Patient-derived cells were less adhesive and more motile than cells derived from healthy controls and their motility was reduced to control cell levels by integrin-blocking antibodies and by inhibition of focal adhesion kinase. Vinculin-stained focal adhesion complexes were significantly smaller and fewer in patient cells. Time-lapse imaging of cells expressing focal adhesion kinase tagged with green fluorescent protein revealed that the disassembly of focal adhesions was significantly faster in patient cells. The evidence for altered motility and focal adhesion dynamics in patient-derived cells is consistent with dysregulated gene expression in the focal adhesion kinase signalling pathway in these cells. Alterations in cell adhesion dynamics and cell motility could bias the trajectory of brain development in schizophrenia.
Kynurenic acid (KYNA), a glia-derived metabolite of the kynurenine pathway (KP) of tryptophan degradation, is an antagonist at glutamate NMDA and a7 nicotinic acetylcholine receptors. Abnormalities in the KP have been described in patients with schizophrenia. Cyclo-oxygenese-2 (COX-2) inhibitors show considerable promise in treating early (but not late) stage schizophrenia and preclinical studies suggest that COX-2 inhibitors decrease KYNA in the brain.
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.
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