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The Sixth Edition of Charney and Nestler's Neurobiology of Mental Illness builds on previous editions of the book and reflects the continuing progress in reintegrating psychiatry into the mainstream of modern biomedical science. This reintegration remains a work in progress, based on the unique complexity of the brain and its diseases. Yet, the research tools that are transforming other branches of medicine-epidemiology, genetics, epigenetics, molecular and cell biology, imaging, and medicinal chemistry, along with fundamental advances in the neurosciences that make it possible to decipher cell types and their larger circuits to an unprecedented degree, are now at long last transforming psychiatry. Collectively, the 75 chapters in this newly renovated textbook describe the developments in genetics and in molecular, cellular, and systems neuroscience that are breaking new ground in the diagnosis, treatment, and prevention of disabling psychiatric disorders. In this updated edition, Section 1 focuses on the major methodological approaches to studying the biological basis of mental illness. Sections 2 through 8 each focus on a major class of mental illness, including schizophrenia, bipolar disorder, depression, anxiety and trauma disorders, substance use disorders, neurodegenerative disorders, and childhood psychiatry disorders. The final section is a collection of essays that address what can be expected over the next decade in terms of improving psychiatric diagnosis, achieving a true precision approach to treating mental illness, along with new avenues of medication and non-medication therapies in the offing.