Oral and Intranasal Ketamine Use in Treatment-Resistant Catatonia: A Clinical Case Report.

BACKGROUND Benzodiazepines and electroconvulsive therapy (ECT) are standard treatment options for catatonia, a life-threatening psychomotor syndrome in people with serious mental illness. The purpose of this study was to discuss the use of ketamine in treatment-resistant catatonia, which has not been established in current literature. CASE REPORT A 63-year-old woman with schizoaffective disorder and many previous psychiatric hospitalizations was initially admitted to a psychiatric unit for severe catatonic condition, including mutism, psychomotor retardation, poor intake, and significant weight loss. She had historically failed many ECT treatments and a course of transcranial magnetic stimulation. She scored 12 on the Bush-Francis Catatonia Rating Scale. After she had no response to lorazepam or ECT, she was started on sublingual ketamine, 50 mg twice a week. She showed significant improvement and her Bush-Francis Catatonia Rating Scale score decreased steadily. She was successfully discharged home but had a quick readmission after missing a dose of ketamine. After it was resumed, she progressively improved and was again discharged home. She continued taking sublingual ketamine, until her insurance approved esketamine nasal spray. Due to a change in insurance approval, later she was switched to a combination of esketamine and sublingual ketamine. She steadily resumed her baseline activities and remained clinically stable. She did not require acute hospitalization in the months that followed. CONCLUSIONS This case highlights a potential use of sublingual ketamine and esketamine nasal spray as a treatment option in patients with chronic catatonia when other treatment choices fail to be effective.

Loss of MPC1 reprograms retinal metabolism to impair visual function.

Glucose metabolism in vertebrate retinas is dominated by aerobic glycolysis (the "Warburg Effect"), which allows only a small fraction of glucose-derived pyruvate to enter mitochondria. Here, we report evidence that the small fraction of pyruvate in photoreceptors that does get oxidized by their mitochondria is required for visual function, photoreceptor structure and viability, normal neuron-glial interaction, and homeostasis of retinal metabolism. The mitochondrial pyruvate carrier (MPC) links glycolysis and mitochondrial metabolism. Retina-specific deletion of MPC1 results in progressive retinal degeneration and decline of visual function in both rod and cone photoreceptors. Using targeted-metabolomics and 13C tracers, we found that MPC1 is required for cytosolic reducing power maintenance, glutamine/glutamate metabolism, and flexibility in fuel utilization.

Metabolic signature of the aging eye in mice.

Aging is a major risk factor for age-related ocular diseases including age-related macular degeneration in the retina and retinal pigment epithelium (RPE), cataracts in the lens, glaucoma in the optic nerve, and dry eye syndrome in the cornea. We used targeted metabolomics to analyze metabolites from young (6 weeks) and old (73 weeks) eyes in C57 BL6/J mice. Old mice had diminished electroretinogram responses and decreased number of photoreceptors in their retinas. Among the 297 detected metabolites, 45-114 metabolites are significantly altered in aged eye tissues, mostly in the neuronal tissues (retina and optic nerve) and less in cornea, RPE/choroid, and lens. We noted that changes of metabolites in mitochondrial metabolism and glucose metabolism are common features in the aged retina, RPE/choroid, and optic nerve. The aging retina, cornea, and optic nerve also share similar changes in Nicotinamide adenine dinucleotide (NAD), 1-methylnicotinamides, 3-methylhistidine, and other methylated metabolites. Metabolites in taurine metabolism are strikingly influenced by aging in the cornea and lens. In conclusion, the aging eye has both common and tissue-specific metabolic signatures. These changes may be attributed to dysregulated mitochondrial metabolism, reprogrammed glucose metabolism and impaired methylation in the aging eye. Our findings provide biochemical insights into the mechanisms of age-related ocular changes.