Personalized medicine for schizophrenia: developing neuropsychological tests at first episode to predict treatment resistance

30% of patients with schizophrenia fail to respond to at least 2 antipsychotics [Treatment resistant schizophrenia (TRS), accounting for 25-50% of total NHS funding for mental health]. Clozapine is the gold-standard treatment for TRS, but recent evidence shows that the probability of response to clozapine diminishes when treatment is delayed, and that the mean delay in SLAM is 4 years. Early identification of TRS is therefore crucial, so that personalised treatment can be given quickly.
There is emerging evidence that TRS can be identified from first episode using neurochemical imaging such as PET and MRS. However, such investigations are costly and burdensome for patients, limiting their utility in clinical practice. Neuropsychological investigations are inexpensive, well tolerated and have great potential, alone or in combination with blood biomarkers, to stratify patients into TRS and non-TRS subtypes.

The proposed PhD will:

(1) combine existing data from first episode psychosis studies:
i. MRC: Aetiology and Ethnicity in Schizophrenia and Other Psychoses: ÆSOP (N=402);
ii. NIHR BRC Genetics and Psychosis: GAP (N=246);
iii. MRC MICA: Schizophrenia Treatment Resistance and Therapeutic Advances: (STRATA) (N=492)

(2) identify neuropsychological predictors distinguishing between treatment-responsive schizophrenia, early-onset TRS and late-onset TRS, in order to

(3) inform the design of a multi-modal approach combining genetic and other data to predict treatment response in schizophrenia.