title: Antipsychotic medication is associated with selective alterations in ventricular cerebrospinal fluid Aβ 40 and tau in patients with intractable unipolar depression.
abstract: OBJECTIVE
  Alterations in plasma and in lumbar cerebrospinal fluid amyloid-B peptide (Aβ) levels have been reported in Alzheimer's disease. Studies have also suggested similar changes in depressed patients. No information is available on the impact of psychotropic drugs on this in patients with depression. We therefore quantified Aβ in ventricular cerebrospinal fluid (CSF) in a population of patients with treatment-resistant depression, with and without antipsychotic medication.
  
  
  METHODS
  A cross-sectional study of 32 patients undergoing subcaudate tractotomy for major (unipolar) depressive disorder. Ventricular CSF concentrations of Aβ peptide 1-40 and 1-42, also p-tau and total tau were determined by Western blotting or enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Patients taking antipsychotic medication in the 2 weeks prior to surgery demonstrated significantly higher levels of Aβ 1-40 (mean ± SD: 727.3 ± 382.3 vs. 440.9 ± 337.2 pg/ml; p = 0.032, Student's t-test) but unaltered Aβ 1-42 (mean 72.1 ± 67.5 vs. 60.0 ± 56.7 pg/ml; p = 0.587) compared to a matched sample not treated with antipsychotic drugs. The same group demonstrated elevated total tau (mean 945.0 ± 422.2 vs. 534.3 ± 388.3 pg/ml; p = 0.010) but not p-tau (mean 98.6 ± 71.5 vs. 88.1 ± 70.5 pg/ml; p = 0.694). No similar effect was found with lithium, antidepressants, carbamazepine or benzodiazepines.
  
  
  CONCLUSIONS
  This preliminary study suggests antipsychotic drugs, widely used in patients with severe depression across all age ranges, may be associated with alteration of Aβ 1-40 and total tau, indices strongly linked with progressive organic brain disease. Further confirmatory work is needed.
authors.affiliation: King's College London, Wolfson Centre for Age-Related Diseases, London, UK.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Clarke
authors.forename: Tobias
authors.initials: T
authors.lastname: Hartmann
authors.forename: Emma L
authors.initials: EL
authors.lastname: Jones
authors.forename: Clive G
authors.initials: CG
authors.lastname: Ballard
authors.forename: Paul T
authors.initials: PT
authors.lastname: Francis
mesh_terms: D000328:Adult; D000368:Aged; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015415:Biomarkers / Q000134:cerebrospinal fluid; D015153:Blotting, Western; D003430:Cross-Sectional Studies; D003865:Major Depressive Disorder / Q000134:cerebrospinal fluid* / Q000188:drug therapy / Q000601:surgery; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011300:Preoperative Care; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D014150:Antipsychotic Agents; D015415:Biomarkers; D016875:tau Proteins