Depression and self-injury are common problems that frequently emerge during the adolescent period. Adolescence is a critical time development during which there are significant changes in behavior and in refinement of neural circuitry. My program of research aims to better understand the aberrant neural processes underlying the onset and maintenance of depression and self-injury in adolescence, and how these abnormalities may change over time and in response to interventions. Current projects include:
(1) Examining developmental trajectories of three neural/behavioral systems as defined by the Research Domains Criteria (RDoC) initiative (Sustained Threat, Self-Knowledge, Cognitive Control) using multiple levels of analysis (brain imaging, cognitive testing, cortisol measurements, self-report) in adolescents with and without non-suicidal self-injury (NSSI). This NIMH-funded R01 has an administrative supplement in Computational Psychiatry to support work applying Bayesian modeling to examine decision-making patterns in adolescents with NSSI, and how this index relates to clinical and neurobiological trajectories.
(2) Exploring efficacy and potential neural mechanisms of intravenous ketamine as a treatment for adolescent depression. We completed 13 adolescent subjects in a protocol that involved 6 infusions of ketamine. Analyses of clinical, neuroimaging and cellular energetics data are underway. Cellular/molecular studies are being conducted by collaborator Susannah Tye at the Mayo Clinic.
(3) Exploring efficacy and potential neural mechanisms of transcranial magnetic stimulation (TMS) as a treatment for adolescent depression. This study involves multi-modal brain imaging and cognitive testing before and after 30 sessions of deep TMS in adolescents with treatment-resistant depression,
(4) Examining neural circuits in adolescents with depression using ultra-high fields (7T).
(5) Examining the links between mitochondrial functioning, inflammation and brain network integrity in adolescents with mood disorders. This is a collaboration with Ana Andreazza at the University of Toronto and Bonnie Klimes-Dougan in the department of Psychology, UMN.
(For a comprehensive list of recent publications, refer to PubMed, a service provided by the National Library of Medicine.)
- Roy AV, Thai M, Klimes-Dougan B, Westlund Schreiner M, Mueller BA, Albott CS, Lim KO, Fiecas M, Tye SJ, Cullen KR. Brain entropy and neurotrophic molecular markers accompanying clinical improvement after ketamine: Preliminary evidence in adolescents with treatment-resistant depression. J Psychopharmacol. 2020 Jul 9:269881120928203.
- Cullen KR, Schreiner MW, Klimes-Dougan B, Eberly LE, LaRiviere L, Lim KO, Camchong J, Mueller BA. Neural correlates of clinical improvement in response to N-acetylcysteine in adolescents with non-suicidal self-injury. Prog Neuropsychopharmacol Biol Psychiatry. 2019 Nov 1:109778.
- Cullen KR, Brown R, Schreiner MW, Eberly LE, Klimes-Dougan B, Reigstad K, Hill D, Lim KO, Mueller BA. White matter microstructure relates to lassitude but not diagnosis in adolescents with depression. Brain Imaging Behav. 2019 Mar 19. doi: 10.1007/s11682-019-00078-8.
- Demers LA, Schreiner MW, Hunt RH, Mueller BA, Klimes-Dougan B, Thomas KM, Cullen KR. Alexithymia is associated with neural reactivity to masked emotional faces in adolescents who self-harm. J Affect Disord. 2019;249:253-261.
- Klimes-Dougan B, Begnel E, Almy B, Thai M, Schreiner MW, Cullen KR. Hypothalamic-pituitary-adrenal axis dysregulation in depressed adolescents with non-suicidal self-injury. Psychoneuroendocrinology. 2018;102:216-224.
- Klimes-Dougan B, Klingbeil DA, Houri A, Cullen KR, Gunlicks-Stoessel M, August G. A Pilot Study of Stress System Activation in Children Enrolled in a Targeted Prevention Program: Implications for Personalization. Int J Mol Sci. 2018 Jan 25;19(2). PMID: 29370111
- Klimes-Dougan B, Westlund Schreiner M, Thai M, Gunlicks-Stoessel M, Reigstad K, Cullen KR. Neural and neuroendocrine predictors of pharmacological treatment response in adolescents with depression: A preliminary study. Prog Neuropsychopharmacol Biol Psychiatry. 2018;81:194-202.
- Chong LS, Thai M, Cullen KR, Lim KO, Klimes-Dougan B. Cortisol awakening response, internalizing symptoms, and life satisfaction in emerging adults. Int J Mol Sci. 2017 Nov 27;18(12). pii: E2501.
- Cullen KR, Klimes-Dougan B, Westlund Schreiner M, Carstedt P, Marka N, Nelson K, Miller MJ, Reigstad K, Westervelt A, Gunlicks-Stoessel M, Eberly LE. N-acetylcysteine for nonsuicidal self-injurious behavior in adolescents: An open-label pilot study. J Child Adolesc Psychopharmacol. 2017 Oct 20. doi: 10.1089/cap.2017.0032
- Westlund Schreiner M, Klimes-Dougan B, Mueller BA, Eberly LE, Reigstad KM, Carstedt PA, Thomas KM, Hunt RH, Lim KO, Cullen KR. Multi-modal neuroimaging of adolescents with non-suicidal self-injury: Amygdala functional connectivity. J Affect Disord. 2017;221:47-55.
- Albott CS, Shiroma PR, Cullen KR, Johns B, Thuras P, Wels J, Lim KO. The antidepressant effect of repeat dose intravenous ketamine Is delayed by concurrent benzodiazepine use. J Clin Psychiatry. 2017;78(3):e308-e309.
- Cullen KR, Jasberg S, Nelson B, Klimes-Dougan B, Lim KO, Croarkin PE. Seizure induced by deep transcranial magnetic stimulation in an adolescent with depression. J Child Adolesc Psychopharmacol. 2016;26(7):637-641.
- Cullen KR, LaRiviere LL, Vizueta N, Thomas KM, Hunt RH, Miller MJ, Lim KO, Schulz SC. Brain activation in response to overt and covert fear and happy faces in women with borderline personality disorder. Brain Imaging Behav. 2016;10(2):319-331.
- Xu T, Cullen KR, Mueller B, Schreiner MW, Lim KO, Schulz SC, Parhi KK. Network analysis of functional brain connectivity in borderline personality disorder using resting-state fMRI. Neuroimage Clin. 2016;11:302-315.
- Bernstein GA, Mueller BA, Schreiner MW, Campbell SM, Regan EK, Nelson PM, Houri AK, Lee SS, Zagoloff AD, Lim KO, Yacoub ES, Cullen KR. Abnormal striatal resting-state functional connectivity in adolescents with obsessive-compulsive disorder. Psychiatry Res. 2016;247:49-56
- Cullen KR, Klimes-Dougan B, Pham DV, Schreiner MW, Mueller BA, Eberly LE, Camchong J, Westerveldt A, Lim KO. Neural correlates of antidepressant treatment response in adolescents with MDD. J Child Adolesc Psychopharmacol. 2016;26(8):705-712.
- Musgrove DR, Eberly LE, Klimes-Dougan B, Basgoze Z, Thomas KM, Mueller BA, Houri A, Lim KO, Cullen KR. Impaired bottom-up effective connectivity between amygdala and subgenual anterior cingulate cortex in unmedicated adolescents with major depression: results from a dynamic causal modeling analysis. Brain Connect. 2015;5:608-619.
- Westlund Schreiner M, Klimes-Dougan B, Begnel ED, Cullen KR. Conceptualizing the neurobiology of non-suicidal self-injury from the perspective of the Research Domain Criteria Project. Neurosci Biobehav Rev. 2015;57:381-391.
- Klimes-Dougan B, Eberly LE, Westlund Schreiner M, Kurkiewicz P, Houri A, Schlesinger A, Thomas KM, Mueller BA, Lim KO, Cullen KR. Multilevel assessment of the neurobiological threat system in depressed adolescents: Interplay between the limbic system and HPA axis. Dev Psychopathol. 2014;26(4 Pt 2):1321-1335.
- Cullen KR, Westlund MK, Klimes-Dougan B, Mueller BA, Houri A, Eberly LE, Lim KO. Abnormal amygdala resting-state functional connectivity in adolescent depression. JAMA Psychiatry. 2014;71:1138-1147.
- Hall LM, Klimes-Dougan B, Hunt RH, Thomas KM, Houri A, Noack E, Mueller BA, Lim KO, Cullen KR. An fMRI study of emotional face processing in adolescent major depression. Journal of Affective Disorder. 2014;168:44-50.
- Cullen KR, Westlund MK, LaRiviere LL, Klimes-Dougan B. An adolescent with nonsuicidal self-injury: a case and discussion of neurobiological research on emotion regulation. Am J Psychiatry. 2013;170:828-831.
- Gunlicks-Stoessel M, Mufson L, Cullen KR, Klimes-Dougan B. A pilot study of depressed adolescents' cortisol patterns during parent-adolescent conflict and response to interpersonal psychotherapy (IPT-A). J Affect Disord. 2013;150(3):1125-1128.