Privacy-preserving record linkage across disparate institutions and datasets to enable a learning health system: The national COVID cohort collaborative (N3C) experience.

Introduction: Research driven by real-world clinical data is increasingly vital to enabling learning health systems, but integrating such data from across disparate health systems is challenging. As part of the NCATS National COVID Cohort Collaborative (N3C), the N3C Data Enclave was established as a centralized repository of deidentified and harmonized COVID-19 patient data from institutions across the US. However, making this data most useful for research requires linking it with information such as mortality data, images, and viral variants. The objective of this project was to establish privacy-preserving record linkage (PPRL) methods to ensure that patient-level EHR data remains secure and private when governance-approved linkages with other datasets occur. Methods: Separate agreements and approval processes govern N3C data contribution and data access. The Linkage Honest Broker (LHB), an independent neutral party (the Regenstrief Institute), ensures data linkages are robust and secure by adding an extra layer of separation between protected health information and clinical data. The LHB's PPRL methods (including algorithms, processes, and governance) match patient records using "deidentified tokens," which are hashed combinations of identifier fields that define a match across data repositories without using patients' clear-text identifiers. Results: These methods enable three linkage functions: Deduplication, Linking Multiple Datasets, and Cohort Discovery. To date, two external repositories have been cross-linked. As of March 1, 2023, 43 sites have signed the LHB Agreement; 35 sites have sent tokens generated for 9 528 998 patients. In this initial cohort, the LHB identified 135 037 matches and 68 596 duplicates. Conclusion: This large-scale linkage study using deidentified datasets of varying characteristics established secure methods for protecting the privacy of N3C patient data when linked for research purposes. This technology has potential for use with registries for other diseases and conditions.

Sex, obesity, diabetes, and exposure to particulate matter among patients with severe asthma: Scientific insights from a comparative analysis of open clinical data sources during a five-day hackathon.

This special communication describes activities, products, and lessons learned from a recent hackathon that was funded by the National Center for Advancing Translational Sciences via the Biomedical Data Translator program ('Translator'). Specifically, Translator team members self-organized and worked together to conceptualize and execute, over a five-day period, a multi-institutional clinical research study that aimed to examine, using open clinical data sources, relationships between sex, obesity, diabetes, and exposure to airborne fine particulate matter among patients with severe asthma. The goal was to develop a proof of concept that this new model of collaboration and data sharing could effectively produce meaningful scientific results and generate new scientific hypotheses. Three Translator Clinical Knowledge Sources, each of which provides open access (via Application Programming Interfaces) to data derived from the electronic health record systems of major academic institutions, served as the source of study data. Jupyter Python notebooks, shared in GitHub repositories, were used to call the knowledge sources and analyze and integrate the results. The results replicated established or suspected relationships between sex, obesity, diabetes, exposure to airborne fine particulate matter, and severe asthma. In addition, the results demonstrated specific differences across the three Translator Clinical Knowledge Sources, suggesting cohort- and/or environment-specific factors related to the services themselves or the catchment area from which each service derives patient data. Collectively, this special communication demonstrates the power and utility of intense, team-oriented hackathons and offers general technical, organizational, and scientific lessons learned.

Antidepressant Regulatory Warnings, Prescription Patterns, Suicidality and Other Aggressive Behaviors in Major Depressive Disorder and Anxiety Disorders.

In 2004 the Food and Drug Administration issued a warning on the risk of suicidality in children and adolescents receiving antidepressants. This was followed by reports of changes in antidepressant prescription patterns, suicidality and other aggressive behaviors, but debate is continuing regarding the nature and magnitude of these changes. We examined a large physician database for impact of the warning on antidepressant prescriptions, suicidality and other aggressive behaviors in major depressive disorder (MDD) and anxiety disorders in adult and pediatric patients. We analyzed electronic database covering over 100,000 patients, treated in Pre- (before 2003) and Post- (after 2004) warning periods. We compared strength of the association between the measures and the time period with two tests. Multivariate logistic regression analyses were performed to ascertain the unique effect of each parameter. Of 10,089 MDD (61.0 %) and anxiety disorders (39.0 %) patients, 65.2 % received antidepressant prescription and 16.1 % were pediatric patients. In post-warning period, there was a greater reduction in adult versus pediatric antidepressant prescription rates. Logistic modeling showed greater likelihood of antidepressant prescription in MDD as compared with anxiety disorders in post-warning period. Pediatric patients were more likely than adults to receive fluoxetine during the post-warning period. There was an overall reduction in suicidality and other aggressive behaviors in the post-warning period. Regulatory warnings may have had an impact on antidepressant benefit/risk assessment and consequent utilization, therapeutic effects, and adverse events. Our observations suggest that psychiatrists may heed regulatory warnings, but may also exert professional independence and discrimination in their application.

Use of augmentation agents for treating depression: analysis of a psychiatric electronic medical record data set.

OBJECTIVE: This study evaluated the relationship between patient characteristics and augmentation strategies for the treatment of major depressive disorder. METHODS: This retrospective, cross-sectional study used data from a psychiatric electronic medical record database for patients with depression without psychosis or psychotic features who initiated augmentation therapy between January 2001 and June 2011. Medical records were evaluated to identify factors predicting use of specific augmentation agents, and a multivariate logistic regression model was used to assess clinical and demographic predictors of augmentation strategy. RESULTS: Of 3,209 patients initiating augmentation therapy for depression, 75% received augmentation with an antidepressant combination and 11% received augmentation with second-generation antipsychotics. Baseline clinical severity (Clinical Global Impressions-Severity score) most strongly and consistently predicted augmentation with second-generation antipsychotics. CONCLUSIONS: Treatment of patients in specialty settings with depression was often augmented with an antidepressant combination, whereas those with severe depression had an increased likelihood of augmentation with second-generation antipsychotics.

Comorbid substance use disorders with other Axis I and II mental disorders among treatment-seeking Asian Americans, Native Hawaiians/Pacific Islanders, and mixed-race people.

Little is known about behavioral healthcare needs of Asian Americans (AAs), Native Hawaiians/Pacific Islanders (NHs/PIs), and mixed-race people (MRs)-the fastest growing segments of the U.S. population. We examined substance use disorder (SUD) prevalences and comorbidities among AAs, NHs/PIs, and MRs (N = 4572) in a behavioral health electronic health record database. DSM-IV diagnoses among patients aged 1-90 years who accessed behavioral healthcare from 11 sites were systematically captured: SUD, anxiety, mood, personality, adjustment, childhood-onset, cognitive/dementia, dissociative, eating, factitious, impulse-control, psychotic/schizophrenic, sleep, and somatoform diagnoses. Of all patients, 15.0% had a SUD. Mood (60%), anxiety (31.2%), adjustment (30.9%), and disruptive (attention deficit-hyperactivity, conduct, oppositional defiant, disruptive behavior diagnosis, 22.7%) diagnoses were more common than others (psychotic 14.2%, personality 13.3%, other childhood-onset 11.4%, impulse-control 6.6%, cognitive 2.8%, eating 2.2%, somatoform 2.1%). Less than 1% of children aged <12 years had SUD. Cannabis diagnosis was the primary SUD affecting adolescents aged 12-17. MRs aged 35-49 years had the highest prevalence of cocaine diagnosis. Controlling for age at first visit, sex, treatment setting, length of treatment, and number of comorbid diagnoses, NHs/PIs and MRs were about two times more likely than AAs to have ≥ 2 SUDs. Regardless of race/ethnicity, personality diagnosis was comorbid with SUD. NHs/PIs with a mood diagnosis had elevated odds of having SUD. Findings present the most comprehensive patterns of mental diagnoses available for treatment-seeking AAs, NHs/PIs, and MRs in the real-world medical setting. In-depth research is needed to elucidate intraracial and interracial differences in treatment needs.

Using electronic health records data to assess comorbidities of substance use and psychiatric diagnoses and treatment settings among adults.

OBJECTIVE: To examine prevalences of substance use disorders (SUD) and comprehensive patterns of comorbidities among psychiatric patients ages 18-64 years (N = 40,099) in an electronic health records (EHR) database. METHOD: DSM-IV diagnoses among psychiatric patients in a large university system were systematically captured: SUD, anxiety (AD), mood (MD), personality (PD), adjustment, childhood-onset, cognitive/dementia, dissociative, eating, factitious, impulse-control, psychotic (schizophrenic), sexual/gender identity, sleep, and somatoform diagnoses. Comorbidities and treatment types among patients with a SUD were examined. RESULTS: Among all patients, 24.9% (n = 9984) had a SUD, with blacks (35.2%) and Hispanics (32.9%) showing the highest prevalence. Among patients with a SUD, MD was prevalent across all age groups (50.2-56.6%). Patients aged 18-24 years had elevated odds of comorbid PD, adjustment, childhood-onset, impulse-control, psychotic, and eating diagnoses. Females had more PD, AD, MD, eating, and somatoform diagnoses, while males had more childhood-onset, impulse-control, and psychotic diagnoses. Blacks had greater odds than whites of psychotic and cognitive/dementia diagnoses, while whites exhibited elevated odds of PA, AD, MD, childhood-onset, eating, somatoform, and sleep diagnoses. Women, blacks, and Native American/multiple-race adults had elevated odds of using inpatient treatment; men, blacks, and Hispanics had increased odds of using psychiatric emergency care. Comorbid MD, PD, adjustment, somatoform, psychotic, or cognitive/dementia diagnoses increased inpatient treatment. CONCLUSION: Patients with a SUD, especially minority members, use more inpatient or psychiatric emergency care than those without. Findings provide evidence for research on understudied diagnoses and underserved populations in the real-world clinical settings.

Cognitive improvement following treatment in late-life depression: relationship to vascular risk and age of onset.

OBJECTIVES: To test the hypothesis that the degree of vascular burden and/or age of onset may influence the degree to which cognition can improve during the course of treatment in late-life depression. DESIGN: Measurement of cognition both before and following 12 weeks of treatment with sertraline. SETTING: University medical centers (Washington University and Duke University). PARTICIPANTS: One hundred sixty-six individuals with late-life depression. INTERVENTION: Sertraline treatment. MEASUREMENTS: The cognitive tasks were grouped into five domains (language, processing speed, working memory, episodic memory, and executive function). We measured vascular risk using the Framingham Stroke Risk Profile measure. We measured T2-based white matter hyperintensities using the Fazekas criteria. RESULTS: Both episodic memory and executive function demonstrated significant improvement among adults with late-life depression during treatment with sertraline. Importantly, older age, higher vascular risk scores, and lower baseline Mini-Mental State Examination scores predicted less change in working memory. Furthermore, older age, later age of onset, and higher vascular risk scores predicted less change in executive function. CONCLUSIONS: These results have important clinical implications in that they suggest that a regular assessment of vascular risk in older adults with depression is necessary as a component of treatment planning and in predicting prognosis, both for the course of the depression itself and for the cognitive impairments that often accompany depression in later life.

Meaningful use of electronic behavioral health data in primary health care.

In August 2011, scientists and policy-makers held a conference entitled "Using IT to Improve Community Health: How Health Care Reform Supports Innovation." One of the conference sessions was entitled "Electronic health records: Meaningful use implementation challenges, innovation, and regulations." This Meeting Report discusses the meaningful use of behavioral health data for the treatment of mental health and substance abuse conditions and optimization of behavioral wellness by primary care physicians.

VisualDecisionLinc: a visual analytics approach for comparative effectiveness-based clinical decision support in psychiatry.

Comparative Effectiveness Research (CER) is designed to provide research evidence on the effectiveness and risks of different therapeutic options on the basis of data compiled from subpopulations of patients with similar medical conditions. Electronic Health Record (EHR) system contain large volumes of patient data that could be used for CER, but the data contained in EHR system are typically accessible only in formats that are not conducive to rapid synthesis and interpretation of therapeutic outcomes. In the time-pressured clinical setting, clinicians faced with large amounts of patient data in formats that are not readily interpretable often feel 'information overload'. Decision support tools that enable rapid access at the point of care to aggregate data on the most effective therapeutic outcomes derived from CER would greatly aid the clinical decision-making process and individualize patient care. In this manuscript, we highlight the role that visual analytics can play in CER-based clinical decision support. We developed a 'VisualDecisionLinc' (VDL) tool prototype that uses visual analytics to provide summarized CER-derived data views to facilitate rapid interpretation of large amounts of data. We highlight the flexibility that visual analytics offers to gain an overview of therapeutic options and outcomes and if needed, to instantly customize the evidence to the needs of the patient or clinician. The VDL tool uses visual analytics to help the clinician evaluate and understand the effectiveness and risk of different therapeutic options for different subpopulations of patients.

The effectiveness of antidepressant monotherapy in a naturalistic outpatient setting.

OBJECTIVE: To assess a representative sample of clinically depressed outpatients during acute treatment with antidepressant medication monotherapy to determine clinical outcomes and evaluate relationships between outcomes and selected baseline/treatment features. METHOD: This naturalistic study examined data on outpatients at the Department of Psychiatry, Duke University Medical Center, Durham, North Carolina, from January 2000 through December 2010. Eligible patients (N = 1,722) had a diagnosis of clinical depression (major depressive disorder, dysthymic disorder, or depressive disorder not otherwise specified as defined in DSM-IV-TR). Sociodemographic/clinical data were gathered at study entry (date of first treatment). The Clinical Global Impressions-improvement (CGI-I) and -severity of illness (CGI-S) scales were administered at entry and at study exit (end of follow-up) after 1 to 9 weeks of treatment. Analysis of variance, F tests, and t tests determined relationships between outcomes and treatment duration, baseline severity, and sociodemographic/clinical features. RESULTS: Thirty-nine percent of participants reported substantial improvement (CGI-I score = 1 or 2) from entry to exit, 33% reported minimal improvement (CGI-I score = 3), 22% reported no change, and approximately 7% reported worsened illness. Greater improvement (CGI-I score) and greater reduction in depressive severity (CGI-S score) were associated with greater baseline depressive severity and longer treatment duration (all P < .001). Participants with greater baseline depressive severity experienced larger reductions in depressive severity but reported worse CGI-I scores at exit. Less improvement in CGI-I scores was seen in women compared to men (P = .018). Less improvement in CGI-I scores and less reduction in CGI-S scores were seen in participants ≤ 60 years of age (P = .040 and P = .025, respectively) and those with comorbid substance abuse (P < .001 and P = .010, respectively) or anxiety (P = .018 and P < .001, respectively) disorders. CONCLUSIONS: Most depressive symptom improvement occurred within the first 4 to 6 weeks of antidepressant monotherapy. Greater baseline severity, comorbid substance abuse, and comorbid anxiety disorders are associated with worse outcomes.

Clinical characteristics and resource utilization of patients with bipolar disorder who have frequent psychiatric interventions.

OBJECTIVE: To compare the demographics, clinical characteristics and resource utilization of patients with bipolar disorder who required frequent psychiatric interventions (FPIs) with those needing fewer interventions in the Duke Healthcare System database between 1999 and 2005. METHODS: This retrospective analysis was conducted using electronic medical records of bipolar patients with FPIs, defined as having ≥4 clinically significant events (CSEs) in any 12-month period while in the Duke University Healthcare System. CSEs were composed of emergency room visits, inpatient hospitalizations, or a change in psychotropic medication due to psychiatric symptoms (score≥4 on the Clinical Global Impressions-Severity scale). Data were compared between patients with and without FPIs. RESULTS: Of 632 patients with bipolar disorder 52.5% were identified as having FPIs. These patients were younger and more often female and African American than those with fewer interventions (p<0.01 for all). Patients with FPIs were generally prescribed more psychotropic and non-psychotropic medications, utilized more healthcare resources and experienced more psychiatric co-morbidities than those who did not require FPIs (p<0.01 for all). LIMITATIONS: These results are from a single healthcare system and may not be generalizable to all patients with bipolar disorder. This analysis was retrospective and relied on availability of adequate information recording and coding of diagnoses by physicians. CONCLUSIONS: Patients with bipolar disorder who required FPIs were significantly different from those with fewer clinically defined interventions with respect to their demographic and clinical characteristics and prescribed medications.

Support for the vascular depression hypothesis in late-life depression: results of a 2-site, prospective, antidepressant treatment trial.

CONTEXT: Research on vascular depression has used 2 approaches to subtype late-life depression, based on executive dysfunction or white matter hyperintensity severity. OBJECTIVE: To evaluate the relationship of neuropsychological performance and white matter hyperintensity with clinical response in late-life depression. DESIGN: Two-site, prospective, nonrandomized controlled trial. SETTING: Outpatient clinics at Washington University and Duke University. PARTICIPANTS: A total of 217 subjects aged 60 years or older met DSM-IV criteria for major depression, scored 20 or more on the Montgomery-Asberg Depression Rating Scale (MADRS), and received vascular risk factor scores, neuropsychological testing, and magnetic resonance imaging; they were excluded for cognitive impairment or severe medical disorders. Fazekas rating was conducted to grade white matter hyperintensity lesions. Intervention Twelve weeks of sertraline treatment, titrated by clinical response. Main Outcome Measure Participants' MADRS scores over time. RESULTS: Baseline neuropsychological factor scores correlated negatively with baseline Fazekas scores. A mixed model examined effects of predictor variables on MADRS scores over time. Baseline episodic memory (P = .002), language (P = .007), working memory (P = .01), processing speed (P < .001), executive function factor scores (P = .002), and categorical Fazekas ratings (P = .05) predicted MADRS scores, controlling for age, education, age of onset, and race. Controlling for baseline MADRS scores, these factors remained significant predictors of decrease in MADRS scores, except for working memory and Fazekas ratings. Thirty-three percent of subjects achieved remission (MADRS < or =7). Remitters differed from nonremitters in baseline cognitive processing speed, executive function, language, episodic memory, and vascular risk factor scores. CONCLUSIONS: Comprehensive neuropsychological function and white matter hyperintensity severity predicted MADRS scores prospectively over a 12-week treatment course with selective serotonin reuptake inhibitors in late-life depression. Baseline neuropsychological function differentiated remitters from nonremitters and predicted time to remission in a proportional hazards model. Predictor variables correlated highly with vascular risk factor severity. These data support the vascular depression hypothesis and highlight the importance of linking subtypes based on neuropsychological function and white matter integrity. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00045773.

Patterns of pharmacotherapy and treatment response in elderly adults with bipolar disorder.

BACKGROUND: Bipolar disorder is a difficult disease to treat because of its cycling nature, frequent residual symptoms, and poor compliance to treatment. Several guidelines have been proposed for treatment, but there is limited data on best treatment practices in elderly, bipolar patients. This study assessed patterns of psychopharmacological treatment and treatment response in acutely ill, bipolar patients over the age of 60. METHODS: Naturalistic pharmacologic data was obtained on 138 acutely ill, elderly bipolar patients from the Duke University Medical Center electronic psychiatric record. Clinical Global Impression (CGI) severity and improvement scale ratings were performed at each visit, and time to response was measured. Pharmacological treatment selected was reviewed. RESULTS: Standard mood stabilizers (lithium, valproate, carbamazepine, and lamotrigine) were the most prescribed medications (68%), followed by antipsychotics (54%) and antidepressants (34%). Combination therapy was more common than monotherapy (57% vs. 38%). Remission was achieved in 35% of subjects, while 32% showed no significant improvement. There was no difference in antipsychotic prescription between old old and young old patients. CONCLUSIONS: In this naturalistic, real-setting study of pharmacologic treatment, acutely ill, elderly bipolar patients were treated primarily with mood-stabilizing agents, followed by antipsychotics and antidepressants. Combination therapy is much more common than monotherapy. Results can be useful in understanding the current clinical standard of care in elderly bipolar patients, and are consistent with current clinical guidelines for mixed-age bipolar patients.

Effect of bupropion extended release on negative emotion processing in major depressive disorder: a pilot functional magnetic resonance imaging study.

BACKGROUND: Prior imaging studies suggest that patients with major depressive disorder have abnormalities in frontal and limbic neural circuitry including the amygdala, which is relatively more activated at rest and in response to negative emotional stimuli (sadness, fear, etc.) in depressed patients than in controls. Concurrently, patients with depression may have decreased activation of attentional executive regions in response to attentional stimuli. This study examined the effect of bupropion XL, an extended release formulation of the nonserotonergic antidepressant agent bupropion, using a paradigm that investigated both negative emotional response and attentional processing. METHOD: Functional magnetic resonance imaging (fMRI) scans and clinical ratings were obtained for 10 patients with DSM-IV-TR-defined major depressive disorder (mean [SD] age = 41 [+/- 7] years, mean [SD] Hamilton Rating Scale for Depression [HAM-D] score = 21 [+/- 4]) before and after 8 weeks of treatment with bupropion XL. The fMRI sessions were conducted during administration of the Emotional Oddball Task; scans were obtained while subjects viewed emotional distracters and performed an attentional executive function task. The primary outcome was fMRI activations evoked by the emotional distracters. The first baseline fMRI scan was performed in December 2004, and the last posttreatment scan was in March 2005. RESULTS: Treatment with bupropion XL was associated with improvements in HAM-D and Clinical Global Impressions scale ratings (p < .05). Treatment reduced fMRI activation during emotional distracters in several regions including right orbital frontal cortex, left dorsomedial prefrontal cortex, right ventromedial prefrontal cortex, right anterior cingulate cortex, right inferior frontal cortex, right amygdala/parahippocampal area, right caudate, right fusiform gyrus, and left posterior cingulate. In addition, changes in fMRI activation in the amygdala correlated with improvements on the HAM-D (p < .05). Treatment increased activation to attentional targets in the following regions: right middle and inferior frontal gyri, right caudate, and bilateral precuneus. CONCLUSION: Despite the limitations of a small sample size and the lack of a placebo control group, this study demonstrated that bupropion XL therapy for 8 weeks may attenuate emotion-induced, blood-oxygen-level-dependent (BOLD) activation responses in the amygdala and related brain regions. Such attenuation may be associated with a positive clinical response in depression. Bupropion XL also improved activation in the executive-function neural network. These fMRI surrogate markers offer promise for studying antidepressant and neurocognitive effects of existing and novel therapies.

Effect of mirtazapine orally disintegrating tablets on health-related quality of life in elderly depressed patients with comorbid medical disorders: a pilot study.

BACKGROUND: There is a need for additional studies on the quality of life (QOL) of elderly depressed subjects with medical comorbidity. METHOD: We conducted a 10-week, open trial of mirtazapine orally disintegrating tablets in 16 elderly subjects with major depressive disorder and one or more serious medical illnesses. Quality of life was measured by the Medical Outcomes Study Short Form-36 Health Status Survey (SF- 36). RESULTS: Treatment with mirtazapine was associated with significant reductions in clinical global impressions-severity of illness scale (CGI-S) score, the Hamilton rating scale for anxiety (HAM-A) total score, the 17-item Hamilton rating scale for depression (HAM-D) total score and the Beck depression inventory (BDI) total scores. The SF-36 "physical functioning", "role limitation physical", "vitality", "social functioning", "role limitation emotional", and "mental health" domains improved significantly. The mean mirtazapine dose at endpoint was 35 mg per day. The drug was relatively well tolerated except for three subjects who dropped out because of side effects. No drug-drug interactions or significant changes in blood pressure or heart rate occurred. CONCLUSION: Mirtazapine orally disintegrating tablets may improve depression, insomnia, anxiety, somatic symptoms, and certain quality-of-life measures in elderly depressed subjects with medical disorders. A randomized, placebo-controlled study is warranted to confirm these promising findings.

Prevalence of HIV infection in a general psychiatric outpatient population.

The prevalence of human immunodeficiency virus (HIV) infection in the general psychiatric population is unknown. The authors conducted a retrospective review of all patients evaluated through the psychiatric outpatient clinics at Duke University Medical Center from 2001 to 2004 in order to determine the prevalence of comorbid HIV infection and mental illness. HIV infection was present in 1.2% of the psychiatric outpatients, approximately four times the occurrence of HIV infection in the general adult population of the United States. The major psychiatric diagnostic categories with a high prevalence of HIV infection were substance abuse disorders (5%), personality disorders (3.1%), bipolar disorders (2.6%), and posttraumatic stress disorder (2.1%).

Cognitive function in late life depression: relationships to depression severity, cerebrovascular risk factors and processing speed.

BACKGROUND: A number of studies have examined clinical factors linked to worse neuropsychological performance in late life depression (LLD). To understand the influence of LLD on cognition, it is important to determine if deficits in a number of cognitive domains are relatively independent, or mediated by depression- related deficits in a basic domain such as processing speed. METHODS: Patients who met DSM-IV criteria for major depression (n = 155) were administered a comprehensive neuropsychological battery of tasks grouped into episodic memory, language, working memory, executive function, and processing speed domains. Multiple regression analyses were conducted to determine contributions of predictor variables to cognitive domains. RESULTS: Age, depression severity, education, race and vascular risk factors all made significant and independent contributions to one or more domains of cognitive function, with all five making independent contributions to processing speed. Age of onset made no independent contribution, after accounting for age and vascular risk factors. Of the five cognitive domains investigated, changes in processing speed were found to most fully mediate the influence of predictor variables on all other cognitive domains. CONCLUSIONS: While slowed processing speed appears to be the most core cognitive deficit in LLD, it was closely followed by executive function as a core cognitive deficit. Future research is needed to help clarify mechanisms leading to LLD- related changes in processing speed, including the potential role of white matter abnormalities.

Medical comorbidity in a bipolar outpatient clinical population.

The presence of medical illnesses among inpatients with bipolar disorder is known to complicate treatment and lengthen hospital stay. However, except for a few specific diseases, little is known about prevalence of medical illnesses in bipolar outpatients and the effect it may have on treatment. The authors sought to assess the presence of medical illnesses in a large outpatient clinical sample of bipolar patients, and the effect that medical illnesses may have on the clinical assessment and treatment of the underlying bipolar disorder. Using the Duke University Medical Center clinical database, the authors categorized the medical diagnoses of 1379 patients who were treated with bipolar disorder from 2001 to 2002 through outpatient psychiatric clinics. The prevalence of medical comorbidities was examined, as well as the effect their presence had on the clinician's assessment of disease severity and time to improvement. As expected, medical comorbidities increased with age. The most common systemic illnesses in bipolar outpatients were Endocrine and Metabolic Diseases (13.6% of the sample), Diseases of the Circulatory System (13.0%), and Diseases of the Nervous System and Sense Organs (10.7%). Significant specific diseases included cardiovascular diseases/hypertension (10.7%), COPD/asthma (6.1%), diabetes (4.3%), HIV infection (2.8%), and hepatitis C infection (1.9%). Clinicians assessed greater severity of illness in patients with increasing numbers of comorbid conditions; however, the time to recovery was not significantly effected by the presence of medical comorbidity. In conclusion, comorbid medical illnesses are common in bipolar outpatients, increasing with age. HIV rates may be increased relative to population norms. Their presence compounds the severity of the illness at time of presentation.

Methodology and preliminary results from the neurocognitive outcomes of depression in the elderly study.

A methodology is presented for following a cohort of older depressed patients to examine neurocognitive outcomes of depression. A total of 265 depressed individuals and 138 healthy, nondepressed controls age 60 and older who completed at least 1 year of follow-up data underwent periodic clinical evaluation by a geriatric psychiatrist. A subset of 141 patients and 137 controls had neuropsychological testing. A consensus panel of experts reviewed 63 depressed subjects with suspected cognitive impairment. Twenty-seven individuals in the depressed group were assigned diagnoses of dementia, including 11 with Alzheimer's disease, 8 with vascular dementia, and 8 with dementia of undetermined etiology. In addition, 25 individuals had other forms of cognitive impairment, and 11 were considered cognitively normal. Among elderly controls, 2 developed substantial cognitive impairment with clinical diagnoses of dementia. Among the depressed group, the incidence rates for dementia for this age are much higher than would be expected. These results are consistent with prior evidence linking depression and later dementia. Future studies are needed to examine neuroimaging and genetic, clinical, and social predictors of neurocognitive decline in depression.