COG…IGNITION! CAN WE JUMP START COGNITION IN PSYCHOTIC DISORDERS?

The following symposium at the 35^th ENCP congress held in Vienna, Austria, began with a talk by Professor Ingrid Melle, Professor of Psychiatry and Co-director of the NORMENT Centre at the University of Oslo, who reviewed the putative mechanisms of impaired neurocognition in schizophrenia and bipolar disorder. The two mechanisms proposed to lead to neurocognitive impairments in psychotic disorders are dysregulated sleep (sleep spindles) and dysregulated immune-mediated synaptic pruning.   

Neurocognition’s importance is well-established and supported by scientific evidence that shows that it is significantly associated with functional outcomes^1,2. At the same time, research evidence also suggests that neurocognition^3,4 and social cognition⁵ are the most impaired long-term in patients with schizophrenia compared to patients with other psychiatric disorders and healthy controls. Furthermore, some effects of neurocognition on impairments in quality of life and functioning in schizophrenia may be mediated by impairments in social cognition^6,7.
Dysregulated sleep may be one of the ways in which neurocognition is affected in psychotic disorders. During sleep, memories are repeatedly reactivated, which leads to the strengthening of some synaptic connections and the weakening of others⁸. Sleep spindles are waxing and waning oscillations in the 12-15 Hz band of shorter durations in the thalamus, a characteristic of slow-wave sleep⁸. These spindles are likely to play a role in memory and long-term representations in cortical networks⁸. However, sleep spindles frequency appears to be reduced in both schizophrenia⁹ and bipolar disorder¹⁰, which may contribute to cognitive impairment.
The second mechanism by which cognition may be impaired is a reduction in synaptic density caused by the ‘overpruning’ activity of the immune system¹¹. Evidence for this emerged in the first genome-wide association study in schizophrenia, which found a signal on chromosome 6 that is linked to the major histocompatibility complex, which is involved in immunity¹². Two years later, a follow-up study identified that the link was more specifically to complement component 4, an area linked to synaptic pruning taking place during brain maturation¹³. Future research may explore how these findings translate to clinical settings and treatment.
 

In the second talk of the session, Dr Rebecca Strawbridge, a post-doctoral Research Associate within the Centre of Affective Disorders at the Institute of Psychiatry, Psychology and Neuroscience at King’s College London, discussed the evidence base for cognitive remediation therapies (CRTs) in schizophrenia and bipolar disorders. She argued that while there is good evidence for the effectiveness and feasibility of CRT for patients with schizophrenia, large randomised controlled trials (RCTs) are still lacking for determining this intervention’s efficacy in bipolar disorders.
It is now well-established that CRT is effective in improving cognition and some aspects of functioning among patients with schizophrenia^14,15, especially when there is a focus on how to transfer these skills and strategies to everyday life^16,17. For this reason, CRTs are increasingly recommended in guidelines and provided in routine services and research is headed towards its successful implementation in early intervention and other mental health services, taking into consideration aspects such as maximising efficacy, cost-effectiveness, etc.¹⁸
For patients with bipolar disorder, there is some evidence to suggest that individual interventions¹⁹ and those that focus on transferring these skills to everyday life are more effective²⁰, but there is a lack of high quality, large RCTs²¹. The International Society of Bipolar Disorders recommends that cognitive remediation programmes only target individuals with an objective cognitive impairment²¹, as the extent of cognitive impairment observed in bipolar disorder is heterogenous, with some patients not showing significant impairment compared to healthy controls. Nevertheless, Dr Strawbridge pointed out that some patients with bipolar disorder still report subjective cognitive impairments that impact their functioning and a reanalysis of their trial results suggests that the degree of impairment before the CRT did not affect improvement²⁰.
Evidence for other forms of cognitive remediation, such as pharmacological options and non-pharmacological options (repetitive transcranial magnetic stimulation or transcranial direct stimulation), is inconclusive because of the lack of RCTs in both schizophrenia and bipolar disorders^22,23.