Antipsychotic medication is associated with selective alterations in ventricular cerebrospinal fluid A beta 40 and tau in patients with intractable unipolar depression

TY - JOUR

T1 - Antipsychotic medication is associated with selective alterations in ventricular cerebrospinal fluid A beta 40 and tau in patients with intractable unipolar depression

AU - Clarke, Nicholas A.

AU - Hartmann, Tobias

AU - Jones, Emma L.

AU - Ballard, Clive G.

AU - Francis, Paul T.

PY - 2011/12

Y1 - 2011/12

N2 - Objective: Alterations in plasma and in lumbar cerebrospinal fluid amyloid-B peptide (A beta) 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 A beta in ventricular cerebrospinal fluid (CSF) in a population of patients with treatment-resistant depression, with and without antipsychotic medication. Method: A cross-sectional study of 32 patients undergoing subcaudate tractotomy for major (unipolar) depressive disorder. Ventricular CSF concentrations of A beta 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 A beta 1-40 (mean +/- SD: 727.3 +/- 382.3 vs. 440.9 +/- 337.2 pg/ml; p = 0.032, Student's t-test) but unaltered A beta 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 A beta 1-40 and total tau, indices strongly linked with progressive organic brain disease. Further confirmatory work is needed. Copyright (C) 2011 John Wiley & Sons, Ltd.

AB - Objective: Alterations in plasma and in lumbar cerebrospinal fluid amyloid-B peptide (A beta) 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 A beta in ventricular cerebrospinal fluid (CSF) in a population of patients with treatment-resistant depression, with and without antipsychotic medication. Method: A cross-sectional study of 32 patients undergoing subcaudate tractotomy for major (unipolar) depressive disorder. Ventricular CSF concentrations of A beta 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 A beta 1-40 (mean +/- SD: 727.3 +/- 382.3 vs. 440.9 +/- 337.2 pg/ml; p = 0.032, Student's t-test) but unaltered A beta 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 A beta 1-40 and total tau, indices strongly linked with progressive organic brain disease. Further confirmatory work is needed. Copyright (C) 2011 John Wiley & Sons, Ltd.

U2 - 10.1002/gps.2678

DO - 10.1002/gps.2678

M3 - Article

SN - 1099-1166

VL - 26

SP - 1283

EP - 1291

JO - International Journal of Geriatric Psychiatry

JF - International Journal of Geriatric Psychiatry

IS - 12

ER -