Table 1.

Alterations of Antioxidant Defense System in Patients with Schizophrenia

AODS	SZ population	Source	Findings	References	Implications/comments
Antioxidants
Proteins
Albumin, Bilirubin	First-episode, neuroleptic-naive	Plasma	Decrease	194, 220	Increased bilirubin consumption may be secondary to oxidative stress.
	Chronic	Plasma	Decrease	194, 268, 275, 290, 292
Biopyrrins	Chronic	Urine	Increase	173	Biopyrrins are oxidative metabolites of bilirubin.
Thioredoxin (TRX)	First-episode, neuroleptic-naive	Serum	Increase	301	Serum TRX levels were also positively correlated with positive symptoms of Positive and Negative Syndrome Scale. Following antipsychotic treatment, reduced TRX levels may provide us with biochemical index of therapeutic outcome.
UA	First-episode, neuroleptic-naive	Plasma	Decrease	219, 284	The potential for steady formation of antioxidant UA from purine catabolism is altered early in the course of SZ (284). UA and inosine (precursor of UA) may be beneficial in the treatment of oxidative stress related neurodegenerative diseases (60, 97, 144, 229, 241).
	Chronic, treated	Plasma	Decrease	289
Vitamins
Ascorbic acid	Chronic	Plasma	Decrease	43, 249	Some (44, 234), though not all (263), studies suggest that add-on supplementation of vitamin C may reduce oxidative stress and improve the outcome of SZ.
		Urine	Decrease	249
Tocopherol	SZ with tardive dyskinesia	Plasma	Decrease	23	Vitamin E levels in plasma were corrected for total lipids.
Glutathione	Untreated	Plasma	Decrease	212	Adjunctive N-acetyl cysteine, a precursor for GSH synthesis, may provide us with a novel therapeutic intervention targeting GSH Dysregulation in SZ (15, 139).
	Chronic	Plasma	Decrease	51
		CSF	Decrease	54
		Prefrontal cortex	Decrease	54
		Postmortem caudate	Decrease	286
Free thiols	Chronic	Serum	Decrease	101
	Chronic	Platelets	Decrease	49
Scavenging enzymes
Superoxide dismutase	Chronic	Serum	Increase	43, 75, 137, 306
		RBC	Increase	1, 169, 217, 289, 305
		Platelets	Decrease	50
		Postmortem brain	Increase	168
	Chronic, untreated	RBC	Increase	290
	Children, untreated	Platelets	Decrease	84
	Early course, untreated	Blood	Increase	129
		RBC	Decrease	177, 212	With progression of the illness, the superoxide dismutase levels may rise as a compensatory response to oxidative stress (177).
	Treated	RBC	Decrease	212
CAT	Untreated	RBC	Decrease	212
	Treated	RBC	Decrease	212
GSH peroxidase	Chronic, treated	RBC	Decrease	85, 169, 193, 212
	Untreated	RBC	Decrease	1
		Plasma	Increase	307
	Neuroleptic-naive	Plasma	Increase	307
NO signaling
NOS activity	Chronic	Postmortem cerebral cortex	Decrease	277	In light of inconsistent findings, it is surmised that NO and its metabolites may not be of diagnostic value to distinguish SZ from healthy controls or other brain disorders.
		Platelets	Increase	45
NOS concentration	Chronic	Postmortem cerebellar vermis	Increase	122
Neuronal NOS expression	Chronic	Postmortem prefrontal cortex	Increase	9
Neuronal NOS expression	Chronic	Hypothalamus	Decrease	16
NO	Chronic	Postmortem caudate	Increase	287
		Serum	Increase	253
		Plasma	Decrease	140, 184
		RBC	Increase	96
NO2−, NO3−	Chronic	CSF	Decrease	213
NO2−	Chronic	Plasma	Increase	308
		Plasma	Decrease	279
NO3−	Chronic	Plasma	Decrease	250
Lipid peroxidation
Thiobarbituric acid reactive species (TBARS)	Chronic	Blood	Increase	3, 65, 75, 85, 88, 137, 189, 193, 198, 207, 208, 302	Findings to date suggest that oxidative stress occurs at very early in the course of illness, and independent of treatment. However, few other studies from Scottish SZ Research Group (230) and Skinner et al. (235) do not support the view that increased lipid peroxidation is associated with the SZ per se.
	First-episode, neuroleptic-naive	Plasma	Increase	153
	Chronic	Platelets	Increase	50
	SZ with tardive dyskinesia	CSF7	Increase	146
Pentane	Chronic	Breath	Increase	134, 202
Ethane	Chronic	Breath	Increase	211
Isoprostanes	Chronic	Urine	Increase	52
Protein modifications
3-Nitrotyrosine	Chronic	Plasma	Increase	51
		Platelets	Increase	49
4-hydroxynonenal	Chronic	Postmortem anterior cingulate	Increase	269

CSF, cerebrospinal fluid; GSH, glutathione; NOS, nitric oxide synthase; RBC, red blood cell; SZ, schizophrenia; UA, uric acid.