le Numéro de décembre 2012 de Biological Psychiatry est consacré à l’autisme.

1. Coccaro EF. What Is the Nature of Serotonergic Abnormalities in Human Aggression ?. Biol Psychiatry ;2012 ;72(12):980-981.

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2. Weisman O, Zagoory-Sharon O, Feldman R. Oxytocin Administration to Parent Enhances Infant Physiological and Behavioral Readiness for Social Engagement. Biol Psychiatry ;2012 ;72(12):982-989.

Background The social milieu provides the context for the organism’s survival, endurance, and adaptation. In mammals, social participation originates within the parent-infant bond and is supported by the oxytocin (OT) system, whose functioning is transmitted from parent to child through patterns of parental care. Human studies indicate that OT administration increases affiliative behavior, including trust, empathy, and social reciprocity. Here, we examine whether OT administration to parent can enhance physiological and behavioral processes that support parental social engagement but, moreover, can have parallel effects on the infant. Methods Utilizing a double-blind, placebo-controlled crossover design, 35 fathers and their 5-month-old infants were observed twice following administration of OT or placebo to father in the face-to-face still-face paradigm. Parent and infant salivary OT were assessed at multiple time points, respiratory sinus arrhythmia (RSA) was measured in the three face-to-face still-face episodes, and social behaviors of the parent and child were micro-coded for indices of social engagement. Results Oxytocin administration increased father salivary OT, RSA during free play, and key parenting behaviors that support parental-infant bonding. Parallel increases were also found in the infant’s salivary OT, RSA response, and engagement behavior, including social gaze, exploration, and social reciprocity. Conclusions Results are the first to demonstrate that OT administration to one attachment partner can have parallel effects on the other and underscore the role of OT in the cross-generation transmission of human social participation. Findings have translational implications for conditions associated with early risk for social-emotional growth, including autism and prematurity, without the need to administer drugs to young infants.

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3. Metin B, Roeyers H, Wiersema JR, van der Meere J, Sonuga-Barke E. A Meta-Analytic Study of Event Rate Effects on Go/No-Go Performance in Attention-Deficit/Hyperactivity Disorder. Biol Psychiatry ;2012 ;72(12):990-996.

Background According to the state regulation deficit model, event rate (ER) is an important determinant of performance of children with attention-deficit/hyperactivity disorder (ADHD). Fast ER is predicted to create overactivation and produce errors of commission, whereas slow ER is thought to create underactivation marked by slow and variable reaction times (RT) and errors of omission. Methods To test these predictions, we conducted a systematic search of the literature to identify all reports of comparisons of ADHD and control individuals’ performance on Go/No-Go tasks published between 2000 and 2011. In one analysis, we included all trials with at least two event rates and calculated the difference between ER conditions. In a second analysis, we used metaregression to test for the moderating role of ER on ADHD versus control differences seen across Go/No-Go studies. Results There was a significant and disproportionate slowing of reaction time in ADHD relative to controls on trials with slow event rates in both meta-analyses. For commission errors, the effect sizes were larger on trials with fast event rates. No ER effects were seen for RT variability. There were also general effects of ADHD on performance for all variables that persisted after effects of ER were taken into account. Conclusions The results provide support for the state regulation deficit model of ADHD by showing the differential effects of fast and slow ER. The lack of an effect of ER on RT variability suggests that this behavioral characteristic may not be a marker of cognitive energetic effects in ADHD.

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4. Coccaro EF, Lee R, Liu T, Mathé AA. Cerebrospinal Fluid Neuropeptide Y-like Immunoreactivity Correlates with Impulsive Aggression in Human Subjects. Biol Psychiatry ;2012 ;72(12):997-1003.

Background Neurochemical studies have pointed to a modulatory role in human aggression for a number of central neurotransmitters ; some (e.g., serotonin) appear to play an inhibitory role, while others (e.g., vasopressin) appear to play a facilitator role in the modulation of aggression. While recent animal studies of neuropeptide Y (NPY) have suggested a facilitator role for central NPY in the modulation of aggression, no human studies of central NPY have yet been reported regarding aggression. Methods Basal lumbar cerebrospinal fluid (CSF) was obtained from 60 physically healthy subjects with personality disorder (PD) (n=40) and from healthy volunteers (n=20). These samples were then assessed for CSF NPY-like immunoreactivity (NPY-LI) and other neurotransmitter-related species in CSF and correlated with measures of aggression and impulsivity. Results Cerebrospinal fluid NPY-LI was higher in PD subjects compared with healthy volunteers and in subjects with intermittent explosive disorder compared with those without intermittent explosive disorder. In PD subjects, CSF NPY-LI was directly correlated with composite measures of aggression and impulsivity and a composite measure of impulsive aggression. Group differences in CSF NPY-LI concentration were accounted for by measures of impulsive aggression. Conclusions These data suggest a direct relationship between CSF NPY-immunoreactivity concentration and measures of impulsive aggression in human subjects. This adds to the complex picture of the central neuromodulatory role of impulsive aggression in human subjects.

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5. Rylands AJ, Hinz R, Jones M, Holmes SE, Feldmann M, Brown G, McMahon AW, Talbot PS. Pre- and Postsynaptic Serotonergic Differences in Males with Extreme Levels of Impulsive Aggression Without Callous Unemotional Traits : A Positron Emission Tomography Study Using 11C-DASB and 11C-MDL100907. Biol Psychiatry ;2012 ;72(12):1004-1011.

Background Impulsive aggression (IA) in adults is associated with brain serotonin (5-HT) system abnormalities and is more common following childhood adversity. Within aggressive behavior, IA and callous unemotional (CU) traits are core components of differentiable factors with opposing 5-HT abnormalities. We aimed to investigate 5-HT abnormalities in IA and potential correlations with severity of childhood adversity while controlling for confounding 5-HT effects of high CU traits and mental disorders. Methods Healthy male subjects (mean age 34 ± 9 years) without high CU traits were recruited with IA ratings in the high (n = 14) and low (n = 13) population extremes. Serotonin transporter (SERT) and 5-HT2A receptor availability was measured in multiple brain regions using positron emission tomography with 11C-DASB and 11C-MDL100907, respectively, and compared between high-IA and low-IA groups. Correlations were measured between SERT and 5-HT2A receptor availability, impulsivity and aggression, and childhood adversity. Results Compared with the low-IA group, SERT were significantly higher in brainstem regions in the high-IA group (by 29.0% ± 11.4%) and modestly lower across cortical regions (by 11.1% ± 6.0%), whereas 5-HT2A receptors were also modestly lower (by 8.6% ± 4.0%). Across all subjects, brainstem SERT were significantly positively correlated with impulsivity, aggression, and childhood trauma ratings. Within the high-IA group, higher brainstem SERT was most strongly predicted by severity of childhood trauma (r = .76 in midbrain). Conclusions Pre-and postsynaptic 5-HT differences are present in men with high levels of IA and are strongly suggestive of a persisting effect of childhood adversity on serotonergic neurodevelopment and emotional-behavioral control.

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6. Esber GR, Roesch MR, Bali S, Trageser J, Bissonette GB, Puche AC, Holland PC, Schoenbaum G. Attention-Related Pearce-Kaye-Hall Signals in Basolateral Amygdala Require the Midbrain Dopaminergic System. Biol Psychiatry ;2012 ;72(12):1012-1019.

Background Neural activity in basolateral amygdala has recently been shown to reflect surprise or attention as predicted by the Pearce-Kaye-Hall model (PKH)—an influential model of associative learning. Theoretically, a PKH attentional signal originates in prediction errors of the kind associated with phasic firing of dopamine neurons. This requirement for prediction errors, coupled with projections from the midbrain dopamine system into basolateral amygdala, suggests that the PKH signal in amygdala may depend on dopaminergic input. Methods To test this, we recorded single unit activity in basolateral amygdala in rats with 6-hydroxydopamine or sham lesions of the ipsilateral midbrain region. Neurons were recorded as the rats performed a task previously used to demonstrate both dopaminergic reward prediction errors and attentional signals in basolateral amygdala neurons. Results We found that neurons recorded in sham lesioned rats exhibited the same attention-related PKH signal observed in previous studies. By contrast, neurons recorded in rats with ipsilateral 6-hydroxydopamine lesions failed to show attentional signaling. Conclusions These results indicate a linkage between the neural instantiations of the basolateral complex of the amygdala attentional signal and dopaminergic prediction errors. Such a linkage would have important implications for understanding both normal and aberrant learning and behavior, particularly in diseases thought to have a primary effect on dopamine systems, such as addiction and schizophrenia.

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7. Onore CE, Nordahl CW, Young GS, Van de Water JA, Rogers SJ, Ashwood P. Levels of Soluble Platelet Endothelial Cell Adhesion Molecule-1 and P-Selectin Are Decreased in Children with Autism Spectrum Disorder. Biol Psychiatry ;2012 ;72(12):1020-1025.

Background Although the etiopathology of autism spectrum disorder (ASD) is not clear, there is increasing evidence that dysfunction in the immune system affects many children with ASD. Findings of immune dysfunction in ASD include increases in inflammatory cytokines, chemokines, and microglial activity in brain tissue and cerebrospinal fluid, as well as abnormal peripheral immune cell function. Methods Adhesion molecules, such as platelet endothelial adhesion molecule-1 (PECAM-1), intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), P-selectin, and L-selectin, function to facilitate leukocyte transendothelial migration. We assessed concentrations of soluble adhesion molecules, sPECAM-1, sICAM-1, sVCAM-1, sP-selectin, and sL-selectin in the plasma of 49 participants with ASD and 31 typically developing controls of the same age, all of whom were enrolled as part of the Autism Phenome Project. Behavioral assessment, the levels of soluble adhesion molecules, and head circumference were compared in the same subjects. Results Levels of sPECAM-1 and sP-selectin were significantly reduced in the ASD group compared to typically developing controls (p < .02). Soluble PECAM-1 levels were negatively associated with repetitive behavior and abnormal brain growth in children with ASD (p = .03). Conclusions Because adhesion molecules modulate the permeability and signaling at the blood–brain barrier as well as leukocyte infiltration into the central nervous system, the current data suggest a role for these molecules in the complex pathophysiology of ASD.

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8. Bartzokis G, Lu PH, Heydari P, Couvrette A, Lee GJ, Kalashyan G, Freeman F, Grinstead JW, Villablanca P, Finn JP, Mintz J, Alger JR, Altshuler LL. Multimodal Magnetic Resonance Imaging Assessment of White Matter Aging Trajectories Over the Lifespan of Healthy Individuals. Biol Psychiatry ;2012 ;72(12):1026-1034.

Background Postmortem and volumetric imaging data suggest that brain myelination is a dynamic lifelong process that, in vulnerable late-myelinating regions, peaks in middle age. We examined whether known regional differences in axon size and age at myelination influence the timing and rates of development and degeneration/repair trajectories of white matter (WM) microstructure biomarkers. Methods Healthy subjects (n = 171) 14–93 years of age were examined with transverse relaxation rate (R2) and four diffusion tensor imaging measures (fractional anisotropy [FA] and radial, axial, and mean diffusivity [RD, AxD, MD, respectively]) of frontal lobe, genu, and splenium of the corpus callosum WM (FWM, GWM, and SWM, respectively). Results Only R2 reflected known levels of myelin content with high values in late-myelinating FWM and GWM regions and low ones in early-myelinating SWM. In FWM and GWM, all metrics except FA had significant quadratic components that peaked at different ages (R2 < RD < MD < AxD), with FWM peaking later than GWM. Factor analysis revealed that, although they defined different factors, R2 and RD were the metrics most closely associated with each other and differed from AxD, which entered into a third factor. Conclusions The R2 and RD trajectories were most dynamic in late-myelinating regions and reflect age-related differences in myelination, whereas AxD reflects axonal size and extra-axonal space. The FA and MD had limited specificity. The data suggest that the healthy adult brain undergoes continual change driven by development and repair processes devoted to creating and maintaining synchronous function among neural networks on which optimal cognition and behavior depend.

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9. Barch DM, Gaffrey MS, Botteron KN, Belden AC, Luby JL. Functional Brain Activation to Emotionally Valenced Faces in School-Aged Children with a History of Preschool-Onset Major Depression. Biol Psychiatry ;2012 ;72(12):1035-1042.

Background Recent research has demonstrated that clinical depression can emerge as early as the preschool period. Here, we examine brain function in children with a history of preschool-onset depression (PO-MDD) in comparison with healthy children. Methods Participants were medication naïve school-aged children (ages 7–11) with PO-MDD (n = 22) or no psychiatric history (n = 16) followed longitudinally as part of the Preschool Depression Study. We used functional magnetic resonance imaging measures of blood oxygen level-dependent signal to examine functional brain activity in response to emotionally valenced faces (sad, fearful, angry, happy, neutral) following a negative mood induction provided to all children. Results In categorical group comparisons, children with PO-MDD demonstrated increased activity in parietal cortex in response to sad faces but no differences in brain activity in a priori regions of interest (e.g., amygdala). However, in dimensional analyses, the severity of depression symptoms at the baseline preschool assessment predicted increased responses to sad faces in amygdala, hippocampal, parietal, and orbital frontal regions. Conclusions School-aged children with a history of PO-MDD showed patterns of functional brain responses to emotionally evocative stimuli similar to patterns found in adults and adolescents with major depression. These patterns were most strongly related to the severity of depression during the preschool period, suggesting that the magnitude of early symptoms may be particularly important for understanding altered brain function. These findings suggest that an early episode of depression before age 6 may be associated with enduring brain change or may represent a biomarker that was present even before the preschool episode.

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10. Walker L, Gozzi M, Lenroot R, Thurm A, Behseta B, Swedo S, Pierpaoli C. Diffusion Tensor Imaging in Young Children with Autism : Biological Effects and Potential Confounds. Biol Psychiatry ;2012 ;72(12):1043-1051.

Background Diffusion tensor imaging (DTI) has been used over the past decade to study structural differences in the brains of children with autism compared with typically developing children. These studies generally find reduced fractional anisotropy (FA) and increased mean diffusivity (MD) in children with autism ; however, the regional pattern of findings varies greatly. Methods We used DTI to investigate the brains of sedated children with autism (n = 39) and naturally asleep typically developing children (n = 39) between 2 and 8 years of age. Tract based spatial statistics and whole brain voxel-wise analysis were performed to investigate the regional distribution of differences between groups. Results In children with autism, we found significantly reduced FA in widespread regions and increased MD only in posterior brain regions. Significant age × group interaction was found, indicating a difference in developmental trends of FA and MD between children with autism and typically developing children. The magnitude of the measured differences between groups was small, on the order of approximately 1%–2%. Subjects and control subjects showed distinct regional differences in imaging artifacts that can affect DTI measures. Conclusions We found statistically significant differences in DTI metrics between children with autism and typically developing children, including different developmental trends of these metrics. However, this study indicates that between-group differences in DTI studies of autism should be interpreted with caution, because their small magnitude make these measurements particularly vulnerable to the effects of artifacts and confounds, which might lead to false positive and/or false negative biological inferences.

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