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Rebecca A Krill, Sanjiv Kumra Department of Psychiatry, University of Minnesota, Minneapolis, MN, USA Objective: To review the metabolic consequences of second-generation antipsychotics in youth and current monitoring and intervention guidelines for optimal treatment. Background: Second-generation antipsychotics have largely replaced the use of first-generation antipsychotics in treating psychotic disorders in youth. In addition, there has been a dramatic increase in using these medications to treat a variety of nonpsychotic disorders. These medications have significant metabolic side effects, including weight gain. This raises concern, given the problem of pediatric obesity. Materials and methods: A review of current literature looking at prescribing practices and possible reasons for the increased use of second-generation antipsychotics in children and adolescents was conducted. Review of the mechanisms for why youth may be particularly vulnerable to the metabolic consequences (particularly weight gain) was similarly completed. In addition, data supporting the efficacy, rationale, and unique side-effect profile of each individual second-generation drug were evaluated to help inform providers on when and what to prescribe, along with current monitoring practices. The current evidence base for possible interventions regarding the management of antipsychotic-induced weight gain was also evaluated. Results and conclusion: On the basis of the literature review, there are several speculated reasons for the increase in prescriptions of second-generation antipsychotics. The choice of antipsychotic for youth should be based upon the disorder being treated along with the unique side-effect profile for the most commonly used second-generation antipsychotics. Monitoring strategies are also individualized to each antipsychotic. The current interventions recommended for antipsychotic-induced weight gain include lifestyle management, switching medication to a drug with a lower propensity for weight gain, and pharmacologic (particularly metformin) treatment. Keywords: antipsychotics, children, youth, metabolic, weight gain

The article reports on the new study on the drug clozapine. It is said that clozapine is more effective than high-dose olanzapine in reducing psychotic symptoms in pediatric patients with treatment-resistant schizophrenia. The patients studied showed significant weight gain, metabolic abnormalities, serious adverse events (AEs) and treatment discontinuation. Further discussions about the study are presented.

This review is a research update of recent literature related to childhood-onset schizophrenia (onset of psychotic symptoms by age 12 years). This subgroup of patients has attracted considerable research interest because patients with a childhood onset may represent a more homogeneous patient population in which to search for risk or etiologic factors. We examine data indicating that childhood-onset schizophrenia (COS) shares the same clinical and neurobiologic features as later-onset forms of the disorder. Compared with adults with schizophrenia, however, this subgroup of patients appears to have more severe premorbid neuro-developmental abnormalities, more cytogenetic anomalies, and potentially greater family histories of schizophrenia and associated spectrum disorders. While preliminary, these data indicate that a greater genetic vulnerability may be one of the underpinnings of COS. Future studies of this subgroup may provide important clues as to the genetic basis for schizophrenia and how gene products influence certain features of the disease, such as age of onset and mode of inheritance. [ABSTRACT FROM AUTHOR]

Objective: Olanzapine, a potent 5-HT2a/2c, dopamine D1D2D4 antagonist with anticholinergic activity, has a profile of known receptor affinity similar to that of clozapine. This pilot study examined the efficacy of olanzapine for treatment-refractory childhood-onset schizophrenia in eight patients who had received 8-week open-label trials. For comparison, data are included from 15 patients who had received 6-week open-label clozapine trials using identical rating instruments (largely by the same raters) in the same treatment setting.Method: Twenty-three children and adolescents with an onset of DSM-III-R schizophrenia by age 12 for whom at least two different typical neuroleptics had been ineffective participated in the two separate studies. Some of the patients were intolerant of clozapine, although it had been effective (n = 4). Patients receiving olanzapine were evaluated over 8 weeks with the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Positive Symptoms, the Scale for the Assessment of Negative Symptoms, and the Clinical Global Impressions Scale for Improvement.Results: For the eight patients who received olanzapine trials, at week 8 there was a 17% improvement in the BPRS total score, a 27% improvement in the Scale for the Assessment of Negative Symptoms, and a 1% improvement in the Scale for the Assessment of Positive Symptoms, relative to "ideal" admission status on typical neuroleptics. In contrast, the magnitude of the effect sizes for each of the clinical ratings was larger at week 6 of the previous clozapine trial than for an 8-week olanzapine trial, relative to admission status on typical neuroleptics. For the four children who had received both clozapine and olanzapine, BPRS total scores were significantly lower at week 6 of clozapine treatment compared with week 6 of olanzapine treatment (p = .03).Conclusion: These data provide preliminary evidence for the efficacy of olanzapine for some children and adolescents with treatment-refractory schizophrenia, but they also suggest the need for a more rigorous double-blind comparison of these two atypical antipsychotics. [ABSTRACT FROM AUTHOR]

We propose a dual-module robotic system to tackle the problem of generating and performing antipodal robotic grasps for unknown objects from the n-channel image of the scene. We present an improved version of the Generative Residual Convolutional Neural Network (GR-ConvNet v2) model that can generate robust antipodal grasps from n-channel image input at real-time speeds (20 ms). We evaluated the proposed model architecture on three standard datasets and achieved a new state-of-the-art accuracy of 98.8%, 95.1%, and 97.4% on Cornell, Jacquard and Graspnet grasping datasets, respectively. Empirical results show that our model significantly outperformed the prior work with a stricter IoU-based grasp detection metric. We conducted a suite of tests in simulation and the real world on a diverse set of previously unseen objects with adversarial geometry and household items. We demonstrate the adaptability of our approach by directly transferring the trained model to a 7 DoF robotic manipulator with a grasp success rate of 95.4% and 93.0% on novel household and adversarial objects, respectively. Furthermore, we validate the generalization capability of our pixel-wise grasp prediction model by validating it on complex Ravens-10 benchmark tasks, some of which require closed-loop visual feedback for multi-step sequencing.

Cannabis is widely perceived as a safe recreational drug and its use is increasing in youth. It is important to understand the implications of cannabis use during childhood and adolescence on brain development. This is the first longitudinal study that compared resting functional connectivity of frontally mediated networks between 43 healthy controls (HCs; 20 females; age M = 16.5 ± 2.7) and 22 treatment-seeking adolescents with cannabis use disorder (CUD; 8 females; age M = 17.6 ± 2.4). Increases in resting functional connectivity between caudal anterior cingulate cortex (ACC) and superior frontal gyrus across time were found in HC, but not in CUD. CUD showed a decrease in functional connectivity between caudal ACC and dorsolateral and orbitofrontal cortices across time. Lower functional connectivity between caudal ACC cortex and orbitofrontal cortex at baseline predicted higher amounts of cannabis use during the following 18 months. Finally, high amounts of cannabis use during the 18-month interval predicted lower intelligence quotient and slower cognitive function measured at follow-up. These data provide compelling longitudinal evidence suggesting that repeated exposure to cannabis during adolescence may have detrimental effects on brain resting functional connectivity, intelligence, and cognitive function., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Recurrent exposure to cannabis in adolescence increases the risk for later development of psychosis, but there are sparse data regarding the impact of cannabis use on brain structure during adolescence. This pilot study investigated the effect of cannabis use disorder (CUD) upon white matter fractional anisotropy (WM FA) values in non-psychotic treatment-seeking adolescents relative to adolescents with early onset schizophrenia-spectrum disorders (EOSS) and to healthy control (HC) participants. Diffusion tensor imaging (DTI) and tractography methods were used to examine fractional anisotropy (FA) of the cingulum bundle, superior longitudinal fasciculus (SLF), corticospinal tract (CST), inferior longitudinal fasciculus (ILF), inferior fronto-occipital fasciculus (IFOF) and uncinate fasciculus in adolescents with EOSS (n=34), CUD (n=19) and HC (n=29). Participants received DTI and substance use assessments at baseline and at 18-month follow-up. Using multivariate analysis of variance, a significant main effect of diagnostic group was observed. Post-hoc testing revealed that adolescents with CUD showed an altered change in FA values in the left ILF and in the left IFOF (trend level) compared with HC adolescents. Greater consumption of cannabis during the inter-scan interval predicted a greater decrease in left ILF FA in CUD. These preliminary longitudinal data suggest that heavy cannabis use during adolescence, or some factor associated with cannabis use, is associated with an altered change in WM FA values in a fiber bundle that has been implicated in the pathophysiology of EOSS (i.e., the left ILF). Additional studies are needed to clarify the clinical significance of these findings., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

During late adolescence, progressive cortical thinning occurs in heteromodal association cortex (HASC) that is thought to subserve cognitive development. However, the impact of cannabis use disorder (CUD) upon cortical gray matter development in both healthy adolescents and adolescents with early-onset schizophrenia (EOS) is unclear. T1-weighted magnetic resonance images were acquired from 79 adolescents at baseline and after an 18-month follow-up: 17 with EOS, 17 with CUD, 11 with EOS+CUD, and 34 healthy controls (HC). Mean age at baseline was 16.4years (CUD+) and 17.0years (CUD-). Using FreeSurfer, measures of cortical thickness for ROIs within HASC were obtained. A 2 (EOS versus no EOS)×2 (CUD versus no CUD) multivariate analysis of covariance was applied to change scores from baseline to follow-up to test for main effects of EOS and CUD and an interaction effect. After adjusting for covariates, a significant main effect of CUD was observed. Adolescents with CUD showed an attenuated loss of cortical thickness in the left and right supramarginal, left and right inferior parietal, right pars triangularis, left pars opercularis, left superior frontal, and left superior temporal regions compared to non-using subjects. Stepwise linear regression analysis indicated that greater cumulative cannabis exposure predicted greater cortical thickness in both the left (p=.008) and right (p=.04) superior frontal gyri at study endpoint after adjusting for baseline cortical thickness for the entire sample. These preliminary longitudinal data demonstrate an atypical pattern of cortical development in HASC in adolescents with CUD relative to non-using subjects, across diagnostic groups. Additional studies are needed to replicate these data and to clarify the clinical significance of these findings., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objective: Repeated exposure to cannabis in nonpsychotic adolescents is associated with impairments in executive control of attention, similar to those observed in young adults with first-episode schizophrenia. To assess the impact of recurrent exposure to cannabis on cognitive function, this study characterized attention performance in both nonpsychotic adolescents and adolescents with early-onset schizophrenia (EOS)., Method: The Attention Network Test, a standard procedure that estimates the functional state of neural networks controlling the efficiency of three different attentional behaviors (alerting, orienting, and executive attention), was administered to four groups of participants: (1) adolescents with EOS and comorbid cannabis use disorder (EOS+CUD; n=18), (2) "Pure" schizophrenia (EOS; n=34), (3) "Pure" cannabis use disorder (CUD; n=29), and (4) Healthy controls (HC; n=53). Task performance was examined with a 2×2 design (EOS+ versus EOS- and CUD+ versus CUD-) using multivariate analysis of covariance. Correlative analyses were conducted between executive attention performance and measures of surface area in the right anterior cingulate cortex., Results: A significant EOS×CUD interaction was observed. In the executive attention network, adolescents with EOS+CUD showed reduced efficiency relative to adolescents with pure EOS, whereas no group differences were found between adolescents with pure CUD and HC. Less efficient executive attention was significantly associated with smaller surface area in the right caudal anterior cingulate cortex in EOS+CUD., Conclusions: These preliminary data suggest that the presence of CUD has a moderating effect on attentional performance in adolescents with schizophrenia compared to nonpsychotic adolescents. These deficits could have a role in difficulties with self-regulation and predisposition to substance misuse in this patient group. The anatomic substrate of this cognitive deficit may be related to surface area in the right caudal anterior cingulate cortex., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objective: To characterize white matter abnormalities in adolescents with early-onset schizophrenia (EOS) relative to 3 comparison groups (adolescents at clinical high risk for developing schizophrenia [CHR], adolescents with cannabis use disorder [CUD], and healthy controls [HC]), and to identify neurocognitive correlates of white matter abnormalities in EOS., Method: We used diffusion tensor imaging and tractography methods to examine fractional anisotropy (FA) of the cingulum bundle, superior longitudinal fasciculus, corticospinal tract (CST), inferior longitudinal fasciculus (ILF), inferior fronto-occipital fasciculus (IFOF), and uncinate fasciculus in adolescents with EOS (n = 55), CHR (n = 21), CUD (n = 31), and HC (n = 55). FA in tracts that were significantly altered in EOS was correlated with neurocognitive performance., Results: EOS and CHR groups had significantly lower FA than HC in 4 tracts, namely, bilateral CST, left ILF, and left IFOF. CUD had lower FA than HC in left IFOF. Lower FA in left IFOF and left ILF predicted worse neurocognitive performance in EOS., Conclusions: This study identified white matter abnormalities of the left ILF and left IFOF as possible biomarkers of vulnerability for developing schizophrenia. Lower FA in these tracts may disrupt functioning of ventral visual and language streams, producing domain-specific neurocognitive deficits that interfere with higher-order cognitive abilities., (Copyright © 2014 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

This article reviews the literature for the most pressing diagnostic and treatment challenges faced in working with adolescents. Diagnosing the treatment interventions required for this population involve psychoeducation, engagement of the patient and family in the treatment process, and use of antipsychotic medications. Cannabis may be a causal risk factor in psychotic illness, and data support recommendations to reduce or cease cannabis use in this population. Treatment strategies are discussed that are effective in adult patients and that may be efficacious for youth to abstain from substances after the resolution of psychotic symptoms., (Copyright © 2013 Elsevier Inc. All rights reserved.)

This study investigated whether major depression in adolescence is characterized by neurocognitive deficits in attention, affective decision making, and cognitive control of emotion processing. Neuropsychological tests including the Wechsler Abbreviated Scale of Intelligence, the Continuous Performance Test-Identical Pairs, the Attention Network Test, the Iowa Gambling Task, the Emotional Go-NoGo Task, and the Face Go-NoGo Task were administered to adolescents with Major Depressive Disorder (MDD) (n = 31) and psychiatric diagnosis free controls (n = 30). Findings indicated that compared with controls, depressed adolescents exhibited impaired sustained attention; a gender by group interaction on affective decision making such that depressed males tended to make less advantageous choices on the IGT; and an inverse pattern of correlations between depressive symptom counts and reaction time to affective stimuli, characterizing greater affective reactivity in depressed adolescents. Findings demonstrate that adolescents with MDD display selective neurocognitive impairments on tasks capturing 'cool' and 'hot' executive functioning., (Copyright © 2011 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.)

Objective: In early-onset schizophrenia (EOS), the earliest structural brain volumetric abnormalities appear in the parietal cortices. Early exposure to cannabis may represent an environmental risk factor for developing schizophrenia. This study characterized cerebral cortical gray matter structure in adolescents in regions of interest (ROIs) that have been implicated in EOS and cannabis use disorders (CUD)., Method: T1-weighted magnetic resonance images were acquired from adolescents with EOS (n = 35), CUD (n = 16), EOS + CUD (n = 13), and healthy controls (HC) (n = 51). Using FreeSurfer, brain volume was examined within frontal, temporal, parietal and subcortical ROIs by a 2 (EOS versus no EOS) × 2 (CUD versus no CUD) design using multivariate analysis of covariance. In ROIs in which volumetric differences were identified, additional analyses of cortical thickness and surface area were conducted., Results: A significant EOS-by-CUD interaction was observed. In the left superior parietal region, both "pure" EOS and "pure" CUD had smaller gray matter volumes that were associated with lower surface area compared with HC. A similar alteration was observed in the comorbid group compared with HC, but there was no additive volumetric deficit found in the comorbid group compared with the separate groups. In the left thalamus, the comorbid group had smaller gray matter volumes compared with the CUD and HC groups., Conclusions: These preliminary data indicate that the presence of a CUD may moderate the relationship between EOS and cerebral cortical gray matter structure in the left superior parietal lobe. Future research will follow this cohort over adolescence to further examine the impact of cannabis use on neurodevelopment.