Some neuroanatomical insights to impulsive aggression in schizophrenia Marcel P. Leclerc a,b, ⁎, Christina Regenbogen a,b,c , Roy H. Hamilton d , Ute Habel a,b a Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Germany b JARA - BRAIN Institute 1: Structure Function Relationship, Jülich, Germany c Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden d Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA abstract article info Article history: Received 23 August 2017 Received in revised form 4 April 2018 Accepted 9 June 2018 Available online xxxx Patients with schizophrenia are at increased risk of engaging in violence towards others, compared to both the general population and most other patient groups. We have here explored the role of cortico-limbic impairments in schizophrenia, and have considered these brain regions specifically within the framework of a popular neuro- anatomical model of impulsive aggression. In line with this model, evidence in patients with aggressive schizo- phrenia implicated structural deficits associated with impaired decision-making, emotional control and evaluation, and social information processing, especially in the orbitofrontal and ventrolateral prefrontal cortex. Given the pivotal role of the orbitofrontal and ventrolateral cortex in emotion control and evaluation, structural deficits may result in inappropriate use of socially relevant information and improper recognition of impulses that are in need for regulation. Furthermore, we have extended the original model and incorporated the striatum, important for the generation of aggressive impulses, as well as the hippocampus, a region critical for decision- making, into the model. Lastly, we discuss the question whether structural impairments are specific to aggressive schizophrenia. Our results suggest, that similar findings can be observed in other aggressive patient populations, making the observed impairments non-specific to aggressive schizophrenia. This points towards a shared condi- tion, across pathologies, a potential common denominator being impulsive aggression. © 2018 Published by Elsevier B.V. Keywords: Ventrolateral prefrontal cortex Orbitofrontal cortex MRI Structural brain imaging Prefrontal cortex 1. Introduction Aggression in schizophrenia (SZ) has been investigated intensively in recent years, yielding insights ranging from characterization of its neuro- biological substrates to the development of novel theoretical frameworks. Modern brain imaging techniques and a growing body of clinically rele- vant insights into the SZ spectrum have helped both the scientific com- munity and clinical professionals to acknowledge the importance of recognizing and understanding structural alterations of the brain that un- derlie aggressive behavior. This knowledge is important to better define and differentiate subtypes of mental illness within the SZ spectrum, and to enhance clinical care and long-term outcomes for these patients. Reasons for aggressive behavior in SZ patients are manifold and in- clude the subjective experiences engendered by the patient's symptoms (e.g., delusions of persecution), neuroanatomical changes, the patient's somatic and psychiatric history, and socio-demographic factors (Silverstein et al., 2015). Although each of these aspects is individually rel- evant, we will here focus on the neuroanatomical alterations that can fre- quently be found in aggressive SZ patients. Aggression in SZ patients typically manifests as impulsive aggression, which is characterized by a lack of clear intent or signs of planning (Barratt and Felthous, 2003). In contrast to more dispassionate instrumental aggression, impulsive ag- gression is situationally bound, reactive, and loaded with affect (Dodge et al., 1997; Stahl, 2014). A few years ago, Coccaro et al. (2011) have presented a neuroana- tomical model of impulsive, or reactive aggression, comprised of a crit- ical corticolimbic circuit. The model is composed of brain structures responsible for aggression generation, response evaluation and deci- sion-making, and a distinct lateral and medial-frontal network involved in emotion regulation. In this review, we will first evaluate the neuroan- atomical findings of aggressive SZ patients in light of this model, and then suggest the model's implications specifically regarding aggressive SZ (Fig. 1). Lastly, we will consider whether the structural alterations within this neural circuit is exclusive to aggressive SZ or if it points to a more ubiquitous pathology observed in other neuropsychiatric condi- tions (Fig. 2; Table 1). 2. Structural deficits in aggressive schizophrenia 2.1. Orbitofrontal cortex & ventral prefrontal cortex The orbitofrontal cortex (OFC) and ventral prefrontal cortex (vPFC) serve a pivotal role in the regulation and modification of behavior. In Schizophrenia Research xxx (2018) xxx–xxx ⁎ Corresponding author at: Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Pauwelstraße 30, 52074 Aachen, Germany. E-mail address: mleclerc@ukaachen.de (M.P. Leclerc). SCHRES-07895; No of Pages 8 https://doi.org/10.1016/j.schres.2018.06.016 0920-9964/© 2018 Published by Elsevier B.V. Contents lists available at ScienceDirect Schizophrenia Research journal homepage: www.elsevier.com/locate/schres Please cite this article as: Leclerc, M.P., et al., Some neuroanatomical insights to impulsive aggression in schizophrenia, Schizophr. Res. (2018), https://doi.org/10.1016/j.schres.2018.06.016