Giovanni Battista Cassano

A role for the protein that mediates the rate-limiting step of steroidogenesis, the 18 kDa Translocator Protein (TSPO), has been suggested in the pathophysiology of Adult Separation Anxiety Disorder (ASAD). It has been shown that ASAD patients have 1) low TSPO expression levels and 2) a high frequency of the allele that substitutes Ala with Thr at position 147 of TSPO. The Thr147 ASAD-associated allele has been recently related with a low pregnenolone production. The aim of the present work was to evaluate the relationship between TSPO expression levels and Ala147Thr single nucleotide polymorphism (SNP), which are the two TSPO biological parameters that we have previously examined separately. A further aim was to confirm the genetic association of Ala147Thr SNP with ASAD in an extended case-control sample and to investigate whether this SNP was related to an anxious attachment style that is thought to be connected to ASAD. TSPO expression levels were compared among patients with ASAD (n=26), without ASAD (n=26) and control samples (n=10) stratified into the two genotype groups: those with the Ala147 genotype (named "normal pregnenolone production") and those with the Thr147 genotype (named "reduced pregnenolone production"). The case-control genetic study included patients with (n=87) or without (n=101) ASAD and 236 controls. In the patient group, the association between the Ala147Thr SNP and an anxious attachment style was analysed by stepwise logistic regression analysis. The genotype with the lowest TSPO expression levels was the "normal pregnenolone production" genotype in the ASAD group. The genetic Ala147Thr SNP confirmed an excess of the Thr147 allele in ASAD patients. Stepwise logistic regression analysis did not show an association with an anxious attachment style. ASAD individuals who expressed normal TSPO levels exhibited the "reduced pregnenolone production" genotype. In contrast, the ASAD individuals with the "normal pregnenolone production" genotype expressed low TSPO levels. It is possible that low TSPO expression levels could compromise normal pregnenolone production. Such evidence may have therapeutic implications because it has been documented that drugs targeting TSPO increased pregnenolone production and have anxiolytic effects.

Background: Instruments that are intended to measure change over time need to emphasize sensitivity to change as a central property. The aims of this report are to test whether the MOODS-SR, a measure of mood spectrum symptomatology, is sensitive to changes during acute and continuation treatment of depression and whether residual mood spectrum symptoms predict relapse in the subsequent 6 months. Methods: The study sample includes 316 patients with nonpsychotic depression participating in the protocol ‘Depression: the search for treatment-relevant phenotypes’. Patients were initially randomized to selective serotonin reuptake inhibitors or interpersonal psychotherapy and then treated for 9 months using an algorithm-based protocol. Measures of mood symptomatology included the self-report version of the structured clinical interview for mood spectrum (MOODS-SR), the Quick Inventory for Depressive Symptomatology and the Hamilton Rating Scale for Depression. Results: Repeated-measures ANOVA indicates that during the acute phase MOODS scores decrease significantly from baseline to weeks 6 and 12. This decrease was significantly different (p < 0.001) between those who remitted and those who did not remit on the depressive, the rhythmicity component and the total score. Nonrelapsing subjects had stable scores across the continuation phase, while among relapsing subjects, a significant increase was found in the depressive component (p < 0.001), the rhythmicity component (p = 0.024) and the total score (p < 0.001), at 2 months, followed by a decrease from 2 to 6 months. Scores on the depressive component at the entry into continuation predicted relapse in the subsequent 6 months. Conclusions: Our findings suggest that the MOODS-SR is sensitive to change in depression status and may help the clinician to detect symptoms and signs not considered by established symptom severity scales.

Schizophrenia is generally a chronic and disabling mental illness. Pharmacological therapy, which is used for relief of acute psychotic episodes and prevention of subsequent relapse, is essential for...

This study explores the psychometric properties of the Spanish adaptation of the Mood Spectrum Self-Report (MOODS-SR), an instrument designed to assess a broad range of manifestations of mood psychopathology. A total of 71 Spanish subjects participated: 49 outpatients who met criteria for a mood disorder or generalized anxiety disorder, and 22 normal controls. The instrument proved to have good internal consistency and test-retest reliability. Significant positive correlations were found between the depressive subdomains of the questionnaire and the Beck Depression Inventory, as well as between the manic-hypomanic subdomains and the Clinician-Administered Rating Scale for Mania. Clinical subjects displayed higher mean scores than normal subjects in all domains, and patients with bipolar disorder displayed higher scores than patients with unipolar disorder in the Manic component, particularly in the Energy and the Cognition subdomains. Differences between patients with generalized anxiety and mood disorders were small. The former, however, did not differ from normal controls in several subdomains, whereas patients with mood disorders did.

A large proportion of the elderly population complains of depressive symptoms. The ideal antidepressant for these patients, who often suffer from numerous concomitant diseases, should not worsen their cognitive functions and should be free of contraindications. To assess the effects of 2 selective serotonin reuptake inhibitors on cognitive functions in elderly depressed patients (ICD-10 criteria), we conducted a double-blind, randomized, parallel-group, multicenter study comparing paroxetine (20-40 mg daily) and fluoxetine (20-60 mg daily) treatment for 1 year. Cognitive performance was evaluated by means of the Buschke Selective Reminding Test, the Blessed Information and Memory Test, the Clifton Assessment Schedule, the Cancellation Task Test, and the Wechsler Paired Word Test; the Hamilton Rating Scale for Depression (HAM-D) and the Clinical Anxiety Scale were administered to assess the course of depressive and anxiety symptoms, respectively. 242 patients were enrolled (mean +/- SD age = 75.4 +/- 6.6 years). During the study, no deterioration of cognition was observed; on the contrary, most of the tested cognitive functions improved. Good antidepressant efficacy was maintained for over 1 year with both drugs, based on the percentage of responders to treatment (patients achieving a HAM-D total score < 10; 60%). Both drugs showed a good tolerability and safety profile. The 2 antidepressants proved to be suitable for the long-term treatment of depression in the elderly and to be devoid of detrimental effects on the tested cognitive functions.

The efficacy of amisulpride in depressive disorders has been demonstrated in dysthymia and in double depression. Limited data are available in major depression. A randomized, double-blind, parallel group, multicentre study was set up to compare the efficacy and tolerability of amisulpride (50 mg o.d.) and paroxetine (20 mg o.d.) for 8 weeks in 272 patients with major depression (DSM-IV and baseline Hamilton Depression Rating Scale (HAMD) score ≥18). The study was designed as a non-inferiority trial based on the proportion of responders (≥50% decrease in HAMD total score) at end-point, with a maximal allowable difference of 15%; secondary end-points included HAMD total and cluster scores, Montgomery and Asberg Depression Rating Scale score and responders rates and Clinical Global Impression improvement. The tolerability evaluation was based on incidence of adverse events and routine laboratory tests. The results did not disclose statistically significant differences between treatments, although the hypothesis of an efficacy difference between the two treatments within the set limit at day 56 could not be accepted. The issue of non-inferiority trials is discussed.

The aim of this study was to evaluate exercise performance in patients affected by anorexia nervosa. We studied 19 patients (all females, mean age 23.1 +/- 5.2 years) affected by anorexia nervosa (mean weight 37.3 kg, body mass index 14.04 +/- 1.4 kg/m2) and 20 constitutionally thin women, matched for age, height and physical activity, with a body mass index < 19 kg/m2. All these women underwent clinical examination, standard ECG and a cardiopulmonary stress test. Patients affected by anorexia nervosa showed a lower heart rate and systolic blood pressure at peak exercise (148.8 +/- 13.8 vs 171 +/- 9.2 b/min, p < 0.001, and 130 +/- 9.5 vs 152 +/- 11.2 mmHg, p < 0.001), work load (85.5 +/- 15.1 vs 117.2 +/- 20.3 W, p < 0.001), rate-pressure product (19 371 +/- 2391 vs 25,986 +/- 2218 b/min/mmHg, p < 0.001), oxygen uptake (VO2) at rest and maximum VO2 (5.4 +/- 1.7 vs 7.1 +/- 1.1 ml/kg/min, p < 0.001, and 28.08 +/- 6.3 vs 40.2 +/- 7.1 ml/kg/min, p < 0.001), anaerobic threshold (15.7 +/- 1.9 vs 20.4 +/- 2.1 ml/kg/min, p < 0.001), VO2 during exercise (9.5 +/- 1.2 vs 12.8 +/- 1.3 ml/min/W, p < 0.001), maximum minute ventilation (34.5 +/- 9.9 vs 48.4 +/- 10.3 /min, p < 0.001), and oxygen pulse (7.2 +/- 2 vs 10.9 +/- 2.4 ml/b, p < 0.001). These data show an abnormal working capacity and cardiovascular responses to exercise in patients affected by anorexia nervosa. The low VO2, both at rest and during exercise, allows them to maintain a relatively high level of physical activity, which contributes to increase the energy expenditure needed for weight loss.