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Environmental risk factors that operate at foetal or neonatal levels increase the vulnerability to schizophrenia, plausibly via stress-immune activation that perturbs the epidermal growth factor (EGF) system, a system critical for neurodevelopment. We investigated potential associations between environmental insults and immune and EGF system changes through a maternal immune activation (MIA) model, using the precocial spiny mice (Acomys cahirinus). After mid-gestation MIA prepubescent offspring showed elevated NF-κB1 protein in nucleus accumbens, decreased EGFR in caudate putamen and a trend for increased PI3K-110δ in ventral hippocampus. Thus, prenatal stress may cause a heightened NF-κB1-mediated immune attenuation of EGF system signalling.

Background: The Montgomery-Asberg Depression Rating Scale (MADRS) is commonly used to assess major depression in Parkinson disease (PD), but studies on its utility are few. This study examines the validity and factor structure of MADRS in population with PD. Methods: In 104 patients with idiopathic PD, major depression was diagnosed by Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision; DSM-IV-TR) criteria, and all patients were rated by MADRS. Results: The MADRS showed good concurrent validity with DSM-IV-TR criteria. The diagnostic cutoff was established as 16/17 (sensitivity 97.43, specificity 100%, positive predictive value 100%, and negative predictive value 98.48%). Factor analysis identified 3 factors, accounting for 76% of total variance: “sadness-anhedonia” comprising apparent sadness, reported sadness, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal ideas; “anxiety” with reduced sleep and inner tension; and “vegetative symptoms” with reduced appetite. Conclusion: The MADRS has diagnostic utility in major depression in PD. The 3-factor structure of MADRS may help to understand the different dimensions of major depression and identify distinct symptom subgroups in this population.

Background Environmental risk factors that operate at maternal, foetal and post-natal levels, causing immune activation are known risk factors for schizophrenia. How this risk is transduced is unknown but one plausible disease mechanism may be through immune activation perturbing central nervous system growth factor systems, such as the epidermal growth factor (EGF) system critical to neuronal differentiation, maturation and plasticity, altering neurodevelopment. These interactions between EGF and immune systems may involve specific critical brain regions and not others. Methods The expression of candidate genes from EGF and immune systems and related signalling pathways, including ligands, receptors and intermediary molecules, were examined in post-mortem dorsolateral prefrontal (DLPFC) (n=114 genes) and orbitofrontal cortical (OFC) (n=105 genes) tissues, from schizophrenia and mood disorder patients and healthy controls (n=68), using the Fluidigm Biomark qRT-PCR platform. Data were analysed by ANOVA or corresponding non-parametric test (Kruskal-Wallis) in GraphPad Prism 6/7 statistical software and p values were adjusted for multiple testing (Benjamini-Hochberg). Results In DLPFC, 68 genes were significantly differently expressed between diagnostic groups. In comparison to healthy controls, 60 genes were differentially expressed in schizophrenia and 14 in the mood disorder group. Collectively these differentially expressed genes belonged predominantly to ERBB signalling and associated MAPK, PI3K and MTOR pathways and with immune pathways involving toll like receptor (TLR), TNF, nuclear factor kappa B (NFB), JAK-STAT, and complement signalling. Although there was some overlap the expression profiles in schizophrenia and mood disorder differed considerably. There were genes (n=15) with significantly lowered expression in both patient groups compared to controls which belonged predominantly to immune pathways such as TNF and TLR. However, 36 genes were differentially expressed between schizophrenia and mood disorder, all of them having lower expression in schizophrenia, predominantly representing pathways PI3K/MTOR, MAPK, TLR and TNF signalling via NFKB. Gene expression in EGF system signalling via MAPK and PI3K pathways, and interleukin signalling via JAK-STAT were significantly lower in schizophrenia than in mood disorder and healthy controls. ErbB4 was the only gene significantly elevated in a patient group (mood disorder) compared to the controls. In comparison to DLPFC, only five genes out of the 105 examined were differentially expressed between the diagnostic groups in OFC, which belonged to NFB, TLR, JAK-STAT and growth factor signalling pathways. In comparison to healthy controls all were differentially expressed in schizophrenia and three genes in the mood disorder group. The expression of most genes was decreased in the patient groups compared to control subjects in both brain regions. Discussion We conclude that there is a prominent regional difference in the expression of EGF and immune system markers, identifying the DLPFC as a region of high activity for the interaction between these two systems relative to the OFC. In this region, the differing profiles of gene expression between schizophrenia and mood disorder involved EGF signalling pathways including PI3K/MTOR and MAPK along with immune pathways such as TNF, TLR and JAK-STAT signalling, possibly reflecting variant pathological processes involving immune and EGF system signalling between these sets of disorders.

Background Depression is common in Parkinson’s disease (PD), and has a significant impact on the functional level of those affected. It is well studied in Western populations but data from Asia is limited. This study aims to estimate the prevalence of depression among PD patients attending a tertiary care outpatient clinic in Sri Lanka and identify potential risk factors. Methods One hundred and four consecutive idiopathic PD patients as defined by the United Kingdom Parkinson’s Disease Society Brain Bank Diagnostic Criteria were recruited to the study. An interviewer administered questionnaire, the Hoehn-Yahr staging scale and the Schwab-England Activities of Daily Living Scale (SEADL) were used for assessment. Depression was diagnosed through a semi-structured clinical interview based on DSM-IV-TR criteria and all subjects were rated with the Montgomery-Asberg Depression Rating Scale (MADRS). Results The prevalence of depression in the study population was 37.5%. Among the depressed 12 (30.8%) had mild depression, 21 (53.8%) moderate depression and 6 (15.4%) had severe depression. Depression was significantly associated with the stage of PD, functional impairment, civil status, educational level, caregiver dependence and concomitant diabetes mellitus. Conclusion A significant proportion of PD patients suffers from depression. The prevalence rate of depression in the sample was similar to that reported in previous studies. Depression in PD is significantly associated with functional impairment.

Clozapine is associated with weight gain. We report three patients with substantial weight loss following treatment with clozapine. The weight loss observed in the three patients was 33, 18 and 14.4 kg with percentage loss of body weight of 49, 18 and 21 respectively. Two patients had diabetes mellitus. History, physical examination and extensive investigations in the three patients did not reveal any cause that could account for the weight loss.