Gene expression in the prefrontal cortex during adolescence: implications for the onset of schizophrenia

<p>Abstract</p> <p>Background</p> <p>Many critical maturational processes take place in the human brain during postnatal development. In particular, the prefrontal cortex does not reach maturation until late adolescence and this stage is associated with substantial white matter volume increases. Patients with schizophrenia and other major psychiatric disorders tend to first present with overt symptoms during late adolescence/early adulthood and it has been proposed that this developmental stage represents a "window of vulnerability".</p> <p>Methods</p> <p>In this study we used whole genome microarrays to measure gene expression in post mortem prefrontal cortex tissue from human individuals ranging in age from 0 to 49 years. To identify genes specifically altered in the late adolescent period, we applied a template matching procedure. Genes were identified which showed a significant correlation to a template showing a peak of expression between ages 15 and 25.</p> <p>Results</p> <p>Approximately 2000 genes displayed an expression pattern that was significantly correlated (positively or negatively) with the template. In the majority of cases, these genes in fact reached a plateau during adolescence with only subtle changes thereafter. These include a number of genes previously associated with schizophrenia including the susceptibility gene neuregulin 1 (NRG1). Functional profiling revealed peak expression in late adolescence for genes associated with energy metabolism and protein and lipid synthesis, together with decreases for genes involved in glutamate and neuropeptide signalling and neuronal development/plasticity. Strikingly, eight myelin-related genes previously found decreased in schizophrenia brain tissue showed a peak in their expression levels in late adolescence, while the single myelin gene reported increased in patients with schizophrenia was decreased in late adolescence.</p> <p>Conclusion</p> <p>The observed changes imply that molecular mechanisms critical for adolescent brain development are disturbed in schizophrenia patients.</p

Bipolar missed states : the diagnosis and clinical salience of bipolar mixed states

Objective: To explore diagnostic and treatment issues concerning bipolar mixed states.Method: Bipolar mixed states are described and concerns about diagnostic and treatment difficulties are summarized and discussed.Result: Mixed states can present with equal admixtures of depressive or manic symptoms, or more commonly one component predominates. There is fair consensus, although little data, regarding the management of manic mixed states. However depressive mixed states are far more complex both in terms of recognition and management. People suffering from mixed states characteristically present with complaints of depression.Conclusions: The boundaries between depressive mixed states and agitated depression are vague, yet carry substantial therapeutic implications. Bipolar mixed states are often difficult to treat, and tend to take much longer to settle than either pure mania or depression.&nbsp; Furthermore there is data that treatment with antidepressants can worsen the course of mixed states. Hence missed diagnoses can potentially have negative clinical implications.&nbsp; Therefore in this paper the clinical presentation, diagnosis and therapy of mixed states is reviewed with a view to improving management.<br /

The glass cage: an ethnography of exposure in schizophrenia

This article draws upon anthropological research conducted with a group of people who have a diagnosis of schizophrenia and are living in a major Australian city. The analysis aims to show how these men and women experience their bodies at a day-to-day level, focusing on how they talk about their bodies, awareness of their bodies, and the relation of their bodies to the lived world. Rather than rely on established psychiatric classificatory models of interpretation, experiences are relocated within a broader framework of embodiment and social practice. The article argues that schizophrenia is not solely a 'disorder of the mind', but an experience which embodies and reproduces a multiplicity of cultural meanings associated with the concept of privacy. Through the close examination of one case study, the cultural logic of privacy is unpacked and shown to be at the core of many bodily experiences associated with schizophrenia. Reinterpreting such experiences in this light has implications for the ways in which those with schizophrenia are understood and treated