The human connectome in health and psychopathology

A basic tenet of biological psychiatry is that psychiatric disorders are driven by abnormalities in brain function, which in turn reflect abnormalities in the underlying brain circuits, i.e., in the wiring of the brain. These circuit abnormalities presumably reflect a complex interplay between genes and environment. Many psychiatric disorders have strong genetic underpinnings: common or rare variants of genes, individually or in combination, elevate the susceptibility to disorders such as autism (1), schizophrenia (2), and many others.Most psychiatric disorders are thought to be neurodevelopmental in nature, either because symptoms typically arise during childhood (e.g., autism) or because the interactions between genes and environment begin early, even if the onset of the disorder becomes evident only in adolescence or adulthood.To better understand, diagnose, and treat psychiatric disorders, it is crucial to obtain deeper insights into brain circuits in health and disease and in humans and animal models. Here, we focus on the relevance of human in vivo neuroimaging, particularly involving magnetic resonance imaging (MRI). We briefly address three major points. First, recent neuroimaging studies have already provided important insights about abnormalities related to brain structure, function, and connectivity in psychopathology. Second, recent advances in neuroimaging of healthy adults, including many driven by the Human Connectome Project, offer exciting prospects for accelerated progress in characterizing disease-related brain connectivity abnormalities. Third, methodological limitations of each neuroimaging method, some of which are inadequately appreciated, require critical assessments and careful interpretation of research findings, especially when placed in the context of the extraordinary complexity of brain circuits revealed by studies of laboratory animals.