Disproportionate neuroanatomical effects of DCC haploinsufficiency in adolescence compared with adulthood: links to dopamine, connectivity, covariance, and gene expression brain maps in mice.

BACKGROUND: Critical adolescent neural refinement is controlled by the DCC (deleted in colorectal cancer) protein, a receptor for the netrin-1 guidance cue. We sought to describe the effects of reduced DCC on neuroanatomy in the adolescent and adult mouse brain. METHODS: We examined neuronal connectivity, structural covariance, and molecular processes in a DCC-haploinsufficient mouse model, compared with wild-type mice, using new, custom analytical tools designed to leverage publicly available databases from the Allen Institute. RESULTS: We included 11 DCC-haploinsufficient mice and 16 wild-type littermates. Neuroanatomical effects of DCC haploinsufficiency were more severe in adolescence than adulthood and were largely restricted to the mesocorticolimbic dopamine system. The latter finding was consistent whether we identified the regions of the mesocorticolimbic dopamine system a priori or used connectivity data from the Allen Brain Atlas to determine de novo where these dopamine axons terminated. Covariance analyses found that DCC haploinsufficiency disrupted the coordinated development of the brain regions that make up the mesocorticolimbic dopamine system. Gene expression maps pointed to molecular processes involving the expression of DCC, UNC5C (encoding DCC's co-receptor), and NTN1 (encoding its ligand, netrin-1) as underlying our structural findings. LIMITATIONS: Our study involved a single sex (males) at only 2 ages. CONCLUSION: The neuroanatomical phenotype of DCC haploinsufficiency described in mice parallels that observed in DCC-haploinsufficient humans. It is critical to understand the DCC-haploinsufficient mouse as a clinically relevant model system.

Ethical challenges in the treatment of psychotic pregnancy denial.

Background: There is a paucity of literature regarding ethical strategies for treating pregnant people with psychosis. While not uncommon, psychotic pregnancy denial is a psychotic illness in which patients have the delusion that they are not pregnant. The authors provide a literature review regarding psychotic pregnancy denial, present an unpublished case and its questions and dilemmas, and offer recommendations for resolving the ethical challenges these cases raise. Case: A 26-year-old, single, unemployed woman of no fixed residence was admitted for suicidal ideation. She had a history of psychosis, had multiple ER visits and at least one previous hospitalization, had minimal contact with psychiatric outpatient clinics, and had been poorly compliant with treatment recommendations. She was discovered to be about 31 weeks pregnant in the emergency room. Ultrasound exams revealed no fetal anomalies. This was the patient's second pregnancy; her previous pregnancy resulted in an abortion. Her sole psychotic symptom was the delusional belief that she was not pregnant. On the rare occasions when the patient acknowledged being pregnant, she requested termination of pregnancy. Despite intensive pharmacological treatment of her psychosis, the patient continued believing that she was not pregnant and repeatedly said she would not participate in the labor and delivery process. She disagreed with the induction of labor or a cesarean section if needed. The patient developed gestational hypertension, an obstetric indication for delivery. Induction of labor was offered to avoid potentially disastrous outcomes for the pregnant woman and the fetus. Conclusion: Psychotic pregnancy denial is potentially life-threatening. Delivery of the fetus requires carefully weighing risks and benefits and thoroughly considering the ethical framework. Teaching points: Treatment of birthing people with psychotic denial of pregnancy is complex; it requires special clinical and ethical skills to determine the patient's level of decision-making impairment and to find a middle ground between the pregnant person's right to autonomy and the physicians' beneficence-based duties. Using a well-coordinated, interdisciplinary approach and a solid ethical framework, the decision to deliver the fetus while engaging the pregnant person, to the extent possible, in the decision-making process is essential.

Risk Factors and Clinical Correlates of Pediatric Serotonin Syndrome in Hospitalized Suicide Attempters.

Objective: To evaluate the risk factors and clinical correlates of pediatric serotonin syndrome (SS) given that research on SS in adults exists, there is a dearth of literature on pediatric SS. Study design: We conducted a retrospective chart review of 183 pediatric patients who were medically hospitalized after a suicide attempt. We investigated associations between SS and several of its risk factors and clinical correlates. We also assessed the sensitivity/specificity of Hunter's criteria and criterion symptoms in predicting SS. Results: SS occurred in 21.7% of patients with a serotonergic overdose. Recent marijuana use and overdose on a selective serotonin reuptake inhibitor were significantly associated with SS. Individuals with SS required a greater number of days to be medically stabilized and had a greater likelihood of being placed on a ventilator during treatment. Hunter's criteria had 66.7% sensitivity and 92.3% specificity in diagnosing SS. Conclusions: Our study reveals both novel risk factors associated with SS (eg, recent marijuana use) and clinical correlates for patients with pediatric SS. In children, Hunter's criteria appeared to have good specificity but poor sensitivity in identifying SS. Our results set the stage for future work aimed at enhancing clinicians' ability to more rapidly identify and treat pediatric SS.

The dermatological aspects of hEDS in women.

Ehlers-Danlos syndrome (EDS) is a group of inherited connective tissue disorders that may present with a wide range of multisystemic symptoms. Hypermobile EDS, one of 13 identified subtypes of EDS, is the only variant without a known associated genetic mutation. A review of the literature suggests the five primary dermatological changes associated with hypermobile EDS are soft skin, atrophic cutaneous scars, piezogenic papules, hyperextensive stretchability, and hematomas. Our paper will address these cutaneous manifestations and delve into how they affect patients (primarily women). Possible consequences and treatment options for these different dermatological changes, as well as other skin manifestations such as livedo reticularis and elastosis perforans serpiginosa, will also be further explored.

Erratum to "The Dermatological Aspects of hEDS in Women". [International Journal of Women's Dermatology 7/3 (2021) 285- 289].

[This corrects the article DOI: 10.1016/j.ijwd.2021.01.020.].