Introduction Nihilistic delusion (ND) is one of an assortment of narrowly defined monothematic delusions characterized by nihilistic beliefs about self's existence or life itself. It is estimated to occur in less than 1% of older adults, 3% of older adults with severe depression (Chiu, 1995), and less than 1% of patients with psychotic disorders (Ramirez-Bermudez et al., 2010; Stompe and Schanda, 2013). There are no standardized treatments for ND, although, case reports have documented effectiveness of pharmacological treatment as well as electro-convulsive treatment (Debruyneet al., 2009; Grover et al., 2014). Recent reports have also brought attention to the role cognitive-behavioral therapy (CBT) techniques for delusions may play in effective treatment (Coltheart et al., 2007). Given the unique content of beliefs in ND, additional research to understand the important role life circumstances – including religious beliefs – play in the development and maintenance of this condition is needed (Ghaffari Nejad et al., 2013). In this report we present the case of ‘Ms. E,’ an individual with spiritually mediated ND in the context of major depressive disorder with catatonic features, and review the relevant literature on biological, psychological, and social factors associated with ND. Methods In this report we present the case of ‘Ms E’ a 74 yr Caucasian female, a retired medical technologist with 47-Year diagnosis of depression (Major Depressive disorder with catatonic features), with mild neurocognitive impairment. Pt has no coexisting medical illness, no substance use disorder, no traumatic brain injury or other neurological diagnosis. Patient's sister who was a SW in mental health facility, indicated that Ms. E suffered her first psychiatric break in a western US state at age 27 requiring in-patient hospitalization in context of “spiritual emergencies” she characterizes it as depersonalization. She was prescribed medication, but never followed up with psychiatric outpatient care due to her preference for treating her condition with prayers. During episodes of depressed mood patient reported having episodes of feeling as if she is in a spiritual realm and that she is “Mother Teresa”. Patient reports two past suicidal attempts in 1980s (overdosing on sleeping pills) and later in 2011 (overdosing on Benadryl pills) requiring ICU admission. Later, after divorce from her husband, patient relocated to New York City. She has been living with her partner for past several years and participates in all activities of daily living. Earlier this year, patient's partner experienced a fall and was admitted to the hospital. Mobile crisis team, activated based on partner's concerns, found patient to be decompensated, grossly oriented, with psychomotor retardation, hesitant speech with long pauses, anxious mood, and restricted affect. Thought process was tangential, and her cooperation was limited due to her preoccupation with delusions that she was dropping in an abyss and progressing towards spiritual crisis of dying. When asked about suicidal ideation (SI) she indicated, “I am already dying, how can I be suicidal?”. Of note, patient's nihilistic beliefs, included strong religiously mediated content, are not shared by her family. A computed tomography (CT) scan (Figure 1) performed in March 2018 revealed Mild to moderate global volume loss for age with cerebral atrophy. No evidence of any white matter abnormality, mass, hydrocephalus, acute intracranial hemorrhage, abnormal extra-axial fluid collection, or obvious cortical infarct in the brain were noted on imaging. Results During patient's month-long admission on the inpatient unit repeated inquiry about her religious experience changed in the content of delusion from literal and concrete beliefs that her ‘spiritual emergency’ was physically leading her to dead to more abstract and metaphorical descriptions of spiritual death, however her belief that spiritually she is destined to be dead persisted. Continued exploration about the patient's observed improvement in daily activities of living (eating, drinking, showering) when posed to patient as evidence that she was in fact improving, she indicated that she was ‘probably improving.’ Approximately 1 month into her admission, she re-gained insight that content of her speech was focus on spirituality, death and self-negation. She was ultimately discharged after 4 weeks of hospitalization. On discharge, the patient's partner and sister noted that she was less delusional with more linear thought process than at baseline. Conclusions Our case of Ms. E underscores the complexity of managing depression with co-existing nihilistic delusions. Given this increased susceptibility for violent acts and self-harm, the presence of delusions characterized by nihilistic beliefs about the body's existence or life itself should prompt vigilance and clinical assessment of violent or self-harm behavior. While co-occurring ND and depression is rare, the consistency and longevity of the delusional content, increased risk of self-harm behavior, presence of significant depressive symptoms, attributional style, and neuropsychological performance can each help to identify ND within this population. Within limitations of a case report, we suggest that co-occurring ND and major depressive disorder may increase the risk of self-harm due to the specific nihilistic content of the delusions. Taking action, or refraining from taking action, as a consequence of nihilistic beliefs about the existence of one's body or of life itself may lower ones inhibition for violence. This research was funded by Not Applicable. (Authors report no relevant disclosures for this report.)