A prospective three-year follow-up study on the clinical significance of anti-neuronal antibodies in acute psychiatric disorders

Abstract

The clinical significance of anti-neuronal antibodies for psychiatric disorders is controversial. We investigated if a positive anti-neuronal antibody status at admission to acute psychiatric inpatient care was associated with a more severe neuropsychiatric phenotype and more frequent abnormalities during clinical work-up three years later. patients admitted to acute psychiatric inpatient care who tested positive for N-methyl-D-aspartate receptor (NMDAR), contactin-associated protein 2 (CASPR2) and/or glutamic acid decarboxylase 65 (GAD65) antibodies (n = 24) were age -and sex matched with antibody-negative patients (1:2) from the same cohort (n = 48). All patients were invited to follow-up including psychometric testing (e.g. Symptom Checklist-90-Revised), serum and cerebrospinal fluid (CSF) sampling, EEG and 3 T brain MRI. Twelve antibody-positive (ab+) and 26 antibody-negative (ab−) patients consented to follow-up. Ab+ patients had more severe symptoms of depression (p = 0.03), psychoticism (p = 0.04) and agitation (p = 0.001) compared to ab− patients. There were no differences in cSf analysis (n = 6 ab+/12 ab−), EEG (n = 7 ab+/19 ab−) or brain MRi (n = 7 ab+/17 ab−) between the groups. In conclusion, anti-neuronal ab+ status during index admission was associated with more severe symptoms of depression, psychoticism and agitation at three-year follow-up. This supports the hypothesis that anti-neuronal antibodies may be of clinical significance in a subgroup of psychiatric patients.The discovery that anti-neuronal antibodies cause distinct clinical syndromes with prominent neuropsychiatric symptoms has shown a remarkable link between immunology and psychiatry 1,2 . Several studies have estimated the prevalence of antibodies in patients with primary psychiatric disorders (including antibodies against N-methyl-D-aspartate receptor (NMDAR), contactin-associated protein 2 (CASPR2), and glutamic acid decarboxylase 65 (GAD65)) 3-8 . However, if anti-neuronal antibodies are clinically important in psychiatric patients who do not fulfill criteria of autoimmune encephalitis remains unknown.Evidence from preclinical models suggest that NMDAR antibodies found in psychiatric patients have pathogenic potential 4,9 . It was recently demonstrated that NMDAR antibodies from patients with schizophrenia alter the surface dynamics and organization of NMDARs in these patients, but not in healthy controls 10 . Most researchers examining the phenotype of anti-neuronal antibody-positive psychiatric patients have focused on patients with psychotic disorders and report quite similar phenotypes in patients with and without NMDAR antibodies as measured with the Positive and Negative Syndrome Scale (PANSS) 4,5 . However, there is a lack of studies

Sera anti‐neuronal antibodies in patients with irritable bowel syndrome and their correlations with clinical profiles

“…They thought autoimmune encephalitis associated with anti‐neuronal antibodies may be challenging to distinguish from primary psychiatric disorders. In contrast, another study showed anti‐neuronal antibody‐positive status during index admission was associated with more severe symptoms of depression, psychoticism and agitation at 3‐year follow‐up, 39 which supported anti‐neuronal antibodies may be of clinical significance in a subgroup of psychiatric patients. It was worth noting all of our patients' neurological symptoms were mild to moderate which restricted to headache, sleeping disorder, anxiety, and depression; none of our patients showed severe neurological symptoms like epilepsy or schizophrenia.…”

Antibodies against N-Methyl D-Aspartate Receptor in Psychotic Disorders: A Systematic Review

“…As we have shown in our review, the same idea may be applicable to purely psychotic AB-positive patients, including even those with ABs against NMDAR NR2 subunit. Some case reports and follow-up studies proved there was a difference between AB titers in acute and more stable phases [96, 97], but further research is certainly required to confirm and clarify the peculiarities of this correlation.…”

“…Patients who were tested positive for IgG ABs in serum, but not CSF, mostly had only psychiatric symptoms and were successfully treated with antipsychotic medications [98]. Schou et al [96] conducted a follow-up study among patients who were tested positive in serum at admission to the acute psychiatric ward. None of them developed autoimmune encephalitis and all were treated as usual, but AB-positive status during admission was associated with more severe symptoms of depression, psychoticism, and agitation at 3-year follow-up [96].…”

“…Schou et al [96] conducted a follow-up study among patients who were tested positive in serum at admission to the acute psychiatric ward. None of them developed autoimmune encephalitis and all were treated as usual, but AB-positive status during admission was associated with more severe symptoms of depression, psychoticism, and agitation at 3-year follow-up [96]. Together, these studies suggest that psychotic patients with ABs against NMDAR NR1 in serum only and without clinical signs of anti-NMDAR encephalitis could be treated with traditional medications.…”

Does circadian dysrhythmia drive the switch into high‐ or low‐activation states in bipolar I disorder?

“…In clinical psychiatry, only rarely has this iterative process led to genuine breakthroughs. Limited examples do exist for various kinds of mood disorders, including: (1) delineation of “vascular depression” among older adults with a first onset of depression in later life after specific cerebrovascular lesions 1 ; (2) onset of depressive disorders after specific infections 2 or the introduction of immune‐active therapies 3 ; and (3) recognition of “atypical” mood disorders in young adults with antineuronal antibodies 4 . The latter discovery has led to the use of immune therapies targeted to underlying pathophysiology 5 .…”