Genetic Findings Are Challenging the Symptom-Based Diagnostic Classification System of Mental Disorders

By Zhang, Chen | General Psychiatry, February 2016 | Go to article overview

Genetic Findings Are Challenging the Symptom-Based Diagnostic Classification System of Mental Disorders


Zhang, Chen, General Psychiatry


Mental illnesses are a group of complex conditions that affect populations. The main symptoms include abnormities in perception and cognition that result in behavioral and volitional impairments. [1] Since the work of Kraepelin, mental disorders have been classified into different diseases or disorders based on the pattern of clinical symptoms and the long-term prognosis of the condition. Influenced by this approach to the classification of mental disorders, it has been assumed that clinically distinct phenotypes have different etiologies and, thus, research about the causes and appropriate treatments for mental disorders has been largely confined to disorder-specific silos. [2] The specific etiology of most mental disorders remains unknown, but most scholars working in the field agree that heredity plays an important role in the onset of nearly every type of mental illness and that these hereditary factors often interact with environmental factors during the development and course of mental disorders. [3] Research in genetic epidemiology has shown that many mental illnesses--including schizophrenia, bipolar disorder, depression, attention deficit hyperactivity disorder, and autism spectrum disorder--have high rates of heritability. [4] A recent cross-disorder genomewide association study found similar genetic sensitivities in these five diagnostically distinct disorders on regions of chromosomes 3p21 and 10q24 and single-nucleotide polymorphisms (SNPs) within two genes that encode L-type voltage-gated calcium channel subunits, CACNA1C and CACNB2. [5] The specific SNPs were correlated with the age of onset of various mental illnesses, and polymorphism of the calcium-channel activity gene in the five disorders suggests that this gene is important in the onset of all of these conditions. These findings show that despite being classified as distinct conditions in the current diagnostic nosology, genetic research indicates many similarities in the etiology of the conditions. [6]

Clearly, cross-disorder genetic studies challenge the validity of the current diagnostic classification system for mental disorders. The history of psychiatry has included many research-driven changes in the classification systems for mental disorders. The currently used diagnostic systems are quite comprehensive, but they still primarily depend on symptomology. We lack sufficient information about the biological etiology of these conditions, [7] so, like the 'blind man and the elephant', we classify mental disorders based on the external phenomena we can observe (symptoms) rather on the internal causes of the external phenomena (etiology). This approach has serious limitations. For example, when a patient complains of 'abdominal pain', even if doctors can accurately describe the characteristics of the pain (e.g., intermittent versus constant, sharp versus dull, etc.), lab tests and X-rays that identify the cause of the pain are much more important in the diagnosis and clinical management of the condition. In most disciplines within modern medicine, diagnostic systems have moved from a symptom-based nosology to classification systems that consider clinical findings (particularly when screening for a condition) but put relatively more emphasis on laboratory results, often requiring them before making a definitive diagnosis. Psychiatry is currently in a transitional period. To move along the trajectory more quickly, increased research emphasis needs to be placed on identifying the genetic and biological mechanisms underpinning mental disorders, and more discussion and debate is needed to decide how best to use this information to supplement or subclassify clinical diagnoses. [8] At present, the calcium-channel activity gene story is the 'hot' research topic in genetic studies of psychiatric disorders; several studies have confirmed its role in a variety of mental disorders, suggesting that it could be a general biomarker for the onset of a wide range of psychiatric conditions. …

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