-O-methyltransferase gene variants in mood disorders in the Italian population.

Dysfunctions of dopaminergic transmission have been implicated in the pathogenesis of mood disorders and variants at the catechol-O-methyltransferase (COMT) gene have been recently reported to be associated with bipolar disorder. In this study, we tried to replicate this finding in an independent sample of participants affected by mood disorders. Eight hundred and five psychiatric in-patients affected by bipolar (n=446) and major depressive (n=359) disorder were included. All patients and 116 controls were typed for the COMT variants using polymerase chain reaction techniques. A subsample of 458 patients was assessed for their lifetime symptomatology. The sample was analyzed alone and pooled with 111 participants and 127 controls collected in the center of Pisa and previously reported. COMT variants were not associated with mood disorders in our sample, a trend was observed toward an excess of COMT*A allele in the pooled sample. The analysis of symptomatology factors did not show any significant difference as well. Possible stratification factors such as sex, current age and age of onset did not affect the observed results. Control subjects from the two centers showed a similar genotype distribution. In conclusion, COMT variants were not a major liability factor for mood disorder and for mood disorder symptomatology in the present sample; however, we could not subdivide our sample on the basis of panic comorbidity as in the original paper and this could be considered a possible reason for the discrepant finding.

Case-Control Studies↗

PubMed2006

Improvement of cognitive functioning in mood disorder patients with depressive symptomatic recovery during treatment: an exploratory analysis.

Depressive symptoms have a large impact on cognitive test performance of mood disorder patients. After remission, some improvement of cognitive functioning has been observed, but also stable deficits have been reported both during depression and remission. In the present study, the authors aimed to investigate the cognitive functioning of mood disorder patients in relation to early symptomatic recovery, by comparing performances at the Wechsler Adult Intelligence Scale-Revised (WAIS-R) of responders and non-responders to the antidepressant treatment. The sample was composed of 51 hospitalized patients for a major depressive episode (major depressives/bipolars = 37/14). All patients were treated with fluvoxamine and evaluated at baseline and after 4 weeks using the 21-item Hamilton Rating Scale for Depression. All subjects were once assessed for their cognitive functioning with the WAIS-R, at the end of the fourth week of treatment. In the current sample, patients who showed a significant symptomatic remission after 4 weeks of treatment showed higher total WAIS-R scores and a lower incidence of cognitive impairment, compared to non-responders to treatment. No major differences could be observed on any particular subtest, but rather a global improving of scores in responders compared to non-responders to pharmacotherapy. Pre-treatment illness severity, that was significantly higher among non-responders, was significantly associated with patients' intelligence quotient scores. Despite a number of limitations, present data support a strong effect of depressive symptoms on patients WAIS-R performances and an early global improvement of cognitive functioning concurrent with symptomathology recovery during pharmacological treatment.

Adult↗

PubMed2005

Transcranial magnetic stimulation in treatment-resistant depressed patients: a double-blind, placebo-controlled trial.

This 5-week, randomized, double-blind, placebo-controlled trial investigated the efficacy and tolerability of high frequency repetitive transcranial magnetic stimulation (rTMS) directed to the left prefrontal cortex in drug-resistant depressed patients. Fifty-four patients were randomly assigned to receive 10 daily applications of either real or sham rTMS. Subjects assigned to receive active stimulation were divided into two further subgroups according to the intensity of stimulation: 80% vs. 100% of motor threshold (MT). At study completion, the response rates were 61.1% (n=11), 27.8% (n=5) and 6.2% (n=1) for the 100% MT group, 80% MT group and sham group, respectively. A significant difference (Pearson chi(2) test) was found between the 100% MT and sham groups, while the 80% MT group did not differ significantly from the sham group. Between the two active groups, a marginally significant difference was observed. Analysis of variance with repeated measures on Hamilton Depression Rating Scale scores revealed a significantly different decrease over time of depressive symptomatology among the three treatment groups. Treatment response appeared to be unrelated to the demographic and clinical characteristics recorded, and on the whole the technique was well tolerated. The results of this double-blind trial showed that rTMS may be a useful and safe adjunctive treatment for drug-resistant depressed patients.

Adult↗

PubMed2005

5-HT 1A polymorphism and self-transcendence in mood disorders.

Recently, an association between serotonin 1A receptor binding potential and self-transcendence scores at the temperament and character inventory (TCI) has been reported. We tested involvement of 5-HT(1A) gene in this trait, in a sample of 40 remitted mood disorder patients. Subjects with the 5-HT(1A)*C/C genotype showed significantly lower scores at the total self-transcendence and at the sub-scales of transpersonal identification and spiritual acceptance. Our preliminary results further support the involvement of the serotoninergic pattern in the self-transcendence character trait.

Adult↗

PubMed2005

Insomnia improvement during antidepressant treatment and CLOCK gene polymorphism.

Sleep disturbances are commonly observed in mood disorders, and sleep manipulations can influence the clinical status. In the present study, we investigated the possible effect of the 3111 T/C circadian locomotor output cycles kaput (CLOCK) gene polymorphism on insomnia symptomatology during antidepressant treatment. One hundred seventy-eight inpatients were treated with fluvoxamine 300 mg/day (n = 147) or paroxetine 20-40 mg/day (n = 31), and either placebo or pindolol in a double blind design for 6 weeks. The severity of depressive symptoms was weekly assessed with the Hamilton Rating Scale for Depression (HAM-D). We observed a significantly higher presence of insomnia throughout the trial in homozygotes for the C variant (P = 0.026). Other demographic and clinical features were found not to be related with CLOCK polymorphisms. Overall, our findings may suggest that CLOCK genotype influences the time course of insomnia during antidepressant treatment. This, together with previous findings on this polymorphism could lead to a further dissection of the complexity of mood disorders.

Adult↗

PubMed2005

Supporting tools in psychiatric treatment decision-making: sertraline outcome investigation with artificial neural network method.

Controlled trials in clinical psychopharmacology may fail to provide reliable information about the benefit of treatment for the patient when considered in a real-life setting rather than as a part of a well-defined sampling procedure. Previously, we applied the mathematical model of an artificial neural network (ANN) to a pool of clinical information gathered through case descriptions provided by senior psychiatrists in clinical charts of patients receiving their first exposure to sertraline. In the present study, we applied the same mathematical model to a larger sample. The performance of the ANN model in forecasting successful and unsuccessful treatment showed an overall accuracy of classification of 97.12%. This result supports our previous finding about the potential application of this method as a reliable predictor of a given psychiatric patient's outcome during a specific psychopharmacological therapy.

Adult↗

PubMed2005

Social adjustment could be associated with the serotonin transporter gene in remitted patients with mood disorders and healthy subjects.

We investigated the serotonin transporter gene (5-HTTLPR) in the functioning of euthymic patients with mood disorders (n=285) and healthy controls (n=94). The 5-HTTLPR genotype showed marginal associations with working, familial and social adjustment, with marked differences between controls and patients. Because of the exploratory nature of our analyses, all results should be viewed with caution. However, we observed how the s/s variant, commonly associated with detrimental effects, could be beneficial in specific areas of social adjustment.

Adult↗

PubMed2005

The influence of Serotonin Transporter Promoter Polymorphism (SERTPR) and other polymorphisms of the serotonin pathway on the efficacy of antidepressant treatments.

The definition of a genetic liability profile for specific antidepressant treatment will soon be available offering considerable help in early detection of effective therapy in affective disorders. The search for genetic factors predisposing to drug response or side-effects in affective disorders started only in the last few years. The efficacy of antidepressant action was associated with several polymorphisms, located on coding genes of proteins thought to be involved in the different mechanisms of action of antidepressant treatments. Among these, gene variants in sequences of serotonin pathway proteins were candidate, both for the well known evidence of its involvement in the development of depressive symptomathology and for the wide-world use of selective serotonin reuptake inhibitors as first choice treatment of depression. A polymorphism in the promoter region of the serotonin transporter (SERTPR) was independently associated with efficacy for a range of treatments, other polymorphism located on the tryptophan hydroxylase gene, 5-HT2a receptor and G-protein beta 3 showed some association, while other candidate genes were not associated with treatment efficacy. Possible liability genes controlling at least to some extent both acute and long-term treatment were identified, and the further objective is to identify other candidate genes in order to define individualized treatments according to genetic profile in a future. The present paper reviews the pharmacogenetic studies published to date, focusing the attention on the serotonergic pathway.

Animals↗

PubMed2005

Sertraline versus fluvoxamine in the treatment of elderly patients with major depression: a double-blind, randomized trial.

BACKGROUND: Major depression is a common psychiatric disorder in the elderly population. The efficacy of tricyclic antidepressants is well established, and selective serotonin reuptake inhibitors appear to have a similar effectiveness along with advantages in terms of tolerability and safety. Given the lack of literature data regarding fluvoxamine in the treatment of depressed elderly patients, the aim of the present study was to compare its efficacy and tolerability with those of sertraline in a sample of elderly patients. METHODS: Under double-blind conditions, 93 hospitalized patients older than 59 years, who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for a major depressive episode, were randomly assigned to receive sertraline (150 mg daily) or fluvoxamine (200 mg daily) for 7 weeks. The clinical response was defined as a reduction on the Hamilton Rating Scale for Depression score to 8 or below. RESULTS: At study completion, the response rates were 55.6% (25/45) and 71.8% (28/39) for sertraline and fluvoxamine, respectively. No significant difference in final response rates was found between the 2 treatment groups (P = 0.12). A repeated-measures analysis of variance on Hamilton Rating Scale for Depression scores revealed a significantly different decrease of depressive symptoms between the 2 treatment groups, favoring fluvoxamine (P = 0.007). The overall safety profile of sertraline and fluvoxamine was favorable with no differences between the 2 drugs. CONCLUSION: The results of this double-blind trial show that sertraline and fluvoxamine may be effective compounds in the treatment of elderly depression with the latter showing some advantage in terms of speed of response. These findings warrant further replication in placebo-controlled studies.

Aged↗

PubMed2005

Dark therapy for mania: a pilot study.

BACKGROUND: Recent findings suggest that extended bed rest and darkness could stabilize mood swings in rapid cycling bipolar patients. METHOD: We exposed 16 bipolar inpatients affected by a manic episode to a regimen of 14 h of enforced darkness from 6 p.m. to 8 a.m. each night for three consecutive days [dark therapy (DT)]. Pattern of mood changes were recorded with the Young Mania Rating Scale (YMRS) and compared with a control group of 16 inpatients matched for age, sex, age at onset, number of previous illness episodes and duration of current episode, and were treated with therapy as usual (TAU). RESULTS: Adding DT to TAU resulted in a significantly faster decrease of YMRS scores when patients were treated within 2 weeks from the onset of the current manic episode. When duration of current episode was longer, DT had no effect. Follow-up confirmed that good responders needed a lower dose of antimanic drugs and were discharged earlier from the hospital. CONCLUSIONS: Chronobiological interventions and control of environmental stimuli can be a useful add-on for the treatment of acute mania in a hospital setting.

Adult↗

PubMed2005

Combined total sleep deprivation and light therapy in the treatment of drug-resistant bipolar depression: acute response and long-term remission rates.

BACKGROUND: Drug resistance remains a persistent source of morbidity and mortality for patients with bipolar depression. A growing number of clinical studies support the usefulness of chronotherapeutic interventions, such as total sleep deprivation (TSD) and light therapy (LT), in the treatment of nonresistant bipolar depression. METHOD: To investigate the clinical usefulness of TSD plus LT in the treatment of drug-resistant bipolar depression, we treated 60 inpatients for 1 week with repeated TSD and LT combined with ongoing antidepressants and lithium salts. All patients had a DSM-IV diagnosis of bipolar I disorder. Drug resistance was rated according to Thase and Rush criteria. The pattern of relapses and recurrences was assessed during a prospective 9-month follow-up. Data were gathered from September 2002 to July 2004. RESULTS: A 2-way repeated-measures analysis of variance with changes in self-rated perceived mood scores as dependent variable and with time and group (history of drug resistance) as independent factors confirmed significant time-by-group interaction (p = .0339). A logistic regression on rates of achievement of response (50% reduction in Hamilton Rating Scale for Depression ratings) confirmed the significance of observed differences: overall, 70% (23/33) of nonresistant versus 44% (12/27) of drug-resistant patients achieved response (p = .045). A survival time analysis (Cox proportional hazards model) showed that history of drug resistance significantly influenced the pattern of relapses and recurrences, with 57% (13/23) of nonresistant responders and 17% (2/12) of drug-resistant responders being euthymic after 9 months (p = .0212). DISCUSSION: The combination of repeated TSD and LT in drug-resistant patients was useful in triggering an acute response. Further clinical research is needed to optimize this treatment option for drug-resistant patients in the long term.

Adult↗