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Here/In This Issue and There/Abstract Thinking: Neurosciences and (Child) Psychiatry

Cortese, Samuele
PMID: 26210326
ISSN: 1527-5418
CID: 1698242

Increased Functional Connectivity Between Subcortical and Cortical Resting-State Networks in Autism Spectrum Disorder

Cerliani, Leonardo; Mennes, Maarten; Thomas, Rajat M; Di Martino, Adriana; Thioux, Marc; Keysers, Christian
IMPORTANCE: Individuals with autism spectrum disorder (ASD) exhibit severe difficulties in social interaction, motor coordination, behavioral flexibility, and atypical sensory processing, with considerable interindividual variability. This heterogeneous set of symptoms recently led to investigating the presence of abnormalities in the interaction across large-scale brain networks. To date, studies have focused either on constrained sets of brain regions or whole-brain analysis, rather than focusing on the interaction between brain networks. OBJECTIVES: To compare the intrinsic functional connectivity between brain networks in a large sample of individuals with ASD and typically developing control subjects and to estimate to what extent group differences would predict autistic traits and reflect different developmental trajectories. DESIGN, SETTING, AND PARTICIPANTS: We studied 166 male individuals (mean age, 17.6 years; age range, 7-50 years) diagnosed as having DSM-IV-TR autism or Asperger syndrome and 193 typical developing male individuals (mean age, 16.9 years; age range, 6.5-39.4 years) using resting-state functional magnetic resonance imaging (MRI). Participants were matched for age, IQ, head motion, and eye status (open or closed) in the MRI scanner. We analyzed data from the Autism Brain Imaging Data Exchange (ABIDE), an aggregated MRI data set from 17 centers, made public in August 2012. MAIN OUTCOMES AND MEASURES: We estimated correlations between time courses of brain networks extracted using a data-driven method (independent component analysis). Subsequently, we associated estimates of interaction strength between networks with age and autistic traits indexed by the Social Responsiveness Scale. RESULTS: Relative to typically developing control participants, individuals with ASD showed increased functional connectivity between primary sensory networks and subcortical networks (thalamus and basal ganglia) (all t >/= 3.13, P < .001 corrected). The strength of such connections was associated with the severity of autistic traits in the ASD group (all r >/= 0.21, P < .0067 corrected). In addition, subcortico-cortical interaction decreased with age in the entire sample (all r
PMCID:5008437
PMID: 26061743
ISSN: 2168-6238
CID: 1709712

Bipolar Disorder and ADHD: Comorbidity and Diagnostic Distinctions

Marangoni, Ciro; De Chiara, Lavinia; Faedda, Gianni L
Attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BD) are neurodevelopmental disorders with onset in childhood and early adolescence, and common persistence in adulthood. Both disorders are often undiagnosed, misdiagnosed, and sometimes over diagnosed, leading to high rates of morbidity and disability. The differentiation of these conditions is based on their clinical features, comorbidity, psychiatric family history course of illness, and response to treatment. We review recent relevant findings and highlight epidemiological, clinical, family history, course, and treatment-response differences that can aid the differential diagnosis of these conditions in an outpatient pediatric setting.
PMID: 26084666
ISSN: 1535-1645
CID: 1632342

Adverse Childhood Experiences and Mental Health, Chronic Medical Conditions, and Development in Young Children

Kerker, Bonnie D; Zhang, Jinjin; Nadeem, Erum; Stein, Ruth E K; Hurlburt, Michael S; Heneghan, Amy; Landsverk, John; McCue Horwitz, Sarah
OBJECTIVE: To determine the relationships between adverse childhood experiences (ACEs) and mental health, chronic medical conditions, and social development among young children in the child welfare system. METHODS: This cross-sectional study used a nationally representative sample of children investigated by child welfare (National Survey of Child and Adolescent Well-Being II) from 2008 to 2009. Our analysis included caregiver interviews and caseworker reports about children aged 18 to 71 months who were not in out-of-home care (n = 912). We examined the associations between ACEs and mental health (measured by the Child Behavior Checklist [CBCL]), reported chronic medical conditions, and social development (measured by the Vineland Socialization Scale) in bivariate and multivariate analyses. RESULTS: Nearly all children (98.1%) were reported to have had an ACE in their lifetime; the average number of ACEs was 3.6. For every additional reported ACE, there was a 32% increased odds of having a problem score on the CBCL (odds ratio [OR] 1.32, 95% confidence interval [CI] 1.14, 1.53) and a 21% increased odds of having a chronic medical condition (OR 1.21, 95% CI 1.05, 1.40). Among children aged 36 to 71 months, for every additional reported ACE, there was a 77% increased odds of a low Vineland Socialization score (OR 1.77, 95% CI 1.12, 2.78). CONCLUSIONS: ACEs were associated with poor early childhood mental health and chronic medical conditions, and, among children aged 3 to 5, social development. Efforts are needed to examine whether providing early intervention to families with multiple stressors mitigates the impact of ACEs on children's outcomes.
PMCID:4562867
PMID: 26183001
ISSN: 1876-2867
CID: 1669022

High glycemic index diet as a risk factor for depression: analyses from the Women's Health Initiative

Gangwisch, James E; Hale, Lauren; Garcia, Lorena; Malaspina, Dolores; Opler, Mark G; Payne, Martha E; Rossom, Rebecca C; Lane, Dorothy
BACKGROUND: The consumption of sweetened beverages, refined foods, and pastries has been shown to be associated with an increased risk of depression in longitudinal studies. However, any influence that refined carbohydrates has on mood could be commensurate with their proportion in the overall diet; studies are therefore needed that measure overall intakes of carbohydrate and sugar, glycemic index (GI), and glycemic load. OBJECTIVE: We hypothesized that higher dietary GI and glycemic load would be associated with greater odds of the prevalence and incidence of depression. DESIGN: This was a prospective cohort study to investigate the relations between dietary GI, glycemic load, and other carbohydrate measures (added sugars, total sugars, glucose, sucrose, lactose, fructose, starch, carbohydrate) and depression in postmenopausal women who participated in the Women's Health Initiative Observational Study at baseline between 1994 and 1998 (n = 87,618) and at the 3-y follow-up (n = 69,954). RESULTS: We found a progressively higher dietary GI to be associated with increasing odds of incident depression in fully adjusted models (OR for the fifth vs. first quintile: 1.22; 95% CI: 1.09, 1.37), with the trend being statistically significant (P = 0.0032). Progressively higher consumption of dietary added sugars was also associated with increasing odds of incident depression (OR for the fifth vs. first quintile: 1.23; 95% CI: 1.07, 1.41; P-trend = 0.0029). Higher consumption of lactose, fiber, nonjuice fruit, and vegetables was significantly associated with lower odds of incident depression, and nonwhole/refined grain consumption was associated with increased odds of depression. CONCLUSIONS: The results from this study suggest that high-GI diets could be a risk factor for depression in postmenopausal women. Randomized trials should be undertaken to examine the question of whether diets rich in low-GI foods could serve as treatments and primary preventive measures for depression in postmenopausal women. The Women's Health Initiative is registered at clinicaltrials.gov as NCT00000611.
PMCID:4515860
PMID: 26109579
ISSN: 1938-3207
CID: 1640962

De novo mutations from sporadic schizophrenia cases highlight important signaling genes in an independent sample

Kranz, Thorsten M; Harroch, Sheila; Manor, Orly; Lichtenberg, Pesach; Friedlander, Yechiel; Seandel, Marco; Harkavy-Friedman, Jill; Walsh-Messinger, Julie; Dolgalev, Igor; Heguy, Adriana; Chao, Moses V; Malaspina, Dolores
Schizophrenia is a debilitating syndrome with high heritability. Genomic studies reveal more than a hundred genetic variants, largely nonspecific and of small effect size, and not accounting for its high heritability. De novo mutations are one mechanism whereby disease related alleles may be introduced into the population, although these have not been leveraged to explore the disease in general samples. This paper describes a framework to find high impact genes for schizophrenia. This study consists of two different datasets. First, whole exome sequencing was conducted to identify disruptive de novo mutations in 14 complete parent-offspring trios with sporadic schizophrenia from Jerusalem, which identified 5 sporadic cases with de novo gene mutations in 5 different genes (PTPRG, TGM5, SLC39A13, BTK, CDKN3). Next, targeted exome capture of these genes was conducted in 48 well-characterized, unrelated, ethnically diverse schizophrenia cases, recruited and characterized by the same research team in New York (NY sample), which demonstrated extremely rare and potentially damaging variants in three of the five genes (MAF<0.01) in 12/48 cases (25%); including PTPRG (5 cases), SCL39A13 (4 cases) and TGM5 (4 cases), a higher number than usually identified by whole exome sequencing. Cases differed in cognition and illness features based on which mutation-enriched gene they carried. Functional de novo mutations in protein-interaction domains in sporadic schizophrenia can illuminate risk genes that increase the propensity to develop schizophrenia across ethnicities.
PMCID:4512856
PMID: 26091878
ISSN: 1573-2509
CID: 1631132

Serotonin (5-HT) 5-HT2A Receptor (5-HT2AR):5-HT2CR Imbalance in Medial Prefrontal Cortex Associates with Motor Impulsivity

Anastasio, Noelle C; Stutz, Sonja J; Fink, Latham H L; Swinford-Jackson, Sarah E; Sears, Robert M; DiLeone, Ralph J; Rice, Kenner C; Moeller, F Gerard; Cunningham, Kathryn A
A feature of multiple neuropsychiatric disorders is motor impulsivity. Recent studies have implicated serotonin (5-HT) systems in medial prefrontal cortex (mPFC) in mediating individual differences in motor impulsivity, notably the 5-HT2AR receptor (5-HT2AR) and 5-HT2CR. We investigated the hypothesis that differences in the ratio of 5-HT2AR:5-HT2CR protein expression in mPFC would predict the individual level of motor impulsivity and that the engineered loss of the 5-HT2CR would result in high motor impulsivity concomitant with elevated 5-HT2AR expression and pharmacological sensitivity to the selective 5-HT2AR antagonist M100907. High and low impulsive rats were identified in a 1-choice serial reaction time task. Native protein levels of the 5-HT2AR and the 5-HT2CR predicted the intensity of motor impulsivity and the 5-HT2AR:5-HT2CR ratio in mPFC positively correlated with levels of premature responses in individual outbred rats. The possibility that the 5-HT2AR and 5-HT2CR act in concert to control motor impulsivity is supported by the observation that high phenotypic motor impulsivity associated with a diminished mPFC synaptosomal 5-HT2AR:5-HT2CR protein:protein interaction. Knockdown of mPFC 5-HT2CR resulted in increased motor impulsivity and triggered a functional disruption of the local 5-HT2AR:5-HT2CR balance as evidenced by a compensatory upregulation of 5-HT2AR protein expression and a leftward shift in the potency of M100907 to suppress impulsive behavior. We infer that there is an interactive relationship between the mPFC 5-HT2AR and 5-HT2CR, and that a 5-HT2AR:5-HT2CR imbalance may be a functionally relevant mechanism underlying motor impulsivity.
PMCID:4811199
PMID: 26120876
ISSN: 1948-7193
CID: 2116592

A tale of two diatheses: Temperament, BIS, and BAS as risk factors for mood disorder

Van Meter, Anna R; Youngstrom, Eric A
OBJECTIVE:Learning more about how biological traits, like temperament and sensitivity in the behavioral inhibition (BIS) and behavioral activation (BAS) systems, relate to mood pathology is consistent with the Research Domain Criteria initiative׳s goal of investigating mechanisms of risk. METHOD/METHODS:Korean young adults (n=128) and American young adults (n=630, of whom 23 has recent treatment for bipolar disorder, and 21for depression) completed self-report questionnaires, including the TEMPS-A, the BIS/BAS scales, Beck Depression Inventory (BDI), and Hypomanic Checklist (HCL-32). Linear regression quantified relations between mood symptoms, sample characteristics, temperament, and BIS/BAS. RESULTS:Temperament styles explained 49% of the variance in BDI scores. BIS explained an additional 1% of the variance in BDI scores. BAS Fun and Reward (p<.01), in addition to cyclothymic and hyperthymic temperaments (p<.001) explained 21% of the variance in HCL-32 scores. Sample characteristics were not significant predictors in the full model. LIMITATIONS/CONCLUSIONS:Differences in sample size, the cross-sectional study design, and lack of collateral report or behavioral measures of constructs are limitations. CONCLUSIONS:Affective temperament and BIS/BAS are complementary but distinct constructs. Affective temperament, particularly cyclothymic, may represent a stronger diathesis for mood pathology, and seems potent irrespective of culture or diagnosis. Assessing temperament may help overcome some challenges in diagnosing mood disorders.
PMID: 25913803
ISSN: 1573-2517
CID: 5004782

Sexual Health Knowledge in a Sample of Perinatally HIV-infected and Perinatally-exposed Uninfected Youth

Gromadzka, Olga; Santamaria, E Karina; Benavides, Jessica M; Dolezal, Curtis; Elkington, Katherine S; Leu, Cheng-Shiun; McKay, Mary; Abrams, Elaine J; Wiznia, Andrew; Bamji, Mahrukh; Ann Mellins, Claude
This study describes sexual health knowledge in perinatally HIV-infected (PHIV+) and perinatally-exposed uninfected (PHIV-) ethnic-minority youth, ages 9-16 years, residing in NYC (n=316). Data on youth sexual health knowledge (e.g., pregnancy, STDs, birth control) and caregiver-adolescent communication about sexual health were examined. Participants in both groups answered only 35% of the sexual health knowledge questions correctly (mean=6.6/19). Higher scores were found among youth who reported more communication about sex with caregivers (vs. those who did not report talking about sex with caregivers; 8.54 vs. 5.84, p<.001) and among PHIV+ youth who were aware of their status (vs. PHIV+ youth who were not; 7.27 vs. 4.70, p<.001). Age was positively correlated with sexual health knowledge (beta=.489, p<.001). Both PHIV+ and PHIV- youth had poor sexual health knowledge, suggesting a need for sexual health education for both groups. Data suggest that interventions focused on caregiver-child risk communication may be important for prevention.
PMCID:4743908
PMID: 26855617
ISSN: 1538-1501
CID: 2911432

Development of Body Part Vocabulary in Toddlers in Relation to Self-Understanding

Waugh, Whitney; Brownell, Celia
To better understand young children's ability to communicate about their bodies, toddlers' comprehension and production of 27 common body part words was assessed using parental report at 20 and 30 months (n = 64), and self-awareness was assessed using mirror self-recognition. Children at both ages comprehended more body part words that referred to themselves than to others' bodies, and more words referring to locations that they could see on themselves than to those they could not see. Children with more advanced mirror self-recognition comprehended and produced more body part words. These findings suggest that with age and better understanding of the self, children also possess a better understanding of the body, and they provide new information about factors that affect how young children begin to talk about their own and others' bodies. They should be useful for practitioners who need to ask children about their bodies and body parts.
PMCID:4505369
PMID: 26195850
ISSN: 0300-4430
CID: 2694752