RUNNING HEAD: Perspectives in Cotard’s Syndrome
Ajay Macherla, Downingtown STEM Academy, April 2021
Email: [email protected]
Abstract:
Cotard’s Syndrome is a rare neuropsychiatric condition characterized by the delusion that one is either nonexistent, dead, or undeserving of life. Cotard’s Syndrome seems to affect the frontotemporoparietal circuitry, which connects the frontal lobes and the temporoparietal junction (see Figure 1). This can lead to psychotic mental states, such as excessive self-criticism and self-starvation. Current treatment options, such as electroconvulsive therapy (ECT) and antipsychotic medication (APM), have been shown to be effective in case studies.
Figure 1: General diagram of frontotemporoparietal circuitry in the brain[1]
Through a retrospective qualitative analysis of five relevant studies on Cotard’s syndrome, this paper aims to synthesize current understanding of the syndrome to form cohesive conclusions about Cotard’s Syndrome etiology and future research on the condition.
The studies discussed in this article used neuroimaging data to show that most cases of Cotard’s syndrome involved lesions or abnormalities in the left hemisphere of the brain. Specifically, central atrophies (loss of brain cells), hypoperfusion (restricted blood flow), and dilation (widening) of ventricles were associated with the prevalence of Cotard’s Syndrome. These represent three areas of interest for clinicians and researchers. Researchers can now streamline their studies on these areas and clinicians can use this data as potential diagnosis criteria when developing a standardised diagnosis method for the condition. Furthermore, ECT and APM were shown to have varied results across case studies, indicating that treatment response depends on the patient’s neurology or physiology. Finally, comorbidities, such as OCD and schizophrenia, were shown to increase the severity of Cotard’s Syndrome, although treatments were still effective.
It was concluded that although a synthesis of current data on Cotard’s Syndrome provided valuable information, more research is required to pinpoint the etiological and pathological aspects of the disease and thus determine more effective diagnosis criteria and treatment alternatives.
Introduction:
First recognised in 1882 by Dr. Jules Cotard, Cotard’s Syndrome, also known as walking corpse syndrome or Cotard’s Delusion, is a neuropsychiatric condition characterized by the delusion that one’s body does not exist or is dead. Comorbidities of Cotard’s Syndrome include depression and self-starvation, due to the affected individual’s insistence that one is dead. Less often, it is reported in association with catatonia, a rare, disturbing mental state involving difficulties in movement.[2]
Figure 2: A theoretical model proposed by Huarcaya-Victoria et al. (2016) to explain Cotard’s Syndrome[3]
The epidemiology of Cotard’s Syndrome is unclear; however, there is a general consensus that the condition is extremely rare. A study published in 1995 investigated the prevalence and incidence of the syndrome.[4] Through a retrospective analysis of 349 Chinese psychogeriatric patients in Hong Kong, the study found a prevalence of 0.57%, but the true incidence of the syndrome remains unknown. As the study lacks cross-cultural validity and a representative sample size, further research is needed to gain insight into the prevalence of the condition.
Due to the rarity of Cotard’s Syndrome, etiology, pathology and treatment options for the syndrome are under-researched. Low disease prevalence means that it is difficult to develop understanding and to conduct clinical trials on potential therapies.
This literature review will comprise a brief overview of the condition, followed by a discussion of advancements in Cotard’s Syndrome research and a proposal of recommendations to take action on learning more about this neurological disease.
Disease Overview:
To provide context on Cotard’s Syndrome, an overview of the condition will be presented in a six-stage framework: etiology, pathology, prognosis, symptoms, diagnosis, and treatments. An in-depth examination of each stage will be presented subsequently.
Etiology:
Cotard’s syndrome is a mental illness that originates in the brain, hence its current classification as a neuropsychiatric condition.[4] The etiology of the syndrome is unknown; in fact, the disease was described as merely a “manifestation of an underlying disorder” that is yet to be discovered.[5] Current research has only studied associations and comorbidities, such as migraines, multiple sclerosis, dementia, cerebral atrophy, and other types of brain injuries.[4]
With this idea in mind, psychiatrists often resort to abstract and mental mechanisms by which the condition arises, such as “unusual perceptual experiences . . . or a tendency to excessive self-attribution.”[6]
Pathology:
An article published in 2017 suggests that abnormal frontotemporoparietal circuitry connecting the frontal lobes and the temporoparietal junction (TPJ) affects the development of the syndrome. However, the subsequent pathophysiology remains unknown. Consequently, more research on this topic is needed to further understand the rare syndrome and devise treatment options for patients.[6]
Prognosis:
Grover et al (2014) proposed a three-stage development model of Cotard’s Syndrome. The prognosis of the condition begins with a germinative stage, characterized primarily by a higher risk of hypochondria and cenesthopathy. Hypochondria is a mental condition in which one is obsessed with the possibility of having an undiagnosed disease, and cenesthopathy is a condition in which patients complain about nonexistent and unexplainable sensations in specific areas of their bodies. As Dr. Cotard notes in his observational study of three cases of Cotard’s Syndrome, a “trigger event” may also play an equal role in the development of the delusion.[7] The second stage is the blooming stage, where delusions of death or inexistence are first expressed. Finally, the third stage is the chronic stage, where the symptoms in the second stage are exacerbated and are ingrained in the mood and mindset of the patient.[2]
Symptoms:
The symptoms of Cotard’s Syndrome are primarily emotional and mental consequences, but they can lead to physical symptoms if the condition is prolonged. A retrospective analysis of 100 cases found that the following symptoms are associated with Cotard’s Syndrome.[8]
- Depression (89%)
- Nihilistic body delusions (86%)
- Nihilistic delusions of existence (65%)
- Anxiety (65%)
- Guilt (63%)
- Delusions of Hypochondria (58%)
- Delusions of Immortality (55%)
The results were controlled for gender, but the researchers found a positive correlation between the likelihood of developing Cotard’s Syndrome and the above outcomes in older populations compared to younger populations.[9] This data suggest that older populations, regardless of gender, are at a relatively higher risk of developing the condition. However, as the sample population of Cotard’s Syndrome was small, more research must be conducted to confirm these findings.
Diagnosis:
Since Cotard’s Syndrome is neither common nor a disease, it does not have a standardised criteria for diagnosing the condition. This lack of standardisation can lead to misdiagnosis and late medical interventions in the prognosis of the condition. One approach to identifying the syndrome is to ask objective questions about risk factors associated with the disease and conducting frequent emotion and cognitive checks on the patients.[10] The method by which these check-ups are achieved are at the discretion of the physician treating a potential Cotard’s Syndrome patient.
Treatments:
Although there is currently no cure for Cotard’s Syndrome, several potential treatments have been identified which alleviate symptoms. Two primary treatments will be explored in this paper: electroconvulsive therapy (ECT) and antipsychotic medication (APM).
Figure 3: Quetiapine, a type of APM used to treat patients with Cotard’s Syndrome[11]
ECT is a psychiatric treatment in which brief electric currents are passed through the brain of the patient, who is under general anesthesia. These electric shocks trigger a seizure in the patient, which can cause “changes in brain chemistry” that can “reverse symptoms of certain mental health conditions.”[12]
Empirical evidence for ECT therapy is two-sided. A Danish case study published in 2016 found that ECT is effective in treating symptoms of Cotard’s Syndrome.[13] Another case study, published in 2012, evaluated the effectiveness of ECT in treating a dementia patient with Cotard’s Syndrome.[14] The study reported a positive outcome in the focus patient, who underwent 12 ECT sessions. At the end of the observation period, the researchers noticed that the patient could use “more expressive words” and the dementia did not progress any further. However, the patient still experienced suicidal thoughts and slurred speech. In the end, the study concluded that ECT is an effective therapy for patients with dementia, but it does not seem to help with Cotard’s Syndrome.
More research on this topic must be conducted for two reasons. Firstly, the current results are contradictory. Secondly, current literature uses case studies, which means it is difficult to generalise to all populations of patients with Cotard’s Syndrome. The rarity of the condition makes it infeasible to gather a large enough sample size to not only increase confidence in results, but also apply the findings to larger populations.
The second treatment for Cotard’s Syndrome is APM. Also known as neuroleptics, APM is a type of medication used to treat mental disorders characterized by a distance from the real world, or psychosis. APM is commonly used for treating schizophrenia, but it can also be used as a mood stabilizer that can decrease nihilistic delusions.[15]
A case report published in January 2009 documents the case of a woman who was admitted to a hospital with Cotard’s Syndrome.[16] The researchers administered sulpiride, fluoxetine, quetiapine, and venlafaxine, all types of APM. The woman had a particularly good response to the latter two medications, as her “psychotic and depressive symptoms almost completely disappeared.” The study concluded that APM appears to be effective in the treatment of Cotard’s Syndrome; however, more research is needed to confirm the results and understand the mechanisms by which the condition arises.
Methods:
This paper employed a retrospective, qualitative analysis of five research studies on the etiology, pathology, comorbidities, and effectiveness of ECT and APM in Cotard’s Syndrome. For the research, studies from the National Center for Biotechnology Information and the PubMed search engine from the National Library of Medicine were utilised to overview the respective studies.
To conduct this study, the following procedure was followed. First, preliminary research on the etiology, pathology, prognosis, diagnosis, symptoms, and treatments for the condition was conducted. These results were refined and synthesized into the six-step disease overview framework presented previously. Second, research studies on Cotard’s Syndrome were searched for on medical search engines with the following keywords: Cotard’s Syndrome, Neuroimaging, Neurophysiology, Psychiatry, Comorbidities, ECT, APM, and Effectiveness.
After selecting literature for the review, each study was evaluated and notes were taken on the research aim, method, results, conclusions, and strengths or limitations of the study. These notes were useful in critically evaluating each study in this paper. Finally, the results were written and synthesized before being compiled into a cohesive conclusions section for this paper.
Discussions:
Despite the lack of understanding in the etiological and pathological aspects of Cotard’s Syndrome, valuable research has been conducted towards this end. In this section, a discussion of advancements in Cotard’s Syndrome research will be presented.
In 2004, a case study on a 27-year-old who was diagnosed with schizophreniform disorder was investigated.[17] Through cranial CT scans, the researchers noticed a dilatation of ventricles, central atrophies, and left temporal, frontal, and parietal hypoperfusion, or reduced blood flow. APM was not effective for the patient, but ECT was. The paper concluded that Cotard’s Syndrome is associated with abnormalities in the left hemisphere of the brain, and ECT “could be the first-line therapy in such patients with psychotic disorder.”
The 2004 study is limited because it uses a sample size of one and the participant was middle-aged, which reduces the ability to generalise the findings to populations of diverse ages. Nonetheless, this paper is unique in that it reveals that perhaps APM, although proven to be effective in patients, is not a universal treatment. Furthermore, the study shows that Cotard’s Syndrome may be characterized by atrophies, dilatations, and hypoperfusion in the left side of the brain.
In 2007, a group of researchers[18] attempted to expound upon current research on the etiological factors of the syndrome by searching key terms (Cotard syndrome, neuroimaging neurophysiology, neuropsychology, among others) in electronic databases, over 100 neurological investigation papers, and literature reviews. The study found that 35 cases of Cotard’s Syndrome were reported with structural neuroimaging findings from CT and MRI scans. The researchers report that “the most common abnormalities in patients with Cotard’s Syndrome were bilateral cerebral atrophy, sylvian and interhemispheric fissure enlargement, and dilatation of lateral ventricles.”[18] Interestingly, they found no differences in basal ganglia or frontal, temporal, and parietal atrophies. It was noted that single-photon emission computed tomography (SPECT) scans found hypoperfusions in a combination of dorsolateral frontal lobes, fronto parietal medial cortex, basal ganglia, and thalamus. Finally, the study reported that most papers in the investigation showed “no EEG abnormalities.”[18]
Although the 2007 study was limited in that it focused primarily on English papers and had a small sample size, the investigation gave a more cohesive insight into the neurophysiological outcomes of Cotard’s Syndrome. These outcomes appear to be characterized by types of atrophies, dilatations, enlargements, and hypoperfusion in various areas of the brain. These results align with the 2004 study mentioned previously as well, hinting a high validity in results.
A more recent research study in 2016 focused on another patient with schizophrenia. A 50-year-old Cajamarca male patient constantly told the researchers that there were people who wanted to kill him. The man claimed to see blurred faces and wanted to die because “he was not in the ‘glory of Lord.’” In fact, the paper reports that the patient once said that he must “leave this world, he was the devil.” The researchers were able to diagnose the patient with Cotard’s Syndrome. After failed treatments of fluoxetine and quetiapine that were administered daily, a daily dose of aripiprazole and clonazepam, both types of APMs, proved to be effective as nihilistic delusions significantly decreased and the patient’s emotions improved. From these positive results, the researchers were able to conclude APMs may also be an effective treatment alternative for patients with Cotard’s Syndrome.[3]
Again, the case study limits generalizability to larger populations of Cotard’s Syndrome patients. However, these results suggest that APMs may also be an effective treatment, similar to ECT. Although ECT was not given to the patient in the case study, APM was able to induce similar results to those of ECT patients. Perhaps the success of APM and ECT in patients depends on the specific neurology of the patient’s brain. If researchers are able to pinpoint this discrepancy, they may be able to develop more accurate treatments for the condition.
A year later, in 2017, a study aimed to conduct a neuropsychiatric analysis of Cotard’s Syndrome through electronic health databases, such as Mayo Clinic.[5] The researchers searched for symptoms of Cotard’s Syndrome in patients with information in their records from 1996 to 2016. This information included both clinical and neuroimaging data. Specifically, 12 patients, with a median age of 25, were selected based on the diagnosis of the syndrome and the participant’s age. The study found varied results: some patients had abnormalities in the frontal lobe, others had volume loss in brain areas, five patients had ischemic changes, and seven patients had bilateral hemisphere lesions. Treatment alternatives, such as ECT, APM, rehydration, and psychotherapy, showed to be effective in alleviating the identified outcomes of the syndrome. The researchers were able to conclude that the exact etiology and pathology of Cotard’s Syndrome may be even more ambiguous than researchers previously thought, considering that neurological, psychiatric, and mental comorbidities varied in the sample population.
Figure 4: Axial brain scans analyzed by researchers in Sahoo and Keith (2017)[5]
A small sample size affects the ability to generalise these results to larger populations. However, the results are unique in that they expound upon current research in Cotard’s syndrome in a different way––by conducting a meta-analysis of known cases rather than individual case studies.
The most recent research study in this evaluation, published in October 2020, introduces a new and interesting hypothesis to the investigation of Cotard’s Syndrome.[19] The paper describes the case of a 49-year-old woman with obsessive-compulsive disorder (OCD) and Cotard’s Syndrome, which was diagnosed three years after OCD. The woman experienced an exacerbated OCD, suicide attempts, and depression. Through psychotic therapy and ECT, the researchers were able to control the patient’s Cotard’s Syndrome. After doing so, the researchers noticed that, interestingly, the patient’s OCD disappeared. It was reported that the woman was no longer affected by her psychosis. Through this interesting dynamic between OCD and Cotard’s Syndrome, the researchers hypothesized that perhaps the syndrome is an “evolution of the initial obsessive-compulsive disorder.”
Again, a small sample size presents issues as the study could not control for gender or age. Furthermore, there is low ecological validity––the presence of the researchers and their facility may have influenced the patient to respond differently to the psychotic therapy and ECT. Nevertheless, the study is unique in that it is one of the only studies evaluating the comorbidity of OCD in Cotard’s Syndrome pathogenesis. With these results, clinicians and researchers have more available information on the effect of comorbidities, such as OCD, on Cotard’s Syndrome. This data can inform future research endeavors on the etiology of the condition.
Conclusions:
In conclusion, Cotard’s Syndrome is a rare neuropsychiatric condition characterized by nihilistic delusions, beliefs of immortality, depression, and self-starvation. Neurologically, the condition is associated with dilations, volume losses, atrophies, and hypoperfusion of certain brain areas, particularly those in the left hemisphere and those in the frontal, temporal, and parietal areas of the brain. Psychologically, the syndrome may be influenced by thoughts of suicide, self-attribution, and psychological trauma. As for prognosis, the syndrome is characterized by three stages: germination, blooming, and chronic. Each stage builds upon each other, exacerbating nihilistic delusions and thoughts of death.
Cotard’s Syndrome is unique in that symptoms and prognosis of the disease varies based on present comorbidities; in this review, schizophrenia and OCD were analyzed. In both diseases, a more severe case of Cotard’s Syndrome was found, but treatment efforts were nonetheless effective and led to a successful alleviation of pertinent health outcomes.
Primary treatment options of Cotard’s Syndrome include ECT and APM. Empirical evidence and case studies have pointed to both as effective treatments for patients with the condition. However, at the same time, some patients did not respond well to both. It appears that the effectiveness of the treatment varies based on the neurology of the specific patient. Researchers’ hypotheses in future studies may indicate that a specific circuit within the fronto-temporoparietal circuitry that certain Cotard’s syndrome patients possess may cause this discrepancy in the effectiveness of existing treatments.
The main conclusion from this review is that Cotard’s Syndrome requires additional research, particularly on the etiological and pathological aspects of the condition, before efforts to develop effective diagnosis and treatment methods are set forth. For example, researchers could perhaps scan the brains of various Cotard’s Syndrome patients with different symptoms and compare the brain anatomies of each person. In doing so, researcher’s can understand how one’s specific neurology affects Cotard\’s delusion. Overall, the studies mentioned in this paper should serve as a starting point for researchers to delve deeper into the syndrome.
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About the Author
Ajay Macherla is a high school junior in southeastern PA who is interested in medicine, biomedical engineering, and psychiatry. Through his independent literature reviews and mentored research projects, Ajay loves to delve deeper into these fields. In the future, he would love to further this passion in medicine by pursuing a career in clinical neurology.