Patients homozygous for the C allele of the T102C serotonin (5-HT) 2a receptor polymorphism have ... more Patients homozygous for the C allele of the T102C serotonin (5-HT) 2a receptor polymorphism have shown increased suicidal ideation or behavior in some reports, but not in others. We conducted a pilot investigation to determine whether this polymorphism might relate more specifically to a dimension of impaired impulse control, which may underlie only a portion of suicides. Rates of commission (impulsive) errors in a variant of the Continuous Performance Test (CPT) were compared across the genotypes of the T102C polymorphism in adults recruited from the community. The 102C/102C genotype was jointly associated with a greater incidence of past mood disorder or substance-use disorder, as well as significantly more commission errors compared to the 102T/102C and 102C/102C genotypes. These preliminary data suggest that the T102C 5-HT2a receptor polymorphism may be a marker for impaired behavior control-perhaps in the context of psychiatric disorder history.
This study employed functional magnetic resonance imaging (fMRI)-based dynamic causal modeling (D... more This study employed functional magnetic resonance imaging (fMRI)-based dynamic causal modeling (DCM) to study the effective (directional) neuronal connectivity underlying inhibitory behavioral control. fMRI data were acquired from 15 healthy subjects while they performed a Go/NoGo task with two levels of NoGo difficulty (Easy and Hard NoGo conditions) in distinguishing spatial patterns of lines. Based on the previous inhibitory control literature and the present fMRI activation results, 10 brain regions were postulated as nodes in the effective connectivity model. Due to the large number of potential interconnections among these nodes, the number of models for final analysis was reduced to a manageable level for the whole group by conducting DCM Network Discovery, which is a recently developed option within the Statistical Parametric Mapping software package. Given the optimum network model, the DCM Network Discovery analysis found that the locations of the driving input into the mo...
Plasma gamma-aminobutyric acid (GABA) levels are decreased in some patients with depression, mani... more Plasma gamma-aminobutyric acid (GABA) levels are decreased in some patients with depression, mania and alcoholism. Medications which increase plasma GABA improve symptoms of mood disorders and can decrease aggression. We examined the relationship between plasma GABA and aggressiveness on the Buss-Durkee Hostility Inventory in 77 psychiatrically healthy adults. In subjects selected for having a first-degree relative with primary unipolar depressive disorder (FH+, n=33), plasma GABA was negatively correlated with aggressiveness (beta=-0.338, P=0.036), as was age (beta=-0.483, P=0.005). A relationship between plasma GABA levels and aggressiveness was not observed in subjects with no such family history (FH-, n=44). Moreover, FH+ subjects had significantly lower plasma GABA concentrations than FH- subjects. These data suggest that low GABA levels may correlate with some aspects of aggressiveness and may be genetically regulated.
To characterize how severe negative affect in women is reflected in objective measures of aggress... more To characterize how severe negative affect in women is reflected in objective measures of aggression and impulsivity, the aggressive and impulsive behavior of 14 hospitalized women with borderline personality disorder (BPD) was compared with that of 17 controls. In an impulsivity task, subjects experienced two sets of 50 trials during which they could choose a smaller, immediate monetary reward or a larger but progressively delayed reward. In a separate task (PSAP), subjects earned monetary reinforcers with repeated button presses, and were provoked by the subtraction of money which was blamed on a fictitious other participant. Subjects could respond by ostensibly subtracting money from the fictitious subject (the aggressive response). While selection frequency of the short-delay responses was similar in patients and controls, BPD patients responded to avoid longer delay of reward across trials, and had higher Barratt Impulsiveness Scale total scores and attentional subscale scores. BPD patients responded to the money losses with roughly three times as many aggressive responses as controls and had higher Buss-Durkee Hostility Inventory (BDHI), Brown History of Violence, and Retrospective Overt Aggression Scale scores than controls. Aggressive responding rates correlated positively with BDHI scores. These results extend previous findings that negative affect in women is reflected in laboratory behavioral measures.
Patients homozygous for the C allele of the T102C serotonin (5-HT) 2a receptor polymorphism have ... more Patients homozygous for the C allele of the T102C serotonin (5-HT) 2a receptor polymorphism have shown increased suicidal ideation or behavior in some reports, but not in others. We conducted a pilot investigation to determine whether this polymorphism might relate more specifically to a dimension of impaired impulse control, which may underlie only a portion of suicides. Rates of commission (impulsive) errors in a variant of the Continuous Performance Test (CPT) were compared across the genotypes of the T102C polymorphism in adults recruited from the community. The 102C/102C genotype was jointly associated with a greater incidence of past mood disorder or substance-use disorder, as well as significantly more commission errors compared to the 102T/102C and 102C/102C genotypes. These preliminary data suggest that the T102C 5-HT2a receptor polymorphism may be a marker for impaired behavior control-perhaps in the context of psychiatric disorder history.
This study employed functional magnetic resonance imaging (fMRI)-based dynamic causal modeling (D... more This study employed functional magnetic resonance imaging (fMRI)-based dynamic causal modeling (DCM) to study the effective (directional) neuronal connectivity underlying inhibitory behavioral control. fMRI data were acquired from 15 healthy subjects while they performed a Go/NoGo task with two levels of NoGo difficulty (Easy and Hard NoGo conditions) in distinguishing spatial patterns of lines. Based on the previous inhibitory control literature and the present fMRI activation results, 10 brain regions were postulated as nodes in the effective connectivity model. Due to the large number of potential interconnections among these nodes, the number of models for final analysis was reduced to a manageable level for the whole group by conducting DCM Network Discovery, which is a recently developed option within the Statistical Parametric Mapping software package. Given the optimum network model, the DCM Network Discovery analysis found that the locations of the driving input into the mo...
Plasma gamma-aminobutyric acid (GABA) levels are decreased in some patients with depression, mani... more Plasma gamma-aminobutyric acid (GABA) levels are decreased in some patients with depression, mania and alcoholism. Medications which increase plasma GABA improve symptoms of mood disorders and can decrease aggression. We examined the relationship between plasma GABA and aggressiveness on the Buss-Durkee Hostility Inventory in 77 psychiatrically healthy adults. In subjects selected for having a first-degree relative with primary unipolar depressive disorder (FH+, n=33), plasma GABA was negatively correlated with aggressiveness (beta=-0.338, P=0.036), as was age (beta=-0.483, P=0.005). A relationship between plasma GABA levels and aggressiveness was not observed in subjects with no such family history (FH-, n=44). Moreover, FH+ subjects had significantly lower plasma GABA concentrations than FH- subjects. These data suggest that low GABA levels may correlate with some aspects of aggressiveness and may be genetically regulated.
To characterize how severe negative affect in women is reflected in objective measures of aggress... more To characterize how severe negative affect in women is reflected in objective measures of aggression and impulsivity, the aggressive and impulsive behavior of 14 hospitalized women with borderline personality disorder (BPD) was compared with that of 17 controls. In an impulsivity task, subjects experienced two sets of 50 trials during which they could choose a smaller, immediate monetary reward or a larger but progressively delayed reward. In a separate task (PSAP), subjects earned monetary reinforcers with repeated button presses, and were provoked by the subtraction of money which was blamed on a fictitious other participant. Subjects could respond by ostensibly subtracting money from the fictitious subject (the aggressive response). While selection frequency of the short-delay responses was similar in patients and controls, BPD patients responded to avoid longer delay of reward across trials, and had higher Barratt Impulsiveness Scale total scores and attentional subscale scores. BPD patients responded to the money losses with roughly three times as many aggressive responses as controls and had higher Buss-Durkee Hostility Inventory (BDHI), Brown History of Violence, and Retrospective Overt Aggression Scale scores than controls. Aggressive responding rates correlated positively with BDHI scores. These results extend previous findings that negative affect in women is reflected in laboratory behavioral measures.
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