Post-traumatic stress disorder: review of DSM criteria and functional neuroanatomy

The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for post-traumatic stress disorder (PTSD) consist of over twenty possible symptoms that can be divided into six broad categories. These categories correlate with specific brain networks that regulate emotions, behaviors, and autonomic function. Normal functioning of these networks depends on two key regions; the prefrontal cortex and the amygdala. The prefrontal cortex provides top-down executive control over amygdala, whereas the amygdala is critical for threat detection and activation of the ‘fight or flight’ response. Events that trigger extreme and/or prolonged fear can cause persisting dysregulation within the prefrontal-amygdala circuit; resulting in PTSD symptomatology. Studies indicate that effective treatment of PTSD, either psychotherapy or medications, reverses this prefrontal-amygdala dysregulation. This review article summarizes current knowledge and theories available in the medical literature from NCBI’s PubMed database regarding the underlying brain networks involved in PTSD

Neural Correlates of Attention Bias to Threat in Post-traumatic Stress Disorder

Attention bias has been proposed to contribute to symptom maintenance in Posttraumatic Stress Disorder (PTSD), although the neural correlates of these processes have not been well defined. When engaging in tasks that require attention, individuals with PTSD have demonstrated altered activity in brain regions such as the dorsolateral prefrontal cortex (dlPFC), anterior cingulate cortex (ACC), ventrolateral prefrontal cortex (vlPFC), and amygdala; however, few PTSD neuroimaging studies have employed tasks that both measure attentional strategies being engaged and included emotionally-salient information, which was the goal of the present study. We administered a modified attention bias task, the dot probe, which is equipped to measure direction and magnitude of bias, to a sample of 37 (19 trauma control, 18 PTSD+) traumatized African-American adults during functional magnetic resonance imaging. Compared to traumatized participants without PTSD, PTSD+ participants demonstrated increased activation in the dlPFC in response to trials including angry/threatening expressions. In addition, attentional avoidance of threat cues corresponded with increased vlPFC and dorsal ACC (dACC) activation in the PTSD group, a pattern that was not observed in controls. These data provide some evidence to suggest that relative increases in dlPFC, dACC and vlPFC activation to threat cues in the context of heightened attentional demands represent neural markers of attentional bias for threat in individuals with PTSD, reflecting selective disruptions in attentional control and emotion processing networks in this disorder

Extended Functional Connectivity of Convergent Structural Alterations Among Anxiety Disorders: A Meta-Analysis and Functional Connectivity Analysis

Anxiety-related disorders are some of the most pervasive mental health disorders affecting adult and youth populations. Despite growing evidence of the neurobiology associated with anxiety-related disorders, a consensus on the neurobiological mechanisms of anxiety-related disorders remains to be elucidated. We first provide background literature on the reasoning behind this dissertation in Chapter 1. In Chapter 2, we conducted a neuroimaging meta-analysis on posttraumatic stress disorder to identify convergent structural and functional alterations associated with this anxiety-related disorder among adults. In Chapter 3, we conducted a neuroimaging meta-analysis to identify convergent structural alterations across diverse groupings of anxiety-related disorders among adults, adolescents, and youth. Chapter 3 included a contrast analysis to examine potential developmental effects of anxiety-related disorders associated with brain structure between adults, adolescents, and youth. In Chapter 4, we conduct an extended functional connectivity analysis to characterize functional profiles of the region of interests (ROIs) identified in Chapter 3. We provide concluding thoughts in Chapter 5. The present collection of studies provides implications for understanding the neurobiology of anxiety-related disorders and brain-based approaches to treatment

The relationship between impulsivity, affect and a history of psychological adversity: a cognitive-affective neuroscience approach

There is increasing evidence that trauma exposure is associated with impulsive behaviour and difficulties regulating affect. The findings of recent studies implicate the disruption of neurobiological mechanisms, particularly those involving the neurotransmitter serotonin, in both impulsivity and affect regulation

Post-traumatic stress disorder: review of DSM criteria and functional neuroanatomy

The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for post-traumatic stress disorder (PTSD) consist of over twenty possible symptoms that can be divided into six broad categories. These categories correlate with specific brain networks that regulate emotions, behaviors, and autonomic function. Normal functioning of these networks depends on two key regions; the prefrontal cortex and the amygdala. The prefrontal cortex provides top-down executive control over amygdala, whereas the amygdala is critical for threat detection and activation of the ‘fight or flight’ response. Events that trigger extreme and/or prolonged fear can cause persisting dysregulation within the prefrontal-amygdala circuit; resulting in PTSD symptomatology. Studies indicate that effective treatment of PTSD, either psychotherapy or medications, reverses this prefrontal-amygdala dysregulation. This review article summarizes current knowledge and theories available in the medical literature from NCBI’s PubMed database regarding the underlying brain networks involved in PTSD

Neural Responses to Fluoxetine in Youths with Disruptive Behavior and Trauma Exposure: A Pilot Study

Objective: A preliminary investigation of the impact of a serotonergic agent (fluoxetine) on symptom profile and neural response in youths with disruptive behavior disorders (DBDs) and a history of trauma exposure. Methods: There were three participant groups: (i) Youths with DBDs and trauma exposure who received fluoxetine treatment for 8 weeks (n = 11); (ii) A matched group of youths with DBDs and trauma exposure who received routine regular follow-up in an outpatient clinic (n = 10); and (iii) Typically developing youths (n = 18). All participants conducted an expression processing functional magnetic resonance imaging task twice, 8 weeks apart: (pretreatment and post-treatment for youths with DBDs). Results: Youths with DBDs and trauma exposure who received fluoxetine treatment compared to the other two groups showed: (i) significant improvement in externalizing, oppositional defiant disorder, irritability, anxiety-depression, and trauma-related symptoms; (ii) as a function of fearful expression intensity, significantly decreased amygdala response and increased recruitment of regions implicated in top-down attention control (insula cortex, inferior parietal lobule, and postcentral gyrus) and emotional regulation (ventromedial prefrontal cortex [vmPFC]); and (iii) correlation between DBD/irritability symptom improvement and increased activation of top-down attention control areas (inferior parietal lobule, insula cortex, and postcentral gyrus) and an emotion regulation area (vmPFC). Conclusions: This study provides preliminary evidence that a serotonergic agent (fluoxetine) can reduce disruptive behavior and mood symptoms in youths with DBDs and trauma exposure and that this may be mediated by enhanced activation of top-down attention control and emotion regulation areas (inferior parietal lobule, insula cortex, and vmPFC)

Alterations in amygdala-prefrontal functional connectivity account for excessive worry and autonomic dysregulation in generalized anxiety disorder

Background: Generalized anxiety disorder (GAD) is characterized by the core symptom of uncontrollable worry. Functional magnetic resonance imaging studies link this symptom to aberrant functional connectivity between the amygdala and prefrontal cortex. Patients with GAD also display a characteristic pattern of autonomic dysregulation. Although frontolimbic circuitry is implicated in the regulation of autonomic arousal, no previous study to our knowledge combined functional magnetic resonance imaging with peripheral physiologic monitoring in these patients to test the hypothesis that core symptoms of worry and autonomic dysregulation in GAD arise from a shared underlying neural mechanism. Methods: We used resting-state functional magnetic resonance imaging and the measurement of parasympathetic autonomic function (heart rate variability) in 19 patients with GAD and 21 control subjects to define neural correlates of autonomic and cognitive responses before and after induction of perseverative cognition. Seed-based analyses were conducted to quantify brain changes in functional connectivity with the right and left amygdala. Results: Before induction, patients showed relatively lower connectivity between the right amygdala and right superior frontal gyrus, right paracingulate/anterior cingulate cortex, and right supramarginal gyrus than control subjects. After induction, such connectivity patterns increased in patients with GAD and decreased in control subjects, and these changes tracked increases in state perseverative cognition. Moreover, decreases in functional connectivity between the left amygdala and subgenual cingulate cortex and between the right amygdala and caudate nucleus predicted the magnitude of reduction in heart rate variability after induction. Conclusions: Our results link functional brain mechanisms underlying worry and rumination to autonomic dyscontrol, highlighting overlapping neural substrates associated with cognitive and autonomic responses to the induction of perseverative cognitions in patients with GAD

The Impact of Childhood Maltreatment: A Review of Neurobiological and Genetic Factors

Childhood maltreatment represents a significant risk factor for psychopathology. Recent research has begun to examine both the functional and structural neurobiological correlates of adverse care-giving experiences, including maltreatment, and how these might impact on a child’s psychological and emotional development. The relationship between such experiences and risk for psychopathology has been shown to vary as a function of genetic factors. In this review we begin by providing a brief overview of neuroendocrine findings, which indicate an association between maltreatment and atypical development of the hypothalamic–pituitary–adrenal axis stress response, which may predispose to psychiatric vulnerability in adulthood. We then selectively review the magnetic resonance imaging (MRI) studies that have investigated possible structural and functional brain differences in children and adults who have experienced childhood maltreatment. Differences in the corpus callosum identified by structural MRI have now been reliably reported in children who have experienced abuse, while differences in the hippocampus have been reported in adults with childhood histories of maltreatment. In addition, there is preliminary evidence from functional MRI studies of adults who have experienced childhood maltreatment of amygdala hyperactivity and atypical activation of frontal regions. These functional differences can be partly understood in the context of the information biases observed in event-related potential and behavioral studies of physically abused children. Finally we consider research that has indicated that the effect of environmental adversity may be moderated by genotype, reviewing pertinent studies pointing to gene by environment interactions. We conclude by exploring the extent to which the growing evidence base in relation to neurobiological and genetic research may be relevant to clinical practice and intervention