Diagnosis and Classification of the Schizophrenia Spectrum Disorders

188 A.R. Rădulescutreatment can be used to provide external inhibitory control over the system,but the intrinsic dynamics quite possibly remains in the unstable regime and ismore prone to relapses. We finally discuss this work’s overreaching goal: developinga neurophysiology-based quantitative chart of brain architecture profiling,usable by clinicians to complement the current behavior-based DSM diagnosticmethods.Keywords Limbic dysregulation · Critical state · Complex systems · Nonlineardynamics · Mathematical modeling · Functional imagingBackground and SignificanceSchizophrenia – A Complex Unsolved ProblemSchizophrenia is a severe mental disorder with a devastating impact on social functioning(having been associated with significantly increased risk for homelessness[1], suicide [2], unemployment [3], and substance abuse [4]). It is a relatively commonillness, affecting annually 1.1% of the population, over 65 million peopleworldwide and 2.2 million in the United States alone [5]. Studies over the past twodecades have found it to be a neurodegenerative disease [6, 7], affecting not only thestructure and function of various cortical and subcortical regions involved in cognitive,emotional and motivational aspects of behavior [8, 9], but also the autonomic[10, 11] and endocrine [12] systems.There are three primary types of clinical manifestations: “negative symptoms”(poverty of quantity or content of speech, flatness of affect, disturbances of volition,catatonia), “positive symptoms” (hallucinations and delusions, disorganized thinkingand behavior, agitation) [13, 14] and cognitive disruption. It has been arguedthat all types of symptoms could be primary to the disease process [15], yet theyhave different development of and prognoses [16], and are not mutually exclusive(many, but not all patients have components of each).This clinical, pathophysiological and etiological heterogeneity has helpedschizophrenia resist many attempts to provide a simple explanation, or establisha disease etiology. The diagnostic criteria, periodically revised in the DiagnosticStatistical Manual [17], are consensually based upon statistically common behavioralsymptoms. Establishing precisely the meaning and severity of these symptomsis not ideal for clinical decisions, since they are often compatible with other diagnoses(e.g., bipolar mania, delusional disorder or psychotic depression). In addition,symptom-based decisions cannot be made until such symptoms develop, which mayalready be too late for optimal intervention [18]. The treatment, typically combiningmedication and therapy, relies on these diagnoses and is often trial-and-error. Atpresent, there is no generically sustainable cure for schizophrenia; despite pharmacologicalprogress, the drugs that are being used may only treat the symptoms of thedisease rather than its cause.