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Howes OD, Bose SK, Turkheimer F, Valli I, Egerton A, Valmaggia LR, Murray RM, McGuire P. Dopamine synthesis capacity before onset of psychosis: a prospective [18F]-DOPA PET imaging study. Am J Psychiatry . 2011 Dec ; 168(12):1311-7. PubMed Abstract

Comments on Paper and Primary News
Comment by:  Anissa Abi-Dargham, SRF Advisor
Submitted 9 January 2012 Posted 9 January 2012

The elegant studies of Oliver Howes and colleagues (Howes et al., 2011; Howes et al., 2009; Howes et al., 2011) have contributed valuable information regarding the high-risk state and dopamine (DA). Because of these studies, it is now clear that striatal dopamine dysregulation precedes onset of psychosis, relates to symptoms, and affects the associative striatum most predominantly, at least initially, extending into the sensorimotor subregion with time (Howes et al., 2011), while the ventral striatum remains relatively spared. These are difficult studies in terms of recruitment, characterization, and retention of subjects for longitudinal follow-up, and represent a great contribution to our field.

The paper discussed here (  Read more

View all comments by Anissa Abi-Dargham

Comment by:  William Carpenter, SRF Advisor (Disclosure)
Submitted 11 January 2012 Posted 11 January 2012

Howes et al. make an important contribution in reporting increased striatal dopamine synthesis in a patient/subject cohort at ultra high risk for psychosis. Most interesting is the correlation between dopamine synthesis and transition to psychosis. An important milestone in the dopamine hypothesis of schizophrenia came with in-vivo neuroimaging evidence of increased dopamine release in persons with schizophrenia reported by Breier and colleagues (Breier et al., 1997) and by Laruelle and colleagues (Laruelle et al., 1996). This was the first direct evidence for the dopamine hypothesis. Howes et a. cite recent reviews by Abi-Dargham and others, and a meta-analysis is now available with advance access in the Schizophrenia Bulletin (Fusar-Poli and Meyer-Lindenberg, 2011) for the interested reader.

This report is timely for several reasons:

  • A rapidly growing and now large literature reporting empirical evidence for the validity of a disorder/syndrome referred to as "at risk...  Read more

View all comments by William Carpenter

Primary News: Signs of Things to Come? Seeking Biomarkers for the Schizophrenia Prodrome

Comment by:  Thomas McGlashan
Submitted 21 January 2012 Posted 21 January 2012

Three very recent publications have detailed that biomarkers can identify and quantify high-risk or prodromally symptomatic subjects who subsequently undergo conversion to psychosis. McGuire and his group (Howes et al., 2011) used fluoro-dopa positron emission tomography scanning to measure dopamine synthesis. Koutsouleris et al. (Koutsouleris et al., 2011) used structural MRI data to develop a neuroanatomical classification system for predicting psychosis conversion, and Amminger et al. (Amminger et al., 2011) used capillary gas chromatography of erythrocyte membrane fatty acid levels to provide information about brain phospholipids. All measures were significantly successful in identifying high-risk or prodromally symptomatic subjects who went on to develop a first episode of psychosis.

These papers point to an exciting future in our efforts to elaborate easily identifiable risk factors that can pinpoint among clinically identified...  Read more

View all comments by Thomas McGlashan
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