American Journal of Medical Genetics Part B (Neuropsychiatric Genetics) 147B:223 –227 (2008)
Brief Research Communication Divergent Backward Masking Performance in Schizophrenia and Bipolar Disorder: Association With COMT Vina M. Goghari1 and Scott R. Sponheim1,2,3* 1
Department of Psychology, University of Minnesota, Twin Cities, Minnesota Department of Psychiatry, University of Minnesota, Twin Cities, Minnesota 3 Veterans Affairs Medical Center, Minneapolis, Minnesota 2
Schizophrenia has been reliably associated with impairments in backward masking performance, while bipolar disorder has less consistently been tied to such a deficit. To examine the genetic determinants of visual perception abnormalities in schizophrenia and bipolar disorder, this study evaluated the diagnostic specificity of backward masking performance deficits and whether masking deficits were associated with catechol-Omethyl transferase (COMT) genotype. A locationbased backward masking task, which equated participants on the perceptual intensity of stimuli, was completed by 41 schizophrenia outpatients, 28 bipolar outpatients, and 43 nonpsychiatric controls. COMT genotype data were available for 39 schizophrenia outpatients, 28 bipolar outpatients, and 20 nonpsychiatric controls. Schizophrenia patients demonstrated impaired backward masking performance compared to controls and bipolar patients. A group by COMT genotype interaction was detected with schizophrenia Met homozygotes performing more poorly than control and bipolar Met homozygotes, and worse than Val homozygote and heterozygote schizophrenia patients. This study provides novel evidence for differential effects of the COMT gene on neural systems underlying visual perception in schizophrenia and bipolar disorder. The COMT Met allele may be associated with deficits in schizophrenia that are unrelated to neural systems supporting sustained attention or working memory. ß 2007 Wiley-Liss, Inc. KEY WORDS:
visual processing; schizophrenia; bipolar disorder; masking; attention; catechol-O-methyl transferase Val108/158Met
Preliminary data from this study were presented at the Society for Research in Psychopathology, San Diego, California, October 12–15, 2006. Grant sponsor: Department of Veterans Affairs Medical Research Service; Grant sponsor: Mental Illness and Neuroscience Discovery (MIND) Institute; Grant sponsor: National Institutes of Mental Health; Grant number: 5R24MH069675. *Correspondence to: Scott R. Sponheim, Ph.D., 116B, VA Medical Center, One Veterans Drive, Minneapolis, MN 55417. E-mail:
[email protected] Received 31 January 2007; Accepted 14 June 2007 DOI 10.1002/ajmg.b.30583
ß 2007 Wiley-Liss, Inc.
Please cite this article as follows: Goghari VM, Sponheim SR. 2008. Divergent Backward Masking Performance in Schizophrenia and Bipolar Disorder: Association With COMT. Am J Med Genet Part B 147B: 223–227. INTRODUCTION Researchers have studied early visual processing deficits in schizophrenia and bipolar disorder by employing tasks that involve disruption of stimulus perception by a ‘‘mask’’ presented after a stimulus (i.e., backward masking). Schizophrenia patients typically require a prolonged period between the stimulus and the subsequent mask to be able to perceive the object [for review, see McClure, 2001]. Findings support the contention that backward masking deficits reflect the expression of vulnerability genes on brain function in schizophrenia. For instance, biological relatives of schizophrenia patients [e.g., Green et al., 2006] and individuals with schizophreniaspectrum symptomatology [e.g., Saccuzzo and Schubert, 1981] show impaired backward masking performance. To date, no published study has assessed whether specific vulnerability genes are associated with masking deficits in schizophrenia and bipolar disorder. The catechol-O-methyl transferase (COMT) Val108/158Met gene has been statistically associated with schizophrenia [Badner and Gershon, 2002] and related to higher cognition and forms of attention in the disorder [Harrison and Weinberger, 2005]. Ramachandran and Cobb [1995] demonstrated that backward masking processes can be influenced by topdown attentional processes. Furthermore, evidence suggests that higher cognitive functions may modulate masking deficits in schizophrenia [Rassovsky et al., 2005]. Cognitive tasks involving attentional processes are thought to have comparatively larger effect sizes in individuals genetically related to schizophrenia patients [Snitz et al., 2006; Gur et al., 2007], thus COMT may relate to a backward masking endophenotype for schizophrenia [Bilder et al., 2002; Gottesman and Gould, 2003]. Researchers have generally found bipolar patients to have masking deficits [for review, see McClure, 1999]. Nevertheless, healthy biological relatives of bipolar patients have demonstrated normal backward masking implying that a masking performance deficit may be specific to genetic liability for schizophrenia [Keri et al., 2001; MacQueen et al., 2004]. To fully test the diagnostic specificity of masking deficits, we compared stable schizophrenia and bipolar outpatients with nonpsychiatric control subjects using a backward masking task that equated all participants for perceptual intensity of stimuli. Since the outpatients generally had low levels of symptomatology, we were able to examine masking performance with minimal influence of clinical state. Because the
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COMT gene has also been associated with bipolar disorder [Badner and Gershon, 2002], we studied the association between visual processing deficits and COMT in both schizophrenia and bipolar disorder to determine whether the specific vulnerability gene may be differentially expressed in masking performance across the two disorders. We formulated our hypotheses based on endophenotype masking studies of individuals genetically related to schizophrenia and bipolar patients. Thus, we predicted that (1) an early visual processing deficit as measured by a location-based backward masking task would be evident in schizophrenia outpatients, but not bipolar outpatients with good community functioning, and (2) the COMT Val allele would be associated with impaired backward masking performance in schizophrenia, but not in bipolar disorder. PARTICIPANTS Schizophrenia and bipolar patients were recruited from outpatient clinics at the Minneapolis VA Medical Center, community support programs for the mentally ill, and a county mental health clinic. Control subjects responded to postings in the community and advertising in VA newsletters. Schizophrenia and bipolar patients completed the Diagnostic Interview for Genetic Studies. Controls completed structured clinical interviews for DSM-IV for Axis I and Cluster A personality traits. Schizophrenia and bipolar patients were additionally assessed using the Brief Psychiatric Rating Scale and Social Adjustment Scale II to evaluate clinical status, adaptive, and community functioning. Participants were excluded if they had English as a second language, IQ less than 70, current alcohol or drug abuse, past drug dependence, current or past central nervous disease, or significant head injury. Controls were further excluded if they had a personal history of or a first-degree biological relative with psychotic symptoms or an affective disorder. COMT Val108/158Met genotype was gathered from a subset of 20 controls and data were missing for two schizophrenia patients. See Sponheim and colleagues [2004] for full description of recruitment and assessment procedures. All subjects participated voluntarily and provided written informed consent. The Veteran’s Affairs Medical Center and University of Minnesota Institution Review Boards approved the protocol. BACKWARD MASKING TASK A computerized visual backward masking procedure was utilized [Version 1.5A; Green et al., 2002, 2006]. The ambient light level of the room was set to 2.6 exposure value (EV) and brightness of the monitor was set to 3.8 EV value for a white square and no light present EV value for a black square. Stimuli were presented on a 1700 150 Hz cathode ray tube computer monitor (NEC MultiSync E750) that was positioned 1 m from the participants’ eyes. Target stimuli were dark gray and appeared on a white background and consisted of a small square (0.278 visual angle) with a space in one side. The mask was four sets of four smaller squares which overlaid the four possible locations of target stimuli (1.038 visual angle from fixation). Participants first completed a procedure to determine the critical stimulus intensity for the masking task. The gray scale of the target was adjusted to a level where participants could obtain an accuracy rate of 84%. Each task trial consisted of a 400 msec fixation cross at the center of visual display, 100 msec of blank screen, the 13.3 msec target stimuli, a stimulus onset asynchrony (SOA) from 0 to 80 msec, and a 26.6 msec high-energy mask. SOA refers to the duration from the onset of the stimulus to the onset of the mask. The experimenter initiated each trial monitoring the participant for alertness. The participant’s task was to verbally identify the location of
the target square, and the participant’s response was entered into the computer by the experimenter. Participants were given 12 practice trials. The experiment consisted of 96 trials consisting of 12 trials per SOA. COMT GENOTYPE COMT Val108/158Met genotype for each individual was determined by a restriction fragment length polymorphism technique. Whole blood was collected on FTA Matrix specimen collection cards (Whatman International Ltd., Brentford, Middlesex, UK). Punches from the FTA blood cards were then prepared for PCR analysis according to Whatman FTA protocol. The washed punch was used directly for PCR amplification. Primers for PCR amplification spanned the COMT Val108/158Met polymorphism (single nucleotide polymorphism rs4680) (forward primer 50 -tactgtggctactcagctgtgc30 ; reverse primer 50 -gtgaacgtggtgtgaacacc-30 ). Amplification was carried out as described by [Bergman-Jungestrom and Wingren, 2001]. PCR reactions were initially denatured at 948C for 3 min followed by 39 cycles of denaturation at 938C for 45 sec, annealing at 558C for 1 min, and extension at 728C for 1 min with a final 4 min extension at 728C. The PCR products were digested with NlaIII (New England Biolabs, Ipswich, MA) for 3 hr at 378C followed by incubation at 608C for 20 min to denature the enzyme. The digestion was then separated by polyacrylamide gel electrophoresis and the digestion products visualized by staining with ethidium bromide. STATISTICAL ANALYSES Mixed-model ANOVAs were conducted to assess the effects of group, SOA, and COMT genotype on backward masking performance. Specific SOAs were investigated to determine if select deficits between the diagnostic groups noted in previous studies were present [Rassovsky et al., 2005; Green et al., 2006]. Significant group by SOA by COMT interaction was followed by three mixed-model ANOVAs (one for each genotype individually) to determine which genotype exhibited differences across diagnostic groups. Only significant genotype effects were followed with between-subject ANOVAs and posthoc tests. Greenhouse-Geisser statistics were reported for within-subject measures. Cohen’s d effect sizes are presented where appropriate: 0.2 is a small effect; 0.5 is a medium effect; 0.8 is a large effect. EFFECT OF DIAGNOSIS ON BACKWARD MASKING Demographic information for the full sample is presented in Table I. Participants were comparable for mean age. The nonpsychiatric control sample had significantly more female participants than both the schizophrenia and bipolar samples. Schizophrenia patients had lower estimated IQ and a trend toward lower educational attainment. Both schizophrenia and bipolar patients had minimal symptomatology. Bipolar outpatients showed good community functioning and demonstrated better work, social, and overall adjustment than schizophrenia outpatients. There was a significant negative correlation between age and masking performance for SOAs 40 msec and above (r’s ¼ 0.36 to 0.48; P’s < 0.001). When age was entered into the repeated measure model as a covariate, there was a significant effect of age (F(1,108) ¼ 38.2, P < 0.001) and age SOA interaction (F(5,496) ¼ 13.3, P < 0.001); however, the group-level ANOVA diagnostic findings remained unchanged. There was no significant effect of gender on masking performance for any of the SOAs (F’s(1,110) ¼ 0.14– 3.4, P’s ¼ 0.07–0.7). A three group (schizophrenia, bipolar, control) seven SOA (0, 13, 27, 40, 53, 67, 80 msec) mixed-model ANOVA revealed a
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TABLE I. Demographic Information on Participants
Demographics N Age (years) % Female Education (years) Estimated IQ Clinical variables BPRS Thinking disorder Withdrawal Anxiety-depression Hostility-suspicion Activity Total Social adjustment scale II Work Household members External family Social leisure General adjustment SPQ total COMT genotype Val/Val:Val/Met:Met/Met SOA (msec)—% correct 0 13 27 40 53 67 80
Schizophrenia
Bipolar
Controls
Test statistics
41 45.2 (10.7) 22a 13.9 (2.8) 98.7 (11.9)a,c
28 43.3 (10.0) 25b 15.3 (2.2) 112.9 (16.0)
43 48.1 (15.1) 54 15.7 (4.6) 111.1 (10.9)
— F(2,109) ¼ 1.3, P ¼ 0.3 2 w (2) ¼ 10.8, P ¼ 0.005 F(2,109) ¼ 2.9, P ¼ 0.06 F(2,109) ¼ 14, P < 0.001
2.2 (0.8)c 1.3 (0.6)c 1.7 (0.7) 2.0 (1.1)c 1.2 (0.5)c 41.6 (10.9)c
1.4 (0.6) 0.7 (0.2) 1.9 (0.7) 1.5 (0.6) 1.5 (0.6) 35.6 (9.4)
— — — — — —
F(1,67) ¼ 25.0, P < 0.001 F(1,67) ¼ 24.3, P < 0.001 F(1,67) ¼ 1.4, P ¼ 0.2 F(1,67) ¼ 5, P ¼ 0.03 F(1,67) ¼ 5.4, P ¼ 0.02 F(1,67) ¼ 5.7, P ¼ 0.02
3.8 (1.7)c 2.3 (1.0) 2.5 (1.0) 3.2 (1.1)c 3.1 (0.8)c —
2.4 (1.3) 2 (1.4) 2.4 (1.3) 2.1 (1.2) 2.2 (1.1) —
— — — — — 9.5 (6.2)
F(1,67) ¼ 14.2, P < 0.001 F(1,43) ¼ 0.8, P ¼ 0.4 F(1,65) ¼ 0.09, P ¼ 0.8 F(1,67) ¼ 16.2, P < 0.001 F(1,67) ¼ 14.3, P < 0.001 —
10:19:10
7:11:10
7:8:5
w2(4) ¼ 1.6, P ¼ 0.8
24.4 (12.8) 26.0 (12)a 29.9 (11.8)a,c 32.5 (15.1)a,c 37.4 (18.4)a,c 44.3 (22.0)c 47.4 (23.5)a,c
27.4 (9.3) 31 (15.4) 36.9 (14.2) 41.7 (17.3) 50.3 (17.0) 61.9 (25.3) 65.2 (26.3)
29.5 (12.6) 33.7 (15.9) 35.7 (13.6) 40.3 (17.8) 45.5 (20.8) 54.3 (26) 62.0 (25.4)
F(2,109) ¼ 1.9, P ¼ 0.2 F(2,109) ¼ 3.1, P ¼ 0.05 F(2,109) ¼ 3.0, P ¼ 0.05 F(2,109) ¼ 3.3, P ¼ 0.04 F(2,109) ¼ 4.1, P ¼ 0.02 F(2,109) ¼ 4.5, P ¼ 0.01 F(2,109) ¼ 5.4, P ¼ 0.006
Means and standard deviations given unless otherwise noted. Estimated IQ was measured using vocabulary and block design subtests [Booker and Cyr, 1986]. BPRS, Brief Psychiatric Rating Scale 24-item version. Average score on BPRS factors was computed using Burger et al. [1997]. BPRS total reflects addition of all 24 items [Ventura et al., 1993]. SAS-II, Social Adjustment Scale II [Weissman, 1978]; SPQ, Schizotypal Personality Questionnaire [Raine, 1991]; SOA, stimulus onset asynchrony (msec). a Schizophrenia patients different from controls (P 0.05). b Bipolar patients different from controls (P 0.05). c Schizophrenia patients different from bipolar patients (P 0.05).
significant effect of group (F(2,109) ¼ 8.7, P < 0.001). Schizophrenia patients had impaired masking performance compared to controls (P ¼ 0.001) and bipolar patients (P < 0.001). Bipolar patients did not differ from controls (P ¼ 0.5). Although there was no interaction of group and SOA (F(8,434) ¼ 1.3, P ¼ 0.2), we directly compared the SOAs between the groups to fully test specific deficits in the bipolar group. Bipolar patients did not differ from controls at any SOA (see Table I). Comparison of specific SOAs showed differences increased between schizophrenia patients and the other groups as SOA increased. EFFECT OF COMT GENOTYPE ON BACKWARD MASKING COMT genotype data were present for a subset of 20 controls (mean age ¼ 38.2, SD ¼ 12.6; 55% female; mean years of education ¼ 17.5, SD ¼ 6.1; mean IQ ¼ 116.1, SD ¼ 9.9). COMT data were missing for two subjects with schizophrenia. Clinical measures failed to be related to COMT genotype. There was no significant difference in Val/Val groups for age (F(2,21) ¼ 2.3, P ¼ 0.13) or gender (w2(2) ¼ 0.02, P ¼ 0.99). The three Val/ Met groups did not differ in age (F(2,35) ¼ 0.15, P ¼ 0.86); however, there was a significant difference in gender (w2(2) ¼ 7.7, P ¼ 0.02). When gender was added as a covariate into the repeated measures model on masking performance, there was no significant effect of gender or interaction with SOA. There was no significant difference between three Met/
Met groups for age (F(2,22) ¼ 1.9, P ¼ 0.17) or gender (w2(2) ¼ 4.2, P ¼ 0.13). A three group three COMT (Val/Val, Val/Met, Met/Met) seven SOA mixed-model ANOVA revealed significant interactions between group (F(2,78) ¼ 12.4, P < 0.001), group SOA (F(8, 313) ¼ 2.5, P ¼ 0.01), group COMT (F(4,78) ¼ 4.2, P ¼ 0.004), and group COMT SOA (F(16,313) ¼ 1.8, P ¼ 0.03). Mixed-model ANOVAs of Val/Val and Val/Met genotype revealed no significant differences between schizophrenia and bipolar patients compared to controls, therefore no follow-up analyses were conducted (see Table II). However, a three group (schizophrenia Met/Met, bipolar Met/Met, control Met/Met) SOA revealed a significant effect of Met/Met group (F(2,22) ¼ 23.7, P < 0.001), and Met/Met group SOA interaction (F(9,97) ¼ 3.9, P < 0.001; see Fig. 1). Schizophrenia Met/ Met patients demonstrated impaired performance compared to both controls and bipolar patients (P’s < 0.001). ANOVAs showed differences between the groups at SOAs: 0, 27, 53, 67, 80 msec (F’s ¼ 3.4–16.4, P’s < 0.001–0.05). Post-hoc comparisons demonstrated schizophrenia Met/Met patients had impaired masking performance compared to both controls and bipolar Met/Met patients at SOAs of 0 msec (P ¼ 0.04, d ¼ 1.0; P ¼ 0.05, d ¼ 1.1, respectively), 53 msec (P ¼ 0.01, d ¼ 1.2; P ¼ 0.001, d ¼ 2.3), 67 msec (P ¼ 0.005, d ¼ 1.5; P < 0.001, d ¼ 2.7), and 80 msec (P < 0.001, d ¼ 2.5; P < 0.001, d ¼ 2.3) and only bipolar patients at 27 msec (P ¼ 0.003, d ¼ 1.8). Lastly, comparisons revealed schizophrenia Met/Met patients were impaired compared to the combined group of
Means and standard deviations given. SOA, stimulus onset asynchrony (msec). For backward masking performance a three group three COMT seven SOA mixed-model ANOVA revealed significant interactions between group COMT and group COMT SOA. Mixed-model ANOVAs of Val/Val and Val/Met genotype revealed no significant differences between schizophrenia and bipolar patients compared to controls. However, a three group (schizophrenia Met/Met, bipolar Met/Met, control Met/Met) SOA revealed a significant effect of Met/Met group and Met/Met group SOA interaction. Follow-up comparisons were conducted. a Schizophrenia Met/Met homozygotes different from control Met/Met homozygotes (P 0.05). b Schizophrenia Met/Met homozygotes different from bipolar Met/Met homozygotes at P 0.05. Schizophrenia Met/Met homozygotes different from schizophrenia Val homozygotes and heterozygotes (P 0.05).
26.2 (8.9) 31 (17.8) 41.7 (10.8) 41.7 (21.5) 57.1 (16.9) 72.6 (20.8) 82.1 (16.3) 25.8 (10) 24.2 (10) 34.2 (11.4) 29.2 (13.2) 39.2 (14.2) 45.0 (18.9) 54.2 (21.3) 36.5 (14.7) 39.6 (17.1) 35.4 (13.2) 34.4 (10.4) 45.9 (25.2) 62.5 (26.4) 66.7 (25.2) 27.3 (9.9) 32.6 (16.0) 29.5 (15.1) 32.6 (11.5) 37.9 (12.6) 43.9 (25.3) 46.2 (26.2) 27.6 (15) 26.7 (12.9) 30.7 (13.6) 34.2 (19.0) 41.2 (22.7) 49.6 (24.6) 50.4 (25.2) 31.7 (17.1) 23.3 (12.4) 30 (18.3) 41.7 (28.3) 56.7 (27.9) 61.7 (23.3) 76.7 (19.9) 28.3 (9.8) 29.2 (14.3) 41.7 (13.0) 51.7 (15.1) 59.2 (13.9) 74.2 (16.4) 74.2 (19.4) 17.5 (10) 28.3 (12.6) 24.2 (4.7)b 33.3 (9.6) 31.7 (10.2)a,b 31.7 (15.1)a,b,c 32.5 (15.9)a,b,c
Bipolar Controls Bipolar SOA (msec)
Schizophrenia
Bipolar
Controls
Schizophrenia
Val/Met Met/Met
TABLE II. Location-Based Backward Masking Performance
Schizophrenia
Val/Val
DISCUSSION This study demonstrated location-based backward masking deficits to be specific to schizophrenia patients. Masking performance deficits were not evident in bipolar disorder. We also found the association of COMT alleles with masking performance diverged in the two disorders. Inconsistent with our hypothesis, the Met homozygote schizophrenia patients exhibited masking deficits compared to nonpsychiatric control and bipolar Met homozygotes and schizophrenia Val homozygotes and heterozygotes. Differential effects for bipolar and schizophrenia patients were most prominent when the target and mask were separated by more than 53 msec. Increased impairment at longer SOAs suggests that visual perception deficits associated with the Met allele of the COMT gene are larger when there are proportionally greater demands on late attentional processes. Generally, the Met allele has been associated with better cognitive functioning; however, more recent evidence suggests this may be mostly limited to a certain category of prefrontal tasks, such as sustained attention or working memory. Findings suggest that the Val and Met allele inverse finding in the current article may be specific to the cognitive processes tapped by the location-based backward masking task, particularly given findings of Val homozygote schizophrenia patients from an overlapping sample having predicted reductions in P300 amplitudes to targets during visual sustained attention [Sponheim et al., 2006]. Although attentional processes may modulate backward masking performance, the backward masking task is significantly influenced by early visual mechanisms. Other studies have revealed inverse Val and Met allele relationships with functioning. Schott and colleagues [2006] evaluated the influence of COMT polymorphisms on brain activity during episodic memory formation in a normative population and found that Met/Met was associated with decreased brain activity in prefrontal and occipital regions; however, Met/Met was also associated with greater functional coupling between the prefrontal cortex and hippocampus. Thaker and colleagues [2004] investigated the effect of COMT genotype on eye tracking and found Met homozygote schizophrenia patients demonstrated significantly poorer eye tracking compared to Met homozygote controls, and marginally poorer than Val homozygote schizophrenia patients. Together, these findings suggest a simple association between a specific COMT vulnerability allele for broad cognitive functioning in the normal population and schizophrenia is not present. Studies of bipolar patients have found deficits in backward masking performance, including euthymic bipolar patients [MacQueen et al., 2001; for review see McClure, 1999]. The current study differs from previous investigations in that it assessed stable bipolar outpatients with minimal symptomatology and adequate community functioning. In addition, the backward masking task implemented a procedure to equate groups on perceptual intensity of stimuli; therefore, these results are not likely to be confounded by psychophysical deficits. In support of the finding of intact masking performance in stable bipolar disorder outpatients, research utilizing healthy relatives of bipolar patients has suggested backward masking deficits are related to state as opposed to trait-related factors. Keri and colleagues [2001] found intact backward masking in siblings of bipolar patients while siblings of schizophrenia patients were impaired compared to controls. MacQueen and colleagues [2004] found never ill offspring of bipolar patients had backward masking performance comparable to controls.
0 13 27 40 53 67 80
Controls
schizophrenia Val/Val and Val/Met patients at 0 msec (F(1,37) ¼ 4.3, P ¼ 0.05, d ¼ 0.8), 67 msec (F(1,37) ¼ 4.5, P ¼ 0.04, d ¼ 0.8), and 80 msec (F(1,37) ¼ 5.7, P ¼ 0.02, d ¼ 1).
28.6 (12.6) 32.1 (16.3) 32.1 (16.3) 45.2 (25) 57.2 (24.3) 58.3 (33) 63.1 (31.1)
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Fig. 1. Backward masking performance of Met homozygote patients and nonpsychiatric controls as a function of stimulus onset asynchrony (SOA) and diagnostic group. *Schizophrenia Met/Met patients show impaired performance compared to nonpsychiatric controls and bipolar patients P 0.05. SCZ, schizophrenia; BPAD, bipolar affective disorder; CON, nonpsychiatric control. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]
The findings of this study need to be replicated in a larger sample. Our sample size is modest, 39 schizophrenia outpatients, 28 bipolar outpatients, and 20 nonpsychiatric controls, and may not have been sufficient to detect small and moderate group differences between genotype groups. Nevertheless, effect sizes indicated the magnitude of the differences between the diagnostic and COMT Met/Met genotype groups were large and noteworthy for the schizophrenia patients and negligible for the bipolar patients compared to nonpsychiatric controls. The current results may serve as an impetus for further investigation of the genetic underpinnings of early visual perception in schizophrenia and bipolar disorder. In summary, this study provides novel preliminary evidence suggesting backward masking deficits may be specific to schizophrenia and that the COMT gene may differentially affect neural systems that support visual perception in schizophrenia and bipolar disorder. ACKNOWLEDGMENTS Ms. Goghari was supported by a PGS Doctoral Award from the Natural Sciences and Engineering Research Council of Canada. We gratefully acknowledge Drs. Bridget Hegeman and Althea Noukki for the supervision of data collection and Danushka Wanduragala, Jeri Angles, Sarah Sass, Tricia Bender, and Melissa Boyer for their assistance in data collection. We thank Laurie Shekels, Ph.D. for her consultation on genotyping and Michael Green, Ph.D. and his laboratory for providing the backward masking computer program and consultation during paradigm implementation. REFERENCES Badner JA, Gershon ES. 2002. Meta-analysis of whole-genome linkage scans of bipolar disorder and schizophrenia. Mol Psychiatry 7:405–411. Bergman-Jungestrom M, Wingren S. 2001. Catechol-O-Methyltransferase (COMT) gene polymorphism and breast cancer risk in young women. Br J Cancer 85:859–862.
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