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In the course of pulmonary edema water accumulates in the extravascular space with a consequent increase of lung density- Therefore, the severity of the disease may be quantified and the time course followed if lung density changes can be measured. A tomographic technique was developed in order to visualize sectional chest planes by means of a collimated linear source of gamma rays and a gamma camera to detect Compton scattered photons at 90° to the primary beam. As the intensity of the Compton effect is a linear function of the scanned tissue density, the resulting image is a map of the distribution of a lung densities along the plane crossed by the incident beam. A computer processing of the original images was performed to clear the views of systematic and/or random acquisition errors. The application of this technique to the study of pulmonary edema and the comparison with x-ray findings are described.

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Thanks to the introduction of detection systems and reconstruction algorithms that allow three-dimensional views of anatomical structures and their functionalities, during the last decade, the imaging solutions for medical issues have suffered a wide expansion and diffusion. The huge amount of available data for a single diagnostic exam requires the development of software able to store the analysis results performed on the acquired images. This article describes a Web infrastructure for the analysis of thorax radiological images obtained through computed tomography (CT) with volumetric acquisition. In particular, the infrastructure is able to perform lung densitometry analysis for pulmonary emphysema diagnosis and follow-up. The infrastructure has been realized as an upgraded version of an offline one sharing, with it, the imaging techniques.

OBJECTIVE: Multiple studies indicate that bipolar disorders are often underrecognized, misdiagnosed, and incorrectly treated. The aim of the present report is to determine which combination of clinical, demographic, and psychopathological factors and corresponding cutoff scores best discriminate patients with unipolar disorder from those with bipolar disorders. METHOD: The study sample includes outpatients and inpatients (N = 1,158) participating in 5 studies carried out in the United States and Italy between October 2001 and March 2008, one of which was a randomized clinical trial. Diagnostic assessment was carried out with the SCID, which allows diagnoses to be made according to DSM-IV-TR criteria. Using an exploratory statistical approach based on a classification tree, we employed 5 mania spectrum factors and 6 depression spectrum factors derived from the Mood Spectrum Self-Report Instrument (MOODS-SR) in combination with demographic and clinical characteristics to discriminate participants with unipolar versus bipolar disorders. RESULTS: The psychomotor activation factor, assessing the presence of thought acceleration, distractibility, hyperactivity, and restlessness for 1 or more periods of at least 3 to 5 days in the lifetime, identified subgroups with an increasing likelihood of bipolar disorder diagnosis. Mixed instability and suicidality contributed to further subtyping the sample into mutually exclusive groups, characterized by a different likelihood of receiving a diagnosis of bipolar disorder. Of the demographic and clinical characteristics included in the analysis, only sex proved to be useful to improve the discrimination. CONCLUSIONS: The psychomotor activation factor proved to be the most potent discriminator of those with unipolar versus bipolar diagnoses. The items that constitute this factor, together with those that constitute the mixed instability, suicidality, and euphoria factors, might be useful in making the differential diagnosis.

Background: Despite the availability of many effective treatments, patients with major depression remain at risk for relapse following remission of a depressive episode. The aims of this report are to estimate the relapse rates associated with the acute treatment strategies employed in this study and to investigate demographic and clinical predictors of relapse. Methods: The study sample includes 225 patients who entered the 6-month continuation treatment phase after remitting from an acute depressive episode. Treatment during the acute phase was interpersonal psychotherapy, SSRI (escitalopram), or the combination of the two when monotherapy did not lead to response. Relapse was defined by a Hamilton Depression Rating Scale score Z15, confirmed by the diagnosis of major depression. The probability of relapsing was modeled using logistic regression. Three separate models were fit with subgroups of covariates. Results: Of the 225 patients, 29 (12.9%) relapsed and 28 (12.4%) discontinued the protocol prematurely. The proportion of patients who relapsed among the group requiring combination treatment to achieve remission was three times as high as among patients who had remitted with monotherapy. In the final logistic regression model, older age, higher baseline HDRS scores, last month (residual) depressive mood spectrum factor score, and requiring combination treatment to achieve remission were each associated with an increased likelihood of relapse. Conclusions: Our results suggest that greater initial depression severity, greater difficulty in stabilizing symptoms, and presence of residual mood spectrum symptoms once remission is achieved are predictive of relapse. Risk of relapse is more likely as age increases, partly because aging confers lower resilience. Depression and Anxiety 28:955–962, 2011. r 2011 Wiley Periodicals, Inc.

Background Efficacy of treatments for panic disorder is well established, but not all patients respond. Adult separation anxiety has been found to predict poorer response to CBT, but its effect on response to medication has not been previously explored. Study aim The aim of this study is to investigate if panic–agoraphobic spectrum factors, including ‘separation anxiety’ factor predict treatment outcome in patients with panic disorder. Study sample Participants who met criteria for PD (n = 57) completed baseline assessment and 12 months follow-up. Patients were administered the Panic Agoraphobic Spectrum Self-Report (PAS-SR, Lifetime and Last-Month Versions), and the Panic Disorder Severity Scale (PDSS). We examined patients who met the following criteria at baseline: 1) PDSS total score > 7; 2) no current Axis I comorbidity with major depression; 3) no lifetime or current bipolar disorder. All patients were treated with evidence-based psychopharmacological treatment for panic disorder during the 12-month observation period. Results Twenty eight patients (48.1%) achieved remission during the follow-up period. In a logistic regression model, controlling for baseline severity, gender and age, only the last-month PAS-SR ‘separation anxiety’ factor was associated with a lower likelihood of remission. Conclusions Signs and symptoms of separation anxiety in adulthood, as assessed with the PAS-SR Last Month version, are predictors of poor treatment outcome in patients with PD. We submit that the assessment of panic–agoraphobic spectrum features, including adult separation anxiety, should become routine of clinical assessment of patients with PD. It is likely that a better psychopathological characterization of patients may inform treatment selection, and result in better treatment outcome.

Background The recognition and assessment of psychomotor retardation may have implications for better definition of the clinical phenotypes of depression. The aim of this study was to assess the clinical correlates of psychomotor retardation endorsed at any time during the patients' lifetime (LPR). Methods The study sample included 291 patients with non-psychotic major depressive disorder (MDD) participating in the clinical trial, “Depression: The Search for Treatment-Relevant Phenotypes.” Psychomotor retardation was measured using a factor derived from the Mood Spectrum Self-Report (MOODS-SR) assessment. Using a pre-defined cut-off score on the lifetime psychomotor retardation (LPR) factor of the MOODS-SR, participants were classified into high and low scorers. Logistic regression analysis was used to evaluate the relationship between LPR and subthreshold bipolarity. Results Compared to low scorers, participants with high scores on the LPR factor had greater severity of depression and more bipolarity indicators. Conclusions The MOODS-SR appears to be helpful to identify clinical phenotypes of unipolar depression and to highlight the usefulness of a lifetime approach to the assessment of psychopathology in the characterisation of patients with unipolar depression.

Background: To date, few randomized controlled trials (RCTs) of major depression have examined suicidal ideation as an outcome measure. Our aim is to determine the incidence of treatment-emergent suicidal ideation (ESI) and behaviors during the acute phase of treatment with an SSRI antidepressant or interpersonal psychotherapy (IPT) in patients with unipolar major depression. Methods: In a two-site RCT, 291 adult outpatients with nonpsychotic major depression and a Hamilton Depression Rating Scale (HDRS) score ≥15 were randomly allocated to IPT or SSRI. Participants who did not remit with monotherapy received augmentation with the other treatment. ESI was defined as a postbaseline HDRS suicidality item score ≥2 or a postbaseline Quick Inventory of Depressive Symptomatology (QIDS) score ≥2 in patients with a baseline score ≤1. Results: Of the 231 participants who had no suicidal ideation at baseline, 32 (13.8%) subsequently exhibited ESI on at least one postbaseline visit. Time to suicidal ideation was significantly longer in patients allocated to SSRI compared to those allocated to IPT (HR = 2.21, 95% CI 1.04-4.66, P = .038), even after controlling for treatment augmentation, benzodiazepine use, and comorbidity with anxiety disorders. Worsening of suicidal ideation occurred in 7/60 patients who had suicidal ideation at baseline. In the large majority of cases, suicidal ideation was successfully managed with the study protocol. Conclusions: In the context of careful monitoring and frequent contact, selective serotonin reuptake inhibitor (SSRI) was associated with a lower risk of ESI than IPT and both SSRI and IPT appeared to be safe treatments for patients with past suicide attempts, none of whom exhibited ESI during the study. Depression and Anxiety 0:1-7, 2011.© 2011 Wiley-Liss, Inc. Language: en

Clinical features and treatment outcome were compared in depressed outpatients with and without a history of emotional and physical abuse (EPA), including childhood maltreatment. Patients were initially randomized to IPT or SSRI and then augmented with the second treatment if they did not remit with monotherapy. Assessments included the SCID-I, the SCID-II for DSM-IV diagnoses, the HRSD, the QIDS and the Mood Spectrum Self-Report (MOODS-SR). Seventy-eight (25%) patients reported a history of EPA; 60 (76.9%) were women. Patients with a history of EPA did not differ from those without on HRSD scores at baseline, but showed an earlier age at onset of depression and a longer duration of illness. The two groups differed on several mood spectrum factors, namely: ‘depressive mood’ (15.6 ± 4.9 vs. 13.5 ± 5.4; p < 0.004), ‘psychomotor retardation’ (11.7 ± 4.5 vs. 9.6 ± 4.7; p < 0.001), ‘drug and illness-related depression’ (1.3 ± 1.3 vs. 0.6 ± 1.0; p < 0.0001), and ‘neurovegetative symptoms’ (8.3 ± 2.6 vs. 6.9 ± 2.9; p < 0.0001). Patients with EPA had also a significantly longer time to remission (89 vs. 67 days, log-rank test, p = 0.035). The need for augmentation treatment was significantly more frequent among patients with EPA than in those without. The present study suggests that patients with a history of EPA show a subtype of depression characterized by poor treatment response and more severe neurovegetative and psychomotor symptoms.

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.

The aim of this article is to examine the onset and clinical correlates of substance use in patients with psychotic disorders. One hundred and eight inpatients and outpatients with DSM-IV psychotic disorders were evaluated with the SCI-SUBS, an instrument designed to explore the spectrum of substance use and its clinical correlates. Comparisons were made between subjects with (n=47) and without (n=61) a DSM-IV diagnosis of substance use disorder (SUD). In patients with an early onset of psychosis (

The short (s) variant of the serotonin transporter gene linked functional polymorphic region (5-HTTLPR) is associated with depression. Stressful life events, gender, and race have been shown to moderate this association. Because features of mania/hypomania seem to constitute an indicator of higher severity of depression, we examined the relationship between 5-HTTLPR genotype and symptoms of mania-hypomania spectrum occurring over the lifetime in patients with major depression. The possible moderating role of gender in this relationship was taken into account. Two hundred twenty-two patients with unipolar major depression were genotyped for 5-HTTLPR and nine other representative polymorphisms, and were administered the Mood Spectrum Questionnaire, Lifetime Version (MOODS-SR). The manic-hypomanic (MH) component score was used for analysis. Using a linear model of the MH score as a function of genotypes and gender, controlling for age, severity of depression, and site, we found significant effects of gender (F = 8.003, df = 1, P = 0.005), of the interaction gender x genotype (F = 4.505, df = 2, P = 0.012), and of the baseline Hamilton score (F = 5.404, df = 1, P = 0.021), non-significant effects of genotype (F = 1.298, df = 2, P = 0.275), age (F = 0.310, df = 1, P = 0.578) site (F = 0.504, df = 1, P = 0.479). Significant associations were also detected at three other SNPs. The association between the manic/hypomanic component of the MOODS-SR and the polymorphisms of the 5-HTTLPR is moderated by gender. This finding is intriguing from a clinical point of view because women with unipolar disorder and the "ss" genotype seem to constitute a sub-group with higher severity of depression. These results should be considered tentative pending replication in other samples.

BACKGROUND: While previous attempts to elucidate the factor structure of depression tended to agree on a central focus on depressed mood, other factors were not replicated across studies. By examining data from a large number of items covering the range of depressive symptoms, the aim of the present study is to contribute to the identification of the structure of depression on a lifetime perspective. METHODS: The study sample consisted of 598 patients with unipolar depression who were administered the Mood Spectrum Self-Report (lifetime version) in Italian (N=415) or English (N=183). In addition to classical exploratory factor analysis using tetrachoric correlation coefficients, an IRT-based factor analysis approach was adopted to analyze the data on 74 items of the instrument that explore cognitive, mood and energy/activity features associated with depression. RESULTS: Six factors were identified, including 'Depressive Mood', 'Psychomotor Retardation', 'Suicidality', 'Drug/Illness related depression', 'Psychotic Features' and 'Neurovegetative Symptoms', accounting overall for 48.3% of the variance of items. LIMITATIONS: Clinical information on onset of depression and duration of illness is available only for 350 subjects. Therefore, differences between sites can only be partially accounted using available data. CONCLUSIONS: Our study confirms the central role of depressed mood, psychomotor retardation and suicidality and identifies the factors 'Drug/Illness related depression', 'Psychotic features' and the neurovegetative dysregulation not captured by the instruments most frequently used in previous studies. The identification of patients with specific profiles on multiple factors may be useful in achieving greater precision in neuroimaging studies and in informing treatment selection.

BACKGROUND: The observation that bipolar disorders frequently go unrecognized has prompted the development of screening instruments designed to improve the identification of bipolarity in clinical and non-clinical samples. Starting from a lifetime approach, researchers of the Spectrum Project developed the Mood Spectrum Self-Report (MOODS-SR) that assesses threshold-level manifestations of unipolar and bipolar mood psychopathology, but also atypical symptoms, behavioral traits and temperamental features. The aim of the present study is to examine the structure of mania/hypomania using 68 items of the MOODS-SR that explore cognitive, mood and energy/activity features associated with mania/hypomania. METHODS: A data pool of 617 patients with bipolar disorders, recruited at Pittsburgh and Pisa, Italy was used for this purpose. Classical exploratory factor analysis, based on a tetrachoric matrix, was carried out on the 68 items, followed by an Item Response Theory (IRT)-based factor analytic approach. RESULTS: Nine factors were initially identified, that include Psychomotor Activation, Creativity, Mixed Instability, Sociability/Extraversion, Spirituality/Mysticism/Psychoticism, Mixed Irritability, Inflated Self-esteem, Euphoria, Wastefulness/Recklessness, and account overall for 56.4% of the variance of items. In a subsequent IRT-based bi-factor analysis, only five of them (Psychomotor Activation, Mixed Instability, Spirituality/Mysticism/Psychoticism, Mixed Irritability, Euphoria) were retained. CONCLUSIONS: Our data confirm the central role of Psychomotor Activation in mania/hypomania and support the definitions of pure manic (Psychomotor Activation and Euphoria) and mixed manic (Mixed Instability and Mixed Irritability) components, bearing the opportunity to identify patients with specific profiles for a better clinical and neurobiological definition.

The heterogeneity of the clinical presentation of panic disorder (PD) has prompted researchers to describe different subtypes of PD, on the basis of the observed predominant symptoms constellation. Starting from a dimensional approach to panic disorder, an instrument to assess lifetime panic-agoraphobic spectrum (PAS) available in interview or self-report form (SCI-PAS, PAS-SR) was developed which proved to have sound psychometric properties and the ability to predict delayed response to treatment in patients with mood disorders. However, the structure of the instrument was defined a priori and an examination of its empirical structure is still lacking. Aim of the present report is to analyse the factor structure of the PAS taking advantage of a large database of subjects with panic disorders (N = 630) assessed in the framework of different studies. Using a classical exploratory factor analysis based on a tetrachoric correlation matrix and oblique rotation, 10 factors were extracted, accounting overall for 66.3% of the variance of the questionnaire: panic symptoms, agoraphobia, claustrophobia, separation anxiety, fear of losing control, drug sensitivity and phobia, medical reassurance, rescue object, loss sensitivity, reassurance from family members. The first two factors comprise the DSM-IV criteria for panic disorder and agoraphobia. The other factors had received limited empirical support to date. We submit that these symptoms profiles might be clinically relevant for tailoring drug treatments or psychotherapeutic approaches to specific needs. Future perspectives might include the use of these factors to select homogeneous subgroups of patients for brain-imaging studies and to contribute to elucidating the causes and pathophysiology of panic disorder at molecular level.

The phenomenon of antidepressant-induced mania/hypomania in patients with unipolar depression has been described since the introduction of the first antidepressant agents. The hypothesis was that antidepressant agents triggered manic/hypomanic symptoms by influencing the central dopamine and serotonin systems (1). The first studies in this field (1, 2) described a relatively low prevalence of treatment-emergent mania/hypomania (TEMH), probably attributable to the heterogeneity of patients and to the relatively infrequent use of antidepressants prior to 1982. Subsequent studies reported TEMH rates of 1–17% (3–8), with the highest rates observed with tricyclic antidepressants and lower rates for bupropion, paroxetine, and moclobemide. Differences in the diagnostic assessment method (clinical diagnosis versus structured interview) may have resulted in a variable proportion of patients with bipolar disorders being misdiagnosed as unipolar across studies (9–12). Indeed, the percentage of correct diagnoses increases when structured interviews are conducted (13). Recently, Goldberg and Truman (14) have tried to define a timeframe after beginning an antidepressant at a specific dose in which newly emergent mania or hypomania could be attributed to the effects of the antidepressant and not to the natural course of a bipolar disorder misdiagnosed as unipolar. They suggested that if mania or hypomania emerges after more than eight weeks of treatment, it should be considered drug induced only if a significant change in dosage preceded the switch. Of note, a recent study suggests that treatment-emergent hypomania can present in patients with chronic resistant depression even after different treatment trials (15), thus suggesting a longer time period at risk for TEMH. Some clinical characteristics seem to be related to a higher risk of TEMH among patients with unipolar depression; these include early age at onset of affective illness, a family history for bipolar disorder and suicide, severity of current episode, hypersomnia, less anxiety and physical complaints, motor retardation, mood lability, and a high rate of recurrences (13, 16–22). The probability of (hypo)mania seems to be independent of the mean doses of antidepressants, whereas a switch seems to be more frequent between two and three weeks after a dose increase (8). In the attempt to characterize patients at risk of TEMH, some studies have focused on the subtype of depression (atypical versus typical depression), temperamental traits (23–25), and on specific psychopathological aspects such as mood lability, energy-activity, and daydreaming (26). The identification of features that predict TEMH is of considerable clinical relevance as both misdiagnoses and subsequent mood destabilization induced by antidepressants may have a direct adverse impact on the course and outcome of an affective disorder. The aim of the present report is to estimate the incidence and describe the clinical characteristics of unipolar patients experiencing TEMH during treatment with a selective serotonin reuptake inhibitor (SSRI) (citalopram or escitalopram), a depression-specific psychotherapy [interpersonal psychotherapy (IPT)], or the combination. All patients were carefully diagnosed by experienced clinicians using the Structured Clinical Interview for Axis I DSM-IV Disorders (SCID) interview for DSM-IV diagnoses.

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The "comet-tail" is an ultrasound sign detectable with ultrasound chest instruments; this sign consists of multiple comet-tails fanning out from the lung surface. They originate from water-thickened interlobular septa and would be ideal for nonradiologic bedside assessment of extravascular lung water. To assess the feasibility and value of ultrasonic comet signs, we studied 121 consecutive hospitalized patients (43 women and 78 men; aged 67 +/- 12 years) admitted to our combined cardiology-pneumology department (including cardiac intensive care unit); the study was conducted with commercially available echocardiographic systems including a portable unit. Transducer frequencies (range 2.5 to 3.5 MHz) were used. In each patient, the right and left chest was scanned by examining predefined locations in multiple intercostal spaces. Examiners blinded to clinical diagnoses noted the presence and numbers of lung comets at each examining site. A patient lung comet score was obtained by summing the number of comets in each of the scanning spaces. Within a few minutes, patients underwent chest x-ray, with specific assessment of extravascular lung water score by 2 pneumologist-radiologists blinded to clinical and echo findings. The chest ultrasound scan was obtained in all patients (feasibility 100%). The imaging time per examination was always

N,N,N'-trimethyl-N'-(2-hydroxy-3-methyl-5-iodobenzyl)-1,3-propanediamine (HIPDM), a synthetic basic compound with high affinity for lung tissue of various animal species, was labeled with 123I and injected into normal smokers (n = 9) and into asymptomatic smokers (n = 9). Time/activity curves were recorded for 90 min by gamma camera. HIPDM lung clearance was described by two exponential components. In smokers, the mean time of the first component, 10 +/- 1.4 min (mean +/- SEM), did not significantly differ from that of nonsmokers (9.7 +/- 0.9 min), whereas the mean time of the second component (12.9 +/- 0.6 h) was longer than that of nonsmokers (6.7 +/- 0.2 h). The intercept to the ordinate of the second exponential component was significantly higher in smokers (90.3 +/- 1.5%) than in nonsmokers (80.7 +/- 1.9%). Control studies in rabbits showed that, 2 min after intravenous injection, 95% of HIPDM is taken up by the lung; time/activity curves were similar to those obtained in humans. The longer pulmonary persistence of HIPDM in smokers may reflect an increased number of cellular binding sites or may be the expression of hindered HIPDM biotransformation. The rabbit can be used as a model to further investigate HIPDM kinetics in relation to lung dysfunction.

Extravascular lung water (idQw1) is measured in vivo from the difference in mean transit times, computed by extrapolating the dilution curves, of two indicators, one freely diffusible, the other confined to the intravascular space. Using 3H2O it has been shown that idQw1 is smaller than the amount of extravascular water obtained from the difference between wet and dry lung weight (Qw1). Extrapolation allows one to use dilution curves for a short time, i.e., up to onset of obvious recirculation. Clearing the dilution curves or recirculation by deconvolution extends the observation time, which then becomes limited by sampling duration rather than onset of recirculation. This procedure entails recording recirculating tracers in the pulmonary artery (PA). Dilutions of tracers at input in PA and output in a systemic artery must be related to each other as continuous time functions. This is accomplished by means of a convolution integral. Deconvolution yields the frequency function of water molecule transit time in the extravascular lung space, l(t). In dogs and men, in both normal and edematous lungs, l(t) exhibits a knee and a fairly long tail. Extravascular lung water computed from l(t), idcQw1, agrees with Qw1 and correlates with data on the extravascular thermal volume of the lung and with radiographic findings of lung edema. A radiographic score of pulmonary edema may be used clinically to assess extravascular lung water in cardiac patients and in patients with adult respiratory distress syndrome.

In order to explore means of providing a convenient and simple method of assessing regional lung ventilation, we characterized a commercially available polydispersed aerosol of human albumin microspheres. The mass median particle diameter was 1.20 μm and nebulization of particles >2.0 μm diameter was prevented. After labelling this aerosol with technetium-99m, a quantitative comparison of regional particle deposition with regional lung ventilation, as assessed by krypton-81m, was made in eight normal subjects and twenty patients with varying degrees of chronic airflow obstruction. There was a strong correlation between the depth of particle penetration and the degree of airflow obstruction as indicated by the FEV1 (r=0.91 p