Archives of General Psychiatry

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ISSN / EISSN : 0003990X / 15383636
Current Publisher: American Medical Association (AMA) (10.1001)
Total articles ≅ 10,674
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Rachel G. Klein, Salvatore Mannuzza, María A. Ramos Olazagasti, Erica Roizen, Jesse A. Hutchison, Erin C Lashua, F. Xavier Castellanos, Erica Roizen Belsky, Erin Lashua-Shriftman
Archives of General Psychiatry, Volume 69, pp 1295-303; doi:10.1001/archgenpsychiatry.2012.271

Abstract:CONTEXT Prospective studies of childhood attention-deficit/hyperactivity disorder (ADHD) have not extended beyond early adulthood. OBJECTIVE To examine whether children diagnosed as having ADHD at a mean age of 8 years (probands) have worse educational, occupational, economic, social, and marital outcomes and higher rates of ongoing ADHD, antisocial personality disorder (ASPD), substance use disorders (SUDs), adult-onset psychiatric disorders, psychiatric hospitalizations, and incarcerations than non-ADHD comparison participants at a mean age of 41 years. DESIGN Prospective, 33-year follow-up study, with masked clinical assessments. SETTING Research clinic. PARTICIPANTS A total of 135 white men with ADHD in childhood, free of conduct disorder, and 136 men without childhood ADHD (65.2% and 76.4% of original cohort, respectively). MAIN OUTCOME MEASURES Occupational, economic, and educational attainment; marital history; occupational and social functioning; ongoing and lifetime psychiatric disorders; psychiatric hospitalizations; and incarcerations. RESULTS Probands had significantly worse educational, occupational, economic, and social outcomes; more divorces; and higher rates of ongoing ADHD (22.2% vs 5.1%, P < .001), ASPD (16.3% vs 0%, P < .001), and SUDs (14.1% vs 5.1%, P = .01) but not more mood or anxiety disorders (P = .36 and .33) than did comparison participants. Ongoing ADHD was weakly related to ongoing SUDs (ϕ = 0.19, P = .04), as well as ASPD with SUDs (ϕ = 0.20, P = .04). During their lifetime, probands had significantly more ASPD and SUDs but not mood or anxiety disorders and more psychiatric hospitalizations and incarcerations than comparison participants. Relative to comparisons, psychiatric disorders with onsets at 21 years or older were not significantly elevated in probands. Probands without ongoing psychiatric disorders had worse social, but not occupational, functioning. CONCLUSIONS The multiple disadvantages predicted by childhood ADHD well into adulthood began in adolescence, without increased onsets of new disorders after 20 years of age. Findings highlight the importance of extended monitoring and treatment of children with ADHD.
Archives of General Psychiatry, Volume 69; doi:10.1001/archgenpsychiatry.2011.1239

Archives of General Psychiatry, Volume 69; doi:10.1001/archpsyc.69.12.1192

James C. Harris
Archives of General Psychiatry, Volume 69; doi:10.1001/archgenpsychiatry.2012.111

Michael F. Green, Gerhard Hellemann, William P. Horan, Junghee Lee, Jonathan K. Wynn
Archives of General Psychiatry, Volume 69, pp 1216-24; doi:10.1001/archgenpsychiatry.2012.652

Abstract:CONTEXT Schizophrenia remains a highly disabling disorder, but the specific determinants and pathways that lead to functional impairment are not well understood. It is not known whether these key determinants of outcome lie on 1 or multiple pathways. OBJECTIVE To evaluate theoretically based models of pathways to functional outcome starting with early visual perception. The intervening variables were previously established determinants of outcome drawn from 2 general categories: ability (ie, social cognition and functional capacity) and beliefs/motivation (ie, defeatist beliefs, expressive and experiential negative symptoms). We evaluated an integrative model in which these intervening variables formed a single pathway to poor outcome. DESIGN This was a cross-sectional study that applied structural equation modeling to evaluate the relationships among determinants of functional outcome in schizophrenia. SETTING Assessments were conducted at a Veterans Administration Medical Center. PARTICIPANTS One hundred ninety-one clinically stable outpatients with schizophrenia or schizoaffective disorder were recruited from the community. RESULTS A measurement model showed that the latent variables of perception, social cognition, and functional outcome were well reflected by their indicators. An initial untrimmed structural model with functional capacity, defeatist beliefs, and expressive and experiential negative symptoms had good model fit. A final trimmed model was a single path running from perception to ability to motivational variables to outcome. It was more parsimonious and had better fit indices than the untrimmed model. Further, it could not be improved by adding or dropping connections that would change the single path to multiple paths. The indirect effect from perception to outcome was significant. CONCLUSIONS The final structural model was a single pathway running from perception to ability to beliefs/motivation to outcome. Hence, both ability and motivation appear to be needed for community functioning and can be modeled effectively on the same pathway.
Laura A. Thomas, Melissa A. Brotman, Eli J Muhrer, Brooke H. Rosen, Brian L. Bones, Richard C. Reynolds, Christen M. DeVeney, Daniel S. Pine, Ellen Leibenluft, Eli M. Muhrer
Archives of General Psychiatry, Volume 69, pp 1257-66; doi:10.1001/archgenpsychiatry.2012.913

Abstract:CONTEXT Youth with bipolar disorder (BD) and those with severe, nonepisodic irritability (severe mood dysregulation [SMD]) exhibit amygdala dysfunction during facial emotion processing. However, studies have not compared such patients with each other and with comparison individuals in neural responsiveness to subtle changes in facial emotion; the ability to process such changes is important for social cognition. To evaluate this, we used a novel, parametrically designed faces paradigm. OBJECTIVE To compare activation in the amygdala and across the brain in BD patients, SMD patients, and healthy volunteers (HVs). DESIGN Case-control study. SETTING Government research institute. PARTICIPANTS Fifty-seven youths (19 BD, 15 SMD, and 23 HVs). MAIN OUTCOME MEASURE Blood oxygenation level-dependent data. Neutral faces were morphed with angry and happy faces in 25% intervals; static facial stimuli appeared for 3000 milliseconds. Participants performed hostility or nonemotional facial feature (ie, nose width) ratings. The slope of blood oxygenation level-dependent activity was calculated across neutral-to-angry and neutral-to-happy facial stimuli. RESULTS In HVs, but not BD or SMD participants, there was a positive association between left amygdala activity and anger on the face. In the neutral-to-happy whole-brain analysis, BD and SMD participants modulated parietal, temporal, and medial-frontal areas differently from each other and from that in HVs; with increasing facial happiness, SMD patients demonstrated increased, and BD patients decreased, activity in the parietal, temporal, and frontal regions. CONCLUSIONS Youth with BD or SMD differ from HVs in modulation of amygdala activity in response to small changes in facial anger displays. In contrast, individuals with BD or SMD show distinct perturbations in regions mediating attention and face processing in association with changes in the emotional intensity of facial happiness displays. These findings demonstrate similarities and differences in the neural correlates of facial emotion processing in BD and SMD, suggesting that these distinct clinical presentations may reflect differing dysfunctions along a mood disorders spectrum.
Theresa L. Osypuk, Eric J Tchetgen Tchetgen, Dolores Acevedo-Garcia, Felton James Earls, Alisa Lincoln, Nicole M. Schmidt, M. Maria Glymour, Eric Tchetgen Tchetgen
Archives of General Psychiatry, Volume 69, pp 1284-94; doi:10.1001/archgenpsychiatry.2012.449

Abstract:CONTEXT Extensive observational evidence indicates that youth in high-poverty neighborhoods exhibit poor mental health, although not all children may be affected similarly. OBJECTIVE To use experimental evidence to assess whether gender and family health problems modify the mental health effects of moving from high- to low-poverty neighborhoods. DESIGN Randomized controlled trial. SETTING Volunteer low-income families in public housing in 5 US cities between 1994-1997. PARTICIPANTS We analyze 4- to 7-year outcomes in youth aged 12 to 19 years (n = 2829, 89% effective response rate) in the Moving to Opportunity Study. INTERVENTION Families were randomized to remain in public housing (control group) or to receive government-funded rental subsidies to move into private apartments (experimental group). Intention-to-treat analyses included intervention interactions by gender and health vulnerability (defined as prerandomization health/developmental limitations or disabilities in family members). MAIN OUTCOME MEASURES Past-year psychological distress (Kessler 6 scale [K6]) and the Behavioral Problems Index (BPI). Supplemental analyses used past-year major depressive disorder (MDD). RESULTS Male gender (P = .02) and family health vulnerability (P = .002) significantly adversely modified the intervention effect on K6 scores; male gender (P = .01), but not health vulnerability (P = .17), significantly adversely modified the intervention effect on the BPI. Girls without baseline health vulnerabilities were the only subgroup to benefit on any outcome (K6: β = -0.21; 95% CI, -0.34 to -0.07; P = .003; MDD: odds ratio = 0.42; 95% CI, 0.20 to 0.85; P = .02). For boys with health vulnerabilities, intervention was associated with worse K6 (β = 0.26; 95% CI, 0.09 to 0.44; P = .003) and BPI (β = 0.24; 95% CI, 0.09 to 0.40; P = .002) values. Neither girls with health vulnerability nor boys without health vulnerability experienced intervention benefits. Adherence-adjusted instrumental variable analysis found intervention effects twice as large. Patterns were similar for MDD, but estimates were imprecise owing to low prevalence. CONCLUSIONS Although some girls benefited, boys and adolescents from families with baseline health problems did not experience mental health benefits from housing mobility policies and may need additional program supports.
Carl Ernst, Christian R. Marshall, Yiping Shen, Kay Metcalfe, Jill Rosenfeld, Jennelle C. Hodge, Alcy Torres, Ian Blumenthal, Colby Chiang, Vamsee Pillalamarri, et al.
Archives of General Psychiatry, Volume 69, pp 1238-1246; doi:10.1001/archgenpsychiatry.2012.660

Abstract:Brain-derived neurotrophic factor (BDNF) is suspected of being a causative factor in psychiatric disorders based on case reports or studies involving large structural anomalies. To determine the involvement of BDNF in human psychopathology Case- Control study Microarray-based comparative genomic hybridization (aCGH) data from seven molecular diagnostic centers including 38, 550 affected subjects and 28, 705 unaffected subjects. Subjects referred to diagnostic screening centers for aCGH for physical or cognitive impairment. Genomic copy number gains and losses We report five individuals with psychopathology and genomic deletion of a critical region including BDNF. The defined critical region was never disrupted in control subjects or diagnostic cases without developmental abnormalities. Hemizygosity of the BDNF region contributes to variable psychiatric phenotypes including anxiety, behavioral, and mood disorders.
Ian Kelleher, Fionnuala Lynch, Michelle Harley, Charlene Molloy, Sarah Roddy, Carol Fitzpatrick, Mary Cannon
Archives of General Psychiatry, Volume 69; doi:10.1001/archgenpsychiatry.2012.164

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In Kyoon Lyoo, Sujung Yoon, Alan M. Jacobson, Jaeuk Hwang, Gail Musen, Jieun E. Kim, Donald C. Simonson, Sujin Bae, Nicolas Bolo, Dajung J. Kim, et al.
Archives of General Psychiatry, Volume 69, pp 1267-76; doi:10.1001/archgenpsychiatry.2012.543

Abstract:CONTEXT Neural substrates that may be responsible for the high prevalence of depression in type 1 diabetes mellitus (T1DM) have not yet been elucidated. OBJECTIVE To investigate neuroanatomic correlates of depression in T1DM. DESIGN Case-control study using high-resolution brain magnetic resonance images. SETTINGS Joslin Diabetes Center and McLean Hospital, Massachusetts, and Seoul National University Hospital, South Korea. PARTICIPANTS A total of 125 patients with T1DM (44 subjects with ≥1 previous depressive episodes [T1DM-depression group] and 81 subjects who had never experienced depressive episodes [T1DM-only group]), 23 subjects without T1DM but with 1 or more previous depressive episodes (depression group), and 38 healthy subjects (control group). MAIN OUTCOME MEASURES Spatial distributions of cortical thickness for each diagnostic group were compared with the control group using a surface-based approach. Among patients with T1DM, associations between metabolic control measures and cortical thickness deficits were examined. RESULTS Thickness reduction in the bilateral superior prefrontal cortical regions was observed in the T1DM-depression, T1DM-only, and depression groups relative to the control group at corrected P < .01. Conjunction analyses demonstrated that thickness reductions related to the influence of T1DM and those related to past depressive episode influence were observed primarily in the superior prefrontal cortical region. Long-term glycemic control levels were associated with superior prefrontal cortical deficits in patients with T1DM (β = -0.19, P = .02). CONCLUSIONS This study provides evidence that thickness reduction of prefrontal cortical regions in patients with T1DM, as modified by long-term glycemic control, could contribute to the increased risk for comorbid depression.