The neurobehavioral cognitive status examination: Psychometric properties in use with psychiatric inpatients

The present investigation sought to enhance clinical utility of the Neuro behavioral Cognitive Status Examination (NCSE; Northern California Neurobehavioral Group, Inc.) by providing reference scores for an inpatient psychiatric sample and assessing construct validity. A total of 866 patients (aged 15-92 years) received an NCSE 2 to 4 days after admission. Examination of means, standard deviations, zscores, and percent who passed each screening item revealed consistently poorer performance for psychiatric patients relative to the original normative sample. Pearson product-moment correlations between age and each NCSE subtest similarly yielded significant negative correlations, particularly on tests predicted to be differentially sensitive to aging. Intercorrelations between subtests, however, failed to yield expected patterns of performance. We conclude that the NCSE provides a moderately valid screening instrument for cognitive impairment.     

Construct validity of a new computer-assisted cognitive neuromotor assessment battery in normal and inpatient psychiatric samples

The construct validity of a computer-assisted battery of neuropsychological tests (CNT) was explored with psychiatric inpatients and normal volunteers. A principal components analysis of inpatient scores revealed simple reaction time, response accuracy, visuomotor skill, and complex processing and memory components. A similar factorial structure was found in normal subjects. However, complex processing and memory measures emerged as separate vigilance and memory components in volunteers. CNT tasks were correlated with nine subtests of the Neurobehavioral Cognitive Status Examination (NCSE). Simple reaction time, and complex processing and memory measures discriminated impaired from nonimpaired inpatients as defined by the NCSE. Recommendations for research on CNT, and computer-assisted tests in general, are made.     

ENIGMA-DTI: Translating reproducible white matter deficits into personalized vulnerability metrics in cross-diagnostic psychiatric research

The ENIGMA-DTI (diffusion tensor imaging) workgroup supports analyses that examine the effects of psychiatric, neurological, and developmental disorders on the white matter pathways of the human brain, as well as the effects of normal variation and its genetic associations. The seven ENIGMA disorder-oriented working groups used the ENIGMA-DTI workflow to derive patterns of deficits using coherent and coordinated analyses that model the disease effects across cohorts worldwide. This yielded the largest studies detailing patterns of white matter deficits in schizophrenia spectrum disorder (SSD), bipolar disorder (BD), major depressive disorder (MDD), obsessive–compulsive disorder (OCD), posttraumatic stress disorder (PTSD), traumatic brain injury (TBI), and 22q11 deletion syndrome. These deficit patterns are informative of the underlying neurobiology and reproducible in independent cohorts. We reviewed these findings, demonstrated their reproducibility in independent cohorts, and compared the deficit patterns across illnesses. We discussed translating ENIGMA-defined deficit patterns on the level of individual subjects using a metric called the regional vulnerability index (RVI), a correlation of an individual's brain metrics with the expected pattern for a disorder. We discussed the similarity in white matter deficit patterns among SSD, BD, MDD, and OCD and provided a rationale for using this index in cross-diagnostic neuropsychiatric research. We also discussed the difference in deficit patterns between idiopathic schizophrenia and 22q11 deletion syndrome, which is used as a developmental and genetic model of schizophrenia. Together, these findings highlight the importance of collaborative large-scale research to provide robust and reproducible effects that offer insights into individual vulnerability and cross-diagnosis features.     

Two novel loci,COBL and SLC10A2, for Alzheimer's disease in African Americans

Introduction

African Americans' (AAs) late-onset Alzheimer's disease (LOAD) genetic risk profile is incompletely understood. Including clinical covariates in genetic analyses using informed conditioning might improve study power.

Dopamine and serotonin receptor binding and antipsychotic efficacy.

The relationship between clinically effective antipsychotic drug dosage and binding affinity to cloned dopamine (DA) and serotonin receptor subtypes was analyzed in an effort to elucidate the contribution of individual receptor subtypes to medication response. Clinically effective dose and binding affinity to D(2) DA receptor were modestly correlated for typical antipsychotic medications (r=0.54, p=0.046), but surprisingly were not correlated for atypical antipsychotics (r=0.41, p=0.31). For typical antipsychotics, a more robust inverse relationship was observed between medication dose and 5-HT(2C) affinity (r=-0.68, p=0.021). The strongest correlation for typical antipsychotics was observed between drug dosage and 5-HT(2C)/D(2) binding affinity ratio (r=-0.81, p=0.003). For atypical antipsychotics, no significant correlations were identified between medication dosage and 5-HT(2C), 5-HT(2A), 5-HT(2C)/D(2), or 5-HT(2A)/D(2) receptor-binding affinities. In contrast, atypical antipsychotic medication dosage was highly correlated with the ratios of D(2) (5-HT(2A)/5-HT(1A)) (r=0.80, p=0.031), and D(2) (5-HT(2C)/5-HT(1A)) (r=0.78, p=0.038) binding affinities. These observations demonstrate an interaction between D(2) and 5-HT(2C) receptor effects contributing to positive symptom response for typical antipsychotic medications, suggesting that signaling through 5-HT(2C) receptors interacts with and improves antipsychotic effects achieved via D(2) receptor blockade. This analysis also demonstrates that, in contrast to typical antipsychotics, therapeutic effects of atypical antipsychotic medications are determined by opposing interactions among three different domains: (1) increasing D(2) DA receptor-binding affinity enhances antipsychotic potency. (2) Increasing 5-HT(2C) and 5-HT(2A) receptor-binding affinities also facilitate antipsychotic efficacy. (3) Increasing 5-HT(1A) receptor-binding affinity, in contrast, reduces antipsychotic efficacy.     

Randomized trial of sertraline in patients with unexplained chest pain of noncardiac origin

BACKGROUND: Between 10% and 30% of patients with symptoms similar to angina and sufficient to justify cardiac catheterization are found to have normal coronary angiograms. Treatment of patients with chest pain with no apparent cardiac cause is a major clinical problem. Our hypothesis was that sertraline would reduce the severity of pain in patients with chest pain of noncardiac origin. METHODS AND RESULTS: This was a single-site, double-blind, placebo-controlled study of the efficacy, tolerability, and safety of sertraline in the treatment of noncardiac chest pain in outpatients. Thirty patients were enrolled in the study. After 1 week of single-blind placebo washout, patients were randomly assigned in a double-blind fashion either to drug or placebo. The Beck Depression Inventory was administered at baseline and at completion of study. Daily pain diaries (visual analogue scale, rating pain on a scale of 1 to 10) were selfadministered and evaluated at baseline and at follow-up visits. Statistical measures were performed with an intention-to-treat approach. Patients who received sertraline over the course of the study showed a statistically significant reduction in pain compared with those who were receiving placebo. CONCLUSIONS: The use of sertraline in patients with noncardiac chest pain produced clinically significant reduction of daily pain. These results suggest the need for further studies of the efficacy and tolerability of sertraline and other selective serotonin reuptake inhibitors in the long-term management of noncardiac chest pain.     

Carcinoma of the cervix: an analysis of prognostic factors, treatment and patterns of failure following Wertheims hysterectomy

A clinicopathologic analysis of 70 patients treated by radiotherapy and/or chemotherapy following primary radical surgery has been undertaken. Clinical stage at presentation was IB (58 patients) and IIA (12 patients). Thirty-five patients (50%) had squamous carcinoma, 23 (33%) had adenosquamous carcinoma, 9 (13%) had adenocarcinoma and 3 (4%) had an undifferentiated neoplasm. The reasons for further treatment were: (i) pelvic lymph node metastases (PLNM), 35 (50%); (ii) inadequate central clearance (ICC), 13 (18%); (iii) recurrent disease (RD), 17 (24%); (iv) others, 5 (8%) cases. Sixty-seven patients had radiotherapy, one of whom also received adjuvant chemotherapy, three patients had chemotherapy alone, and 12 patients received chemotherapy for recurrence following radiotherapy. The 5-year survival in the above referral groups were: (i) 66%; (ii) 62%; (iii) 12%. The site of relapse following treatment was primarily pelvic in groups 2 (ICC) and 3 (RD) and extrapelvic in group 1 (PLNM). Of the histologic parameters studied the only factor of statistical significance in predicting outcome in this group who are recognized to have a generally poor prognosis was the presence of parametrial extension ( P = 0.0066). Six cases (9%) developed complications following therapy, lymphoedema being the most common (66%).     

Early pregnancy complications: endovaginal sonographic findings correlated with human chorionic gonadotropin levels

Endovaginal sonography results were compared with quantitatively determined human chorionic gonadotropin (hCG) levels in 84 women referred for early pregnancy complications. Of the 27 with normal intrauterine pregnancies, an intrauterine gestational sac was prospectively identified in one of five cases (20%) in which hCG levels were below 500 IU/L (Second International Standard), four of five (80%) with hCG levels of 500-1,000 IU/L, and all 17 with hCG levels above 1,000 IU/L. In comparison, 17 of the 26 women with ectopic pregnancies (65%) had hCG levels greater than 1,000 IU/L, and none of the 26 had an intrauterine gestational sac. Endovaginal sonography demonstrated an adnexal mass and/or a gestational sac-like structure in 16 of the 17 cases (94%) in which hCG levels were above 1,000 IU/L, compared with only three of the nine (33%) with lower hCG levels (P less than .01). These findings indicate that an intrauterine gestational sac should be normally visualized with endovaginal sonography when the hCG level exceeds 1,000 IU/L, and that visualization of an extrauterine gestational sac and/or adnexal mass is significantly more likely in ectopic pregnancies when the hCG level exceeds 1,000 IU/L.     

Response to 35% CO2 in patients with chest pain and angiographically normal coronary arteries.

OBJECTIVES: Several interview studies have suggested that panic disorder (PD) exists in patients with angiographically normal coronary arteries (NCA). Interview studies require corroboration by other studies in order to validate them. The purpose of this study is to test whether response to the inhalation of 35% CO2 reliably discriminates between PD and non-panic disorder patients in this population. METHOD: Three groups were studied: six with NCA and PD, five with NCA and no PD, and ten in the control group. All subjects breathed room air, then 35% CO2 in a single-blind fashion. Each completed the Acute Panic Inventory (API) before and during the procedure. RESULTS: The NCA-panic group scored significantly higher than the other two groups on the Acute Panic Inventory from baseline to post-inhalation. CONCLUSION: Despite several methodological limitations including a relatively small number people in each cells, 35% CO2 was shown to trigger more intense responses in panic patients, thus helping to validate the interview findings.