Matrix metalloproteinase 9 (MMP-9) activity, hippocampal extracellular free water, and cognitive deficits are associated with each other in early phase psychosis.

Increasing evidence points toward the role of the extracellular matrix, specifically matrix metalloproteinase 9 (MMP-9), in the pathophysiology of psychosis. MMP-9 is a critical regulator of the crosstalk between peripheral and central inflammation, extracellular matrix remodeling, hippocampal development, synaptic pruning, and neuroplasticity. Here, we aim to characterize the relationship between plasma MMP-9 activity, hippocampal microstructure, and cognition in healthy individuals and individuals with early phase psychosis. We collected clinical, blood, and structural and diffusion-weighted magnetic resonance imaging data from 39 individuals with early phase psychosis and 44 age and sex-matched healthy individuals. We measured MMP-9 plasma activity, hippocampal extracellular free water (FW) levels, and hippocampal volumes. We used regression analyses to compare MMP-9 activity, hippocampal FW, and volumes between groups. We then examined associations between MMP-9 activity, FW levels, hippocampal volumes, and cognitive performance assessed with the MATRICS battery. All analyses were controlled for age, sex, body mass index, cigarette smoking, and years of education. Individuals with early phase psychosis demonstrated higher MMP-9 activity (p < 0.0002), higher left (p < 0.05) and right (p < 0.05) hippocampal FW levels, and lower left (p < 0.05) and right (p < 0.05) hippocampal volume than healthy individuals. MMP-9 activity correlated positively with hippocampal FW levels (all participants and individuals with early phase psychosis) and negatively with hippocampal volumes (all participants and healthy individuals). Higher MMP-9 activity and higher hippocampal FW levels were associated with slower processing speed and worse working memory performance in all participants. Our findings show an association between MMP-9 activity and hippocampal microstructural alterations in psychosis and an association between MMP-9 activity and cognitive performance. Further, more extensive longitudinal studies should examine the therapeutic potential of MMP-9 modulators in psychosis.

Mapping Personal Geographies in Psychosis: From Space to Place.

Recently, there has been a growing interest in the interaction between the urban milieu and the development of psychosis. While growing up in an urban environment constitutes a risk factor for developing psychosis, patients who develop a first episode of psychosis tend to avoid city centers and suffer from isolation. These observations have fostered emerging interest in ways of developing contexts in cities that are favorable to mental health and that may help service users in their paths to recovery. Building on work on place attachment as well as systemic therapy, we present a new approach to map the urban spaces experienced by service users. We propose two tools, the "place attachment diagram" and "life space network," to situate emotional bond and spatial dimension respectively at their center and help service users to map meaningful places in the city. We also suggest that different facets of the illness such as epidemiological risk factors (residential mobility, migration, urban living, trauma), early place attachment and abnormal space experience, may shape individual space and place experience in psychosis. Psychotherapeutic process with patients should aim at turning urban "spaces" into "places" characterized by a sense of familiarity, security and opportunity. Finally, we argue that the "spatial" is a forgotten dimension in psychotherapy and should be taken into account when treating individuals with psychosis.