The neurobiological basis of treatment response in psychosis

Student thesis: Doctoral ThesisDoctor of Philosophy


Antipsychotic treatment response is unpredictable and variable, and there are currently no reliable neurobiological assessment methods to predict treatment efficacy. Previous research suggests that psychosis is associated with several brain abnormalities and that some of these may be associated with poorer treatment response.

This thesis investigated the association between brain function (salience attribution during fMRI and perfusion) and treatment response at 4 and 12 weeks in antipsychotic-naïve patients with their first episode of psychosis. Twenty-five first episode psychosis patients took part in a longitudinal, open-label intervention study, undergoing neuroimaging at baseline and again after treatment with an antipsychotic medication. Matched healthy controls were recruited and underwent two scans across a similar period. Treatment response in patients was assessed using the Positive and Negative Syndrome Scale. Seventeen patients were classed as responders and eight were non-responders. These groups were compared with each other and with healthy controls to explore differences in neurobiological measures associated with treatment response.

A good response was associated with higher implicit adaptive salience scores at baseline. Successful treatment also appeared to be associated with significant decreases in implicit aberrant salience, which was seen in responders but not non-responders. There were also differences in neural activation patterns of responders and non-responders, with greater adaptive salience activation in the insula and midbrain in four-week responders than in non-responders before and after treatment, respectively. Responders and non-responders also differed in terms of resting cerebral blood flow (rCBF), with responders showing higher cerebellar and thalamic rCBF at baseline compared with non-responders.

Furthermore, higher baseline thalamic rCBF was positively correlated with lower positive PANSS scores at follow up, suggesting an association between thalamic perfusion and response. Neurobiological differences between responders and non-responders were more marked than those between patients and controls. Heterogeneity in terms of response to treatment may reflect differences in the underlying neurobiology. Such results may inform personalised treatment of psychosis, allowing antipsychotic medication to be selected based on neurobiology rather than through trial and error.
Date of Award2016
Original languageEnglish
Awarding Institution
  • King's College London
SupervisorPaola Dazzan (Supervisor) & Philip McGuire (Supervisor)

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