Schizoaffective disorder,catatonia and white matter changes – Revisiting the microglial hypothesis

To the Editor

Microglial dysfunction and white matter changes have often been discussed in the context of schizophrenia and mood disorder (Monji et al., 2009), but less commonly in the setting of catatonia. We describe a case of new onset catatonia in the setting of a schizoaffective disorder and white matter changes and discuss its aetiological and therapeutic relevance.

Ms A is a 40-year-old woman with schizoaffective disorder. Her illness was diagnosed at age 22 and had a stable course. In the last 8 months, catatonia has emerged in the clinical picture for the first time. She had five catatonic presentations in the last 8 months each requiring bifrontal electro convulsive therapy (ECT). Magnetic resonance imaging (MRI) identified bilateral frontal and parietal subcortical white matter hyper-intensities, which could have been incidental, suggestive of small vessel ischaemic changes or a demyelinating process (Figure 1).

Figure 1.

Magnetic resonance brain images with axial DWI/T2 SPAIR/FLAIR (a) and (b) denote subcortical frontal hyper-intensities adjacent to putamen and caudate nucleus (c) denotes parietal hyper-intensity adjacent to right lateral ventricle.

There was no history of diabetes, hypercholesterolaemia or hypertension. Cognitive testing results were normal, and on physical examination, there were no obvious abnormalities. ECT was acutely effective, but the response was non-sustained. Despite maintenance treatment with two antipsychotics and a mood stabiliser, catatonic relapses occurred within 2 weeks each of the three times ECT cessation was attempted. With the introduction of maintenance ECT (once every 2 weeks), she has maintained remission for the last 3 months.

There is emerging evidence that suggests neuro-inflammation and subsequent subtle changes in white matter could be the cause of complex neuropsychiatric syndromes such as catatonia in patients with pre-existing psychotic spectrum illness (Hagemeyer et al., 2012). Reduced expression of a myelin gene (2,3-cyclic nucleotide 3-phosphodiesterase) has been associated with ‘catatonia-depression’ syndrome (Hagemeyer et al., 2012). Demyelination is a critical process that can affect neuronal connectivity. We argue that Ms A’s catatonic presentation could be a result of such an inflammatory process that cannot simply be explained by the normal trajectory of her illness but could represent an additional ‘pro inflammatory hit’ as discussed above (Hagemeyer et al., 2012). Repeated electro convulsive shock has been shown to downregulate the immune system and inhibits glial activation in a mouse model (Limoa et al., 2016). This could potentially explain the response to maintenance ECT noted in our patient. We support the notion that glial dysfunction could have aetiological value in complex neuropsychiatric presentations like catatonia. Further research that explores therapeutic strategies that specifically target the immune system to reduce neuro-inflammation could be of significant relevance in neuropsychiatry.