Table 1

Studies evaluating the association between the COMT Val¹⁵⁸Met polymorphism and neuropsychological tests

Study	No. patients	Diagnosis	No. controls (relatives)	Cognitive measures	Main results*
Green et al.16	—		160	MSIT, WASI (vocabulary, similarities, block design, matrix reasoning)	MSIT (accuracy and reaction time): Val/Val ↓ WASI: Val/Val ↓
Gong et al.17	—		700	Digital and spatial working memory spans	No association between COMT and digital and spatial working memory spans
Blanchard et al.18	—		291	Spatial n-back task	No association between COMT and n-back task
Greenwood et al.19	87	Schizophrenia	—	WCST, WAIS-R (digit span)	WCST (category achievement): Val/Met ↓ No association between COMT and WCST (perseverative errors) and digit span
Wishart et al.20	—		95	TMT A–B, D-KEFS (trail-making subtest)	TMT-B: Val/Val Val/Met ↓ No association between COMT and TMT A TMT-B: COMT x ANKK1 interaction: Val carriers + T carriers ↓
Stokes et al.21	—		50	Spatial n-back, go/no-go, Tower of London tasks	No association between COMT and any cognitive measure
Rosa et al.22	67	Schizophrenia and schizoaffective disorder	186	Modified Stroop test (manipulating level of required cognitive stability)	Patients and controls: task requiring cognitive stability: Val/Val ↓ No association between COMT and task requiring cognitive flexibility
Solís-Ortiz et al.23	—		74 F	WCST, Stroop test, CPT (test single and AX task), verbal fluency test	WCST (commission errors) – Stroop test: Val/Val ↑ No association between COMT and CPT and verbal fluency test
Uçok et al.24	99	Schizophrenia	—	WCST, CPT (ZA task)	CPT (commission errors): Val/Val Val/Met ↓ No association between COMT and WCST
Wilkosc et al.25	—		200	WCST	WCST (percentage of nonperseverative errors): Val/Val Val/met ↓ (in males only)
Wirgenes et al.26	315	Schizophrenia-spectrum disorders 137 schizophrenia 27 schizoaffective disorder 7 schizophreniform disorder	340	Bergen n-back task, digit symbol coding test, CVLT, D-KEFS (colour-word interference test, verbal fluency test)	Schizophrenia: n-back task: Val/Val ↓ No association between COMT and other cognitive measures Controls: no association between COMT and any cognitive measures
Pomarol-Clotet et al.27	42	Schizophrenia	31	N-back task (sequential letter version)	No association between COMT and n-back task
Dennis et al.28	—		496 to 1218	CANTAB (paired associates learning, spatial working memory, verbal recognition memory—immediate recall, ID/ED, rapid visual processing, spatial span, spatial recognition memory), Green’s story recall (immediate and delayed), TMT A–B, WAIS-III (forward and backward digit span, digit symbol, symbol search), COWAT, semantic fluency, Stroop colour-word interference	No association between COMT and any cognitive measures
Van den Bos et al.29	—		70	IGT	Val/Val ↑
Yue et al.30	—		21	N-back task (sequential number version)	Val/Met ↓, Val/Val ↑
Krug et al.31	—		80	Verbal fluency	No association between COMT and verbal fluency
Neuhaus et al.32	111	Schizophrenia	—	CPT-IP	Val/Val ↑
Prata et al.33	42	Schizophrenia	48	Verbal fluency task	Schizophrenia: Val/Val Val/Met ↓ Controls: no association between COMT and verbal fluency task
Schmack et al.34	—		44	Monetary incentive delay	No association between COMT and monetary incentive delay
Sheldrick et al.35	—		522	D2 Test of Attention, MWT-B, LNS, TMT B, verbal fluency, Wechsler Memory Scale (spatial span)	TMT-B: Val/Val ↓ No association between COMT and other cognitive measures
Roussos et al.36	—		107	SoC, IGT	SoC: Val/Val ↓ IGT: Val/Val ↑
Roffman et al.37	185	Chronic schizophrenia	—	WCST	No association between COMT and WCST (perseverative errors and category achievement) COMT x MTHFR mutation interaction: Val/Val +T carriers ↓(perseverative errors)
Opgen-Rhein et al.38	63	Schizophrenia	40	ANT	Schizophranie–controls: Val/Val ValMet ↓ reaction time and ↑ conflict effect scores
Mata et al.39	130	First-episode nonaffective psychosis	—	General verbal ability: WAIS-III (vocabulary, similarities, information, and comprehension subtests) Attention and processing speed: CPT (correct trials), WAIS-III (digit symbol coding), WAIS-III (forward digits), TMT-A Executive and perceptual organization function: WAIS-III (backward digits, letter fluency, category fluency), TMT-B Verbal memory: Rey Auditory Verbal Learning Test (initial learning, total learning, short-term recall, long-term recall, recognition) Visual memory: Rey complex figure (immediate reproduction, delayed reproduction) Motor function: Grooved Pegboard Test (dominant and nondominant hand), finger tapping test (dominant and nondominant hand)	No association between COMT and any cognitive domain
Diaz-Asper et al.40	325	Schizophrenia, schizoaffective disorder	330 (359)	Spatial n-back task, WCST, CPT 1–9, WAIS-R (short form: arithmetic, similarities, picture completion and digit symbol), ID/ED	Patients, controls, relatives: N-back task: Val/Val ↓ No association between COMT and other cognitive measures
Bertolino et al.41	—		82	Spatial n-back task, recognition memory paradigm	No association between COMT and any cognitive measures
Aguilera et al.42	—		521	WCST, CPT-IP, WMS-R (backward visual span), WAIS III (LNS)	LNS: Val/Val ↓ No association between COMT and other cognitive measures
Woodward et al.43	86	Schizophrenia	—	ACTT, WCST, WISC-R (mazes), BSRT, CIGT, COWAT, WAIS-R (digit symbol)	ACTT and WCST (perseverative errors): Val/Val ↓ No association between COMT and other cognitive measures
MacDonald et al.44	—		464	N-back task (sequential letter version), CPT (AX/DPX tasks)	CPT (DPX): Val/Val ↓ No association between COMT and performance on N-back
Ehlis et al.45	56	Schizophrenia-spectrum disorders	—	Stroop test, TMT A–B, verbal fluency test	Stroop test: Val/Val Val/Met ↓ (trend significance) No association between COMT and other cognitive measures
Dickerson et al.46	364	Schizophrenia	—	RBANS: immediate memory (list learning and story memory tasks), visuospatial/constructional (figure copy and line orientation tasks), language (picture naming and semantic fluency tasks), attention (digit span and coding tasks) and delayed memory (list recall, story recall, figure recall and list recognition tasks)	No association between COMT and any of the RBANS index
Caldú et al.47	—		75	WCST, Conners’ CPT II, n-back task, WAIS (vocabulary)	WCST and CPT (commission errors): Val/Val Val/Met ↓ No association between COMT and other cognitive measures CPT (commission errors): COMT x DAT interaction: Val/Val and 10/10 ↓
Barnett et al.48	822	Schizophrenia-spectrum disorders	1088	WCST	Patients: no association between COMT and WCST (perseverative errors) Controls: WCST (perseverative errors): Val/Val ↓
Szöke et al.49	66	Schizophrenia	50 (57 SCZ)	TMT A–B, WCST	Patients, controls, relatives: no association between COMT and any cognitive measure
Rybakowski et al.50	79	Schizophrenia	—	WCST	WCST: Val/Val male ↑ (perseverative errors) Val/Val female ↓ (nonperseverative errors)
Krabbendam et al.51	23	Schizophrenia	21 (33)	CPT (Flanker version)	Patients, controls, relatives: Val/Val ↓ (correct responses)
Han et al.52	132M	First-episode schizophrenia, schizoaffective disorder	—	WAIS (information, digit span, vocabulary. arithmetic comprehension, similarity, picture, picture arrangement, block design, object assembly, digit symbol)	Digit span: Val/Val ↓ Similarity: Val/Val ↑
Golimbet et al.53	124	Schizophrenia	116 (79)	Long-term memory, short-term memory, verbal fluency, selectivity of speech relations, calculating with switching over	No association between COMT and any cognitive measure
Bertolino et al.54	—		27	Recognition memory paradigm	Val/Val ↓ (accuracy at retrieval)
Stefanis et al.55	—		527	CPT-IP version	Val/Val Val/Met: higher reaction time variability
Ho et al.56	159	Schizophrenia	84	WCST, digit span backward, TMT A–B	No association between COMT and any cognitive measure
Galderisi et al.57	106	Schizophrenia	—	CPT (AX task), WCST	CPT (AX errors) and WSCT (perseverative errors): Val/Val ↓
Bruder et al.58	—		402	SDR, WSPT, N-back (sequential letter version), LNS, WCST (n = 246)	WCST and LNS: Val/Val ↓ No association between COMT and other cognitive measures
Blasi et al.59	—		23	Variable attentional control task	Val/Val Val/Met ↓
Rosa et al.60	89	Schizophrenia, schizoaffective disorder, psychotic mood disorder, schizophreniform disorder, brief psychotic disorder, delusional disorder, atypical psychosis	(89)	WCST	Patients: no association between COMT and performance on WCST Relatives: Val/Val ↓ (perseverative errors)
Nolan et al.61	26	Schizophrenia, schizoaffective disorder	—	Competing programs task	Val/Val Val/Met ↓ cognitive stability and ↑ cognitive flexibility
de Frias et al.62	—		286 M	Episodic memory (recall test, recognition test), semantic memory (knowledge test, fluency test)	Recall test: Val/Val Val/Met ↓ No association between COMT and other cognitive measures
Tsai et al.63	—		120 F	WCST	No association between COMT and WCST (perseverative errors)
Goldberg et al.64	74	Schizophrenia, schizoaffective disorder (depressed type)	68 (108)	Spatial n-back task, CPT 1–9, WAIS-R (IQ similarities, arithmetic, picture completion and digit symbol)	Patients, controls, relatives: n-back task: Val/Val ↓ No association between COMT and other cognitive measures
Malhotra et al.65	—		73	WCST	WCST (perseverative errors): Val/Val Val/Met ↓
Joober et al.66	94	Schizophrenia	31	WCST	Patients: WCST (perseverative errors): Val/Val Val/Met ↓ Controls: no association between COMT and WCST (perseverative errors)
Bilder1	58	Schizophrenia, schizoaffective disorder	—	General executive and perceptual organization: LNS, WCST, category fluency, letter fluency, block design, visual reproductions I and II Declarative verbal learning and memory: paragraph recall I and II, word list learning I and II Processing speed and attention: TMT A–B, digit symbol	Processing speed and attention domain: Val/Val ↓
Egan et al.67	175	Schizophrenia	55 (219)	WCST, WAIS-R, WRAT	Patients, controls, relatives: WSCT (perseverative errors): Val/Val ↓

ACTT = Auditory Consonant Trigram Test; ANT = Attention Network Test; BSRT = Buschke Selective Reminding Test; CANTAB = Cambridge Neuropsyhological Test Automated Battery; CIGT = Category Instance Generation Test; COMT = catechol-O-methyltransferase; COWAT = Controlled Oral Word Association Test; CPT = Continuous Performance Test; CPT-IP = Continuous Performance Test, Identical Pairs version; CVLT = California Verbal Learning Test; DAT = dopamine transporter; D-KEFS = Delis–Kaplan Executive Function System; F = female; DPX = Dot Pattern Expectancy task; ID/ED = intradimensional/extradimensional shift task; IGT = Iowa Gambling Task; LNS = letter and number sequencing; M = male; MSIT = Multi-Source Interference Task; MWT-B = Mehrfachwahl-Wortschatz-Intelligenztest B; RBANS = Repeatable Battery for the Assessment of Neuropsychological Status; SDR = Spatial Delayed Response; SoC = Stockings of Cambridge; TMT = Trail Making Test; WAIS = Wechsler Adult Intelligence Scale; WAIS III = Wechsler Adult Intelligence Scale-III; WAIS-R = Wechsler Adult Intelligence Scale-Revised; WASI = Wechsler Abbreviated Scale of Intelligence; WCST = Wisconsin Card sorting Test; WISC-R = Wechsler Intelligence Scale for Children-Revised; WMS-R = Wechsler Memory Scale-Revised; WRAT = Wide Range Achievement Test; WSPT = Word Serial Position Test.