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Biomedical subjects

Cristina Colombo

Publications and source records attributed to Cristina Colombo.

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

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

Interaction between serotonin transporter gene, catechol-O-methyltransferase gene and stressful life events in mood disorders.

It is well established that stress is a risk factor for onset of mood disorders. Emerging evidence suggests that genetic vulnerability may also moderate individual responsiveness to stress. The most compelling evidence regards the polymorphism within the promoter region of the serotonin transporter gene (SERTPR), which has been reported to moderate the risk for depression, in conjunction with life stressors. In the present paper we analysed SERTPR in the onset of mood disorders, along with adverse life events, and other candidate genes: the serotonin receptor 1A (5-HT1A), the dopamine receptor D4 (DRD4) and the catechol-O-methyltransferase (COMT). The sample was composed of 686 Italian subjects, affected by major depression and bipolar disorder. Patients were asked to report about life stressors within the year preceding onset of their first mood-disorder episode and genotyped. A 'case-only' design was employed to investigate the interaction between genes and stressors. COMT was associated with depression following exposure to stressors (chi2=13.05, d.f.=2, p=0.0015) and SERTPR also showed a positive association (chi2=6.70, d.f.=2, p=0.035), mainly among women and among major depressives. The interaction between COMT and SERTPR was also significant (p=0.0005). In our retrospective study SERTPR is hypothesized to lead to the onset of major depression via its influence on reaction to adversities, particularly in females. Moreover, COMT was risk factor for onset of both major depression and bipolar disorder, in conjunction with adversities.

Adult↗
PubMed2006

Influence of postpartum onset on the course of mood disorders.

BACKGROUND: To ascertain the impact of postpartum onset (PPO) on the subsequent time course of mood disorders. METHODS: This retrospective study compared per year rates of excited (manic or mixed) and depressive episodes between fifty-five women with bipolar (N = 22) or major depressive (N = 33) disorders with first episode occurring postpartum (within four weeks after childbirth according to DSM-IV definition) and 218 non-postpartum onset (NPPO) controls. Such patients had a traceable illness course consisting of one or more episodes alternating with complete symptom remission and no additional diagnoses of axis I disorders, mental retardation or brain organic diseases. A number of variables reported to influence the course of mood disorders were controlled for as possible confounding factors RESULTS: Bipolar women with postpartum onset disorder had fewer excited episodes (p = 0.005) and fewer episodes of both polarities (p = 0.005) compared to non-postpartum onset subjects. No differences emerged in the rates of depressive episodes. All patients who met criteria for rapid cycling bipolar disorder (7 out of 123) were in the NPPO group. Among major depressives, PPO patients experienced fewer episodes (p = 0.016). With respect to clinical and treatment features, PPO-MDD subjects had less personality disorder comorbidity (p = 0.023) and were less likely to be on maintenance treatment compared to NPPO comparison subjects (p = 0.002) CONCLUSION: Such preliminary findings suggest that PPO mood disorders may be characterized by a less recurrent time course. Future research in this field should elucidate the role of comorbid personality disorders and treatment. Moreover it should clarify whether PPO disorders are also associated with a more positive outcome in terms of social functioning and quality of life.

Adult↗
PubMed2006

Retrospective analysis of psychomotor agitation, hypomanic symptoms, and suicidal ideation in unipolar depression.

In bipolar depression, psychomotor agitation is relatively common and often is associated with other noneuphoric hypomanic symptoms and suicidal ideation. Our goal in this retrospective study was to ascertain the co-occurrence of agitation, bipolar features, and suicidal ideation in unipolar disorder. We retrospectively evaluated 314 inpatients with DSM-IV major depressive disorder (MDD) and no other Axis I diagnosis with the National Institutes of Mental Health (NIMH) Life Chart Method and the Operational Criteria for Psychotic Illness (OPCRIT) checklist to ascertain their symptom profiles across all episodes. Univariate and multivariate comparisons were performed between the subgroups with and without psychomotor agitation (OPCRIT item 23> or =1). Agitated depression (AD, a major depressive episode with psychomotor agitation) was present in 19% of the sample. Compared to nonagitated counterparts, patients with AD were older and had lower educational levels and more dysphoria, insomnia, positive thought disorder, and psychotic manifestations. Hypomanic symptoms other than agitation were relatively uncommon (<10%) and more represented in subjects with AD. No significant differences emerged between AD and control groups with respect to most bipolar validators (gender, familiarity, recurrence). Patients with AD had higher levels of suicidal ideation than non-AD controls; however, such a difference was no longer significant after controlling for psychotic features. Excessive self-reproach, early awakening, diurnal changes, poor appetite, and hypomanic symptoms were independently associated with suicidal thoughts in nonpsychotic MDD. Incomplete information on drug treatment, exclusion of patients with Axis I comorbidity, and tertiary care setting were the most important limitations of the study. Although we failed to support the bipolar nature of MDD-AD by common validators, probably because we used a more heterogeneous definition of agitation compared to similar studies, our data confirm the association of agitation with hypomanic symptoms and suicidal thoughts in major depression, and emphasize the complex phenomenology of AD in an inpatient setting.

Adult↗
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

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

Components of self-esteem in affective patients and non-psychiatric controls.

Decrease in self-esteem (SE) is found in all mood disorders during inter-episode phases. This trait was associated with relapse and suicidality but its genetic basis is still undefined, probably because SE has multiple components. The aim of the current study was to ascertain which of those components were altered in a sample of affective patients. Three hundred and thirty-one outpatients with bipolar (N=199) and major depressive MD (N=132) disorders in remission for at least three months and one hundred controls completed the Rosenberg Self-esteem Scale (RSE; [Rosenberg, M., 1965. The measurement of self-esteem, Society and the Adolescent Self-Image. Princeton University Press, pp.16-36]). Principal component analysis was performed to identify RSE factor structure. Extracted factors were compared across case and control groups in the whole sample (N=431) and in a sub-sample (N=301) with low self-esteem (RSE <20). PCA yielded a two-factor solution with self-confidence (SC) and self-deprecation (SD) that was largely consistent with the existing literature. Such factors were both associated with lower scores in affective patients than controls (SC: F=52, p<0.01; SD: F=43, p<0.01). However in the low RSE group only self-confidence was found to be decreased in subjects with mood disorders (SC: F=13.8, p<0.01; SD: F=0.05, p=0.9). These findings suggest that self-esteem deficit in affective disorders might involve specific components. Implications for research and clinical practice are discussed.

Adult↗
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↗
PubMed2004

Long-term response to lithium salts in bipolar illness is influenced by the glycogen synthase kinase 3-beta -50 T/C SNP.

The molecular mechanisms driving the biological clock in the suprachiasmatic nucleus of the hypothalamus may play a role in mood disorders. A single nucleotide polymorphism (SNP) (-50 T/C) falling into the effective promoter region (nt -171 to +29) of the gene coding for glycogen synthase kinase 3-beta (GSK3-beta) has been linked with different age at onset of bipolar illness and with different antidepressant effects of total sleep deprivation. GSK3-beta codes for an enzyme which is a target for the action of lithium and possibly of valproic acid. We studied the effect of this polymorphism on the therapeutic response to lithium salts of 88 bipolar type I patients. Data about recurrence rate of mood episodes were collected for at least 2 years before lithium and 2 years on lithium. Results showed that homozygotes for the wild variant did not change their recurrence index while carriers of the mutant allele improved, thus supporting the hypothesis that GSK is a target for the therapeutic action of lithium. Results warrant interest for the variants of genes pertaining to the molecular clock as possible endophenotypes of bipolar disorder, but caution ought to be taken in interpreting these preliminary results and future replication studies must be awaited because of the low frequency of the GSK3-beta*C/C genotype in the studied populations.

Adult↗
PubMed2004

A glycogen synthase kinase 3-beta promoter gene single nucleotide polymorphism is associated with age at onset and response to total sleep deprivation in bipolar depression.

The molecular mechanisms driving the biological clock in the suprachiasmatic nucleus of the hypothalamus may play a role in mood disorders. A single nucleotide polymorphism (SNP) (-50T/C) falling into the effective promoter region (nt -171 to +29) of the gene coding for glycogen synthase kinase 3-beta (GSK3-beta) has been linked with different age at onset of bipolar illness. GSK3-beta codes for an enzyme which is a target for the action of lithium and valproic acid, and the inhibition of which causes antidepressant-like behaviors in a preclinical model. We studied the effect of this polymorphism on the acute response to total sleep deprivation of 60 depressed bipolar type I inpatients. Homozygotes for the mutant allele of GSK3-beta promoter (-50T/C) SNP showed a later onset of bipolar illness, and better acute effects of TSD treatment on perceived mood (as rated on VAS). Overall, these observations suggest a protective role for this genotype in respect to bipolar illness. Results warrant interest for the variants of genes pertaining to the molecular clock as possible endophenotypes of bipolar disorder, and for GSK3-beta as a target of a new class of antidepressant drugs, but caution ought to be taken in interpreting these preliminary results and future replication studies must be awaited because of the low frequency of the GSK3-beta*C/C genotype in the studied populations.

Adult↗
PubMed2004

Dopaminergic modulation of oxidative stress and apoptosis in human peripheral blood lymphocytes: evidence for a D1-like receptor-dependent protective effect.

Dopamine (DA) is a neurotransmitter in the central and peripheral nervous system, which can be either cytotoxic or cytoprotective under selected conditions. Such effects involve oxidative mechanisms and are likely to play a role in neurodegenerative disorders. Because increasing evidence points to peripheral blood lymphocytes (PBL) as a feasible model for studying DA-related mechanisms of cell death and survival, we have explored in these cells the effects of DA on oxidative metabolism and apoptosis. Our results show that, whereas DA 100-500 microM resulted in increased intracellular reactive oxygen species (ROS) levels and apoptotic cell death through oxidative stress, DA 0.1-5 microM decreased ROS levels and apoptosis. DA (both 1 and 500 microM) partially counteracted the decrease in Cu/Zn superoxide dismutase levels observed in untreated PBL. However, whereas the effect of the low dose lasted for the whole incubation period (24 h), the effect of DA 500 microM was transient. DA-dependent reduction of ROS levels and apoptosis was prevented by D1-like (but not D2-like) receptor antagonism. The present findings add knowledge about the sensitivity of PBL to DA and strengthen the rationale for exploiting these cells as an easily accessible peripheral model for the ex vivo investigation of oxidative stress-related dopaminergic mechanisms underlying human neurodegenerative diseases.

Apoptosis↗
PubMed2004

A single nucleotide polymorphism in glycogen synthase kinase 3-beta promoter gene influences onset of illness in patients affected by bipolar disorder.

Genetic studies in medicine exploited age of onset as a criterion to delineate subgroups of illness. Bipolar patients stratified with this criterion were shown to share clinical characteristics and patterns of inheritance of illness. The molecular mechanisms driving the biological clock in the suprachiasmatic nucleus of the hypothalamus may play a role in mood disorders. A single nucleotide polymorphism (SNP) (-50 T/C) falling into the effective promoter region (nt -171 to +29) of the gene coding for glycogen synthase kinase 3-beta (GSK3-beta) has been identified. GSK3-beta codes for an enzyme which is a target for the action of lithium and which is also known to regulate circadian rhythms in Drosophila. We studied the effect of this polymorphism on the age at onset of bipolar disorder type I. A homogeneous sample of 185 Italian patients affected by bipolar disorder was genotyped. Age at onset was retrospectively ascertained with best estimation procedures. No association was detected between GSK3-beta -50 T/C SNP and the presence of bipolar illness. Homozygotes for the wild variant (T/T) showed an earlier age at onset than carriers of the mutant allele (F=5.53, d.f.=2,182, P=0.0047). Results warrant interest for the variants of genes pertaining to the molecular clock as possible endophenotypes of bipolar disorder, but caution ought to be taken in interpreting these preliminary results and future replication studies must be awaited.

Adolescent↗
PubMed2004

Lormetazepam in depressive insomnia: new evidence of phase-response effects of benzodiazepines.

Benzodiazepines can shift the phase of circadian rhythms in mammalian species, but few data are available on their phase-response effects in humans, and on possible links between timing of administration and hypnotic efficacy. Using a placebo-controlled, cross-over design, we evaluated the hypnotic effect of lormetazepam 0.03 mg/kg and placebo in 38 inpatients who were affected by a major depressive episode. Patients were divided into three groups, receiving treatment at 18.00 h, 20.00 h or 22.00 h, respectively. Sleep and psychiatric symptoms were evaluated with self-administered scales and a sleep diary. The results demonstrate that active treatment significantly improved insomnia independent of the severity of depression, which remained unchanged. Timing of treatment influenced changes in timing of sleep observed with active treatment. Although sleep duration was equally improved in all treatment groups, patients who received treatment at 20.00 h showed an acute advance of sleep onset, with no changes in morning awakening. Patients who received treatment at 22.00 h showed an acute delay in morning awakening, with no changes of sleep onset. Finally, patients who received treatment at 18.00 h showed a non-significant trend in the same direction. These effects reverted with cross-over return to placebo. The perceived degree of improvement of insomnia was proportional to the advance in timing of sleep onset obtained with treatment. Our results suggest that the effects of lormetazepam on the subjective sleep of patients affected by a major depressive episode depend upon the timing of administration, and that improvement in subjective sleep is related to advance of sleep onset, and not to delay of morning awakening.

Administration, Oral↗
PubMed2004

Cerebral D2 and 5-HT2 receptor occupancy in Schizophrenic patients treated with olanzapine or clozapine.

We report the results of a double-blind, randomized prospective trial on D2 and 5-HT2 receptor occupancy and the clinical effects of olanzapine versus clozapine in a sample of neuroleptic-refractory schizophrenic patients. Receptor occupancy was evaluated in different cortical areas and in basal ganglia using [18F] fluoro-ethyl-spiperone ([18F] FESP) and positron emission tomography (PET). A total of 15 neuroleptic-free patients completed the study undergoing a baseline and a post-treatment PET scan (olanzapine, nine patients, one female; clozapine, six patients, three female) 8 weeks after starting treatment. PET data were analysed both by regions of interest and on a voxel-by-voxel basis using Statistical Parametric Mapping (SPM96). Olanzapine and clozapine induced a similar and significant inhibition of [18F] FESP binding index in the cortex. In the basal ganglia, receptor occupancy was significantly higher with olanzapine than with clozapine (p=0.0018). By contrast, no differences in receptor occupancy were detected at the level of the pituitary gland. Clinical outcomes, in particular a full extra pyramidal tolerability, were similar. In this sample of neuroleptic-refractory schizophrenic patients, olanzapine and clozapine showed a different pattern of occupancy of D2-like receptor despite a common lack of extrapyramidal side-effects.

Adult↗