Schizophrenia in the near future

Professor William Carpenter, Maryland, USA, gave an insightful presentation during SIRS 2018 in which he gave his personal perspectives on where schizophrenia research is headed in the near future.

However, to put future developments into perspective, he briefly presented his views of schizophrenia research in the past and outlined where he believed springboards for future research were likely to be situated. Thus, from the disease described by Bleuler and Kraepelin to the present day, he explained how 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

Syndrome deconstruction

Deconstruction of the schizophrenia “syndrome” is widely endorsed and work is being done to get at the relevant dimensions of the condition to determine how they can be influenced. As dimensions of psychiatric diseases cross disorder boundaries, it may be that the same pathology is present in several conditions. Indeed, regulatory bodies have begun conceptualizing psychopathology rather than syndromes as indications for pharmacotherapies. It has taken us too long to get to this position, Dr Carpenter stated, and there are still several clear unmet needs yet to be addressed.

Near future predictions

Dr 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 at 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, he believes that primary prevention of schizophrenia will become a reality in some cases. As he explained, evidence has begun to be gathered to support its feasibility. For example, neonatal developmental delay in prepulse inhibition is associated with attentional problems as the child matures. While still 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. He stated 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 summation, or as he called it, ‘Wars won!’ Dr Carpenter was optimistic in the progress that had been made. No more genes versus environment; no more biology versus psychology; less ideology, more integration and 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. Indeed, the neural network hypotheses that have recently been proposed as forming the basis of mental illness and its manifesting pathophysiologies should already prove amenable to treatment.

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