Cognition and inflammation as transdiagnostic dimensions in psychiatry

Cognition has long been considered a core symptomatic dimension of depression. Increasingly this dimension is seen as transdiagnostic, cutting across syndromic conceptualisations of psychiatric illness. The importance of this dimension, not only on subjective patient experience, but also on patient functioning has become a focus of interest.   Cognitive deficits are prominent in schizophrenia and research in this disorder has preceded that in other psychiatric disorders. Impairments have also been identified in all phases of bipolar disorder, as well as during the remitted state. Recently, interest in the cognitive impairments associated with depression have mobilised academic, and clinical attention as a result of treatments claiming to have a specific effect on this dimension. Clearly, cognitive impairment is a prominent symptomatic domain in attention deficit disorder. It has become a clinical imperative to appropriately assess the cognitive dimension of psychiatric disorders.  The causes of the cognitive deficits seen in psychiatric illness have not been completely elucidated. Although it is possible the causes vary and are unique in each condition, it is also conceivable that other transdiagnostic factors such as inflammation may contribute to the cognitive deficits of psychiatric disorders. Inflammatory processes have been identified in several psychiatric disorders; for example, a pro-inflammatory state is seen in schizophrenia, bipolar disorder and depression. The treatment of psychiatric disorders has also been associated with changes in inflammatory markers. The somatic treatment of these disorders is predominantly pharmacological with antipsychotics in the case of schizophrenia and with antidepressants, as well as with antipsychotics in the case of depression. Both antipsychotics and antidepressants are associated with an anti-inflammatory effect.  There is evidence to suggest that inflammation is associated with cognitive deficits and it is intriguing to consider that this may be the case in psychiatric disorders, particularly depression and that these transdiagnostic dimensions may be related.  This thesis presents an extensive review of the literature which demonstrates that psychiatric conditions are characterised by cognitive deficits which contribute to the impact of these conditions on functioning. This review confirms the importance of the clinical evaluation of cognition. As a response to the need to develop clinical tools to evaluate cognition, a French version of the Screen for Cognitive Impairment in Psychiatry was validated (Article 1). Once developed, this tool was tested in two clinical populations, characterised by major depression and adult attention deficit disorder respectively. The link between cognitive deficit and functioning is demonstrated in these two clinical populations. The important observation, established in schizophrenia, of a relative discordance between self and objective evaluation of cognition is also found in these diagnostic categories. An overview of the literature reveals the ubiquitous presence of a pro-inflammatory state in psychiatric conditions and confirms the link between cognitive deficits and inflammatory markers. A meta-analysis confirms the anti-inflammatory effect of anti-psychotics (Article 5). This work contributes to the demonstration that it is possible to measure cognition with a brief and rapid tool, as well as to the advancement of knowledge regarding inflammation in schizophrenia. Future research will need to focus on clarifying the contribution of inflammation to the cognitive deficits characteristic of psychiatric disorders.

Keyphrases: Cognition, Inflammation, Psychiatry, Schizophrenia, Depression, Attention Deficit Disorder with or without Hyperactivity (ADHD), Trandiagnostic, Antidepressant, Antipsychotic