Progress Towards Better Treatment of Mental Disorders
Specific brain mechanisms may provide a new target for treatment.
Posted July 30, 2025 | Reviewed by Monica Vilhauer Ph.D.
We’re seeing continued advances in making psychiatric diagnoses—and, therefore, improved treatment. A major step in this direction occurred in 2009 when the National Institute of Mental Health (NIMH) embraced the Research Domain Criteria (RDoC). 1 The impetus was clear. Reliance on DSM / ICD diagnoses had produced no improvement in care, and research demonstrated no association of them with underlying pathophysiological abnormalities in the brain or elsewhere. Most thought the failures resulted from: i) the isolated focus on symptoms employed by DSM/ICD criteria, and ii) using a categorical approach where the number of symptoms was critical for a diagnosis; for example, 5 major symptoms of depression made the diagnosis, but 3 or 4 did not.
Instead, the RDoC sought to better understand mental illness by evaluating multiple factors in addition to symptoms and studying them in a continuous or dimensional way. They did this by identifying these six functional (and process) domains of responses to various life stimuli: positive valence, negative valence, social processes, cognitive, sensorimotor, and arousal/regulatory. The idea was that such functional understanding might better explain symptoms. Looking at these functions on a dimensional basis, they then evaluated them across the lifespan in interactions with the environment using multiple units of analysis (genetic, MRI, brain circuitry, self-report, etc.).
While research supports the new idea, data are not yet sufficiently robust to inform treatment, and clinical practice still defers to DSM/ICD diagnoses. Happily, this systems approach also eschews psychiatry’s unidimensional idea that a brain disease causes each mental illness. Rather, the new approach looks for processes within the brain that correspond to symptoms of DSM/ICD disorders.
In another example from a previous post, I reviewed Kenneth Kendler’s idea that critical causal pathways in the brain mediate (rather than cause) DSM/ICD disorders. 2 These “risk factors” can be biological, psychological, or social. He illustrated this with examples where schizophrenia risk genes are prominent only in the brain, while alcohol use disorder risk genes reside mainly in the liver and gut. In the first instance, the brain mediates the mental disorder, while the liver does in the latter.
We learn more of the importance of different mediating factors in a new report from Tristam Lett and colleagues who aver that the present day lack of neurobiological understanding of DSM/ICD disorders precludes effective treatment. 3 Instead, when we understand the mechanism, we can develop treatments that specifically target the underlying neurobiology. Lett et al. studied 1003 patients from several pre-existing databases that included complete DSM/ICD diagnoses and other clinical assessments and a wide variety of neuroimaging data across multiple time points. Compared to controls, using a rigorous research design, they predicted symptom patterns from brain imaging findings. The psychological symptoms predicted came from the DSM/ICD symptoms in their database. The neurobiological predictors re-shuffled them into six new symptom groups reflective of mental illnesses: i) Excitability/Impulsive score, ii) Depressive/Distress score, iii) Anxiety (plus several others) score, iv) Stress score, v) Eating Pathology score, and vi) Social Fear /Avoidance score. Thus, while derived from the original DSM/ICD diagnoses, the symptoms had to be realigned to make them meaningful.
While these data show several dimensions of psychopathology based on quantifiable neurobiological measures, the variance explained was only moderate, so that we cannot yet apply them clinically. Nevertheless, the researchers have shown unique neurophysiological correlates of psychological distress symptoms.
The significance of the RDoC, Kendler, and Lett examples extends well beyond better diagnosis and treatment of mental illnesses. Because these works consider multiple interacting biological, psychological, and social factors to define mental disorders, they employ basic systems theory concepts—and demonstrate their potential for improving mental health care. Unfortunately, this is an alien concept in medicine and psychiatry. Such trailblazing work as I’ve cited here can perhaps spur change. I explain in greater detail exactly how to do this in Has Medicine Lost Its Mind? 4
Doherty JL, Owen MJ. The Research Domain Criteria: moving the goalposts to change the game. The British journal of psychiatry : the journal of mental science 2014;204:171-3. (In eng) ( http://www.ncbi.nlm.nih.gov/pubmed/24590970 ).
Kendler KS. Are Psychiatric Disorders Brain Diseases?-A New Look at an Old Question. JAMA Psychiatry 2024. DOI: 10.1001/jamapsychiatry.2024.0036.
Lett TA, Vaidya N, Jia T, et al. Framework for Brain-Derived Dimensions of Psychopathology. JAMA Psychiatry 2025. DOI: 10.1001/jamapsychiatry.2025.1246.
Smith R. Has Medicine Lost Its Mind?—Why Our Mental Health System Is Failing Us and What Should Be Done to Cure It. Essex, CT: Prometheus Books (an imprint of The Globe Pequot Publishing Group, Inc.), 2025.
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Robert C. Smith, M.D. , is a University Distinguished Professor, Medicine and Psychiatry, Division of General Internal Medicine, at Michigan State University.
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