This paper reviews aspects of Letten F. Saugstad’s Maturation Theory in relation to the Kraepelinian dichotomy and psychiatric classification. The maturation theory is based on existing neuroscience, cross-national and mental health case register data and offers an innovative alternative to current etiological formulations. The maturational theory holds (1) that manic depressive illness relates to early maturation and (2) the schizophrenic syndrome relates to late maturation. The foundation of these processes lies in cerebral pruning of excitatory synapses particularly at puberty but also at a number of earlier crucial periods in development. The process of synaptic pruning has by puberty eliminated some 40% of the synapses, leading to the disappearance of glutematergic excitatory synapses without apparently appreciably influencing inhibitory GABAergic neurons. As a consequence, early maturation is related to the manic-depressive syndrome and characterized by increased neural excitability. Conversely, late maturation is related to schizophrenia characterized by diminished neural activity. Saugstad demonstrates using cross-national and neuroscience studies the multifactoral and environmental influences on rates of maturation and thereby mental illness. Using these data Saugstad reasons her agreement with the Kraepelinian dichotomy based on the existence of two extremes in brain structure and function developed through interactions between the person and the environment.