Prevalence of pain flashbacks in post-traumatic stress disorder arising from exposure to multiple traumas or childhood traumatization

Background: Flashbacks are a form of multisensory memory that are experienced with a ‘happening in the present’ quality. Pain flashbacks are a re-experiencing of pain felt at the time of a traumatic event. It is unclear how common pain flashbacks are. Aims: The current study was designed primarily to assess the prevalence of pain flashbacks in a sample of patients with post-traumatic stress disorder (PTSD). Methods: We assessed the prevalence of pain flashbacks over a period of two years in patients (n = 166) referred to a psychological trauma service in the UK. Patients underwent a clinical screen for PTSD, and completed a self-report measure of pain flashbacks. Results: Pain flashbacks were classified as present in 49% of a sample of complex trauma patients meeting criteria for PTSD. Pain flashbacks were positively associated with the extent of pain at the time of trauma. Conclusions: Pain re-experiencing in PTSD, and its relative absence in non-clinical populations, supports an account of memory in which perceptual details can be re- experienced when memories have been encoded under conditions of extreme stress. It may be possible to conceptualize some cases of unexplained pain as pain flashbacks, or of having a trauma origin

Sex-specific effects of gender identification on pain study recruitment

Epidemiological, clinical and laboratory studies show sex differences in pain responses, with women more sensitive to nociceptive stimulation and more vulnerable to long term pain conditions than men. Given evidence that males are culturally reinforced for the ability to endure (or under-report) pain, some of these findings might be explained by socio-cultural beliefs about gender-appropriate behaviour. One potential manifestation of these effects might be differential participation in pain studies, with males adhering to stereotypical masculine roles viewing participation as a way to demonstrate their masculinity. To test this possibility, we assessed gender identification in 137 healthy participants. At the end of the assessment, they were asked if they would like to participate in other research studies. Interested participants were then asked to participate in a study involving administration of pain-evoking stimulation. We compared individuals who agreed to participate in the pain study to those who declined. We observed a significant sex by participation interaction in masculine gender identification, such that males (but not females) who agreed to participate identified significantly more with masculine gender. Among masculine gender traits examined, we found that high levels of aggression and competitiveness were the strongest predictors of pain study participation. Our results suggest that male samples in pain studies might have higher levels of masculine gender identification than the wider male population. Taken together with previous findings of lower pain sensitivity (or reporting) in masculine-identifying males, these results suggest an explanation for some of the sex-related differences observed in pain responses. Perspective : To examine whether sex and gender affect willingness to participate in pain studies, we assessed gender identification in male and female participants, then attempted to recruit them to participate in a pain study. Males who agree to participate in pain studies are significantly higher in masculine gender identification than males who decline to participate or females who agree to participate. Males who agreed to participate were particularly high in aggressiveness and competitiveness

Long-term follow-up and treatment in nine boys with X-linked creatine transporter defect

The creatine transporter (CRTR) defect is a recently discovered cause of X-linked intellectual disability for which treatment options have been explored. Creatine monotherapy has not proved effective, and the effect of treatment with L-arginine is still controversial. Nine boys between 8 months and 10 years old with molecularly confirmed CRTR defect were followed with repeated 1H-MRS and neuropsychological assessments during 4–6 years of combination treatment with creatine monohydrate, L-arginine, and glycine. Treatment did not lead to a significant increase in cerebral creatine content as observed with H1-MRS. After an initial improvement in locomotor and personal-social IQ subscales, no lasting clinical improvement was recorded. Additionally, we noticed an age-related decline in IQ subscales in boys affected with the CRTR defect

Creatine Transporter (CrT; Slc6a8) Knockout Mice as a Model of Human CrT Deficiency

Mutations in the creatine (Cr) transporter (CrT; Slc6a8) gene lead to absence of brain Cr and intellectual disabilities, loss of speech, and behavioral abnormalities. To date, no mouse model of CrT deficiency exists in which to understand and develop treatments for this condition. The purpose of this study was to generate a mouse model of human CrT deficiency. We created mice with exons 2–4 of Slc6a8 flanked by loxP sites and crossed these to Cre:CMV mice to create a line of ubiquitous CrT knockout expressing mice. Mice were tested for learning and memory deficits and assayed for Cr and neurotransmitter levels. Male CrT−/y (affected) mice lack Cr in the brain and muscle with significant reductions of Cr in other tissues including heart and testes. CrT−/y mice showed increased path length during acquisition and reversal learning in the Morris water maze. During probe trials, CrT−/y mice showed increased average distance from the platform site. CrT−/y mice showed reduced novel object recognition and conditioned fear memory compared to CrT+/y. CrT−/y mice had increased serotonin and 5-hydroxyindole acetic acid in the hippocampus and prefrontal cortex. Ubiquitous CrT knockout mice have learning and memory deficits resembling human CrT deficiency and this model should be useful in understanding this disorder

Preserved emotional awareness of pain in a patient with extensive bilateral damage to the insula, anterior cingulate, and amygdala

Functional neuroimaging investigations of pain have discovered a reliable pattern of activation within limbic regions of a putative "pain matrix" that has been theorized to reflect the affective dimension of pain. To test this theory, we evaluated the experience of pain in a rare neurological patient with extensive bilateral lesions encompassing core limbic structures of the pain matrix, including the insula, anterior cingulate, and amygdala. Despite widespread damage to these regions, the patient's expression and experience of pain was intact, and at times excessive in nature. This finding was consistent across multiple pain measures including self-report, facial expression, vocalization, withdrawal reaction, and autonomic response. These results challenge the notion of a "pain matrix" and provide direct evidence that the insula, anterior cingulate, and amygdala are not necessary for feeling the suffering inherent to pain. The patient's heightened degree of pain affect further suggests that these regions may be more important for the regulation of pain rather than providing the decisive substrate for pain's conscious experience

Resting state cortico-thalamic-striatal connectivity predicts pesponse to dorsomedial prefrontal rTMS in major depressive disorder

Despite its high toll on society, there has been little recent improvement in treatment efficacy for Major Depressive Disorder (MDD). The identification of biological markers of successful treatment response may allow for more personalized and effective treatment. Here we investigate whether resting state functional connectivity predicted response to treatment with rapid transcranial magnetic stimulation (rTMS) to dorsomedial prefrontal cortex (dmPFC). Twenty five individuals with treatment-refractory MDD underwent a 4-week course of dmPFC-rTMS. Before and after treatment, subjects received resting state functional MRI scans and assessments of depressive symptoms using the Hamilton Depresssion Rating Scale (HAMD17). We found that higher baseline cortico-cortical connectivity (dmPFC-subgenual cingulate and subgenual cingulate to dorsolateral PFC) and lower cortico-thalamic, cortico-striatal and cortico-limbic connectivity were associated with better treatment outcomes. We also investigated how changes in connectivity over the course of treatment related to improvements in HAMD17 scores. We found that successful treatment was associated with increased dmPFC-thalamic connectivity and decreased sgACC-caudate connectivity, Our findings provide insight into which individuals might respond to rTMS treatment and the mechanisms through which these treatments work

Individualized markers optimize class prediction of microarray data

BACKGROUND: Identification of molecular markers for the classification of microarray data is a challenging task. Despite the evident dissimilarity in various characteristics of biological samples belonging to the same category, most of the marker – selection and classification methods do not consider this variability. In general, feature selection methods aim at identifying a common set of genes whose combined expression profiles can accurately predict the category of all samples. Here, we argue that this simplified approach is often unable to capture the complexity of a disease phenotype and we propose an alternative method that takes into account the individuality of each patient-sample. RESULTS: Instead of using the same features for the classification of all samples, the proposed technique starts by creating a pool of informative gene-features. For each sample, the method selects a subset of these features whose expression profiles are most likely to accurately predict the sample's category. Different subsets are utilized for different samples and the outcomes are combined in a hierarchical framework for the classification of all samples. Moreover, this approach can innately identify subgroups of samples within a given class which share common feature sets thus highlighting the effect of individuality on gene expression. CONCLUSION: In addition to high classification accuracy, the proposed method offers a more individualized approach for the identification of biological markers, which may help in better understanding the molecular background of a disease and emphasize the need for more flexible medical interventions