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Major depressive disorder is a common diagnosis associated with a high burden of disease that has proven to be highly heterogeneous and unreliable. Treatments currently available demonstrate limited efficacy and effectiveness. New drug development is urgently required but is likely to be hindered by diagnostic limitations.
Autoimmune NMDA-R encephalitis (ANRE) shares clinical features with schizophrenia. Recent research also indicates that both disorders are associated with dysfunction of the N-Methyl-D-Aspartate glutamate receptors (NMDA-R) subunit 1.
We present the case of Ms A, 16 years old. Ms A presented with acute personality change, bizarre behaviour, delusional ideas and atypical seizures. She had a family history of psychotic disorders, and autistic traits diagnosed in childhood. She was initially diagnosed with a psychotic disorder. Delayed testing of CSF indicated ANRE. As the patient was a Jehovah's witness the treating team was unable to use gammaglobulin therapy; they instead relied on combined plasmapheresis and rituximab. To exclude the possibility that the affected members of this family shared a gene coding for an abnormal configuration of the NMDA receptor subunit 1 we sequenced the region of the GRIN1 gene in DNA extracted from blood in both Ms A and her grandmother.
Ms A’s condition improved dramatically, though her long-term memory is still demonstrably impaired. No genetic abnormality was detected.
This case emphasizes how important it is, for a first episode psychosis, to exclude ANRE and other autoimmune synaptic encephalitides, even in the face of significant family history, and if seronegative, the importance of testing for CSF autoantibodies.
Primary headache disorders are among the most prevalent conditions affecting various populations worldwide. Personality traits and psychiatric disorders are important comorbid and possibly causal conditions in migraine and mediators of stress impact on migraine or tension-type headache. These include neuroticism, anxiety, panic disorder, depression, and post-traumatic stress disorders. Post-traumatic stress disorder (PTSD) is a well-recognized risk for and modulator of headache. Peterlin and colleagues evaluate the relative frequency of PTSD in episodic migraine (EM), chronic daily headache (CDH), and the impact on headache-related disability. The goal of behavioral management for stress must be to improve headache frequency and severity and to improve quality of life by increasing patient self-knowledge, disease knowledge, and sense of control and self-efficacy. The role of stress as a modifier or trigger of headache should be actively evaluated in all patients with recurrent or chronic headache disorders.
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