Large Multicenter Sample Research Articles

The need to improve detection and treatment of physical pain of homeless people with schizophrenia and bipolar disorders. Results from the French Housing First Study

ObjectiveThe aim of this study was to investigate the prevalence and associated factors of physical pain in a large multicenter sample of Homeless Schizophrenia and Bipolar (HSB) patients. MethodsThis multicenter study was conducted in 4 French cities: Lille, Marseille, Paris and Toulouse. Pain was measured by EQ5D-3 L questionnaire with no specified period or location. In addition, sociodemographic information, duration of homelessness, illness severity using the Modified Colorado Symptom Index (MCSI) and drug information were collected. ResultsOverall, 655 HSB patients, mean age 38.8 years and 82.6% men were included, 448 (68.9%) were diagnosed with schizophrenia and 202 (31.1%) with bipolar disorder. More than half patients (N = 337, 51.5%) reported moderate to extreme physical pain while only 2.7% were administered analgesic drugs. In the multivariate analysis, self-reported moderate to extreme physical pain was associated with antidepressant consumption (adjusted odd ratio aOR = 2.56[1.25;5.26], p = .01), female gender (aOR = 1.72[1.03;2.86], p = .04), bipolar disorders (vs. schizophrenia) (aOR = 1.81[1.19;2.77], p = .006), older age (aOR = 1.03 [1.01;1.05], p = .01), with higher MCSI psychotic score (a0R = 1.04[1.01;1.06],p = .002), independently of the number of days in the street during the last 180 days, MCSI depression score, alcohol and substance use disorders, psychotropic drugs and analgesic treatments. No association with education level, antipsychotics, mood stabilizers, anxiolytic, hypnotic or medication adherence was found (all p > .05). ConclusionPhysical pain was highly reported in homeless patients with severe mental illness with insufficient care. Physical pain should be systematically explored and treated in this population. Bipolar disorders, antidepressant consumption and female gender may be targeted in priority. Age and psychotic symptomatology were found to influence self-reported pain in a marginal way.

Histogram Analysis Parameters Apparent Diffusion Coefficient for Distinguishing High and Low-Grade Meningiomas: A Multicenter Study

Low grade meningiomas have better prognosis than high grade meningiomas. The aim of this study was to measure apparent diffusion coefficient (ADC) histogram analysis parameters in different meningiomas in a large multicenter sample and to analyze the possibility of several parameters for predicting tumor grade and proliferation potential. Overall, 148 meningiomas from 7 institutions were evaluated in this retrospective study. Grade 1 lesions were diagnosed in 101 (68.2%) cases, grade 2 in 41 (27.7%) patients, and grade 3 in 6 (4.1%) patients. All tumors were investigated by MRI (1.5 T scanner) by using diffusion weighted imaging (b values of 0 and 1000 s/mm2). For every lesion, the following parameters were calculated: mean ADC, maximum ADC, minimum ADC, median ADC, mode ADC, ADC percentiles P10, P25, P75, P90, kurtosis, skewness, and entropy. The comparison of ADC values was performed by Mann–Whitney-U test. Correlation between different ADC parameters and KI 67 was calculated by Spearman's rank correlation coefficient. Grade 2/3 meningiomas showed statistically significant lower ADC histogram analysis parameters in comparison to grade 1 tumors, especially ADC median. A threshold value of 0.82 for ADC median to predict tumor grade was estimated (sensitivity = 82.2%, specificity = 63.8%, accuracy = 76.4%, positive and negative predictive values were 83% and 62.5%, respectively).All ADC parameters except maximum ADC showed weak significant correlations with KI 67, especially ADC P25 (P = −.340, P = .0001).

Homeless women with schizophrenia reported lower adherence to their medication than men: results from the French Housing First experience.

The aim of this study was to investigate the factors associated with non-adherence to medication in a large multi-center sample of homeless schizophrenia (HSZ) patients. This multi-center study was conducted in four French cities: Lille, Marseille, Paris, and Toulouse. In addition to the Medication Adherence Rating Scale (MARS), sociodemographic information, history of homelessness, illness severity using the Modified Colorado Symptom Index (MCSI) and the Multnomah Community Integration Scale (MCAS), and drug information were collected. In total, 218 HSZ patients (16.1% women, mean age 36.8±9.3years) were included in this study. In the multivariate analysis, being a woman and having higher illness severity (MCSI score) and lower "acceptance of illness" (MCAS score) were significantly associated with lower MARS index scores. Compared to men, women had lower MARS dimension 1 ('medication adherence behavior') and dimension 3 ('negative side effects and attitudes toward psychotropic medication') scores. First-generation antipsychotic use was also associated with lower MARS dimension 3 scores. HSZ women reported lower adherence than men, mainly due to having more subjective negative side effects and worse attitudes toward psychotropic medication. Future longitudinal studies should confirm these findings and explore the applicability of specific pharmacological and non-pharmacological treatment strategies for HSZ women, including treatment dose adaptation and psychoeducation. Clinical trial number NCT01570712.

Job Strain and Cardiovascular Health Score (from the Brazilian Longitudinal Study of Adult Health [ELSA-Brasil] Baseline)

We aimed to study the association between the American Heart Association cardiovascular health (CVH) score and job strain in the Brazilian Longitudinal Study of Adult Health baseline. We analyzed data from 11,351 active workers (aged 35 to 74years) without overt cardiovascular disease and who had complete data. Job strain was assessed using the 17-item Brazilian version of the Swedish Job Demand-Control-Support Questionnaire. Clinical (fasting plasma glucose, total cholesterol, and blood pressure) and lifestyle (diet, physical activity, smoking, and body mass index) components of CVH score were assessed according to the American Heart Association criteria. We used quasi-Poisson and multinomial regression models, adjusted for age, gender, race, educational level and income, and positive relative predicted score differences (rPSDs) indicate greater predicted scores. Subjects with low skill discretion scores had lower global (rPSD:-1.8%; p= 0.021) and lifestyle (rPSD:-3.6%; p= 0.018) CVH scores. Participants with low decision authority (rPSD:-2.4%; p= 0.029) and low social support scores (rPSD:-3.3%; p= 0.001) also had lower lifestyle CVH scores. In conclusion, we found significant associations between job strain and CVH scores in this large multicenter sample.

Multicenter Validation of an MMSE-MoCA Conversion Table.

Accumulating evidence points to the superiority of the MoCA over the MMSE as a cognitive screening tool. To facilitate the transition from the MMSE to the MoCA in clinical and research settings, authors have developed MMSE-MoCA conversion tables. However, it is unknown whether a conversion table generated from Alzheimer's disease (AD) patients would apply to patients with other dementia subtypes like vascular dementia or frontotemporal dementia. Furthermore, the reliability and accuracy of MMSE-MoCA conversion tables has not been properly evaluated. We retrospectively examined the MMSE-MoCA relationship in a large multicenter sample gathered from 3 Memory Clinics in Quebec, Canada (1492 patients). We produced an MMSE-MoCA conversion table using the equi-percentile method with log-linear smoothing. We then cross-validated our conversion table with the ADNI dataset (1202 patients) and evaluated its accuracy for future predictions. The MMSE-MoCA conversion table is consistent with previously published tables and has an intra-class correlation of 0.633 with the ADNI sample. However, we found that the MMSE-MoCA relationship is significantly modified by diagnosis (P < .01), with dementia subtypes associated with a dysexecutive syndrome showing a trend towards higher MMSE than other dementia syndromes for a given MoCA score. The large width of 95% confidence interval (CI) for a new prediction suggests questionable reliability for clinical use. In this study, we validated a conversion table between MMSE and MoCA using a large multicenter sample. Our results suggest caution in interpreting the tables in heterogeneous clinical populations, as the MMSE-MoCA relationship may be different across dementia subtypes.

A Multisite Study of Family Functioning Impairment in Pediatric Obsessive-Compulsive Disorder

Familial aspects of pediatric obsessive-compulsive disorder (OCD), including accommodation and treatment, have received notable and warranted attention. However, individual perspectives of its repercussions on family functioning, including emotional and occupational parental burden, have not been closely examined. The present study details this topic using a large multicenter sample. Participants included 354 youth affected with OCD and their mothers and fathers ascertained through OCD programs in Boston, Massachusetts (n= 180) and Vancouver, British Columbia (n= 174). The validated OCD Family Functioning Scale and standard OCD measurements were completed. Descriptive, between-site, and cross-perspective comparative analyses were followed by regression model testing to predict family impairment. Family functioning was negatively affected from youth, mother, and father perspectives. Impairment was reportedly more extensive at the time of worst OCD severity and was greater from maternal versus paternal viewpoints. Most frequently affected family tasks and implicated OCD symptoms included morning and bedtime routines and intrusive thoughts. Emotional repercussions in all members included stress and anxiety, followed by frustration or anger in youth and sadness in parents. Nearly half of mothers and one third of fathers reported daily occupational impairment. Compared with youth self-report, parents perceived fewer social and academic effects on their child. Family accommodation most consistently predicted family impairment, especially from parent perspectives. OCD and compulsion severity, contamination and religious obsessions, and comorbidities also predicted various perspectives of family subdomain impairment. This study quantitatively details the pervasive burden that pediatric OCD places on families, as reported from complementary relative perspectives. Further attention to this topic is warranted in clinical and research realms.

The moderating effect of religiosity on caregiving burden and depressive symptoms in caregivers of patients with dementia

ABSTRACTObjectives: This study explored whether religiosity/spirituality has a protective role against negative caregiving outcomes, in a large multicenter nationwide sample of caregivers of patients with dementia in South Korea. Additionally, this study was the first to examine whether religiosity/spirituality could affect caregiving outcomes according to the various religious affiliations of caregivers.Methods: The study was conducted on a sample of 476 caregivers of patients with dementia participated in the Clinical Research Center for Dementia of South Korea (CREDOS). We examined the moderating effect of each of the three dimensions of religiosity/spirituality (organizational religious activity, ORA; non-organizational religious activity, NORA; intrinsic religiosity, IR) on the relationship between activities of daily living (ADL) of patients with dementia and caregiving burden and depressive symptoms of caregivers, using a series of hierarchical regression analyses. In addition, these analyses were conducted according to the religious affiliations of the caregivers.Results: ORA, NORA, and IR of religiosity/spirituality alleviated the effect of ADL of patients on caregiving burden. ORA and IR moderated the relationship between ADL of patients and depressive symptoms of caregivers. These moderating effects of religiosity on caregiving outcomes were different according to various religious groups.Conclusion: We have identified religiosity/spirituality as a protective factor for caregivers of patients with dementia. The sub-dimensions of religiosity as moderators were different by religious affiliations of caregivers. Further studies are needed to investigate the specific religiosity-related factors which could positively impact the mental health of the caregivers of patients with dementia by religions.

MULTICENTER VALIDATION OF AN MMSE-MOCA CONVERSION TABLE

Accumulating evidence point to the superiority of the MoCA over the MMSE as a cognitive screening tool. Yet, since the MMSE has established itself as a gold-standard proxy of cognitive function over the years, the transition from the MMSE to the MoCA is limited by the absence of a reliable conversion table between both tests. We retrospectively examined the MMSE-MoCA relationship in a large multicenter sample gathered from memory clinics in Quebec, Canada (1492 patients, 1942 visits) and the ADNI dataset (1202 patients, 4288 visits). We then produced conversion table from the MoCA scores (uncorrected for education) to MMSE scores using the equi-percentile method with log-linear smoothing and evaluated its accuracy over the spectrum of MoCA scores. The MoCA→MMSE conversion table is reliable for MoCA scores of 20 and over, and is not significantly influenced by age, education and diagnosis. The table is unreliable when MoCA <20 (<50% of MMSE scores in a ±1 range of predicted score, mean deviation >2).

Cerebral amyloid angiopathy and its co-occurrence with Alzheimer's disease and other cerebrovascular neuropathologic changes

We examined the relationship between cerebral amyloid angiopathy (CAA), Alzheimer's disease neuropathologic changes, other vascular brain pathologies, and cognition in a large multicenter autopsy sample. Data were obtained from the National Alzheimer's Coordinating Center on autopsied subjects (N = 3976) who died between 2002 and 2012. Descriptive statistics and multivariable regression models estimated the associations between CAA and other pathologies, and between CAA severity and cognitive test scores proximal to death. CAA tended to co-occur with Alzheimer's disease neuropathologic changes but a minority of cases were discrepant. CAA was absent in 22% (n = 520) of subjects with frequent neuritic plaques but present in 20.9% (n = 91) of subjects with no neuritic plaques. In subjects with no/sparse neuritic plaques, nonhemorrhagic brain infarcts were more common in those with CAA pathology than without (p = 0.007). In subjects without the APOE ε4 allele, CAA severity was associated with lower cognition proximal to death, factoring in other pathologies. The presence of CAA in patients without Alzheimer's disease may indicate a distinct cerebrovascular condition.

Facility variation and predictors of serum potassium monitoring after initiation of a mineralocorticoid receptor antagonist in patients with heart failure

Mineralocorticoid receptor antagonists (MRAs) have been shown to reduce morbidity and mortality in patients with heart failure (HF) with reduced ejection fraction but are associated with hyperkalemia. We sought to evaluate the frequency, variation, and predictors associated with serum potassium monitoring in patients with HF initiated on an MRA among facilities in the Veterans Affairs (VA) Health Care System. We performed a retrospective cohort analysis of patients with HF across 133 Veterans Affairs facilities from 2003 to 2013 who were given a new prescription of an MRA. The primary outcome was the mean percentage of patients per facility with serum potassium monitoring within 14 days of MRA dispensing. Univariate and covariate analyses were performed to determine factors associated with monitoring. There were 142,880 patients identified with HF initiated on an MRA who met the study inclusion and exclusion criteria. The mean (SD) percentage of patients per facility with serum potassium monitoring within 14 days was 41.6% (standard deviation 8.0%; minimum 18.9%, maximum 56.7%). Facilities with a higher frequency of monitoring were associated with membership in the Council on Teaching Hospitals (n = 70, P < .0001), had academic affiliations (n = 100, P < .0001), and a higher annual volume of patients with HF (≥200 patients, P < .0001). In a large multicenter national sample of patients with HF receiving a new MRA prescription, the frequency of serum potassium monitoring was below recommended guidelines. Academic facilities and those with a higher volume of patients with HF were associated with an increased frequency of monitoring.

FRI0408 Analysis of Disease Activity and Response to Treatment in A Large Cohort from the Spanish Society of Rheumatology Registry of Patients with Systemic Lupus Erythematosus (RELESSER)

ObjectivesTo analyze activity and response to therapies in a large multicenter sample of patients with systemic lupus erythematosus (SLE).MethodsStudy design: national, multicenter, cross-sectional. Patients: SLE patients according to ACR criteria....

A Multicenter Tractography Study of Deep White Matter Tracts in Bipolar I Disorder

Tractography studies investigating white matter (WM) abnormalities in patients with bipolar disorder have yielded heterogeneous results owing to small sample sizes. The small size limits their generalizability, a critical issue for neuroimaging studies of biomarkers of bipolar I disorder (BPI). To study WM abnormalities using whole-brain tractography in a large international multicenter sample of BPI patients and to compare these alterations between patients with or without a history of psychotic features during mood episodes. A cross-sectional, multicenter, international, Q-ball imaging tractography study comparing 118 BPI patients and 86 healthy control individuals. In addition, among the patient group, we compared those with and without a history of psychotic features. University hospitals in France, Germany, and the United States contributed participants. Participants underwent assessment using the Diagnostic Interview for Genetic Studies at the French sites or the Structured Clinical Interview for DSM-IV at the German and US sites. Diffusion-weighted magnetic resonance images were acquired using the same acquisition parameters and scanning hardware at each site. We reconstructed 22 known deep WM tracts using Q-ball imaging tractography and an automatized segmentation technique. Generalized fractional anisotropy values along each reconstructed WM tract. Compared with controls, BPI patients had significant reductions in mean generalized fractional anisotropy values along the body and the splenium of the corpus callosum, the left cingulum, and the anterior part of the left arcuate fasciculus when controlling for age, sex, and acquisition site (corrected for multiple testing). Patients with a history of psychotic features had a lower mean generalized fractional anisotropy value than those without along the body of the corpus callosum (corrected for multiple testing). In this multicenter sample, BPI patients had reduced WM integrity in interhemispheric, limbic, and arcuate WM tracts. Interhemispheric pathways are more disrupted in patients with than in those without psychotic symptoms. Together these results highlight the existence of an anatomic disconnectivity in BPI and further underscore a role for interhemispheric disconnectivity in the pathophysiological features of psychosis in BPI.

Long-term posttraumatic stress symptoms vary inversely with early opiate dosing in children recovering from serious burns

Children surviving serious burns are at risk for developing posttraumatic stress disorder (PTSD) as a function both of the injury and of its treatment. Short-term studies in such children have demonstrated reduced PTSD symptoms with intensive early pain control. However, the long-term impact of early pain control strategies on posttraumatic stress symptoms in children recovering from serious burn injuries has not been examined. This was a retrospective review of a multiple time point data collection involving a cohort of 147 infants, children, and teenagers with 4 years of follow-up after serious burns conducted at 4 pediatric burn centers to examine the impact of early opiate dosing on long-term posttraumatic stress symptoms. The main outcome measure was the nine-item Short Form Child Stress Disorders Checklist, which is an established and validated assessment. The impact of total opiate dosing during the first 7 days on these scores was assessed. Subjects had an average age of 11 years and average injury size of 22% total body surface area burned (%TBS). The correlation between opiate units (OUs) and %TBS was 0.46 at baseline, OU increasing with increasing %TBS. OUs were strongly predictive of Child Stress Disorders Checklist scores up to 4 years, with higher OU (10 units vs. 6 and 2 units) remaining constantly different up to 4 years in predicting lower stress scores for both smaller and larger burns. Early opiate management of pain associated with acute burn wounds and burn treatment predicts the development and resolution rate of PTSD symptoms in a large multicenter sample of children hospitalized for serious burns. The effect seems to be dose related and durable at least up to 4 years in a range of burn sizes. Prognostic/epidemiologic study, level II.

Commentary on “Measuring Advanced Motor Skills in Children With Cerebral Palsy

“How could I apply this information?” Challenge has been developed as an adjunct to the Gross Motor Function Measure (GMFM-66) to assess gross motor function in children and youth with cerebral palsy who have limitations in advanced motor skills (Gross Motor Function Classification System, level I). This article provides clinicians with a unique look into the rigorous, multistep process of test development allowing for conversations between clinicians and test developers during this refinement process. “What should I be mindful about when applying this information?” Clinicians must be mindful that the time/distance cut-points derived from the performance of children with typical development will be further refined through Rasch scaling with a large multicenter sample of children with cerebral palsy. Therefore, although the test items may remain the same, the cutoff points will likely change after the Rasch scaling. Barbara Sargent, PT, PhD, PCS University of Southern California Los Angeles, California Linda Fetters, PT, PhD, FAPTA University of Southern California Los Angeles, California

Predicting On‐Road Assessment Pass and Fail Outcomes in Older Drivers with Cognitive Impairment Using a Battery of Computerized Sensory‐Motor and Cognitive Tests

To generate a robust model of computerized sensory-motor and cognitive test performance to predict on-road driving assessment outcomes in older persons with diagnosed or suspected cognitive impairment. A logistic regression model classified pass–fail outcomes of a blinded on-road driving assessment. Generalizability of the model was tested using leave-one-out cross-validation. Three specialist clinics in New Zealand. Drivers (n=279; mean age 78.4, 65% male) with diagnosed or suspected dementia, mild cognitive impairment, unspecified cognitive impairment, or memory problems referred for a medical driving assessment. A computerized battery of sensory-motor and cognitive tests and an on-road medical driving assessment. One hundred fifty-five participants (55.5%) received an on-road fail score. Binary logistic regression correctly classified 75.6% of the sample into on-road pass and fail groups. The cross-validation indicated accuracy of the model of 72.0% with sensitivity for detecting on-road fails of 73.5%, specificity of 70.2%, positive predictive value of 75.5%, and negative predictive value of 68%. The off-road assessment prediction model resulted in a substantial number of people who were assessed as likely to fail despite passing an on-road assessment and vice versa. Thus, despite a large multicenter sample, the use of off-road tests previously found to be useful in other older populations, and a carefully constructed and tested prediction model, off-road measures have yet to be found that are sufficiently accurate to allow acceptable determination of on-road driving safety of cognitively impaired older drivers.

Right Ventricular Strain in Pulmonary Hypertension

Since 2009, there have been ≥170 articles published in the cardiopulmonary literature on right ventricular (RV) echocardiographic strain imaging, including several in Circulation: Cardiovascular Imaging . Of particular interest has been the effort to use RV echocardiographic strain imaging to assess RV systolic function in pulmonary hypertension and the relationship of RV strain to disease severity and outcomes. In this issue of Circulation: Cardiovascular Imaging , Fine et al,1 from the Mayo Clinic echo group, report on retrospectively evaluated data on the relationship of RV strain to outcomes in the largest such study to date, encompassing 575 patients with known or suspected pulmonary hypertension without elevated pulmonary venous pressure during a median follow-up period of 16.5 months.1 The data show a strong association between reductions in mean longitudinal strain and all-cause mortality, and cardiopulmonary mortality and cardiopulmonary events. An exhaustive biostatistical analysis shows the relationship to be quantitative, stronger than that of other echo indices including tricuspid annular plane systolic excursion, independent of clinical covariates and resulting in a significant improvement in predictive value when combined with relevant clinical variables, as reflected in a significant increase in the integrated discrimination improvement index and the c-statistic for the primary end point. Thus, the results promise to improve clinical risk assessment significantly for such patients and may improve clinical decision making. Article see p 711 The apparent benefit is, in large part, a reflection of the relatively weak performance of older 2-dimensional (2D) echocardiographic indices of RV performance including fractional area change and tricuspid annular plane systolic excursion in this setting. RV imaging has been a minefield for echocardiography in adults since its inception. The complexity of ventricular shape, the thinness of the RV free wall, and the limitations in adults of transthoracic and subcostal windows in permitting full visualization …

Association of functional DBH genetic variants with alcohol dependence risk and related depression and suicide attempt phenotypes: Results from a large multicenter association study

ObjectiveDopamine-beta-hydroxylase (DBH) metabolizes the conversion of dopamine to noradrenaline. DBH, located on chromosome 9q34.2 has variants with potential functional consequences which may be related to alterations of neurotransmitter function and several psychiatric phenotypes, including alcohol dependence (AD), depression (MD) and suicidal behavior (SA). The aim of this association study in a large multicenter sample of alcohol-dependent individuals and controls is to investigate the role of DBH SNPs and haplotypes in AD risk and associated phenotypes (AD with MD or SA). Method1606 inpatient subjects with DSM-IV AD from four addiction treatment centers and 1866 control subjects were included. Characteristics of AD, MD and SA were obtained using standardized structured interviews. After subjects were genotyped for 4 DBH polymorphisms, single SNP case–control and haplotype analyses were conducted. Resultsrs1611115 (near 5′) C-allele and related haplotypes were significantly associated with alcohol dependence in females. This association with female alcohol dependence also accounts for the significant relationship between this variant and comorbid conditions and traits. ConclusionsThis study presents evidence for a potentially functional DBH variant influencing the risk for alcohol dependence while other comorbid conditions are not independently influenced by this SNP. However, the study also supports the possible role of the dopamine system in the etiology of female alcohol dependence.

Clinical features of pure obsessive-compulsive disorder

ObjectivePsychiatric comorbidity is the rule in obsessive-compulsive disorder (OCD); however, very few studies have evaluated the clinical characteristics of patients with no co-occurring disorders (non-comorbid or “pure” OCD). The aim of this study was to estimate the prevalence of pure cases in a large multicenter sample of OCD patients and compare the sociodemographic and clinical characteristics of individuals with and without any lifetime axis I comorbidity. MethodA cross-sectional study with 955 adult patients of the Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders (C-TOC). Assessment instruments included the Yale-Brown Obsessive-Compulsive Scale, the Dimensional Yale-Brown Obsessive-Compulsive Scale, The USP-Sensory Phenomena Scale and the Brown Assessment of Beliefs Scale. Comorbidities were evaluated using the Structured Clinical Interview for DSM-IV Axis I Disorders. Bivariate analyses were followed by logistic regression. ResultsOnly 74 patients (7.7%) presented pure OCD. Compared with those presenting at least one lifetime comorbidity (881, 92.3%), non-comorbid patients were more likely to be female and to be working, reported less traumatic experiences and presented lower scores in the Y-BOCS obsession subscale and in total DY-BOCS scores. All symptom dimensions except contamination-cleaning and hoarding were less severe in non-comorbid patients. They also presented less severe depression and anxiety, lower suicidality and less previous treatments. In the logistic regression, the following variables predicted pure OCD: sex, severity of depressive and anxious symptoms, previous suicidal thoughts and psychotherapy. ConclusionsPure OCD patients were the minority in this large sample and were characterized by female sex, less severe depressive and anxious symptoms, less suicidal thoughts and less use of psychotherapy as a treatment modality. The implications of these findings for clinical practice are discussed.

Robust Automated Detection of Microstructural White Matter Degeneration in Alzheimer’s Disease Using Machine Learning Classification of Multicenter DTI Data

Diffusion tensor imaging (DTI) based assessment of white matter fiber tract integrity can support the diagnosis of Alzheimer’s disease (AD). The use of DTI as a biomarker, however, depends on its applicability in a multicenter setting accounting for effects of different MRI scanners. We applied multivariate machine learning (ML) to a large multicenter sample from the recently created framework of the European DTI study on Dementia (EDSD). We hypothesized that ML approaches may amend effects of multicenter acquisition. We included a sample of 137 patients with clinically probable AD (MMSE 20.6±5.3) and 143 healthy elderly controls, scanned in nine different scanners. For diagnostic classification we used the DTI indices fractional anisotropy (FA) and mean diffusivity (MD) and, for comparison, gray matter and white matter density maps from anatomical MRI. Data were classified using a Support Vector Machine (SVM) and a Naïve Bayes (NB) classifier. We used two cross-validation approaches, (i) test and training samples randomly drawn from the entire data set (pooled cross-validation) and (ii) data from each scanner as test set, and the data from the remaining scanners as training set (scanner-specific cross-validation). In the pooled cross-validation, SVM achieved an accuracy of 80% for FA and 83% for MD. Accuracies for NB were significantly lower, ranging between 68% and 75%. Removing variance components arising from scanners using principal component analysis did not significantly change the classification results for both classifiers. For the scanner-specific cross-validation, the classification accuracy was reduced for both SVM and NB. After mean correction, classification accuracy reached a level comparable to the results obtained from the pooled cross-validation. Our findings support the notion that machine learning classification allows robust classification of DTI data sets arising from multiple scanners, even if a new data set comes from a scanner that was not part of the training sample.

2793 – A multicenter tractography study of structural connectivity in bipolar disorder and effects of psychotic features

Introduction A number of studies have investigated white matter abnormalities in patients with bipolar disorder (BD) using diffusion tensor imaging. However, tractography studies yielded heterogeneous results partly due to small sample sizes. Aims In this work we aimed to study white matter abnormalities using whole-brain tractography in a large multicenter sample of patients with BD I with and without psychotic features. Objectives To compare mean generalized fractional anisotropy (GFA) along deep white matter tracts between patients with BD with a positive history of psychosis during illness phases, no such history and healthy controls. Methods We acquired diffusion-weighted MRI for 118 patients with BD I and 86 healthy controls using the same acquisition parameters and scanning hardware. We used Q-ball imaging tractography and an automatized segmentation technique to reconstruct 22 known deep white matter tracts and to obtain the mean GFA along each tract. Results Patients with BD had lower GFA values than controls along the corpus callosum (body and splenium), the left cingulum and the left arcuate fasciculus, when controlling for age, gender and acquisition site. All results with an exception for the long fibers of the left cingulum were driven by patients with a positive history of psychotic symptoms. Conclusions We demonstrated a reduced integrity of interhemispheric, limbic and arcuate white matter tracts in patients with BD I. Further, interhemispheric pathways were more disrupted in patients with psychotic symptoms, underscoring the role of interhemispheric connectivity in the pathophysiology of BD with psychosis.