Neuropsychopharmacology: The Interface Between Genes and Psychiatric Nosology

By Thomas A. Ban

1. Overview

        The observation that mental illness runs in families received substantial support in family, twin and adoption studies. Nonetheless, the heterogeneity within the diagnostic categories of schizophrenia and manic-depressive illness has precluded any meaningful research in the genetics of these disorders. To break the impasse in genetic research of mental illness consideration was given to split psychiatric disorders into simpler biological or behavioral components. However, all alternative approaches fall short of psychiatric nosology in classifying mental illness in a clinically relevant manner. Neuropsychopharmacology has the unique capability of linking the effect of a psychotropic drug on mental illness with the effect of the substance on brain structures involved in the action mechanism of the drug. Since the primary targets of psychotropic drugs are encoded by genes which have been identified, any form of disease which corresponds with the treatment responsive population to a psychotropic drug is suitable for the generation and testing of genetic hypotheses relevant to mental illness. To provide orientation points about what nosology could offer genetic research, the history of psychiatric nosology is reviewed. It is brought to attention that Kraepelin's (1899) diagnostic concepts of "dementia praecox" and "manic-depressive insanity" are artificially derived nosologic constructs; that Wernicke's (1899) classification is based on scientific developments which were to become the foundation of neuroscience; and that Schneider's (1950) rudimentary classification is the first nosology in which it is recognized that mental pathology is expressed in the mode ("form") in which the experience appears (processed) and not in the "content" of the experience. Specially devised diagnostic instruments are described to provide more homogenous populations for genetic research in mental illness. However, the use of "nosologic homotypes," derived by the employment of a specially devised "nosologic matrix" is recommended for obtaining interpretable findings. The data collected by using the "nosologic matrix" could also serve as the starting point for the development of an empirically derived, pharmacologically meaningful classification of mental illness.

2. Introduction

        The observation that mental illness runs in families has been documented since the mid-18th century (Battie 1758; Chiarugi 1793-1794). The first genetic theory of mental illness was formulated in mid-1850s (Shorter 1997). Morel's (1857) "theory of degeneration" is based on the assumption that mental illness is the result of an "innate biological defect" that becomes manifest in increasingly severe mental syndromes in "lineal descents."

        Morel's (1857) "degeneration theory " was replaced by Moebius' (1893) "endogeny theory" which implied a "constitutionally determined predisposition" for developing mental illness. The dichotomy of "endogenous" and "psychogenic" (Wimmer 1916) psychoses has been lingering on to-date.