Neurophysiological Biomarkers for Drug Development in Schizophrenia

Overview

Journal Nat Rev Drug Discov

Specialty Pharmacology

Date 2007 Dec 8

PMID 18064038

Citations 141

Authors

Daniel C Javitt

Kevin M Spencer

Gunvant K Thaker

Georg Winterer

Mihaly Hajos

Affiliations

Soon will be listed here.

Abstract

Schizophrenia represents a pervasive deficit in brain function, leading to hallucinations and delusions, social withdrawal and a decline in cognitive performance. As the underlying genetic and neuronal abnormalities in schizophrenia are largely unknown, it is challenging to measure the severity of its symptoms objectively, or to design and evaluate psychotherapeutic interventions. Recent advances in neurophysiological techniques provide new opportunities to measure abnormal brain functions in patients with schizophrenia and to compare these with drug-induced alterations. Moreover, many of these neurophysiological processes are phylogenetically conserved and can be modelled in preclinical studies, offering unique opportunities for use as translational biomarkers in schizophrenia drug discovery.

Citing Articles

Quantitative analysis of literature on diagnostic biomarkers of Schizophrenia: revealing research hotspots and future prospects.

Jin L, Wu L, Zhang J, Jia W, Zhou H, Jiang S BMC Psychiatry. 2025; 25(1):186.

PMID: 40025442 PMC: 11872302. DOI: 10.1186/s12888-025-06644-3.

Schizophrenia and Bone Marrow Disorders: An Emerging Clinical Association.

Jayakumar J, Ginjupalli M, Kalaivani Babu A, Rajarajan S, Jakkam Setty M Cureus. 2025; 16(12):e75822.

PMID: 39816323 PMC: 11735017. DOI: 10.7759/cureus.75822.

Endophenotype 2.0: updated definitions and criteria for endophenotypes of psychiatric disorders, incorporating new technologies and findings.

Liu C, Gershon E Transl Psychiatry. 2024; 14(1):502.

PMID: 39719446 PMC: 11668880. DOI: 10.1038/s41398-024-03195-1.

Biomarker discovery using machine learning in the psychosis spectrum.

Yassin W, Loedige K, Wannan C, Holton K, Chevinsky J, Torous J Biomark Neuropsychiatry. 2024; 11.

PMID: 39687745 PMC: 11649307. DOI: 10.1016/j.bionps.2024.100107.

Alcohol Modulates Frontal Cortex and BLA Network States Which Correlate with Future Voluntary Alcohol Consumption.

DiLeo A, Antonodiou P, Blandino K, Conlin E, Melon L, Maguire J eNeuro. 2024; 11(12).

PMID: 39626949 PMC: 11649967. DOI: 10.1523/ENEURO.0017-24.2024.

References

Porteous D, Thomson P, Brandon N, Kirsty Millar J . The genetics and biology of DISC1--an emerging role in psychosis and cognition. Biol Psychiatry. 2006; 60(2):123-31. DOI: 10.1016/j.biopsych.2006.04.008. View

Braff D, Geyer M, Swerdlow N . Human studies of prepulse inhibition of startle: normal subjects, patient groups, and pharmacological studies. Psychopharmacology (Berl). 2001; 156(2-3):234-58. DOI: 10.1007/s002130100810. View

Staubli U, Xu F . Effects of 5-HT3 receptor antagonism on hippocampal theta rhythm, memory, and LTP induction in the freely moving rat. J Neurosci. 1995; 15(3 Pt 2):2445-52. PMC: 6578162. View

Winterer G, Musso F, Beckmann C, Mattay V, Egan M, Jones D . Instability of prefrontal signal processing in schizophrenia. Am J Psychiatry. 2006; 163(11):1960-8. DOI: 10.1176/ajp.2006.163.11.1960. View

Kegeles L, Abi-Dargham A, Zea-Ponce Y, Mann J, van Heertum R, Cooper T . Modulation of amphetamine-induced striatal dopamine release by ketamine in humans: implications for schizophrenia. Biol Psychiatry. 2000; 48(7):627-40. DOI: 10.1016/s0006-3223(00)00976-8. View

Buchanan R, Freedman R, Javitt D, Abi-Dargham A, Lieberman J . Recent advances in the development of novel pharmacological agents for the treatment of cognitive impairments in schizophrenia. Schizophr Bull. 2007; 33(5):1120-30. PMC: 2632365. DOI: 10.1093/schbul/sbm083. View

Umbricht D, Vyssotky D, Latanov A, Nitsch R, Brambilla R, DAdamo P . Midlatency auditory event-related potentials in mice: comparison to midlatency auditory ERPs in humans. Brain Res. 2004; 1019(1-2):189-200. DOI: 10.1016/j.brainres.2004.05.097. View

Friedman D, Cornblatt B, Vaughan Jr H, Erlenmeyer-Kimling L . Auditory event-related potentials in children at risk for schizophrenia: the complete initial sample. Psychiatry Res. 1988; 26(2):203-21. DOI: 10.1016/0165-1781(88)90075-3. View

Thaker G, Ross D, Cassady S, Adami H, Laporte D, Medoff D . Smooth pursuit eye movements to extraretinal motion signals: deficits in relatives of patients with schizophrenia. Arch Gen Psychiatry. 1998; 55(9):830-6. DOI: 10.1001/archpsyc.55.9.830. View

10.

Light G, Malaspina D, Geyer M, Luber B, Coleman E, Sackeim H . Amphetamine disrupts P50 suppression in normal subjects. Biol Psychiatry. 1999; 46(7):990-6. DOI: 10.1016/s0006-3223(99)00034-7. View

11.

Roth W, Cannon E . Some features of the auditory evoked response in schizophrenics. Arch Gen Psychiatry. 1972; 27(4):466-71. DOI: 10.1001/archpsyc.1972.01750280034007. View

12.

Siuciak J, Chapin D, McCarthy S, Guanowsky V, Brown J, Chiang P . CP-809,101, a selective 5-HT2C agonist, shows activity in animal models of antipsychotic activity. Neuropharmacology. 2006; 52(2):279-90. DOI: 10.1016/j.neuropharm.2006.07.024. View

13.

Javitt D, Schroeder C, Steinschneider M, Arezzo J, Vaughan Jr H . Demonstration of mismatch negativity in the monkey. Electroencephalogr Clin Neurophysiol. 1992; 83(1):87-90. DOI: 10.1016/0013-4694(92)90137-7. View

14.

ODonnell B, Vohs J, Hetrick W, Carroll C, Shekhar A . Auditory event-related potential abnormalities in bipolar disorder and schizophrenia. Int J Psychophysiol. 2004; 53(1):45-55. DOI: 10.1016/j.ijpsycho.2004.02.001. View

15.

Umbricht D, Koller R, Schmid L, Skrabo A, Grubel C, Huber T . How specific are deficits in mismatch negativity generation to schizophrenia?. Biol Psychiatry. 2003; 53(12):1120-31. DOI: 10.1016/s0006-3223(02)01642-6. View

16.

Cancelli I, Cadore I, Merlino G, Valentinis L, Moratti U, Bergonzi P . Sensory gating deficit assessed by P50/Pb middle latency event related potential in Alzheimer's disease. J Clin Neurophysiol. 2006; 23(5):421-5. DOI: 10.1097/01.wnp.0000218991.99714.ee. View

17.

Brockhaus-Dumke A, Tendolkar I, Pukrop R, Schultze-Lutter F, Klosterkotter J, Ruhrmann S . Impaired mismatch negativity generation in prodromal subjects and patients with schizophrenia. Schizophr Res. 2005; 73(2-3):297-310. DOI: 10.1016/j.schres.2004.05.016. View

18.

MacDonald 3rd A, Carter C, Kerns J, Ursu S, Barch D, Holmes A . Specificity of prefrontal dysfunction and context processing deficits to schizophrenia in never-medicated patients with first-episode psychosis. Am J Psychiatry. 2005; 162(3):475-84. DOI: 10.1176/appi.ajp.162.3.475. View

19.

Knott V, Scherling C, Blais C, Camarda J, Fisher D, Millar A . Acute nicotine fails to alter event-related potential or behavioral performance indices of auditory distraction in cigarette smokers. Nicotine Tob Res. 2006; 8(2):263-73. DOI: 10.1080/14622200600576669. View

20.

Porjesz B, Almasy L, Edenberg H, Wang K, Chorlian D, Foroud T . Linkage disequilibrium between the beta frequency of the human EEG and a GABAA receptor gene locus. Proc Natl Acad Sci U S A. 2002; 99(6):3729-33. PMC: 122592. DOI: 10.1073/pnas.052716399. View