Current treatment approaches for posttraumatic stress disorder (PTSD) include the use of medications, psychotherapy, or a combination of both, but they are limited in their effectiveness as only some have access to or are able to tolerate exposure therapy, and pharmacotherapy is largely nonspecific and only partially effective. As PTSD incurs substantial cost both to individuals (e.g., disruptions in daily life functioning, health status, and well-being) and to society (with elevated rates of substance use, hospitalization, and suicidal behavior), the development of more effective pharmacological treatments is critical and requires a better understanding of the neurobiological mechanisms implicated in the pathogenesis of PTSD. Kelmendi, Adams, Southwick, Abdallah, and Krystal (2017) provide a comprehensive review of neurotransmitter systems implicated in PTSD and highlight that the understanding of neurotransmitters and the modulatory systems involved is essential for sophisticated use of pharmacotherapy in PTSD. It is important, however, to take into consideration that neurotransmitter "abnormalities" occur within an anatomical/functional context, that is within specific neural circuits, which perform specific functions and thus lead to specific symptoms. For example, exaggerated norepinephrine (NE) in the amygdala might lead to one symptom, but exaggerated NE secretion in the hippocampus or prefrontal cortex might lead to a different set of symptoms. Thus, understanding the role of neural circuits involved in different intermediate phenotypes and disorder subtypes (Liberzon & Abelson, 2016) will be critical for designing more specific treatment approaches. Further, the fact that dysfunction in neurotransmitter systems can be affected by an individual's genetic factors has been gaining increased attention, and related concepts have led to the development of "personalized medicine" in other fields, such as cancer therapy. Certain genotypes, or epigenetic processes, such as DNA methylation, or histone acetylation, can not only constitute risk or resilience factors for PTSD development, but may also serve as the biomarkers of outcomes of specific treatments. Kelmendi et al. (2017) briefly mention the role of individual genetic profiles, in the context of limited efficacy and lack of specificity of available PTSD treatments, but we believe these important topics deserve further attention, as they have critical implications for clinical practice. We also mention another important factor that was not directly addressed in the review by Kelmendi et al., but we believe should be considered in developing effective treatment approaches, which is the timing of an intervention, within the dynamics of PTSD development. NEUROCIRCUITRY-BASED MODELS OF PTSD: REPRESENTING ALTERED BRAIN FUNCTIONS AND DIFFERENT INTERMEDIATE PHENOTYPES As noted by Kelmendi et al. (2017), dysregulations on an anatomical level lie within distinct neural systems.Advances in affective neuroscience in the last decade have unveiled specific neural system...