Structural and functional brain connectivity abnormalities associated with adolescent conduct disorder in females

Background: Antisocial behavior (ASB) in childhood and adolescence is indexed by the diagnosis of conduct disorder (CD) and is associated with high rates of comorbid mental disorders, such as anxiety, depression, alcohol and drug dependence, as well as maltreatment. Elevated levels of psychopathic traits further complicate the clinical picture of adolescents with CD. Those who persist with severe ASB into adulthood will meet criteria for antisocial personality disorder (ASPD). Others will continue to display less severe ASB, and thereby not meet the diagnostic criteria for ASPD, but will experience a wide range of adverse outcomes, including persisting comorbid mental disorders and impaired psychosocial adjustment. Many studies have explored neural abnormalities associated with ASB, yet there are several key gaps in the extant literature: (I) Females with ASB have rarely been studied. (II) There has been no study of adult women who presented CD as adolescents, but who did not progress to ASPD. (III) Past studies have typically excluded CD participants with comorbid disorders (making them unrepresentative of clinical cases) or failed to take account of these disorders when examining neural correlates of ASB. (IV) No study has taken account of childhood maltreatment. (IV) There has been no study of associations of brain connectivity and subsyndromal psychopathic traits in females.

Method: Three groups of young adult women, aged on average 24 years, completed clinical assessments and magnetic resonance imaging: women who consulted for substance misuse as adolescents and who were enrolled in a longitudinal study (n=44), sisters of ex-clients also enrolled in the longitudinal study (n=31), and newly recruited healthy women (n=24). Clinical data (diagnoses, psychopathic traits and other measures) from past waves and the current wave of data collection were used to characterize participants. Measures of brain structural connectivity (integrity of white matter tracts connecting specific regions) and functional connectivity (correlated resting-state activity between regions and Graph Theory topology) were investigated in four studies.

Results: The women who had presented CD in adolescence presented high levels of lifetime comorbid anxiety and depression disorders, alcohol and drug dependence, childhood maltreatment, higher levels of psychopathic traits than in the general population, and poor psychosocial functioning and more aggressive behavior than the healthy women. Three main findings emerged: (1) CD prior to age 15 was associated with abnormalities of white matter integrity in adulthood despite low rates of progression to ASPD (Study I and II). These abnormalities were similar to those reported in previous studies featuring male or mixed-sex samples with CD and/or ASPD. (2) Most of the differences in white matter integrity between young adult women with a history of CD and healthy peers were explained by comorbid lifetime mental disorders and maltreatment (Study I and II). (3) Psychopathic traits were associated with unique structural and functional connectivity abnormalities (Study III and IV).

Conclusions: We show for the first time that young women who presented CD as adolescents were characterized by structural connectivity abnormalities, despite not presenting ASPD but showing several indices of ASB. Even subsyndromal psychopathic traits presented by these women had unique connectivity correlates. Our findings emphasize the importance of treating CD in adolescence, as well as the comorbid mental disorders, and assessing and stopping maltreatment, so as to ensure a healthy transition to adulthood. Future studies investigating the neural correlates of CD, ASB in general, and psychopathic traits, need to take account of comorbid disorders and maltreatment.

List of scientific papers

I. Lindner P., Savic I., Sitnikov R., Budhiraja M., Liu Y., Jokinen J., Tiihonen J., Hodgins S. (2016). Conduct disorder in females is associated with reduced corpus callosum structural integrity independent of comorbid disorders and exposure to maltreatment. Translational Psychiatry. 6:e714.
https://doi.org/10.1038/tp.2015.216

II. Lindner, P., Flodin, P., Larm, P., Budhiraja, M., Savic, I., Jokinen, J., Tiihonen, J., Hodgins, S. Amygdala-orbitofrontal structural and functional connectivity in females with anxiety disorders, with and without a history of conduct disorder. [Submitted]

III. Lindner, P., Budhiraja, M., Westerman, J., Savic, I., Jokinen, J., Tiihonen, J., Hodgins, S. (2017). White matter correlates of psychopathic traits in a female community sample. Social Cognitive and Affective Neuroscience. 12 July 2017.
https://doi.org/10.1093/scan/nsx070

IV. Lindner, P., Flodin, P., Budhiraja, M., Savic, I., Jokinen, J., Tiihonen, J., Hodgins, S. Associations of psychopathic traits with local and global brain network topology in young adult women. [Submitted]