Large-scale collaborative efforts have begun to generate broad phenotypic batteries that encompass environmental and contextual factors, brain structure and function, as well as multiple domains of cognition, behavior, and genetics. These datasets hold great potential for clinical researchers seeking to map links across diverse neural and cognitive states.

Psychiatric illnesses arise through a web of interactions linking brain function, behavior, and a lifetime of experiences. Research on illness etiology will only progress through the collection of comprehensive phenomic-level datasets.

Mounting evidence suggests that healthy variation is ubiquitous in natural populations, and must be interpreted in terms of cost–benefit tradeoffs.

Implicit in modern dimensional theories of psychiatric illness is the assumption that population variability and illness vulnerability are interchangeable constructs.

Clear evidence supports a dimensional view of psychiatric illness. Within this framework the expression of disorder-relevant phenotypes is often interpreted as a breakdown or departure from normal brain function. Conversely, health is reified, conceptualized as possessing a single ideal state. We challenge this concept here, arguing that there is no universally optimal profile of brain functioning. The evolutionary forces that shape our species select for a staggering diversity of human behaviors. To support our position we highlight pervasive population-level variability within large-scale functional networks and discrete circuits. We propose that, instead of examining behaviors in isolation, psychiatric illnesses can be best understood through the study of domains of functioning and associated multivariate patterns of variation across distributed brain systems.

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Glossary

the relation between the size of the body as a whole and the size of a specific structure. Although a given component may differ to a greater degree than another, they must show a predictable relationship. This can differ from isometric scaling, where organisms maintain geometric similarity as they change in size (e.g., the relationship linking surface area and body mass).

a measurable indicator whose presence is an objective sign of a given biological state or condition, including pathogenic processes or pharmacologic responses to a therapeutic intervention.

the multilayered sheet of grey matter 2–3 mm in thickness that covers both hemispheres and supports sensory and motor functions as well as the ‘higher’ mental processes that are theorized to distinguish humans from other animals.

the study of causation or origination. Etiology is often used to refer to the cause of a pathological or abnormal condition.

reproductive success of a genotype or phenotype within a given environment.

observed phenotypic variation that is attributable to genetic variation and is transmissible from parent to offspring.

refers to similar structures, physiological characteristics, or development in related species that have been inherited through their descent from a common ancestor.

a taxonomic family of primates that includes humans, the great apes (bonobos, chimpanzees, gorillas, orangutans), and their extinct ancestors.

the medial surface of the frontal lobe encompassing both granular cortical areas [medial aspects of Brodmann areas (BA) 9 and 10] and agranular regions (BA 24, 25, and 32), which include the peri-/subgenual anterior cingulate cortex (BA 24), infralimbic cortex (BA 25), and prelimbic cortex (BA 32).

a phenomenon where only a fraction of a population is migratory; some individuals may participate in seasonal migration while others do not.

the area of biology concerned with the measurement of phenomes, or the full set of physical and biological traits belonging to a given organism. Phenomics can also refer to the acquisition of high-dimensional phenotypic data.

the set of observable characteristics of an individual resulting from the interaction of its genotype with the environment.

the evolutionary development and history of a species or higher taxonomic grouping of organisms.