Prevalence and burden of bipolar disorders in European countries

A literature search, supplemented by an expert survey and selected reanalyses of existing data from epidemiological studies was performed to determine the prevalence and associated burden of bipolar I and II disorder in EU countries. Only studies using established diagnostic instruments based on DSM-III-R or DSM-IV, or ICD-10 criteria were considered. Fourteen studies from a total of 10 countries were identified. The majority of studies reported 12-month estimates of approximately 1% (range 0.5–1.1%), with little evidence of a gender difference. The cumulative lifetime incidence (two prospective-longitudinal studies) is slightly higher (1.5–2%); and when the wider range of bipolar spectrum disorders is considered estimates increased to approximately 6%. Few studies have reported separate estimates for bipolar I and II disorders. Age of first onset of bipolar disorder is most frequently reported in late adolescence and early adulthood. A high degree of concurrent and sequential comorbidity with other mental disorders and physical illnesses is common. Most studies suggest equally high or even higher levels of impairments and disabilities of bipolar disorders as compared to major depression and schizophrenia. Few data are available on treatment and health care utilization

Region-dependent effects of flibanserin and buspirone on adenylyl cyclase activity in the human brain

The mode of action of antidepressant drugs may be related to mechanisms of receptor adaptation, involving overall the serotonin 1A (5-HT1A) receptor subtype. However, so far, the clinical effectiveness of selective compounds acting at this level has proved disappointing. This could be explained by the heterogeneity of 5-HT1A receptors within the central nervous system. In animals, two 5-HT1A agonists, flibanserin and buspirone, have shown different pharmacological properties, depending on the brain region. Since no evidence supports this observation in humans, this study sought to investigate whether these two drugs exert different effects on 5-HT1A receptor activation in three different human brain areas: the prefrontal cortex, hippocampus and raphe nuclei. 5-HT1A-mediated inhibition of forskolin-stimulated adenylyl cyclase (AC) was taken as an index of 5-HT1A receptor activation. Flibanserin significantly reduced the activity of AC post-synaptically, i.e. in the prefrontal cortex [EC50 (mean +/- S.E.M.), 28 +/- 10.2 nM; Emax, 18 +/- 2.3%] and in the hippocampus (EC50, 3.5 +/- 3.1 nM; Emax, 20 +/- 4.0%), but had no effect in the raphe nuclei, i.e. at pre-synaptic level. Vice versa, buspirone was only slightly but significantly effective in the raphe (EC50, 3.0 +/- 2.8 nM; Emax, 12 +/- 1.9%). Agonist effects were sensitive to the 5-HT1A antagonists WAY-100135 and pindobind 5-HT1A in the cortex and raphe nuclei, whereas buspirone antagonized flibanserin in the hippocampus. These findings suggest a region-related action of flibanserin and buspirone on forskolin-stimulated AC activity in human brain

Internal consistency and discriminant validity of the Structured Clinical Interview for Panic Agoraphobic Spectrum (SCI-PAS)

This paper reports on the feasibility, acceptability and psychometric properties of the Structured Clinical Interview for Panic-Agoraphobic Spectrum (SCI-PAS). This interview was designed to assess the lifetime presence of symptoms and other clinical features considered to comprise the panic-agoraphobic spectrum. The interview has 114 items grouped into nine domains. A total of 422 subjects, from 11 centres located throughout Italy, participated in this study. Data were collected from three groups of subjects: psychiatric patients meeting DSM-IV criteria for panic disorder (n = 141), cardiovascular patients (n = 140), including 29 with post-myocardial infarction, and university students (n = 141). The inter-rater reliability and the internal consistency of the SCI-PAS measures were assessed using the intra-class correlation coefficient and the Kuder-Richardson coefficient, respectively. Discriminant validity was assessed by comparing results in patients with panic disorder to those in the other groups. The interview required an average of 25 (±5) minutes to administer. Patients and clinicians found the scale to be highly useful, providing information not previously obtained. Internal consistency was good (>0.70) for six out of nine SCI-PAS domains. The inter-rater reliability was excellent (>0.70) for all the domains except for 'other phobias' (0.467). Patients with panic disorder scored significantly higher on each domain, and on the overall panic spectrum, than did the control subjects. In conclusion, the SCI-PAS is a useful clinical interview, which can be administered in a reasonable period of time. This assessment further demonstrates good internal consistency, discriminant validity, and inter-rater reliability. Copyright © 1999 Whurr Publishers Ltd

Maintenance drug therapy of panic disorder

The efficacy of tricyclics and benzodiazepines in the short term (approximately 2-4 months) treatment of panic disorder is well demonstrated, but efficacy over the longer term is not considered established. The present study provided systematic data from a double blind comparison of maintenance therapy (up to 8 months) of panic disorder with or without agoraphobia with alprazolam, imipramine, or placebo in 181 patients who had responded to the same regimen in a randomized 8-week treatment trial. All three groups had improved during the first 2 months (active treatments more than placebo and about equal to each other), and all maintained or extended their improvement over the next 6 months without any significant change in dose. More than twice as many alprazolam and imipramine than placebo patients (15%) remained in treatment for the full 8 months and did slightly better on symptom measures than the remaining placebo patients. Both medications were well tolerated during the maintenance period. The data suggest sustained efficacy and safety of imipramine and alprazolam over an extended period. More specifically, they suggest that tolerance does not develop to the therapeutic effects of either drug.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31052/1/0000729.pd

Pain threshold is reduced in depression.

Pain and depression may share common neurochemical substrates, therefore the study of pain sensation in depression might be valuable in the investigation of the pathophysiology of depression itself. In order to investigate the sensation of pain in depression, we measured pain threshold and sensory threshold by means of a dental tester, comparing a group of depressed patients with healthy volunteers. The results showed the presence of a higher sensory threshold and pain threshold in patients than in controls. This may be related to a hyperfunction of the opiate system, which in turn might be primary or secondary to a decreased modulatory function of other neurotransmitters, in particular of serotonin, whose abnormalities in depressive states are well-documented

Validity and reliability of the Structured Clinical Interview for the Trauma and Loss Spectrum (SCI-TALS)

Background. DSM-IV identifies three stress response disorders (acute stress Disorder (ASD), post-traumatic stress Disorder (PTSD) and adjustment disorders (AD)) that derive from specific life events. An additional condition of complicated grief (CG), well described in the literature, is triggered by bereavement. This paper reports on the reliability and validity of the Structured Clinical Interview for Trauma and Loss Spectrum (SCI-TALS) developed to assess the spectrum of stress response. The instrument is based on a spectrum model that emphasizes soft signs, low-grade symptoms, subthreshold syndromes, as well as temperamental and personality traits comprising clinical and subsyndromal manifestations. Methods. Study participants, enrolled at 6 Italian Departments of Psychiatry located at six sites, included consecutive patients with PTSD, 44 with CG and a comparative group of 48 unselected controls. Results. We showed good reliability and validity of the SCI-TALS. Domain scores were significantly higher in participants with PTSD or CG compared to controls. There were high correlations between specific SCI-TALS domains and corresponding scores on established measures of similar constructs. Participants endorsing grief and loss events reported similar scores on all instruments, except those with CG who scored significantly higher on the domain of grief reactions. Conclusion. These findings provide strong support for the internal consistency, the discriminant validity and the reliability of the SCI-TALS. These results also support the existence of a specific grief-related condition and the proposal that different forms of stress response have similar manifestations

Global exposure of population and land‐use to meteorological droughts under different warming levels and SSPs: a CORDEX‐based study

Global warming is likely to cause a progressive drought increase in some regions, but how population and natural resources will be affected is still underexplored. This study focuses on global population, forests, croplands and pastures exposure to meteorological drought hazard in the 21st century, expressed as frequency and severity of drought events. As input, we use a large ensemble of climate simulations from the Coordinated Regional Climate Downscaling Experiment (CORDEX), population projections from the NASA-SEDAC dataset and land-use projections from the Land-Use Harmonization 2 project for 1981–2100. The exposure to drought hazard is presented for five Shared Socioeconomic Pathways (SSP1-SSP5) at four Global Warming Levels (GWLs: 1.5°C to 4°C). Results show that considering only Standardized Precipitation Index (SPI; based on precipitation), the SSP3 at GWL4 projects the largest fraction of the global population (14%) to experience an increase in drought frequency and severity (versus 1981–2010), with this value increasing to 60% if temperature is considered (indirectly included in the Standardized Precipitation-Evapotranspiration Index, SPEI). With SPEI, considering the highest GWL for each SSP, 8 (for SSP2, SSP4, SSP5) and 11 (SSP3) billion people, that is, more than 90%, will be affected by at least one unprecedented drought. For SSP5 at GWL4, approximately 2 × 10$^{6}$ km$^{2}$ of forests and croplands (respectively, 6% and 11%) and 1.5 × 10$^{6}$ km$^{2}$ of pastures (19%) will be exposed to increased drought frequency and severity according to SPI, but for SPEI this extent will rise to 17 × 10$^{6}$ km$^{2}$ of forests (49%), 6 × 10$^{6}$ km$^{2}$ of pastures (78%) and 12 × 10$^{6}$ km$^{2}$ of croplands (67%), being mid-latitudes the most affected. The projected likely increase of drought frequency and severity significantly increases population and land-use exposure to drought, even at low GWLs, thus extensive mitigation and adaptation efforts are needed to avoid the most severe impacts of climate change

Screening and diagnostic breast MRI:how do they impact surgical treatment? Insights from the MIPA study

Objectives: To report mastectomy and reoperation rates in women who had breast MRI for screening (S-MRI subgroup) or diagnostic (D-MRI subgroup) purposes, using multivariable analysis for investigating the role of MRI referral/nonreferral and other covariates in driving surgical outcomes. Methods: The MIPA observational study enrolled women aged 18-80 years with newly diagnosed breast cancer destined to have surgery as the primary treatment, in 27 centres worldwide. Mastectomy and reoperation rates were compared using non-parametric tests and multivariable analysis. Results: A total of 5828 patients entered analysis, 2763 (47.4%) did not undergo MRI (noMRI subgroup) and 3065 underwent MRI (52.6%); of the latter, 2441/3065 (79.7%) underwent MRI with preoperative intent (P-MRI subgroup), 510/3065 (16.6%) D-MRI, and 114/3065 S-MRI (3.7%). The reoperation rate was 10.5% for S-MRI, 8.2% for D-MRI, and 8.5% for P-MRI, while it was 11.7% for noMRI (p ≤ 0.023 for comparisons with D-MRI and P-MRI). The overall mastectomy rate (first-line mastectomy plus conversions from conserving surgery to mastectomy) was 39.5% for S-MRI, 36.2% for P-MRI, 24.1% for D-MRI, and 18.0% for noMRI. At multivariable analysis, using noMRI as reference, the odds ratios for overall mastectomy were 2.4 (p < 0.001) for S-MRI, 1.0 (p = 0.957) for D-MRI, and 1.9 (p < 0.001) for P-MRI. Conclusions: Patients from the D-MRI subgroup had the lowest overall mastectomy rate (24.1%) among MRI subgroups and the lowest reoperation rate (8.2%) together with P-MRI (8.5%). This analysis offers an insight into how the initial indication for MRI affects the subsequent surgical treatment of breast cancer. Key points: • Of 3065 breast MRI examinations, 79.7% were performed with preoperative intent (P-MRI), 16.6% were diagnostic (D-MRI), and 3.7% were screening (S-MRI) examinations. • The D-MRI subgroup had the lowest mastectomy rate (24.1%) among MRI subgroups and the lowest reoperation rate (8.2%) together with P-MRI (8.5%). • The S-MRI subgroup had the highest mastectomy rate (39.5%) which aligns with higher-than-average risk in this subgroup, with a reoperation rate (10.5%) not significantly different to that of all other subgroups

Magnetic resonance imaging before breast cancer surgery: results of an observational multicenter international prospective analysis (MIPA).

Funder: Bayer AGFunder: Università degli Studi di MilanoOBJECTIVES: Preoperative breast magnetic resonance imaging (MRI) can inform surgical planning but might cause overtreatment by increasing the mastectomy rate. The Multicenter International Prospective Analysis (MIPA) study investigated this controversial issue. METHODS: This observational study enrolled women aged 18-80 years with biopsy-proven breast cancer, who underwent MRI in addition to conventional imaging (mammography and/or breast ultrasonography) or conventional imaging alone before surgery as routine practice at 27 centers. Exclusion criteria included planned neoadjuvant therapy, pregnancy, personal history of any cancer, and distant metastases. RESULTS: Of 5896 analyzed patients, 2763 (46.9%) had conventional imaging only (noMRI group), and 3133 (53.1%) underwent MRI that was performed for diagnosis, screening, or unknown purposes in 692/3133 women (22.1%), with preoperative intent in 2441/3133 women (77.9%, MRI group). Patients in the MRI group were younger, had denser breasts, more cancers ≥ 20 mm, and a higher rate of invasive lobular histology than patients who underwent conventional imaging alone (p < 0.001 for all comparisons). Mastectomy was planned based on conventional imaging in 22.4% (MRI group) versus 14.4% (noMRI group) (p < 0.001). The additional planned mastectomy rate in the MRI group was 11.3%. The overall performed first- plus second-line mastectomy rate was 36.3% (MRI group) versus 18.0% (noMRI group) (p < 0.001). In women receiving conserving surgery, MRI group had a significantly lower reoperation rate (8.5% versus 11.7%, p < 0.001). CONCLUSIONS: Clinicians requested breast MRI for women with a higher a priori probability of receiving mastectomy. MRI was associated with 11.3% more mastectomies, and with 3.2% fewer reoperations in the breast conservation subgroup. KEY POINTS: • In 19% of patients of the MIPA study, breast MRI was performed for screening or diagnostic purposes. • The current patient selection to preoperative breast MRI implies an 11% increase in mastectomies, counterbalanced by a 3% reduction of the reoperation rate. • Data from the MIPA study can support discussion in tumor boards when preoperative MRI is under consideration and should be shared with patients to achieve informed decision-making