How research on the meta-structure of psychopathology aids in understanding biological correlates of mood and anxiety disorders

The stated goal of the Diagnostic and Statistical Manual for Mental Disorders (DSM) is threefold: to provide a helpful guide to clinical practice, to facilitate research and improve communication among clinicians and researchers, and to serve as an educational tool for teaching psychopathology (DSM-IV-R 4th ed., pp xxiii). Historically, DSM began as a broad set of vignettes that depicted common clinical manifestations of mental disorders, but diagnoses listed in early DSMs were not reliably diagnosed by clinicians, and as a result had little validity [1]. By introducing explicit sets of diagnostic criteria, the DSM-III was instrumental in refining the boundaries of diagnoses so that clinicians were discussing the same clinical entities, supposedly distinct from others. DSM-III also introduced exclusionary criteria that sought to limit overlap between diagnostic sets. DSM-IV did little to change the basic scheme of the DSM-III, which had grown to include hundreds of distinct diagnostic categories. This degree of presumed diagnostic differentiation often contrasts with clinical experiences, where patients typically meet criteria for multiple DSM diagnoses, a phenomenon referred to as comorbidity [2–6], or related experiences where patients present with symptom configurations “not otherwise specified”(NOS), as opposed to symptoms that cohere into a clear DSM-defined focal syndrome [2]. As a result, questions about the validity of DSM-IV’s approach to psychodiagnosis are frequently raised [1, 7].

Research focusing on the problem of diagnostic comorbidity has resulted in a literature that has converged on an empirical model of the meta-structure of common mental disorders, or the way in which multiple mental disorders delineate spectrums of interrelated conditions. There is mounting evidence to suggest that common forms of psychopathology are defined by the higher-order groupings or spectrums of internalizing and externalizing, and that this shared underlying meta-structure contributes to the comorbidity among disorders [8–11]. As shown in Figure 1[9], internalizing is indicated by unipolar mood disorders and anxiety disorders, like major depressive disorder, generalized anxiety disorder, social and specific phobias, and panic, that load highly on the internalizing factor. Externalizing is indicated by disinhibitory and substance abuse disorders including drug, alcohol, and nicotine dependence, antisocial personality disorder and antisocial traits, pathological gambling, and conduct disorder. Within the higher-order internalizing dimension, some studies have revealed two sub-dimensions: distress, representing unipolar mood disorders and generalized anxiety, and fear, representing panic disorder, social and specific phobia [9], while others have not found evidence of these subfactors [12].

In expanding this work to encompass rarer forms of psychopathology, a recent study in a clinical sample analyzed data on 25 disorders, spanning both rarer and more common disorders, as well as Axes I and II. The best-fitting model consisted of 5 factors: (1) internalizing, which included anxiety and eating disorders, major depressive episodes, as well as cluster C (anxious and inhibited) personality disorders, borderline and paranoid personality disorders; (2) externalizing, including the substance use disorders and antisocial personality disorder; (3) thought disorder, including psychosis, mania, and cluster A personality disorders; (4) somatoform disorders; and (5) antagonism, including cluster B and paranoid personality disorders [13]. This work is important in that it replicates findings from previous work in a clinical sample and demonstrates that the same methods used to establish the existence of the internalizing-externalizing model can be used to extend that model to rarer disorders observed in clinical populations.

The search for biological correlates of psychopathology stands to benefit from being interwoven with the empirical structure of psychopathology. Models of the empirical structure of psychopathology provide a coherent framework through which to interpret biological findings, which can accommodate comorbidity and improve ecological validity. It is important that subsequent versions of the DSM come to reflect the presence of the meta-structure underlying mental disorders if it aims to reflect our current empirical understanding of the data. A DSM-5 study group has proceeded towards the aim of representing the metastructure by developing a group of 11 ‘validating criteria’ that suggest aetiological relatedness between a cluster of disorders. The criteria are (1) genetic factors, (2) familiality, (3) early environmental adversity, (4) temperamental antecedents, (5) neural substrates, (6) biomarkers, (7) cognitive and emotional processing, (8) differences and similarities in symptomatology, (9) comorbidity, (10) course, and (11) treatment. A recent review of the literature has suggested that there is a case for the DSM to unify related disorders under the category of internalizing, also called emotional, disorders [15]. Although the meta-analysis found differences between disorders in the proposed cluster, specifically in the domains of cognitive and emotional processing, neural substrates, and familial studies, there were more similarities than differences in these disorders within the 11 domains studied. The authors suggest that a reorganization of the DSM to reflect this knowledge is possible, and further clarify that the proposed clustering would not remove traditional diagnostic categories, but only reorganize them to better reflect our current understanding. Although our understanding of etiology is still in its nascent stages, to preserve the current classification system with all its flaws until a definitive solution becomes clear would impede biologically and diagnostically-based research [16]. Insofar as the DSM 5 will reflect changes to our understanding of the nature of diagnostic categories, it will be progressing towards a system that will be better suited to research biological underpinnings.