QTc interval diurnal variations in patients treated with psychotropic medications: implications for the evaluation of drug induced QTc changes.

Psychotropic drugs such as antipsychotics may prolong the QTc interval, increasing the risk of torsades de pointes (TdP) and sudden cardiac death. To assess QTc prolongation by psychotropic drugs, an electrocardiogram (EKG) is usually recorded before and after starting treatment. Circadian variations in the QTc interval have been described but have not been adequately studied in patients taking psychotropic drugs. In psychiatric clinical practice, EKGs before and after treatment initiation are often compared, without considering the time of day at which the two EKGs are recorded. To determine whether there is a circadian change in the QTc interval in patients treated with psychotropic drugs, we evaluated the EKGs of a group of patients treated with psychotropic drugs (85% on antipsychotics) and the EKGs of a group of patients that were not treated with medications. In each group, we compared the EKGs recorded before 11:00 am with those recorded after 5:00 pm. The QTc value was significantly longer in the group treated with psychotropic drugs than in the group without drugs at both morning and evening evaluations (p ≤ 0.001). In each group, a statistically significant difference was found between the EKGs recorded before 11:00 a.m. and the EKGs recorded after 5:00 p.m. In patients treated with medications, the mean QTc in the morning was 453.3 ± 25.4 while the mean QTc in the afternoon was 428.4 ± 24.7 (p < 0.0001). In patients who were not receiving any medication, the morning mean QTc was 422.4 ± 22.6 while the mean afternoon QTc was 409.4 ± 19.6 (p = 0.002). These results suggest that a circadian variation in QTc is observed both in patients taking psychotropic drugs and in patients not taking medication. We conclude that any comparison of EKGs to test the effect on QTc of a medication, should be referred to EKGs recorded at the same time of day.

Lithium and suicide prevention in mood disorders and in the general population: A systematic review.

Suicide contributes to 1-4 % of deaths worldwide every year. We conducted a systematic review aimed at summarizing evidence on the use of lithium for the prevention of suicide risk both in mood disorders and in the general population. We followed the PRISMA methodology (keywords: "lithium", "suicide" AND "suicidal" on Pubmed, Cochrane CENTRAL, Clinicaltrial.gov, other databases). Inclusion criteria: lithium therapy in mood disorder or found in drinking water or scalp in the general population. Exclusion criteria: no lithium administration. From 918 screened references, 18 prospective (number of participants: 153786), 10 retrospective (number of participants: 61088) and 16 ecological studies (total sample: 2062) were included. Most of the observational studies reported a reduction in suicide in patients with mood disorders. All studies about lithium treatment's duration reported that long-term lithium give more benefits than short-term lithium in suicide risk The evidence seems to attribute an intrinsic anti-suicidal property of lithium, independent of its proven efficacy as a mood stabilizer.

Real-world effectiveness of long acting aripiprazole: Treatment persistence and its correlates in the Italian clinical practice.

OBJECTIVES: To identify the variables that are associated with persistence to Aripiprazole-Long Acting (A-LAI), in adult patients with schizophrenia. METHODS: Observational, retrospective, non-interventional study involving 261 patients with schizophrenia. RESULTS: Eighty-six percent of study subjects were persistent for at least 6 months. All subjects with baseline CGI-S of 1 or 2, 95% of subjects with CGI-S of 3, 86% with CGI-S of 4, 82% of subjects with CGI-S of 5, 73% of subjects with CGI of 6 and 90% of subjects with CGI of 7 were persistent. A-LAI treatment continuation rate was higher in patients with: 1) baseline CGI score ≤ 4; 2) schizophrenia dimension (LDPS) mania score ≤ 5; 3) psychotic spectrum schizoid score ≤ 11. CONCLUSIONS: A relatively high number of patients (n = 225, 86%) were persistent to A-LAI for at least 6 months. Not surprisingly, very severe patients were more unlikely to be persistent. However, it is noteworthy that a large number of subjects with high CGI score at the time when A-LAI was started (82% of subjects with CGI-S of 5, 73% of subjects with CGI of 6 and 90% of subjects with CGI of 7) were persistent. Larger, controlled, prospective and longer studies are warranted.

The impact of affective temperaments on clinical and functional outcome of Bipolar I patients that initiated or changed pharmacological treatment for mania.

BACKGROUND: Affective temperaments have been shown to impact on the clinical manifestations and the course of bipolar disorder. We investigated their influence on clinical features and functional outcome of manic episode. METHOD: In a naturalistic, multicenter, national study, a sample of 194 BD I patients that initated or changed pharmacological treatment for DSM-IV-TR manic episode underwent a comprehensive evaluation including briefTEMPS-M, CTQ, YMRS, MADRS, FAST, and CGI-BP. Factorial, correlation and comparative analyses were conducted on different temperamental subtypes. RESULTS: Depressive, cyclothymic, irritable and anxious temperaments resulted significantly correlated with each other. On the contrary, hyperthymic temperament scores were not correlated with the other temperamental dimensions. The factorial analysis of the briefTEMPS-M sub-scales total scores allowed the extraction of two factors: the Cyclothymic-Depressive-Anxious (Cyclo-Dep-Anx) and the Hyperthymic. At final evaluation Dominant Cyclo-Dep-Anx patients reported higer scores in MADRS and in CTQ emotional neglect and abuse subscale scores than Dominant Hyperthymic patients. The latter showed a greater functional outcome than Cyclo-Dep-Anx patients. CONCLUSIONS: Affective temperaments seem to influence the course of mania. Childhood emotional abuse and neglect were related to the cyclothymic disposition. Cyclothymic subjects showed more residual depressive symptoms and Hyperthymic temperament is associated with a better short-term functional outcome.

Aripiprazole use during pregnancy, peripartum and lactation. A systematic literature search and review to inform clinical practice.

BACKGROUND: Aripiprazole is used relatively frequently in women with bipolar disorder or schizophrenia in childbearing years, owing to its efficacy and relatively favorable side effect profile. As is the case for other psychotropic medications, for ethical reasons, no prospective randomized placebo controlled trial to assess aripiprazole safety during pregnancy has ever been conducted. However, animal data are available and the amount of exposure and outcome data for human fetuses and infants has recently increased, providing published prospective safety data in relatively large numbers of pregnant women treated with aripiprazole. The aim of this study was to perform a systematic literature search and review to critically evaluate the available data on the use of aripiprazole during pregnancy, peripartum and lactation. METHODS: PubMed, PsychInfo, and Cochrane Library were searched using the following search builder: (pregnancy OR pregnant OR gestation OR malformations OR perinatal OR reproduction OR organogenesis OR delivery OR breast-feeding OR lactation or peripartum or obstetric) AND aripiprazole. Reports that met the following pre-defined criteria were included in the present review: (1) published in English language in a peer-reviewed journal; (2) clearly defined use of aripiprazole during pregnancy and/or lactation and/or postpartum; (3) case report, case series, prospective, retrospective or cross-sectional studies. United States and European Medicine Agency prescribing information for aripiprazole were consulted as well and all the references of selected papers were cross checked for information pertaining to the use of aripiprazole during pregnancy, peripartum and lactation. RESULTS: A total of 549 items published in a period ranging from 1995 to 2017, were retrieved from the search databases and reference cross check. One-hundred-fifty-three duplicate items were removed, 176 titles were deemed as not pertinent, 220 abstracts and 122 full-text articles were assessed for eligibility and 93 titles were included for qualitative synthesis. United States and European Medicine Agency prescribing information for aripiprazole were consulted and the selected manuscript references were cross checked. No randomized placebo controlled trial was found but relatively large prospective studies, large database studies, and several case reports and case studies were identified and summarized. CONCLUSIONS: As is the case for other antipsychotics, definitive evidence on aripiprazole reproductive safety is lacking, but newer safety data are relatively reassuring. In many cases, the potential benefits of aripiprazole for patients with bipolar disorder or schizophrenia outweigh the potential risks.

Solar insolation in springtime influences age of onset of bipolar I disorder.

OBJECTIVE: To confirm prior findings that the larger the maximum monthly increase in solar insolation in springtime, the younger the age of onset of bipolar disorder. METHOD: Data were collected from 5536 patients at 50 sites in 32 countries on six continents. Onset occurred at 456 locations in 57 countries. Variables included solar insolation, birth-cohort, family history, polarity of first episode and country physician density. RESULTS: There was a significant, inverse association between the maximum monthly increase in solar insolation at the onset location, and the age of onset. This effect was reduced in those without a family history of mood disorders and with a first episode of mania rather than depression. The maximum monthly increase occurred in springtime. The youngest birth-cohort had the youngest age of onset. All prior relationships were confirmed using both the entire sample, and only the youngest birth-cohort (all estimated coefficients P < 0.001). CONCLUSION: A large increase in springtime solar insolation may impact the onset of bipolar disorder, especially with a family history of mood disorders. Recent societal changes that affect light exposure (LED lighting, mobile devices backlit with LEDs) may influence adaptability to a springtime circadian challenge.

Adult Autism Subthreshold Spectrum (AdAS Spectrum): Validation of a questionnaire investigating subthreshold autism spectrum.

AIM: Increasing literature has shown the usefulness of a dimensional approach to autism. The present study aimed to determine the psychometric properties of the Adult Autism Subthreshold Spectrum (AdAS Spectrum), a new questionnaire specifically tailored to assess subthreshold forms of autism spectrum disorder (ASD) in adulthood. METHODS: 102 adults endorsing at least one DSM-5 symptom criterion for ASD (ASDc), 143 adults diagnosed with a feeding and eating disorder (FED), and 160 subjects with no mental disorders (CTL), were recruited from 7 Italian University Departments of Psychiatry and administered the following: SCID-5, Autism-Spectrum Quotient (AQ), Ritvo Autism and Asperger Diagnostic Scale 14-item version (RAADS-14), and AdAS Spectrum. RESULTS: The AdAS Spectrum demonstrated excellent internal consistency for the total score (Kuder-Richardson's coefficient=.964) as well as for five out of seven domains (all coefficients>.80) and sound test-retest reliability (ICC=.976). The total and domain AdAS Spectrum scores showed a moderate to strong (>.50) positive correlation with one another and with the AQ and RAADS-14 total scores. ASDc subjects reported significantly higher AdAS Spectrum total scores than both FED (p<.001) and CTL (p<.001), and significantly higher scores on the Childhood/adolescence, Verbal communication, Empathy, Inflexibility and adherence to routine, and Restricted interests and rumination domains (all p<.001) than FED, while on all domains compared to CTL. CTL displayed significantly lower total and domain scores than FED (all p<.001). A significant effect of gender emerged for the Hyper- and hyporeactivity to sensory input domain, with women showing higher scores than men (p=.003). A Diagnosis* Gender interaction was also found for the Verbal communication (p=.019) and Empathy (p=.023) domains. When splitting the ASDc in subjects with one symptom criterion (ASD1) and those with a ASD, and the FED in subjects with no ASD symptom criteria (FED0) and those with one ASD symptom criterion (FED1), a gradient of severity in AdAS Spectrum scores from CTL subjects to ASD patients, across FED0, ASD1, FED1 was shown. CONCLUSIONS: The AdAS Spectrum showed excellent internal consistency and test-retest reliability and strong convergent validity with alternative dimensional measures of ASD. The questionnaire performed differently among the three diagnostic groups and enlightened some significant effects of gender in the expression of autistic traits.

Development, acceptability and efficacy of a standardized healthy lifestyle intervention in recurrent depression.

BACKGROUND: Research evidence on the effects of integrated multifaceted lifestyle interventions for depression is scanty. The aim of the present study is to report on the development, acceptability and efficacy of a standardized healthy lifestyle intervention, including exercise, eating habits, sleep hygiene and smoking cessation in preventing relapses. METHODS: One hundred-sixty outpatients with recurrent unipolar depression or bipolar disorder were recruited after achieving full remission or recovery from the most recent depressive episode. Patients were randomized to 3-months of usual care or to an intervention aimed at promoting a healthy lifestyle (HLI), as an augmentation of pharmacological maintenance treatment. Usual care consisted of clinical management visits. At the end of the intervention, follow-up visits were scheduled at 3,6,9 and 12 months. RESULTS: During the intervention phase, 1 relapse occurred in the HLI group and 4 in the control group. Over the 12 months of follow-up, relapses were 5 in the HLI group and 16 in control group. Using an intent-to-treat approach, the overall percentage of relapses was 6/81 (7.4%) in the HLI group vs. 20/79 (25.3%) in the control group.. In a Kaplan-Meier survival analysis the risk of relapse was significantly lower in patients receiving the HLI intervention (log-rank test, p=0.003) over the 60 weeks of observation. The majority of patients assigned to HLI adhered to the program, and were highly motivated throughout the intervention. LIMITATIONS: The retention rate was low because patients were recruited during the maintenance phase and the 1-year follow-up was relatively short to detect a long-term effect of HLI. CONCLUSIONS: The HLI program proved to be efficacious in preventing relapses. Given the absence of contraindications and its cost-effectiveness in routine practice, the use of HLI should be encouraged to promote the well-being of patients with recurrent depression.

Influence of birth cohort on age of onset cluster analysis in bipolar I disorder.

PURPOSE: Two common approaches to identify subgroups of patients with bipolar disorder are clustering methodology (mixture analysis) based on the age of onset, and a birth cohort analysis. This study investigates if a birth cohort effect will influence the results of clustering on the age of onset, using a large, international database. METHODS: The database includes 4037 patients with a diagnosis of bipolar I disorder, previously collected at 36 collection sites in 23 countries. Generalized estimating equations (GEE) were used to adjust the data for country median age, and in some models, birth cohort. Model-based clustering (mixture analysis) was then performed on the age of onset data using the residuals. Clinical variables in subgroups were compared. RESULTS: There was a strong birth cohort effect. Without adjusting for the birth cohort, three subgroups were found by clustering. After adjusting for the birth cohort or when considering only those born after 1959, two subgroups were found. With results of either two or three subgroups, the youngest subgroup was more likely to have a family history of mood disorders and a first episode with depressed polarity. However, without adjusting for birth cohort (three subgroups), family history and polarity of the first episode could not be distinguished between the middle and oldest subgroups. CONCLUSION: These results using international data confirm prior findings using single country data, that there are subgroups of bipolar I disorder based on the age of onset, and that there is a birth cohort effect. Including the birth cohort adjustment altered the number and characteristics of subgroups detected when clustering by age of onset. Further investigation is needed to determine if combining both approaches will identify subgroups that are more useful for research.

Validation of the Italian version of the Functioning Assessment Short Test (FAST) for bipolar disorder.

Aim. The Functioning Assessment Short Test (FAST) is a useful instrument for the assessment of overall functioning of people with bipolar disorder, showing good psychometric properties. The aim of this study is to validate the Italian version of FAST. Methods. Translation and back-translation of the original FAST Spanish version were performed. Participants with bipolar disorder (n = 132) and healthy controls (n = 132) completed the FAST as a part of an assessment package including the Montgomery-Asberg Depression Rating Scale and the Young Mania Rating Scale. Internal consistency, inter-rater reliability, construct and discriminant validity were assessed. Results. The FAST Italian version showed good internal consistency, inter-rater reliability and discriminant validity. The cut-off discriminating patients from controls was 15, with a sensitivity of 0.79 and a specificity of 0.80. Principal component analysis with oblique rotation showed factor loadings consistent with the a priori structure of the instrument. Conclusions. This study confirmed the psychometric properties of FAST and extended its generalization and validity to the Italian population.

Individualizing antipsychotic treatment selection in schizophrenia: characteristics of empirically derived patient subgroups.

Treatment of schizophrenia with antipsychotic drugs is frequently sub-optimal. One reason for this may be heterogeneity between patients with schizophrenia. The objectives of this study were to identify patient, disease and treatment attributes that are important for physicians in choosing an antipsychotic drug, and to identify empirically subgroups of patients who may respond differentially to antipsychotic drugs. The survey was conducted by structured interview of 744 randomly-selected psychiatrists in four European countries who recruited 3996 patients with schizophrenia. Information on 39 variables was collected. Multiple component analysis was used to identify dimensions that explained the variance between patients. Three axes, accounting for 99% of the variance, were associated with disease severity (64%), socioeconomic status (27%) and patient autonomy (8%). These dimensions discriminated between six discrete patient subgroups, identified using ascending hierarchical classification analysis. The six subgroups differed regarding educational level, illness severity, autonomy, symptom presentation, addictive behaviors, comorbidities and cardiometabolic risk factors. Subgroup 1 patients had moderately severe physician-rated disease and addictive behaviours (23.2%); Subgroup 2 patients were well-integrated and autonomous with mild to moderate disease (6.7%); Subgroup 3 patients were less well-integrated with mild to moderate disease, living alone (11.2%); Subgroup 4 patients were women with low education levels (5.4%), Subgroup 5 patients were young men with severe disease (36.8%); and Subgroup 6 patients were poorly-integrated with moderately severe disease, needing caregiver support (16.7%). The presence of these subgroups, which require confirmation and extension regarding potentially identifiable biological markers, may help individualizing treatment in patients with schizophrenia.

Treatment-emergent suicidal ideation during 4 months of acute management of unipolar major depression with SSRI pharmacotherapy or interpersonal psychotherapy in a randomized clinical trial.

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 post-baseline HDRS suicidality item score ≥2 or a post-baseline 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 post-baseline 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.

Does psychomotor retardation define a clinically relevant phenotype of unipolar depression?

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.

Predictors and moderators of time to remission of major depression with interpersonal psychotherapy and SSRI pharmacotherapy.

BACKGROUND: Although many studies suggest that, on average, depression-specific psychotherapy and antidepressant pharmacotherapy are efficacious, we know relatively little about which patients are more likely to respond to one versus the other. We sought to determine whether measures of spectrum psychopathology are useful in deciding which patients with unipolar depression should receive pharmacotherapy versus depression-specific psychotherapy. METHOD: A total of 318 adult out-patients with major depression were randomly assigned to escitalopram pharmacotherapy or interpersonal psychotherapy (IPT) at academic medical centers at Pittsburgh, Pennsylvania and Pisa, Italy. Our main focus was on predictors and moderators of time to remission on monotherapy at 12 weeks. RESULTS: Participants with higher scores on the need for medical reassurance factor of the Panic-Agoraphobic Spectrum Self-Report (PAS-SR) had more rapid remission with IPT and those with lower scores on the psychomotor activation factor of the Mood Spectrum Self-Report (MOODS-SR) experienced more rapid remission with selective serotonin reuptake inhibitor (SSRI) pharmacotherapy. Non-specific predictors of longer time to remission with monotherapy included several panic spectrum and mood spectrum factors and the Social Phobia Spectrum (SHY) total score. Higher baseline scores on the 17- and 25-item Hamilton Depression Rating Scales (HAMD-17 and HAMD-25) and the Work and Social Adjustment Scale (WSAS) also predicted a longer time to remission, whereas being married predicted a shorter time to remission. CONCLUSIONS: This exploratory study identified several non-specific predictors but few moderators of psychotherapy versus pharmacotherapy outcome. It offers useful indicators of the characteristics of patients that are generally difficult to treat, but only limited guidance as to who benefits from IPT versus SSRI pharmacotherapy.

Comparative outcomes among the problem areas of interpersonal psychotherapy for depression.

BACKGROUND: Although interpersonal psychotherapy (IPT) is an efficacious treatment for acute depression, the relative efficacy of treatment in each of the four IPT problem areas (grief, role transitions, role disputes, interpersonal deficits) has received little attention. We evaluated the specificity of IPT by comparing treatment success among patients whose psychotherapy focused on each problem area. Moreover, we sought to understand how the patient characteristics and interpersonal problems most closely linked to the onset of a patient's current depression contributed to IPT success. METHODS: Patients meeting DSM-IV criteria for an episode of major depressive disorder (n=182) were treated with weekly IPT. Remission was defined as an average Hamilton Rating Scale for Depression 17-item score of 7 or below over 3 weeks. Personality disorders were diagnosed using the Structured Clinical Interview for DSM-IV Personality Disorders. RESULTS: Contrary to our prediction that patients whose treatment was focused on interpersonal deficits would take longer to remit, survival analyses indicated that patients receiving treatment focused on each of the four problem areas did not differ in their times to remission. Nor were patients in the interpersonal deficits group more likely to have an Axis II diagnosis. Patients whose treatment focused on role transitions remitted faster than those whose treatment focused on role disputes, after controlling for covariates. CONCLUSION: With skillful use of IPT strategies and tactics and with careful medication management where appropriate, patients in this study whose treatment focused on each problem area were treated with equal success by trained IPT clinicians.

Self-reported cognitive problems predict employment trajectory in patients with bipolar I disorder.

BACKGROUND: Cognitive impairment in bipolar disorder has been associated with poor functional outcomes. We examined the relation of self-reported cognitive problems to employment trajectory in patients diagnosed with bipolar I disorder. METHODS: 154 bipolar I disorder patients were followed for 15-43months at the Bipolar Disorders Center for Pennsylvanians. Using a multinomial logistic regression we examined predictors of employment group including self-reported cognitive problems, mood symptoms, education and age. Cognitive functioning was measured via 4 self-report items assessing memory/concentration at baseline and termination. Employment status was recorded at baseline and termination. Employment was categorized as working (full-time, part-time, homemaker, volunteer) or not working (leave of absence, disability, unemployed, no longer volunteering) at each time point. Patients were categorized as good stable, improving, worsening and poor stable. RESULTS: Baseline self-reported concentration problems and years of education significantly predicted employment trajectory. LIMITATIONS: Post-hoc analyses of existing clinical data. CONCLUSIONS: Self-reported concentration problems assessed in the context of specific areas of functioning may serve as a sensitive predictor of functional outcome in patients diagnosed with bipolar I disorder.

Gender moderates the relationship between mania spectrum and serotonin transporter polymorphisms in depression.

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.

The factor structure of lifetime depressive spectrum in patients with unipolar depression.

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.

The structure of lifetime manic-hypomanic spectrum.

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.