Affective Circuitry and Risk for Alcoholism in Late Adolescence: Differences in Frontostriatal Responses Between Vulnerable and Resilient Children of Alcoholic Parents

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65950/1/j.1530-0277.2007.00605.x.pd

Altered brain response to reward and punishment in adolescents with Anorexia nervosa

Adults recovered from Anorexia nervosa (AN) have altered reward modulation within striatal limbic regions associated with the emotional significance of stimuli, and executive regions concerned with planning and consequences. We hypothesized that adolescents with AN would show similar disturbed reward modulation within the striatum and the anterior cingulate cortex, a region connected to the striatum and involved in reward-guided action selection. Using functional magnetic resonance imaging, twenty-two adolescent females (10 restricting-type AN, 12 healthy volunteers) performed a monetary guessing task. Time series data associated with monetary wins and losses within striatal and cingulate regions of interest were subjected to a linear mixed effects analysis. All participants responded more strongly to wins versus losses in limbic and anterior executive striatal territories. However, AN participants exhibited an exaggerated response to losses compared to wins in posterior executive and sensorimotor striatal regions, suggesting altered function in circuitry responsible for coding the affective context of stimuli and action selection based upon these valuations. As AN individuals are particularly sensitive to criticism, failure, and making mistakes, these findings may reflect the neural processes responsible for a bias in those with AN to exaggerate negative consequences

White matter disease in midlife is heritable, related to hypertension, and shares some genetic influence with systolic blood pressure.

White matter disease in the brain increases with age and cardiovascular disease, emerging in midlife, and these associations may be influenced by both genetic and environmental factors. We examined the frequency, distribution, and heritability of abnormal white matter and its association with hypertension in 395 middle-aged male twins (61.9 ± 2.6 years) from the Vietnam Era Twin Study of Aging, 67% of whom were hypertensive. A multi-channel segmentation approach estimated abnormal regions within the white matter. Using multivariable regression models, we characterized the frequency distribution of abnormal white matter in midlife and investigated associations with hypertension and Apolipoprotein E-ε4 status and the impact of duration and control of hypertension. Then, using the classical twin design, we estimated abnormal white matter heritability and the extent of shared genetic overlap with blood pressure. Abnormal white matter was predominantly located in periventricular and deep parietal and frontal regions; associated with age (t = 1.9, p = 0.05) and hypertension (t = 2.9, p = 0.004), but not Apolipoprotein ε4 status; and was greater in those with uncontrolled hypertension relative to controlled (t = 3.0, p = 0.003) and normotensive (t = 4.0, p = 0.0001) groups, suggesting that abnormal white matter may reflect currently active cerebrovascular effects. Abnormal white matter was highly heritable (a2 = 0.81) and shared some genetic influences with systolic blood pressure (rA = 0.26), although there was evidence for distinct genetic contributions and unique environmental influences. Future longitudinal research will shed light on factors impacting white matter disease presentation, progression, and potential recovery

White matter disease in midlife is heritable, related to hypertension, and shares some genetic influence with systolic blood pressure.

White matter disease in the brain increases with age and cardiovascular disease, emerging in midlife, and these associations may be influenced by both genetic and environmental factors. We examined the frequency, distribution, and heritability of abnormal white matter and its association with hypertension in 395 middle-aged male twins (61.9 ± 2.6 years) from the Vietnam Era Twin Study of Aging, 67% of whom were hypertensive. A multi-channel segmentation approach estimated abnormal regions within the white matter. Using multivariable regression models, we characterized the frequency distribution of abnormal white matter in midlife and investigated associations with hypertension and Apolipoprotein E-ε4 status and the impact of duration and control of hypertension. Then, using the classical twin design, we estimated abnormal white matter heritability and the extent of shared genetic overlap with blood pressure. Abnormal white matter was predominantly located in periventricular and deep parietal and frontal regions; associated with age (t = 1.9, p = 0.05) and hypertension (t = 2.9, p = 0.004), but not Apolipoprotein ε4 status; and was greater in those with uncontrolled hypertension relative to controlled (t = 3.0, p = 0.003) and normotensive (t = 4.0, p = 0.0001) groups, suggesting that abnormal white matter may reflect currently active cerebrovascular effects. Abnormal white matter was highly heritable (a2 = 0.81) and shared some genetic influences with systolic blood pressure (rA = 0.26), although there was evidence for distinct genetic contributions and unique environmental influences. Future longitudinal research will shed light on factors impacting white matter disease presentation, progression, and potential recovery

Altered BOLD Response during Inhibitory and Error Processing in Adolescents with Anorexia Nervosa

<div><p>Background</p><p>Individuals with anorexia nervosa (AN) are often cognitively rigid and behaviorally over-controlled. We previously showed that adult females recovered from AN relative to healthy comparison females had less prefrontal activation during an inhibition task, which suggested a functional brain correlate of altered inhibitory processing in individuals recovered from AN. However, the degree to which these functional brain alterations are related to disease state and whether error processing is altered in AN individuals is unknown.</p><p>Methodology/Principal Findings</p><p>In the current study, ill adolescent AN females (n = 11) and matched healthy comparison adolescents (CA) with no history of an eating disorder (n = 12) performed a validated stop signal task (SST) during functional magnetic resonance imaging (fMRI) to explore differences in error and inhibitory processing. The groups did not differ on sociodemographic variables or on SST performance. During inhibitory processing, a significant group x difficulty (hard, easy) interaction was detected in the right dorsal anterior cingulate cortex (ACC), right middle frontal gyrus (MFG), and left posterior cingulate cortex (PCC), which was characterized by less activation in AN compared to CA participants during hard trials. During error processing, a significant group x accuracy (successful inhibit, failed inhibit) interaction in bilateral MFG and right PCC was observed, which was characterized by less activation in AN compared to CA participants during error (i.e., failed inhibit) trials.</p><p>Conclusion/Significance</p><p>Consistent with our prior findings in recovered AN, ill AN adolescents, relative to CA, showed less inhibition-related activation within the dorsal ACC, MFG and PCC as inhibitory demand increased. In addition, ill AN adolescents, relative to CA, also showed reduced activation to errors in the bilateral MFG and left PCC. These findings suggest that altered prefrontal and cingulate activation during inhibitory and error processing may represent a behavioral characteristic in AN that is independent of the state of recovery.</p></div

Mean reaction time (MRT) in milliseconds for post-error slowing (trials following a failed inhibition trial) for errors that occurred on easy stop trials and hard stop trials.

<p>As represented by the uppercase letters on the barplot, the MRT for post-error slowing was significantly faster [F(1,21)  = 4.6, p = 0.04, g = 0.9] for AN (689.0±135.3 ms) than CA (800.7±133.1 ms). Error bars represent the standard error for each group. AN: ill adolescents with anorexia nervosa, restricting-type; CA: healthy comparison adolescents.</p

Analysis of variance results within regions of interest demonstrating an interaction of group by inhibition accuracy (successful inhibit, failed inhibit).

<p>Note: Failed inhibition are trials in which participants failed to inhibit motor response when an auditory stop cue was presented, whereas successful inhibition are trials in which the participant correctly inhibited a motor response when the auditory stop cue was presented. BA: Brodmann Area; CA: healthy comparison adolescents; L: left; R: right; AN: adolescents ill with anorexia nervosa, restricting-type.</p

Voxelwise analysis of variance reporting significant clusters for an interaction of group x inhibition accuracy.

<p>Note: BA: Brodmann Area; B: bilateral; L: left; R: right.</p

Voxelwise analysis of variance reporting significant clusters for an interaction of group x difficulty.

<p>Note: BA: Brodmann Area; B: bilateral; L: left; R: right.</p

Behavioral accuracy performance on the stop signal task.

<p>The percent of inhibition errors (failed inhibits) for easy stop trials vs. hard stop trails for each group. No group or group x trial type differences were revealed for accuracy of performance. Bars with different letters (A vs. B) are significantly different from one another: participants made significantly more errors during the hard stop trials than during the easy stop trials [F(1,21)  =  264,6, p<0.001, g = 6.5]. Error bars represent the standard error for each group. AN: ill adolescents with anorexia nervosa, restricting-type; CA: healthy comparison adolescents.</p