Appropriate
biological treatment and psychosocial support are essential to achieve and maintain recovery for patients with
schizophrenia. Despite extensive efforts to clarify the underlying disease mechanisms, the main cause and pathophysiology of
schizophrenia remain unclear. This is due in large part to disease heterogeneity, which results in biochemical differences within a single disease entity. Other factors include variability across clinical symptoms and disease course, along with varied risk factors and treatment responses. Although
schizophrenia's positive symptoms are largely managed through treatment with atypical
antipsychotics, new classes of drugs are needed to address the unmet medical need for improving
cognitive dysfunction and promoting recovery of negative symptoms in these patients. Accumulation of toxic reactive dicarbonyls, such as
methylglyoxal, are typical indicators of carbonyl stress, and result in the modification of
proteins and the formation of
advanced glycation end products, such as
pentosidine. In June 2010, we reported on idiopathic carbonyl stress in a subpopulation of
schizophrenia patients, leading to a failure of metabolic systems with plasma
pentosidine accumulation and serum
pyridoxal depletion. Our findings suggest two markers,
pentosidine and
pyridoxal, as beneficial for distinguishing a specific subgroup of schizophrenics. We believe that this information, derived from in vitro and in vivo studies, is beneficial in the search for personalized and hopefully more effective treatment regimens in
schizophrenia. Here, we define a subtype of
schizophrenia based on carbonyl stress and the potential for using carbonyl stress as a
biomarker in the challenge of overcoming heterogeneity in
schizophrenia treatment.