Professor William Carpenter, Maryland, USA, gave an insightful presentation during the Schizophrenia International Research Society (SIRS) Conference 2018 in which he shared his personal perspectives on where schizophrenia research is headed in the near future.
To put future developments into perspective, he briefly presented his views on schizophrenia research in the past and outlined where he believed springboards for future research were likely to be situated. From the disease described by Bleuler and Kraepelin to the present day, he explained that many now see schizophrenia as a “syndrome” with heterogeneous underlying causal factors and psychopathologies.
Many now see schizophrenia as a 'syndrome' with heterogeneous underlying causal factors and psychopathologies
Deconstruction of the schizophrenia 'syndrome' is widely endorsed. Work is being done to establish the relevant dimensions of the condition and to determine how to exert influence on them. As the dimensions of psychiatric diseases cross disorder boundaries, it may be that the same pathology is present in several conditions. Indeed, regulatory bodies have begun conceptualising psychopathology rather than syndromes as indications for pharmacotherapies. It has taken us too long to get to this position, Professor Carpenter says, and there are several clear unmet needs yet to be addressed.
Near future predictions
Professor Carpenter made several predictions for therapies that are likely to become available in the near future. Some will be based on research that describes the underlying pathological mechanisms, which in turn will reveal potential treatment targets. Furthermore, treatment will target factors such as resiliency, compensation and also motor abnormalities. Neural network hypotheses suggest that therapies may already be available for such targeting if used appropriately. Secondary prevention has already begun in high-risk groups and is being rolled out to cover not only function but also emotion and psychosis.
Primary prevention a reality soon?
In the near future, Professor Carpenter believes that primary prevention of schizophrenia will become a reality in some cases, and emerging evidence is beginning to support its feasibility. For example, neonatal developmental delay in prepulse inhibition is associated with attentional problems as the child matures. While still in its early stages, it appears that intervening during pregnancy may influence the risk of schizophrenia incidence, albeit at this stage assessed through use of a surrogate marker.
Intervening during pregnancy may influence the risk of schizophrenia
KAT II inhibitors and KYNA
Novel mechanism-based treatments are also likely to be developed. Professor Carpenter suggested that one such therapy might be kynurenine aminotransferase II (KAT II) inhibitors. Fluctuations in brain kynurenic acid (KYNA) levels bi-directionally regulate extracellular concentrations of glutamate and other major neurotransmitters. Even minor elevations in KYNA during early brain development or later in life, impair cognitive functions. Astrocytic KAT II is a major determinant of the rapid formation of neuroactive KYNA in the mammalian brain. Acute down-regulation of brain KYNA, which is now possible with several recently developed KAT II inhibitors, has been shown to improve cognitive function in preclinical research. Testing of the potential pro-cognitive effects of KAT II inhibition in humans is expected in the not-so-distant future.
Testing of pro-cognitive effects of KAT II inhibition in humans is anticipated
Progress is being made
In summary, or as he called it, ‘War's won!’ Professor Carpenter was optimistic about the progress that has been made. No more genes versus environment; no more biology versus psychology; less ideology, more integration and a less inflated view of progress have been achieved. And with wisdom comes clarity regarding mechanisms and novel therapies instead of ‘me too’ drugs, he suggested. Individualized treatment will become the norm as the underlying pathologies or causes of schizophrenia are uncovered.