High plasma monoamine metabolite levels in Cotard's syndrome

Abstract

Cotard's syndrome, characterized by nihilistic delusions, mostly occurs in presenile women and is accompanied by depression. The French physician Jules Cotard first presented a case of this syndrome in 1880.1 Its cause, however, still remains unclear. ‘I have no brain, heart, stomach or entrails. My body has entirely fallen into decay and only spirit exists. I can't even die and would live forever.’ These are the words of a 62-year-old woman diagnosed with Cotard's syndrome at our hospital. We consider this case significant because of the marked biochemical changes that occurred in her body, or ‘the dead body,’ according to her. The patient commenced treatment for depression in 2007, and was admitted to our hospital in April 2010 because of nihilistic delusions, appetite loss, and furious excitement. Before admission, her adherence to medication was poor, and she took only paroxetine (10 mg/day) irregularly. On admission, she had neither fever nor consciousness-related disorders. The results of various tests revealed only minor changes, for example, slight dehydration and undernourishment. No laboratory finding indicated renal failure, inflammation, or endocrine abnormality. The brain magnetic resonance imaging scan showed slight cortical atrophy compatible with her age. However, considerable changes were observed in the plasma monoamine metabolite levels on admission; the homovanillic acid (HVA, dopamine metabolite) level was 154.8 ng/mL (normal range for 50–60-year-old subjects, 4–15 ng/mL); the total 3-methoxy-4-hydroxyphenylglycol (MHPG, noradrenaline metabolite) level was 202.1 ng/mL (normal range, 16–26 ng/mL); and the free MHPG level was 57.9 ng/mL (normal range, 4–7 ng/mL). The patient was diagnosed with Cotard's syndrome that developed during the course of psychotic depression. After admission, she was treated with an antidepressant (amoxapine, 50–90 mg/day) and antipsychotics (mainly olanzapine, 2.5–10 mg/day). The varied psychotic symptoms gradually improved, and the monoamine levels returned to approximately normal. At the time of discharge in June, the patient said ‘My spirit comes back to my body.’ Recently, researchers have tried to formulate a neuropsychological theory to explain this syndrome and to identify the structural changes associated with this syndrome.2 However, these approaches have failed to adequately explain the severe and enigmatic symptoms of this syndrome, even though previous studies have demonstrated high dopaminergic activities in psychotic depression.3 In this case, we focused on the plasma monoamine metabolite levels, which had drastically increased, and then normalized, on improvement of clinical symptoms. The high levels of HVA and total and free MHPG were not thought to be due to medication before admission, taking into account that her adherence to medication was poor. In addition, laboratory findings did not suggest any physical condition that could be responsible for the increased plasma monoamine metabolite levels. We attribute the symptoms of this patient to the broad disruption of the neurotransmission systems, including the dopamine and noradrenaline systems. In conclusion, we introduce a new standpoint: some patients develop Cotard's syndrome in the presence of other neurochemical disorders.