Multimodal Treatment With ECT for Identity Integration in a Patient With Dissociative Identity Disorder, Complex Post-traumatic Stress Disorder, and Major Depressive Disorder: A Rare Case Report

The legitimacy and etiology of Dissociative Identity Disorder (DID) remains a controversial topic within Psychiatry. The two schools of thought are the Post-Traumatic Model (PTM) and the Socio-Cognitive Model (SCM). This case highlights the validity of PTM in an individual who suffered severe and prolonged physical, psychological, and sexual abuse from 2 years old through adulthood. The reported abuse was corroborated and proven on two separate occasions via medical professionals/rape kit and the police. This resulted in the incarceration of one of her abusers. The only way for the patient to cope with the trauma she suffered was to dissociate, which resulted in the development of four full identity alters. In addition to being diagnosed with DID, the patient has been diagnosed with Major Depressive Disorder (MDD), Post-Traumatic Stress Disorder (PTSD), and chronic suicidality. Unable to manage the suicidal ideations and MDD after nearly 10 years of therapy and psychiatric medications, the patient was referred for Electroconvulsive Therapy (ECT). Upon receiving ECT weekly for 2 years, the patient reported having “lost the others.” As ECT progressed she went from having four alters to no alters and at the time of this report only being able to vaguely hear alter #4. With the integration of these alters she had access to the memories and pain that the alters had protected her from. Prior to losing the alters, her long-term memory was impaired by dissociative processes. Her long-term memory was also impaired because when one of the alters was in control of consciousness only that alter remembered what had happened during that time, unless that alter shared what had happened with one or more of the others. It is unclear if frequent ECT was the catalyst that lead to the integration of her alters however, integration finally began following prolonged ECT. This case highlights the importance of the PTM as an etiological description for DID and the importance of mental health providers further studying and researching the effects of ECT on patients with chronic MDD, PTSD, and suicidal intent, especially if these are comorbid with DID

HMG I/Y regulates long-range enhancer-dependent transcription on DNA and chromatin by changes in DNA topology

The nature of nuclear structures that are required to confer transcriptional regulation by distal enhancers is unknown. We show that long-range enhancer-dependent β-globin transcription is achieved in vitro upon addition of the DNA architectural protein HMG I/Y to affinity-enriched holo RNA polymerase II complexes. In this system, HMG I/Y represses promoter activity in the absence of an associated enhancer and strongly activates transcription in the presence of a distal enhancer. Importantly, nucleosome formation is neither necessary for long-range enhancer regulation in vitro nor sufficient without the addition of HMG I/Y. Thus, the modulation of DNA structure by HMG I/Y is a critical regulator of long-range enhancer function on both DNA and chromatin-assembled genes. Electron microscopic analysis reveals that HMG I/Y binds cooperatively to preferred DNA sites to generate distinct looped structures in the presence or absence of the β-globin enhancer. The formation of DNA topologies that enable distal enhancers to strongly regulate gene expression is an intrinsic property of HMG I/Y and naked DNA

Visualization of double-stranded RNAs from the myotonic dystrophy protein kinase gene and interactions with CUG-binding protein

Myotonic dystrophy (DM) is associated with a (CTG) (n) triplet repeat expansion in the 3'-untranslated region of the myotonic dystrophy protein kinase (DMPK) gene. Using electron microscopy, we visualized large RNAs containing up to 130 CUG repeats and studied the binding of purified CUG-binding protein (CUG-BP) to these RNAs. Electron microscopic examination revealed perfect double-stranded (ds)RNA segments whose lengths were that expected for duplex RNA. The RNA dominant mutation model for DM pathogenesis predicts that the expansion mutation acts at the RNA level by forming long dsRNAs that sequester certain RNA-binding proteins. To test this model, we examined the subcellular distribution and RNA-binding properties of CUG-BP. While previous studies have demonstrated that mutant DMPK transcripts accumu-late in nuclear foci, the localization pattern of CUG-BP in both normal and DM cells was similar. Although CUG-BP in nuclear extracts preferentially photocrosslinked to DMPK transcripts, this binding was not proportional to (CUG) (n) repeat size. Moreover, CUG-BP localized to the base of the RNA hairpin and not along the stem, as visualized by electron micro-scopy. These results provide the first visual evidence that the DM expansion forms an RNA hairpin structure and suggest that CUG-BP is unlikely to be a sequestered factor

mdm2 Is Critical for Inhibition of p53 during Lymphopoiesis and the Response to Ionizing Irradiation

The function of the p53 tumor suppressor protein must be highly regulated because p53 can cause cell death and prevent tumorigenesis. In cultured cells, the p90(MDM2) protein blocks the transcriptional activation domain of p53 and also stimulates the degradation of p53. Here we provide the first conclusive demonstration that p90(MDM2) constitutively regulates p53 activity in homeostatic tissues. Mice with a hypomorphic allele of mdm2 revealed a heretofore unknown role for mdm2 in lymphopoiesis and epithelial cell survival. Phenotypic analyses revealed that both the transcriptional activation and apoptotic functions of p53 were increased in these mice. However, the level of p53 protein was not coordinately increased, suggesting that p90(MDM2) can inhibit the transcriptional activation and apoptotic functions of p53 in a manner independent of degradation. Cre-mediated deletion of mdm2 caused a greater accumulation of p53, demonstrating that p90(MDM2) constitutively regulates both the activity and the level of p53 in homeostatic tissues. The observation that only a subset of tissues with activated p53 underwent apoptosis indicates that factors other than p90(MDM2) determine the physiological consequences of p53 activation. Furthermore, reduction of mdm2 in vivo resulted in radiosensitivity, highlighting the importance of mdm2 as a potential target for adjuvant cancer therapies

Tumor suppression and normal aging in mice with constitutively high p53 activity

The p53 inhibitor murine double-minute gene 2 (Mdm2) is a target for potential cancer therapies, however increased p53 function can be lethal. To directly address whether reduced Mdm2 function can inhibit tumorigenesis without causing detrimental side effects, we exploited a hypomorphic murine allele of mdm2 to compare the effects of decreased levels of Mdm2 and hence increased p53 activity on tumorigenesis and life span in mice. Here we report that mice with decreased levels of Mdm2 are resistant to tumor formation yet do not age prematurely, supporting the notion that Mdm2 is a promising target for cancer therapeutics