Comprehensive immunoprofiling of neurodevelopmental disorders suggests three distinct classes based on increased neurogenesis, Th-1 polarization or IL-1 signaling.

Neurodevelopmental disorders (NDDs) are a spectrum of conditions with commonalities as well as differences in terms of phenome, symptomatome, neuropathology, risk factors and underlying mechanisms. Immune dysregulation has surfaced as a major pathway in NDDs. However, it is not known if neurodevelopmental disorders share a common immunopathogenetic mechanism. In this study, we explored the possibility of a shared immune etiology in three early-onset NDDs, namely Autism Spectrum Disorder (ASD), Attention Deficit Hyperactivity Disorder (ADHD) and Intellectual Disability Disorder (IDD). A panel of 48 immune pathway-related markers was assayed in 135 children with NDDs, represented by 45 children with ASD, ADHD and IDD in each group, along with 35 typically developing children. The plasma levels of 48 immune markers were analyzed on the Multiplex Suspension Assay platform using Pro Human cytokine 48-plex kits. Based on the cytokine/chemokine/growth factor levels, different immune profiles were computed. The primary characteristics of NDDs are depletion of the compensatory immune-regulatory system (CIRS) (z composite of IL-4, IL-10, sIL-1RA, and sIL-2R), increased interleukin (IL)-1 signaling associated with elevated IL-1α and decreased IL-1-receptor antagonist levels, increased neurogenesis, M1/M2 macrophage polarization and increased IL-4 as well as C-C Motif Chemokine Ligand 2 (CCL2) levels. With a cross-validated sensitivity of 81.8% and specificity of 94.4%, these aberrations seem specific for NDDs. Many immunological abnormalities are shared by ASD, ADHD and IDD, which are distinguished by minor differences in IL-9, IL-17 and CCL12. In contrast, machine learning reveals that NDD group consists of three immunologically distinct clusters, with enhanced neurogenesis, Th-1 polarization, or IL-1 signaling as the defining features. NDD is characterized by immune abnormalities that have functional implications for neurogenesis, neurotoxicity, and neurodevelopment. Using machine learning, NDD patients could be classified into subgroups with qualitatively distinct immune disorders that may serve as novel drug targets for the treatment of NDDs.

Evolution of anhedonia in adolescent depression: An interpretative phenomenological analysis study.

INTRODUCTION: Anhedonia is a symptom complex currently linked to dysfunctional reward processing. Phenomenological studies capture anhedonia as a loss of hedonic and eudemonic pleasure. However, there is a lack of integration between neurobiological understanding and clinical phenomenology. This study used a qualitative method to explore the interplay of sociocultural contexts and individual factors associated with the evolution of dysfunctional reward processing in adolescents with depression and anhedonia. METHODS: Ten female adolescents with a current or prior diagnosis of major depressive disorder were recruited from a public tertiary care child and adolescent psychiatry service. In-depth interviews were conducted, voice recorded, and transcribed verbatim. The transcripts were analyzed using Interpretative Phenomenological Analysis (IPA). FINDINGS: The adolescents hailed from urban families. Educational stress and relational difficulties figured prominently. Amotivation was the most important subdomain of anhedonia affected. An integrated framework for understanding the evolution of anhedonia is presented. Five main patterns of dysfunctional reward processing emerged in our study: an overworked system, erroneous reward valuation, reward-effort imbalance, and diversion of the reward processing system for self-preservation. CONCLUSION: There is a necessity to build robust theoretical models of the evolution of anhedonia, hence finding homogenous sub-groups, paving the way for person-centric interventions for anhedonia.

Why was the study done? Adolescents suffering from depression lack interest in pleasurable activities along with sad moods and negative thoughts. It becomes very difficult to motivate adolescents to do meaningful and or pleasurable activities during or after other symptoms of depression have been reduced with medicines or therapy. The study was done to understand how and why the lack of interest comes about, and the different components of this symptom, so that it can help in understanding the symptom and finding new treatment strategies. What did the researchers do? The research team did an in-depth interview with ten adolescents suffering from depression who had lost interest in pleasurable activities to understand their lived experiences. Their experiences were recorded and analyzed in detail. A theoretical model of the symptom was derived in terms of brain pathways for reward. What did the researchers find? The lack of motivation rather than the lack of pleasure in doing activities was seen. The adolescents' own proclivities along with the environment influenced (that is, family, peers, school, and society) what activities they found pleasure in. Their motivation was initially due to societal pressures, however, with time they were truly motivated from within to do these activities. This true inner motivation was lost when there was academic stress or difficult relationships with family or peers. When motivation was lost, it reduced their confidence in themselves, and over time they stopped doing any meaningful activities.

Co-morbidities and outcome of childhood psychogenic non-epileptic seizures--an observational study.

PURPOSE: To assess the psychiatric diagnoses and outcome in children with psychogenic non-epileptic seizures (PNES). METHODOLOGY: This hospital based observational study was performed on 44 children aged <16 years, who suspected to have psychogenic non-epileptic seizures based on video-EEG, from August 2005 to August 2012. The parameters noted were the psychiatric diagnosis, co-morbidities, management assessment and interventions (pharmacological and psychosocial), number and duration of follow-up visits, symptoms at follow-up, functioning as reflected by involvement in the social and scholastic work. RESULTS: All forty four children completed the evaluation. Thirty four children were diagnosed as having PNES and the underlying psychiatric diagnosis was conversion disorder (n=34, 77.3%). Co-morbid psychiatric disorders were present in 17 children (50%). The common co-morbidities were intellectual disability (n=8, 23.5%), specific learning disorder (n=5, 14.7%), and depression (n=5, 14.7%). Co-morbid epilepsy was present in 8 (23.5%) children and family history of epilepsy was present in 10 (29.4%) cases. About 17 of 34 (50.0%) patients had a minimum follow-up of 6 months (13.9 ± 4.8 months). Twenty six children (76.5%) remained symptom free at the follow-up of 9.8 ± 7 months. The remaining 10 children (22.7%) had non-epileptic seizures with underlying diagnosis of Attention Deficit Hyperactivity Disorder (ADHD), gratification disorder and other physiological conditions. CONCLUSIONS: Conversion disorder is a common diagnosis underlying psychogenic non-epileptic seizures. Outcome was good in 76.5% children with PNES. A multidisciplinary approach is needed in the diagnosis and management of PNES.

A Placebo Controlled Trial on Add-on Modafinil on the Anti-psychotic Treatment Emergent Hyperglycemia and Hyperlipidemia.

UNLABELLED: Modafinil is non stimulant drug which is marketed for mainly Narcolepsy and daytime drowsiness. The clinical experience and Summary of Product Characteristics (SPC) of the drug also mentions Anorexia as one of the side effects. Anorexia can have a direct impact on the carbohydrate and fat intake, which may, in turn, regulate antipsychotic induced dyslipidemia and Hyperglycaemia. AIM: To compare the effects of Modafinil- ADDON with Placebo add on with olanzapine, Clozapine and Risperidone in drug naive subjects and people who were started on the drugs within 15days of assessment. MATERIALS AND METHODS: Randomized, Double blind, Placebo controlled study, which was conducted at two centres, one at department of Psychiatry, S.V Medical College, Tirupati and the other at Asha hospitals, Hyderabad. Seventy two patient were randomised, sixty three patients have completed the total study period of three months. The dose of Modafinil was 200 mgs constantly as Flexible doses of Olanzapine, Clozapine and Risperidone as per clinical need was given. A baseline, three week and twelve week assessments of Fasting blood Glucose and fasting Serum cholesterol were made and the groups were compared on these parameters. RESULTS: From baseline to week 3 there was a significant raise in Fasting serum cholesterol followed by a fall from week 3 to week 12 in the Modafinil addon group, though it could not be considered a drug for hypercholesteremia like Statins in controlling hyperlipidaemia. The implications of these findings were discussed.