To determine a) whether polyIC-induced maternal immune activation leads to changes in the levels of KP metabolites in preadolescent offspring (postnatal days (PNDs) 31-33); b) whether treatment with a COX-2 inhibitor (celecoxib) at PNDs 35-47 prevents the development of behavioural abnormalities characteristic in adult offspring of polyIC treated mothers. Methods: Pregnant rats were treated with polyIC at gestational day 19. KP metabolites were quantified in serum of offspring at PNDs 31-33 using HPLC and GC/MS. mRNA expression of COX-2, cytokines (IL6, TNF-a) and KP enzymes (KATII, KMO) were measured in the hippocampus using qPCR. Offspring were given celecoxib (2.5 and 5 mg/kg/day) from PNDs 35-47. Hyperlocomotor response to MK801 (0.3mg/kg) was tested in adulthood (PNDs>90).
Offspring of polyIC treated mothers had decreased kynurenine (KYN) (29%, p=0.009), KYNA (27%, p=0.055) and increased quinolinic acid (p=0.055) in serum at PNDs 31-33. In the hippocampus, KATII mRNA was reduced by 16% (p=0.037) and KMO mRNA was reduced by 54% (p=0.02). COX2, IL6 and TNF-a mRNAs were not significantly altered. Correlations were observed between KYN levels in serum and KATII (r=0.681, p=0.003) and KMO (r=-0.484, p=0.049) expression in the brain. Treatment with 2.5-5 mg/kg/day celecoxib prevented the increase in MK-801induced hyperlocomotion found in adults with prenatal polyIC exposure.
Prenatal polyIC has significant effects on the KP metabolomics in both brain and periphery in preadolescent offspring. COX-2 inhibition appears to prevent the adult schizophrenia-like behavioural changes associated with prenatal polyIC.
Up to 45% of patients with schizophrenia are treatment resistant to conventional drugs leaving clozapine as the only effective option. Its severe side-effects however limit it to a late stage option and the development of a biomarker to predict treatment response would be of high clinical utility. Our previous data demonstrate clozapine augments epidermal growth factor receptor (EGFR) signalling and hence we examined if EGF levels may be altered in treatment resistant schizophrenia (TRS) and are influenced by clozapine treatment. To determine if EGF levels are influenced by clozapine in TRS and can serve as a biomarker for clozapine response. Serum EGF levels were measured by ELISA in patients with TRS at baseline, 2, 6 and 26 weeks of clozapine treatment and in age and sexed matched healthy controls. Positive and Negative Syndrome Scale (PANSS) and CGI data were collected at baseline, 6 and 26 weeks.
Evidence from genetic association studies implicate genes involved in neural migration associated with schizophrenia risk. Neural stem/progenitor cell cultures (neurosphere-derived cells) from olfactory mucosa of schizophrenia patients have significantly dysregulated expression of genes in focal adhesion kinase signalling, a key pathway regulating cell adhesion and migration. The aim of this study was to investigate whether olfactory neurosphere-derived cells from schizophrenia patients have altered cell adhesion, cell motility, and focal adhesion dynamics. Olfactory neurosphere-derived cells from nine male schizophrenia patients and nine male healthy control subjects were used. Cells were assayed for cell adhesion and cell motility and analysed for integrins and focal adhesion kinase proteins. Focal adhesions were counted and measured in fixed cells and time-lapse imaging was used to assess cell motility and focal adhesion dynamics.
Post-mortem analyses of cortical brain tissue in schizophrenia have been shown to display epigenetic changes that reflect early life experience. These affect the regulation of gene expression at the level of transcription, through changes in chromatin structure; and post-transcriptionally through non-coding RNAs, such as microRNA (miRNA). The aim of the current study was to investigate the role of miRNA in the brains’ response to maternal immune activation and adolescent cannabis exposure, alone and in combination, as both have been identified as environmental risk factors for schizophrenia.
NOTE: Only available in Mp3 audio file. Traumatic insanity has been acknowledged since Meyer (1904), however, Psychosis Following Traumatic Brain Injury (PFTBI) has received modest empirical investigation, and is subsequently poorly understood, identified, and treated. Systematic and standardised neuropsychological research of PFTBI has not been reported, with work relying on retrospective chart reviews, case studies, and loosely defined self-reported Traumatic Brain Injury (TBI).
The dopamine system plays a crucial role in mediating cognitive and affective processes. Aberrant dopamine neurotransmission is also thought to underlie the symptoms of schizophrenia. Dopamine-dependent prefrontal response relies on the regulation of both dopamine availability and the relative balance of D1/D2 receptor mediated action. This study aimed to determine the extent to which the catechol-O-methyltransferase (COMT) val108/158met (rs4680) and dopamine D2 receptor (DRD2) G-T (rs2283265) polymorphisms combine additively to determine prefrontal brain activity during cognitive-affective processing in healthy people and in schizophrenia.
This presentation, "Responding to the needs of consumers with complex trauma histories a consumer perspective" focuses on the needs of adult survivors of child abuse, highlighting the frequent