J Abnorm Child Psychol DOI 10.1007/s10802-013-9810-4
Paralimbic Gray Matter Reductions in Incarcerated Adolescent Females with Psychopathic Traits Lora M. Cope & Elsa Ermer & Prashanth K. Nyalakanti & Vince D. Calhoun & Kent A. Kiehl
# Springer Science+Business Media New York 2013
Abstract Psychopathy-related paralimbic and limbic structural brain abnormalities have been implicated in incarcerated adult and adolescent male samples. However, there have been few neuroimaging studies of psychopathic traits in females in general and no studies from incarcerated female youth in particular. Here we present the first study to examine the relationship between brain gray matter volumes and psychopathic traits (assessed using the Psychopathy Checklist-Youth Version [PCL-YV]) in a sample of maximum-security incarcerated female adolescents (N =39; mean age=17.6 years). Consistent with male samples, regional gray matter volumes were negatively related to psychopathic traits in female youth offenders in limbic and paralimbic areas, including orbitofrontal cortex, parahippocampal cortex, temporal poles, and left hippocampus. These results provide evidence that Electronic supplementary material The online version of this article (doi:10.1007/s10802-013-9810-4) contains supplementary material, which is available to authorized users. L. M. Cope : K. A. Kiehl Department of Psychology, University of New Mexico, Albuquerque, NM, USA L. M. Cope : P. K. Nyalakanti : V. D. Calhoun : K. A. Kiehl The Mind Research Network and Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM, USA E. Ermer Derner Institute Psychology Department, Adelphi University, Garden City, NY, USA V. D. Calhoun Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, NM, USA L. M. Cope (*) Addiction Research Center and Department of Psychiatry, The University of Michigan, 4250 Plymouth Rd., Ann Arbor, MI 48109, USA e-mail: [email protected]
psychopathic traits manifest similar neural abnormalities across sex and age. Keywords Voxel-based morphometry (VBM) . Psychopathic traits . Adolescentfemales . Paralimbicstructures . Psychopathy Checklist-Youth Version (PCL-YV) . Incarcerated offenders Antisocial behavior in youth is a severe social problem costing U.S. taxpayers roughly $56.7 billion per year1 (Caldwell et al. 2006b). Although behavioral problems tend to be more prevalent in boys (American Psychiatric Association 2000), girls still constitute a considerable portion of adolescent antisociality (Silverthorn and Frick 1999). Considerable efforts have been applied to examining the psychological and social factors that contribute to antisociality in adolescence; however, relatively little work has specifically examined these factors in female youth. Indeed, traditional theories of youth antisociality were developed specifically about males (e.g., Moffitt 1993), leading some to question whether these theories can be generalized to females (Silverthorn and Frick 1999). For some antisocial adolescent girls, problematic behavior persists and becomes more severe, often leading to arrests, mental health problems, and maladaptive drug and alcohol use in adulthood (Silverthorn and Frick 1999). Adults on the life-course persistent trajectory often meet diagnostic criteria for psychopathy, which is an important predictor of persistence in criminal activity and recidivism (Hemphill et al. 1998; Yang et al. 2010). 1 This figure is based on two factors: a) The estimated cost of all crime in the United States in 1987 was $257 billion (Cohen et al. 1994), and b) Juveniles accounted for 22 % of all arrests in that year (Federal Bureau of Investigation 1996). Considering that the annual burden of crime in today’s dollars has been estimated at $1 trillion (Anderson 1999) and individuals under 18 accounted for over 14 % of all arrests in 2009 (Federal Bureau of Investigation 2010), $56.7 billion per year is undoubtedly an underestimate.
J Abnorm Child Psychol
Psychopathy is a personality disorder characterized by interpersonal, antisocial, and affective traits such as glibness, impulsivity, and lack of empathy, guilt, and remorse (Cleckley 1976; Hare 2003). Psychopathy in adults is commonly assessed with the Hare Psychopathy Checklist-Revised (PCL-R; Hare 2003), the most widely accepted diagnostic instrument for psychopathy. The PCL-R can be meaningfully divided into two factors, with Factor 1 comprising interpersonal and affective traits (conceptually similar to callous and unemotional traits in youth) and Factor 2 comprising lifestyle and antisocial traits (conceptually similar to conduct disorder in youth). Given the strong evidence that psychopathic symptoms manifest early in development (Lahey and Kazdin 1990), Hare and colleagues constructed a downward extension of the PCL-R, the Psychopathy Checklist-Youth Version (PCL-YV; Forth et al. 2003), for use in adolescent samples. It is important to note that psychopathy in youth does not imply that adolescents with these traits are on a predetermined and/or unchangeable path of antisociality and/or adult psychopathy. Indeed, recent evidence suggests that early interventions show great promise for reducing antisocial outcomes in high risk youth (Caldwell et al. 2006a). Evidence from electrophysiology (e.g., Kiehl et al. 1999), functional neuroimaging (e.g., Birbaumer et al. 2005; Harenski et al. 2010; Kiehl et al. 2001; Muller et al. 2003), structural neuroimaging (e.g., De Oliveira-Souza et al. 2008; Ermer et al. 2012; Muller et al. 2008), and brain damage and lesion studies (e.g., Malloy et al. 1993) suggests that paralimbic cortex and limbic structures are involved in psychopathic symptomology (reviewed in Kiehl 2006). Results from structural MRI studies support the hypothesis that limbic and paralimbic regions (e.g., De Oliveira-Souza et al. 2008; Ermer et al. 2012; Muller et al. 2008; Tiihonen et al. 2008) as well as prefrontal areas (De Oliveira-Souza et al. 2008; Yang et al. 2005) are impaired in psychopathy, however these studies have generally been limited to adult males. Results from a recent large-scale structural study of incarcerated male youth (N =191; mean age 17.3) support the notion that psychopathic traits may manifest with neural differences in adolescence (Ermer et al. 2013). In Ermer et al. (2013), adolescent males were assessed for psychopathy with the PCL-YV and regional differences in gray matter volume were examined using voxel-based morphometry (VBM). Brain volume, age, and substance use were covaried in order to isolate the effects of psychopathy on gray matter. Decreases in gray matter volume were found in the posterior cingulate cortex and orbitofrontal cortex, extending into the parahippocampal cortex and temporal poles. Additionally, there was an area of positive association between psychopathic traits and gray matter volume in medial prefrontal cortex. These findings are consistent with the hypothesis that psychopathy is a neurodevelopmental disorder. Other studies have shown that boys with conduct disorder (CD) have
reduced volumes in the temporal lobe (M = 16 years; Kruesi et al. 2004), insula and amygdala (M =13 years; Sterzer et al. 2007), and temporal lobes, amygdala, hippocampus, orbitofrontal cortex, and ventromedial prefrontal cortex (M =14 years; Huebner et al. 2008). However, one study of boys from the community (M =11 years) with callous and unemotional traits found increased gray matter volume in superior temporal gyrus, orbitofrontal cortex, anterior cingulate cortex, left hippocampus, insula, and posterior cingulate cortex (De Brito et al. 2009). These studies on male adolescents and adults suggest that psychopathic traits are associated with altered gray matter development, but the extent to which these differences are found in adolescent female offenders is unknown. Though one study of adolescent females found gray matter reductions in a conduct disorder group versus healthy controls (Fairchild et al. 2013), to our knowledge no studies have addressed the effect of psychopathic traits on gray matter volume in incarcerated adolescent female offenders using the PCL-YV. Here we begin to address this gap by presenting results from VBM analyses on the relationship between brain structure and psychopathic traits (assessed using the PCL-YV) in a sample of maximum-security incarcerated female adolescents (N =39; mean age=17.6 years). Here we test the hypothesis that, as in samples of adult and adolescent males, elevated psychopathic traits will be associated with reduced gray matter volumes in the parahippocampus, amygdala, hippocampus, temporal poles, anterior and posterior cingulate, and orbitofrontal cortex in incarcerated female youth.
Methods Participants These data were drawn from female participants in the National Institute of Mental Health (NIMH)-funded SouthWest Advanced Neuroimaging Cohort, Youth sample (SWANC-Y), collected between June, 2007, and March, 2011, at a maximum-security youth detention facility in New Mexico. This research was approved by the University of New Mexico Health Sciences Center Human Research Review Committee and individuals volunteered to participate after providing written informed consent (if≥18 years or age) or after providing written informed assent and parent/guardian written informed consent (if1 h were excluded (n =1); information was not available for n =1 participant. Trained researchers administered the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (KSADS-PL; Kaufman et al. 1997). Participants with any history of psychotic (n =2) or bipolar (n =1) disorders were excluded from analyses. Substance Use Psychopathic traits are frequently comorbid with substance use in adults (Smith and Newman 1990) and adolescents (O’Neill et al. 2003). We assessed substance use in two ways: 1) Using the KSADS, the total number of substances (alcohol and drugs) for which an individual met the lifetime dependence diagnostic criteria was calculated (substance dependence; theoretical range: 0–8). 2) Using a
modified version of the Addiction Severity Index (McLellan et al. 1992), years of use were summed for each substance (alcohol and drug) that the participant reported using on a regular basis (i.e., three or more times per week for a minimum of 1 month). These summed scores were then divided by age and a square root transformation was applied to correct for skew (years of regular use). MRI Acquisition High-resolution T1-weighted structural MRI scans were acquired on the Mind Research Network Siemens 1.5 T Avanto mobile scanner, stationed at the maximum-security detention facility, using a multi-echo MPRAGE pulse sequence (repetition time=2530 ms, echo times=1.64 ms, 3.50 ms, 5.36 ms, 7.22 ms, inversion time=1100 ms, flip angle=7°, slice thickness=1.3 mm, matrix size=256×256) yielding 128 sagittal slices with an in-plane resolution of 1.0 mm×1.0 mm. Data were pre-processed and analyzed using Statistical Parametric Mapping software (SPM5; Wellcome Department of Cognitive Neurology, London, UK; http://www.fil.ion.ucl.ac.uk/ spm). T1 images were manually inspected by an operator blind to subject identity and realigned to ensure proper spatial normalization. Images were spatially normalized to the SPM5 T1 Montreal Neurological Institute (MNI) template using non-linear registration, segmented into gray matter, white matter, and cerebrospinal fluid, and modulated with the Jacobian determinants to preserve total volume (Ashburner and Friston 2000, 2005). The modulated, normalized gray matter segments were then averaged to create a customized, study-specific template. Next, the original gray matter segments were normalized to the customized template. Finally, the images were resampled to 2 ×2× 2 mm and smoothed with a 10 mm full-width at half-maximum (FWHM) Gaussian kernel. Voxels with a gray matter value of1 h, and n =3 with a history of psychotic or bipolar disorders. Primary Whole Brain Analyses Multiple regression analyses were performed on a voxel-by-voxel basis over the whole brain using the general linear model to evaluate the relationship between PCL-YV and regional gray matter volumes. Psychopathy scores can be treated continuously or discretized (i.e., low, medium, high), and many researchers agree that
J Abnorm Child Psychol
both analytic approaches are valid (e.g., De Oliveira-Souza et al. 2008; Muller et al. 2008). Here PCL-YV score was examined as a continuous variable. All analyses included a measure of substance use as a covariate. Substance use can affect gray matter, although the direction and duration of effects of substance use on gray matter, and the role of related third variables (like psychopathy), is currently unsettled (Tanabe et al. 2009; Yuan et al. 2009). Adolescence is a period of rapid developmental changes in brain structure (Giedd 2004) and gray matter volume decreases with age (Good et al. 2001). Thus, age was included a covariate in all analyses. Volumetric analyses require a control for individual variation in brain size; here we included brain volume (white matter + gray matter) as a covariate in all analyses in order to focus on regionally-specific brain differences (Pell et al. 2008). In multiple regression analyses evaluating the relationship between the psychopathy factors and regional gray matter volume, both factors were included in the model simultaneously, in addition to the substance use, age at time of scan, and brain volume covariates. Results from an independent incarcerated adult male sample (Ermer et al. 2012) indicate that gray matter volume differences are extensively distributed in paralimbic and limbic regions, but the effect size at each voxel is small. We therefore used a method that tests for potentially small but distributed effects in whole-brain analyses by estimating the cluster size necessary to correspond to a desired statistical threshold. Monte Carlo simulation conducted using AlphaSim (Ward 2000) determined that a 1366 voxel-extent at a height threshold of p
Paralimbic Gray Matter Reductions in Incarcerated Adolescent Females with Psychopathic Traits Lora M. Cope & Elsa Ermer & Prashanth K. Nyalakanti & Vince D. Calhoun & Kent A. Kiehl
# Springer Science+Business Media New York 2013
Abstract Psychopathy-related paralimbic and limbic structural brain abnormalities have been implicated in incarcerated adult and adolescent male samples. However, there have been few neuroimaging studies of psychopathic traits in females in general and no studies from incarcerated female youth in particular. Here we present the first study to examine the relationship between brain gray matter volumes and psychopathic traits (assessed using the Psychopathy Checklist-Youth Version [PCL-YV]) in a sample of maximum-security incarcerated female adolescents (N =39; mean age=17.6 years). Consistent with male samples, regional gray matter volumes were negatively related to psychopathic traits in female youth offenders in limbic and paralimbic areas, including orbitofrontal cortex, parahippocampal cortex, temporal poles, and left hippocampus. These results provide evidence that Electronic supplementary material The online version of this article (doi:10.1007/s10802-013-9810-4) contains supplementary material, which is available to authorized users. L. M. Cope : K. A. Kiehl Department of Psychology, University of New Mexico, Albuquerque, NM, USA L. M. Cope : P. K. Nyalakanti : V. D. Calhoun : K. A. Kiehl The Mind Research Network and Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM, USA E. Ermer Derner Institute Psychology Department, Adelphi University, Garden City, NY, USA V. D. Calhoun Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, NM, USA L. M. Cope (*) Addiction Research Center and Department of Psychiatry, The University of Michigan, 4250 Plymouth Rd., Ann Arbor, MI 48109, USA e-mail: [email protected]
psychopathic traits manifest similar neural abnormalities across sex and age. Keywords Voxel-based morphometry (VBM) . Psychopathic traits . Adolescentfemales . Paralimbicstructures . Psychopathy Checklist-Youth Version (PCL-YV) . Incarcerated offenders Antisocial behavior in youth is a severe social problem costing U.S. taxpayers roughly $56.7 billion per year1 (Caldwell et al. 2006b). Although behavioral problems tend to be more prevalent in boys (American Psychiatric Association 2000), girls still constitute a considerable portion of adolescent antisociality (Silverthorn and Frick 1999). Considerable efforts have been applied to examining the psychological and social factors that contribute to antisociality in adolescence; however, relatively little work has specifically examined these factors in female youth. Indeed, traditional theories of youth antisociality were developed specifically about males (e.g., Moffitt 1993), leading some to question whether these theories can be generalized to females (Silverthorn and Frick 1999). For some antisocial adolescent girls, problematic behavior persists and becomes more severe, often leading to arrests, mental health problems, and maladaptive drug and alcohol use in adulthood (Silverthorn and Frick 1999). Adults on the life-course persistent trajectory often meet diagnostic criteria for psychopathy, which is an important predictor of persistence in criminal activity and recidivism (Hemphill et al. 1998; Yang et al. 2010). 1 This figure is based on two factors: a) The estimated cost of all crime in the United States in 1987 was $257 billion (Cohen et al. 1994), and b) Juveniles accounted for 22 % of all arrests in that year (Federal Bureau of Investigation 1996). Considering that the annual burden of crime in today’s dollars has been estimated at $1 trillion (Anderson 1999) and individuals under 18 accounted for over 14 % of all arrests in 2009 (Federal Bureau of Investigation 2010), $56.7 billion per year is undoubtedly an underestimate.
J Abnorm Child Psychol
Psychopathy is a personality disorder characterized by interpersonal, antisocial, and affective traits such as glibness, impulsivity, and lack of empathy, guilt, and remorse (Cleckley 1976; Hare 2003). Psychopathy in adults is commonly assessed with the Hare Psychopathy Checklist-Revised (PCL-R; Hare 2003), the most widely accepted diagnostic instrument for psychopathy. The PCL-R can be meaningfully divided into two factors, with Factor 1 comprising interpersonal and affective traits (conceptually similar to callous and unemotional traits in youth) and Factor 2 comprising lifestyle and antisocial traits (conceptually similar to conduct disorder in youth). Given the strong evidence that psychopathic symptoms manifest early in development (Lahey and Kazdin 1990), Hare and colleagues constructed a downward extension of the PCL-R, the Psychopathy Checklist-Youth Version (PCL-YV; Forth et al. 2003), for use in adolescent samples. It is important to note that psychopathy in youth does not imply that adolescents with these traits are on a predetermined and/or unchangeable path of antisociality and/or adult psychopathy. Indeed, recent evidence suggests that early interventions show great promise for reducing antisocial outcomes in high risk youth (Caldwell et al. 2006a). Evidence from electrophysiology (e.g., Kiehl et al. 1999), functional neuroimaging (e.g., Birbaumer et al. 2005; Harenski et al. 2010; Kiehl et al. 2001; Muller et al. 2003), structural neuroimaging (e.g., De Oliveira-Souza et al. 2008; Ermer et al. 2012; Muller et al. 2008), and brain damage and lesion studies (e.g., Malloy et al. 1993) suggests that paralimbic cortex and limbic structures are involved in psychopathic symptomology (reviewed in Kiehl 2006). Results from structural MRI studies support the hypothesis that limbic and paralimbic regions (e.g., De Oliveira-Souza et al. 2008; Ermer et al. 2012; Muller et al. 2008; Tiihonen et al. 2008) as well as prefrontal areas (De Oliveira-Souza et al. 2008; Yang et al. 2005) are impaired in psychopathy, however these studies have generally been limited to adult males. Results from a recent large-scale structural study of incarcerated male youth (N =191; mean age 17.3) support the notion that psychopathic traits may manifest with neural differences in adolescence (Ermer et al. 2013). In Ermer et al. (2013), adolescent males were assessed for psychopathy with the PCL-YV and regional differences in gray matter volume were examined using voxel-based morphometry (VBM). Brain volume, age, and substance use were covaried in order to isolate the effects of psychopathy on gray matter. Decreases in gray matter volume were found in the posterior cingulate cortex and orbitofrontal cortex, extending into the parahippocampal cortex and temporal poles. Additionally, there was an area of positive association between psychopathic traits and gray matter volume in medial prefrontal cortex. These findings are consistent with the hypothesis that psychopathy is a neurodevelopmental disorder. Other studies have shown that boys with conduct disorder (CD) have
reduced volumes in the temporal lobe (M = 16 years; Kruesi et al. 2004), insula and amygdala (M =13 years; Sterzer et al. 2007), and temporal lobes, amygdala, hippocampus, orbitofrontal cortex, and ventromedial prefrontal cortex (M =14 years; Huebner et al. 2008). However, one study of boys from the community (M =11 years) with callous and unemotional traits found increased gray matter volume in superior temporal gyrus, orbitofrontal cortex, anterior cingulate cortex, left hippocampus, insula, and posterior cingulate cortex (De Brito et al. 2009). These studies on male adolescents and adults suggest that psychopathic traits are associated with altered gray matter development, but the extent to which these differences are found in adolescent female offenders is unknown. Though one study of adolescent females found gray matter reductions in a conduct disorder group versus healthy controls (Fairchild et al. 2013), to our knowledge no studies have addressed the effect of psychopathic traits on gray matter volume in incarcerated adolescent female offenders using the PCL-YV. Here we begin to address this gap by presenting results from VBM analyses on the relationship between brain structure and psychopathic traits (assessed using the PCL-YV) in a sample of maximum-security incarcerated female adolescents (N =39; mean age=17.6 years). Here we test the hypothesis that, as in samples of adult and adolescent males, elevated psychopathic traits will be associated with reduced gray matter volumes in the parahippocampus, amygdala, hippocampus, temporal poles, anterior and posterior cingulate, and orbitofrontal cortex in incarcerated female youth.
Methods Participants These data were drawn from female participants in the National Institute of Mental Health (NIMH)-funded SouthWest Advanced Neuroimaging Cohort, Youth sample (SWANC-Y), collected between June, 2007, and March, 2011, at a maximum-security youth detention facility in New Mexico. This research was approved by the University of New Mexico Health Sciences Center Human Research Review Committee and individuals volunteered to participate after providing written informed consent (if≥18 years or age) or after providing written informed assent and parent/guardian written informed consent (if1 h were excluded (n =1); information was not available for n =1 participant. Trained researchers administered the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (KSADS-PL; Kaufman et al. 1997). Participants with any history of psychotic (n =2) or bipolar (n =1) disorders were excluded from analyses. Substance Use Psychopathic traits are frequently comorbid with substance use in adults (Smith and Newman 1990) and adolescents (O’Neill et al. 2003). We assessed substance use in two ways: 1) Using the KSADS, the total number of substances (alcohol and drugs) for which an individual met the lifetime dependence diagnostic criteria was calculated (substance dependence; theoretical range: 0–8). 2) Using a
modified version of the Addiction Severity Index (McLellan et al. 1992), years of use were summed for each substance (alcohol and drug) that the participant reported using on a regular basis (i.e., three or more times per week for a minimum of 1 month). These summed scores were then divided by age and a square root transformation was applied to correct for skew (years of regular use). MRI Acquisition High-resolution T1-weighted structural MRI scans were acquired on the Mind Research Network Siemens 1.5 T Avanto mobile scanner, stationed at the maximum-security detention facility, using a multi-echo MPRAGE pulse sequence (repetition time=2530 ms, echo times=1.64 ms, 3.50 ms, 5.36 ms, 7.22 ms, inversion time=1100 ms, flip angle=7°, slice thickness=1.3 mm, matrix size=256×256) yielding 128 sagittal slices with an in-plane resolution of 1.0 mm×1.0 mm. Data were pre-processed and analyzed using Statistical Parametric Mapping software (SPM5; Wellcome Department of Cognitive Neurology, London, UK; http://www.fil.ion.ucl.ac.uk/ spm). T1 images were manually inspected by an operator blind to subject identity and realigned to ensure proper spatial normalization. Images were spatially normalized to the SPM5 T1 Montreal Neurological Institute (MNI) template using non-linear registration, segmented into gray matter, white matter, and cerebrospinal fluid, and modulated with the Jacobian determinants to preserve total volume (Ashburner and Friston 2000, 2005). The modulated, normalized gray matter segments were then averaged to create a customized, study-specific template. Next, the original gray matter segments were normalized to the customized template. Finally, the images were resampled to 2 ×2× 2 mm and smoothed with a 10 mm full-width at half-maximum (FWHM) Gaussian kernel. Voxels with a gray matter value of1 h, and n =3 with a history of psychotic or bipolar disorders. Primary Whole Brain Analyses Multiple regression analyses were performed on a voxel-by-voxel basis over the whole brain using the general linear model to evaluate the relationship between PCL-YV and regional gray matter volumes. Psychopathy scores can be treated continuously or discretized (i.e., low, medium, high), and many researchers agree that
J Abnorm Child Psychol
both analytic approaches are valid (e.g., De Oliveira-Souza et al. 2008; Muller et al. 2008). Here PCL-YV score was examined as a continuous variable. All analyses included a measure of substance use as a covariate. Substance use can affect gray matter, although the direction and duration of effects of substance use on gray matter, and the role of related third variables (like psychopathy), is currently unsettled (Tanabe et al. 2009; Yuan et al. 2009). Adolescence is a period of rapid developmental changes in brain structure (Giedd 2004) and gray matter volume decreases with age (Good et al. 2001). Thus, age was included a covariate in all analyses. Volumetric analyses require a control for individual variation in brain size; here we included brain volume (white matter + gray matter) as a covariate in all analyses in order to focus on regionally-specific brain differences (Pell et al. 2008). In multiple regression analyses evaluating the relationship between the psychopathy factors and regional gray matter volume, both factors were included in the model simultaneously, in addition to the substance use, age at time of scan, and brain volume covariates. Results from an independent incarcerated adult male sample (Ermer et al. 2012) indicate that gray matter volume differences are extensively distributed in paralimbic and limbic regions, but the effect size at each voxel is small. We therefore used a method that tests for potentially small but distributed effects in whole-brain analyses by estimating the cluster size necessary to correspond to a desired statistical threshold. Monte Carlo simulation conducted using AlphaSim (Ward 2000) determined that a 1366 voxel-extent at a height threshold of p
