Categories and dimensions, brain and behavior: the yins and yangs of psychopathology.

In this issue of JAMAPsychiatry, Bebko et al1 present an innovative multisite study that uses both categorical and dimensional approaches to test associations between brain activity and symptoms in youth with severe emotional and behavioral dysregulation.Using functional magnetic resonance imaging (fMRI) and a rewardguessing task in 105 youth, the authors examined associations between brain activation andDSM-IV categories and between brain activation and dimensional measures of mania, depression,anxiety,andriskforbipolarspectrumdisorder (BPSD,measured by the Parent General Behavior Inventory 10-Item Mania Scale [PGBI-10M]). During reward trials, Bebko et al found associations between frontal activation and both dimensional and categorical clinical measures. Specifically, using dimensional measures, they identified associations between PGBI10M score and middle prefrontal cortical (mPFC) activity and between anxiety and dorsal anterior cingulate cortical (dACC) activity.However, theyalso reportdecreasedventrolateralprefrontal cortex (VLPFC) activity in youth categorized as having a disruptive behavior disorder (DBD, ie, conduct disorder and oppositional defiant disorder). Thus, whenmapping patients’ symptoms onto brain activity, Bebko et al found that both dimensional and categorical approaches were useful. Theuseof bothdimensional and categorical approaches is one important innovation by Bebko et al, but it is not the only one.Because theauthors testedassociationsbetweenbrainactivity and multiple categories and dimensions, they needed a largesamplesize; this in turnnecessitatedamultisite study. Importantly,whereasmost large-sample imagingstudiesusestructural or resting-state approaches, Bebko et al used task-based fMRI, which allowed them to examine associations among symptoms, diagnoses, and brain activity while the participants engaged inbehavior relevant to their psychopathology— all this in a sample of youth with severe psychiatric illness. In integratingcategorical anddimensional approaches, the workofBebkoet al couldnotbemore timely.The relativemeritsof these2approaches topsychopathologyhavereceivedconsiderable recent attentionwith thepublicationofDSM-5 (a categorical system, like previous DSMs) and the advent of the Research Domain Criteria,2 a dimensional framework for National Institute of Mental Health–funded research. The question is not whether the dimensional or categorical perspective will prevail but how the two can be integrated most effectively to facilitate discoveries thatwill lead to new treatments and efforts tomatch individual patientswith the interventions most likely to help them. Clinicians will never be able to escape diagnostic categories because treatment planning requires a series of categorical decisions, eg, to treat or not, to treat with onemedication or psychotherapeutic approach or another. Indeed, even that most dimensional of physiologic measures, blood pressure, yields to a categorical approach in the context of treatment guidelines that introducecutpoints into thedimensionalmeasureandthenmakecategorical recommendations for the treatment of stage 1, stage 2, and severe hypertension.3 Although these cut points are based on data, the data informing them are not physiologic but instead define the point at which the risk of untreated hypertension surpasses the risk of currently available treatment. Psychiatric and psychological research demonstrate that, inmany instances, symptoms, genetic risk for mental illness, and the brain mechanisms mediating behavior are better describedby continua thanby categories. As withhypertension, cutpointsmustbe imposedonthesephysiologic continua to guide clinical care, and ideally those cut points should be informed by clinical data defining the risks and benefits of available treatments. However, froma strictly physiologic perspective, the categories will always remain somewhatarbitrarybecause theywill be imposedon fully continuous, smooth distributions. Against this background, Bebko et al1 tested the usefulness of a dimensional formulation in elucidating neural dysfunction in children with complex and severe psychiatric illness. Most fMRI studies compare patients with a specific categoricalDSM-IVdiagnosiswithhealthy individuals.Posthoc analysesmay examine associations between dimensional severitymeasuresof the illness andbrainactivityor test the contribution of comorbid DSM-IV illnesses to the primary findings. In contrast, Bebko et al focused on a group of children who are of interest precisely because, although their clinical presentation is both commonandvery impairing, their symptoms defy attempts to fit themneatly into one diagnostic category. The patients scanned by Bebko et al are a subsample fromtheLongitudinalAssessmentofManicSymptoms (LAMS) study, in which the target group of interest was the 621 children who scored higher than 12 on the PGBI-10M. The PGBI10M, a screening instrument for BPSD in youth, asks parents howoften their children exhibit periods of intense happiness accompanied by other manic-like symptoms, such as increased energy, irritability, insomnia, and restlessness. In the LAMS study, childrenwith scores of 12 or higher on the PGBI10M had a mean (SD) of 2.6 (1.3) DSM-IV diagnoses: 43%met criteria for a mood disorder, 76% for attention-deficit/ hyperactivitydisorder,and53%foraDBD.4ApproximatelyoneRelated article page 71 Opinion