استراحت فعالیت پیشانی مغز: ارتباط با افسردگی مادر و وضعیت اجتماعی و اقتصادی در میان نوجوانان

Abstract We tested the prediction that resting frontal brain asymmetry would be a marker of vulnerability for depression among adolescents. Baseline electroencephalographic (EEG) activity was recorded from 12 to14-year-old adolescents whose mothers had a history of depression (high risk group) and whose mothers were lifetime-free of axis I psychopathology (low risk group). High risk adolescents demonstrated the hypothesized pattern of relative left frontal hypo-activity on alpha-band measures. Such effects were specific to the mid-frontal region and generally consistent across reference montages. Socio-economic status (SES) also predicted alpha asymmetry. When the effects of SES and risk status were jointly assessed, SES contributed unique variance to the prediction of frontal brain asymmetry. The implications of the observed relations among maternal depression, SES, and frontal brain asymmetry are discussed.

. Results 6.1. Depressive symptoms We examined CDI scores from four of the yearly assessments to examine whether high and low risk participants differed on symptoms of depression prior to or after the EEG recording. Across the two yearly assessments preceding and the two yearly assessments following the EEG session, the mean low risk CDI was 3.9 (S.D.=3.7) and the mean high risk CDI was 4.5 (S.D.=3.4). Thus, both groups clearly scored in the non-depressed range. Separate t-tests on risk status conducted at each of the four time points revealed the absence of any differences with respect to CDI scores, all Full-size image (<1 K), all Full-size image (<1 K). Consistent with these results, an omnibus risk status X time ANOVA failed to yield any significant main effects or interactions, all Full-size image (<1 K). During the eight weeks prior to the EEG session, the week of the EEG session, and the eight weeks following the EEG session, all participants averaged less than 2 (i.e., possible mild depressive symptoms) on the retrospective measure of weekly depressive symptoms (potential range=1–6). All low risk participants received scores of one (no depressive symptoms) on this scale for every week during this time period. With the exception of four adolescents, all high risk participants received scores of two or below during this time period (i.e., mild symptoms of major depressive disorder). The remaining four received scores of three or four on this measure (indicating some symptoms of major depressive disorder and impairment, but falling short of the criteria for major depressive disorder). Thus, no low risk and high risk participants met criteria for major depressive disorder during the two-months prior to and the two months after the EEG recording. When the analyses reported below were redone with those four individuals who demonstrated symptoms of major depressive disorder removed, the results and conclusions were unchanged. 6.2. Lifetime criteria for mood disorders Based on the K-SADS-E administered at baseline and K-LIFE administered at the first yearly follow-up interview, no low risk participant met lifetime criteria for any mood disorder. One high risk participant met lifetime criteria for dysthymia. When the analyses reported below were redone with this individual removed, the results and conclusions were unchanged. 6.3. Electroencephalographic data 6.3.1. Effects of risk status on mid-frontal alpha asymmetry As noted above, the primary focus of analyses was the alpha (8.5–12.5 Hz) frequency band. Because the majority of prior studies linking frontal brain asymmetry to depression have focused on the mid-frontal (F3/F4) recording sites, we focused on measures of alpha asymmetry in this region. We predicted that high risk participants would demonstrate greater relative left frontal hypo-activity (greater relative left versus right alpha-band power) than low risk participants. Table 1 shows mean log-transformed alpha power density (in μV) values for the mid-frontal sites (F4 and F3) and mean asymmetry scores [ln(F4) − ln(F3)] derived from the three reference montages for males and females. Recall that more positive asymmetry scores indicate greater relative left frontal activity. Because of how the asymmetry metric is computed, a main effect of risk status on asymmetry values is equivalent to an interaction between risk status and hemisphere on log power density values. Analyses used to test hypotheses in the current study focused on asymmetry values rather than on log power density. When analyses were done on log power values from each of the three reference montages with hemisphere as a factor, no main effects of risk status were observed that would indicate between-group differences on overall power averaged across the two frontal sites (all Full-size image (<1 K)). In addition, no between-group differences were yielded by separate analyses of F3 and F4 log power density (all Full-size image (<1 K)). These results reflect the likelihood that a high proportion of the between-subject variability in power is due to skull thickness and other factors that are not of substantive interest. For these reasons, to simplify the presentation of results, we report below only the results of analyses performed on asymmetry values. Table 1. Mid-frontal (F3/F4) alpha-band log power density (in μV) and asymmetry for and low risk adolescents High Risk Low risk F3 power F4 power F3/F4 asymmetry F3 power F4 power F3/F4 asymmetry Averaged-ears Male 1.200 (0.579) 1.208 (0.572) 0.009 (0.049) 1.448 (0.353) 1.496 (0.372) 0.047 (0.041) Female 1.634 (0.540) 1.629 (0.536) −0.004 (0.067) 1.320 (0.572) 1.366 (0.551) 0.046 (0.057) All 1.442 (0.588) 1.444 (0.581) 0.001 (0.059) 1.380 (0.451) 1.450 (0.448) 0.047 (0.047) Average Male 0.388 (0.589) 0.379 (0.563) −0.009 (0.094) 0.760 (0.558) 0.796 (0.579) 0.039 (0.126) Female 0.825 (0.576) 0.824 (0.574) −0.001 (0.120) 0.509 (0.604) 0.600 (0.612) 0.091 (0.086) All 0.633 (0.611) 0.629 (0.601) −0.004 (0.107) 0.644 (0.570) 0.706 (0.578) 0.061 (0.114) Vertex (Cz) Male 0.932 (0.637) 0.953 (0.598) 0.021 (0.092) 1.200 (0.553) 1.172 (0.543) −0.027 (0.082) Female 1.059 (0.576) 1.054 (0.580) −0.005 (0.056) 0.739 (0.721) 0.844 (0.709) 0.105 (0.035) All 1.002 (0.594) 1.010 (0.578) 0.007 (0.073) 0.987 (0.653) 0.621 (0.172) 0.034 (0.093) Note: High risk male N=11. High risk female N=14. Low risk male N=7. Low risk female N=6. Standard deviations are indicated in parentheses. Table options Fig. 1 shows the mean log-transformed mid-frontal alpha asymmetry values, derived from three reference montages, for low risk and high risk adolescents. This figure indicates that across all three montages, there was greater relative left frontal activity in the low risk group compared to the high risk group. The results of risk status (low risk/high risk) X sex (male/female) ANOVAs performed on computer-averaged-ears referenced and average referenced mid-frontal EEG asymmetry values were consistent with these observations. The analysis of computer-averaged-ears referenced data revealed a significant main effect of risk status, F(1,37) = 5.49, P<0.05, but no significant effects of sex, F(1,37) = 0.23, P>0.50, or the risk status X sex interaction, F(1,37) = 0.09, P>0.50. Similarly, the analysis of average referenced mid-frontal asymmetry revealed a significant main effect of risk status, F(1,37) = 5.37, P<0.05, but no significant main effect of sex, F(1,37) = 0.50, P>0.40, and no significant interaction between risk status and sex, F(1,37) = 1.44, P>0.20. Mid-frontal (F3/F4) alpha asymmetry [ln(left) − ln(right)] across three ... Fig. 1. Mid-frontal (F3/F4) alpha asymmetry [ln(left) − ln(right)] across three reference montages for high risk (N=25) and low risk (N=13) adolescents. Error bars indicate one standard error of the mean. Figure options Although the marginal means for vertex (Cz) referenced asymmetry values shown in Fig. 1 indicates greater relative left frontal activity in the low risk group, Fig. 2 indicates more complex, interactive relations with sex. As this figure indicates, high risk females, but not high risk males, demonstrated relative left frontal hypo-activity when compared to their low risk counterparts. The analysis of Cz asymmetry in the mid-frontal region revealed no main effect of risk status, F(1,37) = 1.21, P>0.20, no main effect of sex, F(1,37) = 1.49, P>0.20, but a significant risk status X sex interaction, F(1,37) = 10.49, P<0.01. Subsequent simple effects analyses indicated that, among females, high risk adolescents demonstrated significantly greater left frontal hypo-activity when compared to low risk participants, F(1,19) = 19.43, P<0.01. No significant effects were yielded by the simple effects analysis performed on males’ asymmetry values, F(1,17) = 1.20, P>0.25. Mid-frontal (F3/F4) vertex (Cz)-referenced alpha asymmetry [ln(left) − ... Fig. 2. Mid-frontal (F3/F4) vertex (Cz)-referenced alpha asymmetry [ln(left) − ln(right)] for male and female high and low risk adolescents. Error bars indicate one standard error of the mean. Figure options 6.3.2. Effects of risk status on mid-frontal EEG Asymmetry in other bands We computed two-way risk status X sex ANOVAs on mid-frontal (F3/F4) EEG asymmetry in each of the six EEG bands extracted: delta (1.5–3.5 Hz), theta (4.0–7.0 Hz), alpha 1 (i.e., low alpha; 8.5–10.5), alpha 2 (i.e., high alpha; 11.0–12.5), beta 1 (13.5–19.5 Hz), and beta 2 (20.5–29.5 Hz). We assessed effects in alpha 1 and alpha 2 separately because: (1) in some previous studies, differential effects have been observed in these bands (e.g., Davidson et al., 2000); and, (2) the fact that our participants were young adolescents suggested that such effects might be particularly likely to occur (see the discussion of band selection in Section 5). Such analyses were computed for each of the three references. Because the number of ANOVAs was large, we used a step-down Bonferroni procedure to control for multiple significance tests (e.g., Westfall et al., 1999 and Westfall and Young, 1992). Three sets of corrections were used (i.e., one per reference montage). After step-down Bonferroni correction, there were highly significant main effects for risk status in the theta band on both computer-averaged-ears referenced [corrected P<0.001, low risk M (S.D.) = 0.071 (0.077); high risk (M) = −0.032 (0.060)] and average referenced [corrected P<0.001, low risk M (S.D.) = 0.120 (0.117); high risk (M) =−0.037 (0.090)] mid-frontal asymmetry. We also found a significant main effect of risk status on average referenced delta band asymmetry [corrected P<0.025, low risk (M) S.D. = 0.110 (0.136); high risk M = −0.017 (0.121)] and on Cz-referenced asymmetry in the low alpha-band (corrected P<0.02). These significant effects all indicated that high risk participants showed greater relative power in the left relative to right frontal region for the target band. Thus, the direction of these effects parallels that of the alpha-band (8.5–12.5 Hz) effects reported above. No other significant effects were observed. 6.3.3. Effects of risk status on EEG alpha asymmetry in other regions For each of the three references, we computed two-way risk status X sex ANOVAs on EEG asymmetry in each of five regions: lateral frontal (F7/F8), parietal (P3/P4), anterior temporal (T3/T4), posterior temporal (T5/T6), and central (C3/C4). Because the clear focus of our predictions was alpha asymmetry in the mid-frontal sites and because the number of ANOVAs was large, we once again used a step-down Bonferroni procedure to control for multiple significance tests. Across all three references, the only significant effects that emerged were main effects of region (all Full-size image (<1 K)). These effects reflected topographic differences in the patterning of asymmetry. Most importantly, there were no significant main effects or interactions involving risk status (all Full-size image (<1 K)). Table 2 conveys the overall direction and strength of the relation between risk status and alpha-band asymmetry across regions. Presented are point biserial correlations between the dichotomous variable risk status (coded 0 for low risk and 1 for high risk) and measures of brain asymmetry [ln(right − ln(left)] in a given band. Consistent with the main effects of risk status on mid-frontal asymmetry presented above, the correlations between risk status and ears-referenced (r=−0.37) and average-referenced (r=−0.36) mid-frontal asymmetry are both significantly greater than 0. Although the correlation involving Cz-referenced frontal asymmetry is not significant, recall that the ANOVAs revealed a more complex risk status X sex interaction on this measure. Although the correlations involving lateral frontal asymmetry (F7/F8) are in the predicted direction, their magnitude is lower than that of the mid-frontal correlations and is not statistically significant. Overall, other than the aforementioned mid-frontal correlations, only one of the correlations shown in Table 3 was statistically significant when considered in isolation (Cz-referenced P3/P4; P=0.03). Moreover, even this value was not statistically significant when step-down Bonferroni corrections were used to account for the total number of correlations computed among the five regions that were not of the focus of our initial hypotheses (P=0.15). Table 2. Correlations between risk status and alpha-band asymmetry across regions Region Reference montage Averaged-ears Average Vertex (Cz) Mid-frontal (F3–F4) −0.37** −0.36** −0.16 Lateral frontal (F7–F8) −0.24 −0.25 −0.09 Central (C3–C4) 0.15 0.16 0.08 Anterior temporal (T3–T4) 0.25 0.06 0.08 Posterior temporal (T5–T6) −0.15 −0.19 −0.14 Parietal (P3–P4) −0.17 −0.19 −0.35* Note: N=38. Point-biserial correlations are shown. Risk status coding: 0 = low risk, 1 = high risk. Mid-frontal correlations were evaluated at a per-correlation alpha level = 0.05. Within each reference montage, step-down Bonferroni corrections were applied to correlations involving the five other sites. * Uncorrected P<0.05, but step-down Bonferroni corrected P>0.15. ** P<0.05. Table options Table 3. Multiple regression analyses predicting mid-frontal alpha asymmetry Predictors Mid-frontal asymmetry measure Ears reference Average reference Vertex (Cz) First-order Risk status β −0.067 −0.128 −0.122 Sr2 0.003 0.011 0.010 Sex β 0.094 −0.096 −0.175 Sr2 0.009 0.009 0.030 SES β 0.529** 0.432* 0.096 Sr2 0.191 0.128 0.006 R2Increment (set) 0.336** 0.270* 0.064 Two-way interactions Risk status × sex β 0.005 0.136 0.631** Sr2 0.000 0.011 0.226 Risk status × SES β 0.211 −0.069 −0.249 Sr2 0.011 0.001 0.016 Sex × SES β −0.170 −0.243 0.120 Sr2 0.016 0.032 0.008 R2Increment (set) 0.054 0.102 0.277* Three-way interaction Risk status × sex × SES β −0.344 0.004 0.091 Sr2 0.028 0.000 0.002 R2Increment (set) 0.028 0.000 0.002 A hierarchical structure was used in which first-order terms were entered in an initial step, followed by two-interaction terms, and the three-way interaction in subsequent steps. For first-order terms, the β’s are standardized coefficients. For second-order terms, the β’s are the unstandardized coefficients for terms that are the product of standardized variables but are not standardized themselves. This procedure was followed in order to yield test statistics and probability values that are invariant with respect to the unstandardized analyses of the raw data values. Sr2: squared semi-partial correlation. R2Increment (set): the increment in proportion of variance accounted for by the set of predictors entered in a given step. * P<0.025. ** P<0.005. Table options 6.3.4. Effects of socio-economic status 6.3.4.1. Zero-order correlations One subsidiary goal was to assess the relation between SES and frontal asymmetry. This question is particularly salient in the present context because the high risk and low risk groups differed on SES. When participants in both risk status groups were pooled into one sample, we observed a significant overall correlation between SES and alpha-band mid-frontal asymmetry for two of the three reference montages, computer-averaged-ears reference r=0.57, P<0.001, average reference r=0.50, P<0.001, Cz reference r=0.16, P>0.30. These correlations indicate that higher SES predicted greater relative left frontal activity. Fig. 3 shows scatter plots depicting the relation between frontal brain asymmetry (derived from three reference montages) and SES, with risk status symbolically indicated. Although this figure makes evident the small number of low SES participants in the low risk group, it also clearly illustrates the relation between relative left frontal activity and SES. Scatter plots of the relation between SES and mid-frontal (F3/F4) alpha ... Fig. 3. Scatter plots of the relation between SES and mid-frontal (F3/F4) alpha asymmetry for each of three reference montages. Top panel: averaged-ears reference; middle panel: average reference; bottom panel: vertex (Cz) reference; H: high risk adolescents; L: low risk adolescents. Figure options To investigate further the relation between alpha asymmetry in the mid-frontal region and social class, correlations were computed separately for each risk group. Within the high risk group, frontal asymmetry measures derived using the computer-averaged-ears and average references both correlated significantly with SES, computer-averaged-ears reference r=0.56, P<0.004, average reference r=0.50, P<0.01, Cz reference r=0.14, P>0.50. Within the low risk group, there were no significant correlations between SES and frontal brain asymmetry, computer-averaged-ears reference r=0.04, average reference r=0.05, Cz reference r=−0.03, all Full-size image (<1 K). Clearly, however, caution is necessary here because: (1) differences between relevant pairs of correlations (e.g., high risk computer-averaged-ears versus low risk computer-averaged-ears) were not statistically significant (all Full-size image (<1 K)); (2) there was a restricted range of SES in the low risk group that could significantly influence the magnitude of the observed correlation (low risk M=53.2, S.D.=6.8; high risk M=37.3, S.D.=13.3) and, (3) due to the differences in variability, comparisons of unstandardized beta weights are likely more appropriate than comparisons of correlations (e.g., Tukey, 1954). Such comparisons constituted the SES X risk status interaction effects tested in the multiple regression analyses reported below. 6.3.4.2. Multiple regression results To investigate further the relations among SES, frontal brain asymmetry, and risk status, we conducted multiple regression analyses in which risk status, sex, and SES were specified as predictors of mid-frontal asymmetry in the alpha-band. These analyses were designed to test the unique effects of each of the three predictors on frontal asymmetry and to test for moderator effects. For example, a significant risk status X SES two-way interaction would suggest that the magnitude of the relation between SES and frontal asymmetry is conditional on risk status and, conversely, that the relation between risk status and frontal asymmetry is conditional on level of SES. A hierarchical structure (Cohen and Cohen, 1983) was used for the three analyses (one per reference). In the first step, the three predictors were entered simultaneously (risk status, sex, and SES). This step was used to test for the main effects of each predictor on frontal asymmetry removing shared variance with the other predictors. In the second step, the three two-way interaction terms (risk status X SES, risk status X sex, sex X SES) were entered as a set. In the third step, we entered the risk status X sex X SES three-way interaction term. At each step, we tested the statistical significance of each of the individual regression coefficients in the set just entered and the significance of the incremental variance attributable to the set. To facilitate the interpretation of coefficients, we centered SES (i.e., expressed it as deviations from its mean, thus resulting in a transformed mean of 0, e.g., Aiken and West, 1991). We used dummy codes for the categorical variables of risk status (0 = low risk, 1 = high risk) and sex (0 = females, 1 = males). It is important to note that identical results and conclusions were yielded when alternative model-testing strategies were used (e.g., for descriptions of alternative approaches, see, e.g., Aiken and West, 1991). Table 3 shows the results of the regressions on alpha-band asymmetry for each of the three references. To provide an interpretable metric, this table displays standardized regression coefficients β’s for each first-order (i.e., main effect) term (risk status, sex, SES). The test statistics and P values for such first-order coefficients are identical to those for the unstandardized coefficients that were yielded by an analysis of the raw data values in their original metric. In the case of two- and three-way interactions, the coefficients shown in Table 3 are actually the unstandardized coefficients yielded by an analysis of interaction terms that were the product of standardized first-order terms. Such interaction terms were not, however, themselves standardized. By this means, we were able to present interaction coefficients that had both a reasonably interpretable metric and test statistics and significance levels identical to those yielded by analyses of the raw data values in their original metric ( Aiken and West, 1991 and Friedrich, 1982). Also shown in Table 3 are squared semi-partial correlations denoting the proportion of the total variance in asymmetry scores uniquely attributable to each predictor (see, e.g., Cohen and Cohen, 1983) and R2 values indicating the increment in variance accounted for by each set of predictors. As indicated by Table 3, the results of the regressions of mid-frontal asymmetry on the first-order terms (risk status, SES, and sex) were consistent across the ears referenced and average referenced montages. In each case, SES, but not risk status or sex, contributed significant unique variance to the prediction of alpha-band asymmetry (ears referenced P<0.005, average referenced P<0.025). The squared semi-partial correlation coefficients shown in Table 3 indicate that SES accounted for a notably higher proportion of the variance in ears referenced and average referenced frontal asymmetry scores than the other two predictors (see Table 3). We should emphasize that the effects shown for each of the three predictors in Table 3 are adjusted for the effects of the other two predictors in the equation (i.e., the three predictors were entered simultaneously as a set). When Cz-referenced mid-frontal asymmetry was the outcome variable, no effects for first-order terms were significant. In subsequent steps testing for moderation, we entered the two-way and three-way interaction terms in the regression equations. As shown in Table 2, the only significant effect across all three dependent measures was the risk status X sex interaction on Cz-referenced mid-frontal asymmetry (P<0.005). This effect was also yielded by the risk status X sex ANOVA reported above and reflects greater differences between the high and low risk groups among females relative to males. There were no significant two- or three-way interactions involving SES (all Full-size image (<1 K)). 6.3.4.3. Components of SES We also examined the relations between the components of SES and alpha-band asymmetry. Our measure of SES (Hollingshead, 1975) is derived primarily from parental occupation, education, and marital status. We first calculated zero-order correlations between risk status and these three components of SES. To orient readers to the scaling and direction of relations, occupation ranged from 0 (unemployed) to 9 (higher professional), education ranged from 1 (less that 6 years of schooling) to 7 (more than 18 years of schooling), and marital status was coded as either 0 (unmarried) or (1) married. The high and low risk groups differed on these components of SES in a manner that paralleled the differences on the composite SES index reported above (occupation P<0.001; education P<0.005; marital Status P<0.02). Parents of low risk participants were more likely to have attained higher occupation and educational levels and were more likely to be married. When participants in both risk status groups were pooled into one sample, we observed a significant overall correlation between occupation and alpha-band mid-frontal asymmetry for two of the three reference montages, ears reference r=0.50, P<0.002, average reference r=0.45, P<0.01, Cz reference r=0.06, P>0.50. We also observed a significant overall correlation between education and alpha-band mid-frontal asymmetry for two of the three reference montages, ears reference r=0.33, P<0.05, average reference r=0.38, P<0.05, Cz reference r=0.19, P>0.20. Finally, we observed a significant overall correlation between marital status and alpha-band mid-frontal asymmetry for one of the three reference montages, ears reference r=0.42, P<0.0.01, average reference r=0.20, P>0.20, Cz reference r=0.12, P>0.40. Thus, higher occupation, more years of education, and being married generally predicted greater relative left frontal activity.