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Definition and description of schizophrenia in the DSM-5

Tandon, Rajiv; Gaebel, Wolfgang; Barch, Deanna M; Bustillo, Juan; Gur, Raquel E; Heckers, Stephan; Malaspina, Dolores; Owen, Michael J; Schultz, Susan; Tsuang, Ming; Van Os, Jim; Carpenter, William
Although dementia praecox or schizophrenia has been considered a unique disease for over a century, its definitions and boundaries have changed over this period and its etiology and pathophysiology remain elusive. Despite changing definitions, DSM-IV schizophrenia is reliably diagnosed, has fair validity and conveys useful clinical information. Therefore, the essence of the broad DSM-IV definition of schizophrenia is retained in DSM-5. The clinical manifestations are extremely diverse, however, with this heterogeneity being poorly explained by the DSM-IV clinical subtypes and course specifiers. Additionally, the boundaries of schizophrenia are imprecisely demarcated from schizoaffective disorder and other diagnostic categories and its special emphasis on Schneiderian "first-rank" symptoms appears misplaced. Changes in the definition of schizophrenia in DSM-5 seek to address these shortcomings and incorporate the new information about the nature of the disorder accumulated over the past two decades. Specific changes in its definition include elimination of the classic subtypes, addition of unique psychopathological dimensions, clarification of cross-sectional and longitudinal course specifiers, elimination of special treatment of Schneiderian 'first-rank symptoms', better delineation of schizophrenia from schizoaffective disorder, and clarification of the relationship of schizophrenia to catatonia. These changes should improve diagnosis and characterization of individuals with schizophrenia and facilitate measurement-based treatment and concurrently provide a more useful platform for research that will elucidate its nature and permit a more precise future delineation of the 'schizophrenias'.
PMID: 23800613
ISSN: 1573-2509
CID: 575812

Left ventricular twist and untwist rate provide reliable measures of ventricular function in myocardial ischemia and a wide range of hemodynamic states

Zhou, Wei; Benharash, Peyman; Ho, Jonathan; Ko, Yoshihiro; Patel, Nikhil A; Mahajan, Aman
Although rotational parameters by speckle tracking echocardiography (STE) have been previously compared to sonomicrometry and cardiac magnetic resonance imaging, few have examined the relationship between left ventricular (LV) rotational mechanics and intraventricular measures of load-independent contractility, LV stiffness, or ventriculoarterial coupling. The aim of this study was to compare the changes in LV rotational indices to intraventricular pressure-volume (PV) relationships under a range of inotropic states induced by pharmacological interventions, acute ischemia, and changes in preload. In nine pigs, simultaneous echocardiographic imaging and LVPV measurements were performed during pharmacologically induced high or low inotropy and during acute ischemia by ligation of the left anterior descending coronary artery (LAD). Maximal ventricular elastance (Emax), arterial elastance (Ea), ventricular-arterial coupling (Emax/Ea), dP/dt, tau, and other hemodynamic parameters were determined. Dobutamine and esmolol infusions led to inversely correlated changes in hemodynamic measurements of LV function. Apical but not basal rotation and diastolic rotation rate were decreased by esmolol and increased by dobutamine. The LV twist correlates well with Emax (r = 0.83) and Emax/Ea (r = 0.80). Apical diastolic rotation rate also correlates with dP/dtmin (r = -0.63), Ï„ (r = -0.81), and LV stiffness (r = -0.52). LAD ligation decreased systolic and diastolic LV rotation in apical (P < 0.05), but not basal myocardium. Occlusion of the inferior vena cava, to reduce preload, increased apical rotation in systole and diastole. LV rotational parameters measured by STE provide quantitative and reproducible indices of global LV systolic and diastolic function during acute changes in hemodynamics.
PMCID:3841045
PMID: 24303181
ISSN: 2051-817x
CID: 4292962

Patterns of out-of-home placement decision-making in child welfare

Chor, Ka Ho Brian; McClelland, Gary M; Weiner, Dana A; Jordan, Neil; Lyons, John S
Out-of-home placement decision-making in child welfare is founded on the best interest of the child in the least restrictive setting. After a child is removed from home, however, little is known about the mechanism of placement decision-making. This study aims to systematically examine the patterns of out-of-home placement decisions made in a state's child welfare system by comparing two models of placement decision-making: a multidisciplinary team decision-making model and a clinically based decision support algorithm. Based on records of 7816 placement decisions representing 6096 children over a 4-year period, hierarchical log-linear modeling characterized concordance or agreement, and discordance or disagreement when comparing the two models and accounting for age-appropriate placement options. Children aged below 16 had an overall concordance rate of 55.7%, most apparent in the least restrictive (20.4%) and the most restrictive placement (18.4%). Older youth showed greater discordant distributions (62.9%). Log-linear analysis confirmed the overall robustness of concordance (odd ratios [ORs] range: 2.9-442.0), though discordance was most evident from small deviations from the decision support algorithm, such as one-level under-placement in group home (OR=5.3) and one-level over-placement in residential treatment center (OR=4.8). Concordance should be further explored using child-level clinical and placement stability outcomes. Discordance might be explained by dynamic factors such as availability of placements, caregiver preferences, or policy changes and could be justified by positive child-level outcomes. Empirical placement decision-making is critical to a child's journey in child welfare and should be continuously improved to effect positive child welfare outcomes.
PMID: 23768934
ISSN: 0145-2134
CID: 911472

Future research directions in sleep and ADHD: report of a consensus working group

Owens, Judith; Gruber, Reut; Brown, Thomas; Corkum, Penny; Cortese, Samuele; O'Brien, Louise; Stein, Mark; Weiss, Margaret
OBJECTIVE: To explore relationships between basic and translational science research regarding sleep and ADHD in children. METHOD: A multidisciplinary group of experts in pediatric sleep medicine and ADHD convened in November 2010 to summarize the current literature, delineate knowledge gaps, and formulate recommendations regarding future research directions and priorities. RESULTS: Six major research areas of interest were identified: (a) brain centers regulating sleep, arousal, and attention; (b) neurotransmitter systems involved in both sleep and attention regulation; (c) alterations of neural systems regulating sleep in ADHD; (d) phenotypic similarities between behavioral, mood, and cognitive manifestations of insufficient/disrupted sleep and ADHD; (e) hypoarousal and sleepiness in ADHD; and (f) external sleep-wake signals that affect sleep regulation in ADHD. CONCLUSION: An enhanced understanding of the complex mechanisms regulating sleep promotion, wakefulness, and attention may contribute to new insights regarding the core impairments in ADHD and lead to the development of new therapies.
PMID: 22982880
ISSN: 1087-0547
CID: 703822

Development and Preliminary Evaluation of an Integrated Treatment Targeting Parenting and Depressive Symptoms in Mothers of Children With Attention-Deficit/Hyperactivity Disorder

Chronis-Tuscano, Andrea; Clarke, Tana L; O'Brien, Kelly A; Raggi, Veronica L; Diaz, Yamalis; Mintz, Abigail D; Rooney, Mary E; Knight, Laura A; Seymour, Karen E; Thomas, Sharon R; Seeley, John; Kosty, Derek; Lewinsohn, Peter
Objective: More than 50% of mothers of children with attention-deficit/hyperactivity disorder (ADHD) have a lifetime history of major depressive disorder (MDD). Maternal depressive symptoms are associated with impaired parenting and predict adverse developmental and treatment outcomes for children with ADHD. For these reasons, we developed and examined the preliminary efficacy of an integrated treatment targeting parenting and depressive symptoms for mothers of children with ADHD. This integrated intervention incorporated elements of 2 evidence-based treatments: behavioral parent training (BPT) and cognitive behavioral depression treatment. Method: Ninety-eight mothers with at least mild depressive symptoms were randomized to receive either standard BPT (n = 51) or the integrated parenting intervention for ADHD (IPI-A; n = 47). Participants were assessed at baseline, posttreatment, and 3- to 6-month follow-up on measures of (a) self-reported maternal depressive symptoms, (b) observed positive and negative parenting, and (c) observed and mother-reported child disruptive behavior and mother-reported child and family impairment. Results: The IPI-A produced effects of small to moderate magnitude relative to BPT on maternal depressive symptoms, observed negative parenting, observed child deviance, and child impairment at posttreatment and on maternal depressive symptoms, child disruptive behavior, child impairment and family functioning at follow-up. Contrary to expectations, the BPT group demonstrated moderate to large effects relative to IPI-A on observed positive parenting at follow-up. Conclusions: This treatment development study provides encouraging preliminary support for the integrated intervention targeting parenting and depressive symptoms in mothers of children with ADHD. Future studies should examine whether this integrated intervention improves long-term developmental outcomes for children with ADHD. (PsycINFO Database Record (c) 2013 APA, all rights reserved).
PMCID:3783529
PMID: 23477479
ISSN: 0022-006x
CID: 316562

Neurobiology of secure infant attachment and attachment despite adversity: a mouse model

Roth, T L; Raineki, C; Salstein, L; Perry, R; Sullivan-Wilson, T A; Sloan, A; Lalji, B; Hammock, E; Wilson, D A; Levitt, P; Okutani, F; Kaba, H; Sullivan, R M
Attachment to an abusive caregiver has wide phylogenetic representation, suggesting that animal models are useful in understanding the neural basis underlying this phenomenon and subsequent behavioral outcomes. We previously developed a rat model, in which we use classical conditioning to parallel learning processes evoked during secure attachment (odor-stroke, with stroke mimicking tactile stimulation from the caregiver) or attachment despite adversity (odor-shock, with shock mimicking maltreatment). Here we extend this model to mice. We conditioned infant mice (postnatal day (PN) 7-9 or 13-14) with presentations of peppermint odor and either stroking or shock. We used (14) C 2-deoxyglucose (2-DG) to assess olfactory bulb and amygdala metabolic changes following learning. PN7-9 mice learned to prefer an odor following either odor-stroke or shock conditioning, whereas odor-shock conditioning at PN13-14 resulted in aversion/fear learning. 2-DG data indicated enhanced bulbar activity in PN7-9 preference learning, whereas significant amygdala activity was present following aversion learning at PN13-14. Overall, the mouse results parallel behavioral and neural results in the rat model of attachment, and provide the foundation for the use of transgenic and knockout models to assess the impact of both genetic (biological vulnerabilities) and environmental factors (abusive) on attachment-related behaviors and behavioral development.
PMCID:4047794
PMID: 23927771
ISSN: 1601-183X
CID: 2349392

High and low roads to odor valence? A choice response-time study

Olofsson, Jonas K; Bowman, Nicholas E; Gottfried, Jay A
Valence and edibility are two important features of olfactory perception, but it remains unclear how they are read out from an olfactory input. For a given odor object (e.g., the smell of rose or garlic), does perceptual identification of that object necessarily precede retrieval of information about its valence and edibility, or alternatively, are these processes independent? In the present study, we studied rapid, binary perceptual decisions regarding odor detection, object identity, valence, and edibility for a set of common odors. We found that decisions regarding odor-object identity were faster than decisions regarding odor valence or edibility, but slower than detection. Mediation analysis revealed that odor valence and edibility decision response times were predicted by a model in which odor-object identity served as a mediator along the perceptual pathway from detection to both valence and edibility. According to this model, odor valence is determined through both a "low road" that bypasses odor objects and a "high road" that utilizes odor-object information. Edibility evaluations are constrained to processing via the high road. The results outline a novel causal framework that explains how major perceptual features might be rapidly extracted from odors through engagement of odor objects early in the processing stream.
PMCID:3962799
PMID: 23875569
ISSN: 1939-1277
CID: 1936012

Serum perfluorooctanoic acid and perfluorooctane sulfonate concentrations in relation to birth outcomes in the Mid-Ohio Valley, 2005-2010

Darrow, Lyndsey A; Stein, Cheryl R; Steenland, Kyle
BACKGROUND:Previous research suggests perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) may be associated with adverse pregnancy outcomes. OBJECTIVE:We conducted a population-based study of PFOA and PFOS and birth outcomes from 2005 through 2010 in a Mid-Ohio Valley community exposed to high levels of PFOA through drinking-water contamination. METHODS:Women provided serum for PFOA and PFOS measurement in 2005-2006 and reported reproductive histories in subsequent follow-up interviews. Reported singleton live births among 1,330 women after 1 January 2005 were linked to birth records (n = 1,630) to identify the outcomes of preterm birth (< 37 weeks gestation), pregnancy-induced hypertension, low birth weight (< 2,500 g), and birth weight (grams) among full-term infants. RESULTS:We observed little or no evidence of association between maternal serum PFOA or PFOS and preterm birth (n = 158) or low birth weight (n = 88). Serum PFOA and PFOS were both positively associated with pregnancy-induced hypertension (n = 106), with adjusted odds ratios (ORs) per log unit increase in PFOA and PFOS of 1.27 (95% CI: 1.05, 1.55) and 1.47 (95% CI: 1.06, 2.04), respectively, but associations did not increase monotonically when categorized by quintiles. Results of subanalyses restricted to pregnancies conceived after blood collection were consistent with the main analyses. There was suggestion of a modest negative association between PFOS and birth weight in full-term infants (-29 g per log unit increase; 95% CI: -66, 7), which became stronger when restricted to births conceived after the blood sample collection (-49 g per log unit increase; 95% CI: -90, -8). CONCLUSION/CONCLUSIONS:Results provide some evidence of positive associations between measured serum perfluorinated compounds and pregnancy-induced hypertension and a negative association between PFOS and birth weight among full-term infants.
PMCID:3801459
PMID: 23838280
ISSN: 1552-9924
CID: 3143252

ADHD Preschoolers With and Without ODD: Do They Act Differently Depending On Degree of Task Engagement/Reward?

Gopin, CB; Berwid, O; Marks, DJ; Mlodnicka, A; Halperin, JM
Objective: To examine the impact of reinforcement on reaction time (RT) and RT variability (RT standard deviation [RTSD]) in preschoolers with ADHD with and without oppositional defiant disorder (ODD), and a typically developing (TD) comparison group. Method: Participants were administered a computerized task consisting of two conditions: simple RT (SRT) and reinforced SRT (SRTr). Data were analyzed using two-way (Group x Condition) mixed ANOVAs and followed-up using pairwise comparisons. Results: RTs were significantly shorter and less variable during the SRTr than the SRT condition. A significant Group x Condition interaction was observed for RTSD (F= 3.38, p < .05); post hoc analyses indicated that the RTSD of the ADHD + ODD group was significantly more variable than that of the TD group during the SRT condition (F = 4.81, p < .05). However, their RTSD was statistically indistinguishable from the other groups during the SRTr condition. Conclusion: Preschoolers who are oppositional/defiant and hyperactive are the most responsive to feedback/reward. (J. of Att. Dis. 2011; XX(X) 1-XX).
PMID: 22323121
ISSN: 1087-0547
CID: 164593

An inventory of European data sources for the long-term safety evaluation of methylphenidate

Murray, Macey L; Insuk, Suppachai; Banaschewski, Tobias; Neubert, Antje C; McCarthy, Suzanne; Buitelaar, Jan K; Coghill, David; Dittmann, Ralf W; Konrad, Kerstin; Panei, Pietro; Rosenthal, Eric; Sonuga-Barke, Edmund J; Wong, Ian C K
To compile an inventory of European healthcare databases with potential to study long-term effects of methylphenidate (MPH) in patients with attention deficit hyperactivity disorder (ADHD). Potential databases were identified through expert opinion, the website of the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance, and literature search. An online survey was conducted among database providers/coordinators to ascertain the databases' appropriateness for inclusion into the inventory. It included questions about database characteristics, sample size, availability of information on drug exposure, clinical data and accessibility. Forty-two databases from 11 countries were identified and their coordinators invited to participate; responses were obtained for 22 (52.4 %) databases of which 15 record ADHD diagnoses. Eleven had sufficient data on ADHD diagnosis, drug exposure, and at least one type of outcome information (symptoms/clinical events, weight, height, blood pressure, heart rate) to assess MPH safety. These were Aarhus University Prescription Database, Danish National Birth Cohort (Denmark); German Health Interview and Examination Survey for Children and Adolescents; Health Search Database Thales, Italian ADHD Register, Lombardy Region ADHD Database (Italy); Avon Longitudinal Study of Parents and Children, General Practice Research Database, The Health Improvement Network, QResearch (UK) and IMS Disease Analyzer (UK, Germany, France). Of the 20 databases with no responses, information on seven from publications and/or websites was obtained; Pedianet and the Integrated Primary Care Information database were considered suitable. Many European healthcare databases can be used for multinational long-term safety studies of MPH. Methodological research is underway to investigate the feasibility of their pooling and analysis.
PMCID:3830128
PMID: 23508655
ISSN: 1018-8827
CID: 903992