Figure 4. Simplified hypothesized cellular-level mechanisms in schizophrenia (SCZ) and major depression (MD): central role of glutamatergic neurotransmission. This simple “inverted U” model illustrates the role of glutamate across clinical conditions such as MD and SCZ. This conceptual example is based on evidence that glutamatergic therapies involving acute N-methyl D-aspartate receptor antagonism act therapeutically on mood in the context of MD,¹⁷⁴ but result in exacerbation of psychotic symptoms in individuals diagnosed with a psychotic disorder.¹⁷⁷ This conceptual illustration highlights the idea that it may be important to understand the role of glutamatergic deficits across psychiatric conditions and role of pharmacotherapies targeting this complex system.¹²⁴ .