[3] Associated symptoms occur along a continuum in the population and must reach a certain severity and level of impairment before a diagnosis is made.
[10] DSM-5 also recommends that a better distinction be made between a current condition of schizophrenia and its historical progress, to achieve a clearer overall characterization.
[14] A 2015 systematic review investigated the diagnostic accuracy of first rank symptoms: The DSM-IV-TR contained five sub-classifications of schizophrenia.
[17] The Russian version of the ICD-10 includes additional four sub-classifications of schizophrenia: hypochondriacal (F20.801), cenesthopathic (F20.802), childhood type (F20.803), and atypical (F20.804).
[18] People with schizophrenia often have additional mental health problems such as anxiety, depressive, or substance-use disorders.
[31] Together, the differences in causes, response to treatment and pathophysiology suggest schizophrenia is heterogeneous from an etiological standpoint.
[42] It may be necessary to rule out a delirium, which can be distinguished by visual hallucinations, acute onset and fluctuating level of consciousness, and indicates an underlying medical illness.
[46] Structural alterations have, however, been identified in schizophrenia, most commonly enlarged ventricles, and decreased grey matter volume in the cortex and hippocampus.
[48] In the last decade interest has grown in the use of machine learning to automatically perform the diagnosis task using brain imaging data.
While these algorithms are very robust at distinguishing schizophrenia patients from healthy subjects, they still cannot perform the tasks clinicians struggle the most with – differential diagnosis and treatment selection.
[50] Serum levels of hormones typically active in the hypothalamic pituitary adrenal (HPA) axis, such as cortisol and acetylcholine, have also been correlated with symptoms and progression of schizophrenia.
[51] Cytokines and growth factors are consistently identified as candidates by different studies, but variation in identity and direction of the correlation is common.
[50] In recent years, markers of oxidative stress, epigentic methylation, mRNA transcription, and proteomic expression have also been targets of research, with their potential still to be determined.
[54] Although many genetic variants associated with schizophrenia have been identified, their effects are usually very small, so they are combined onto a polygenic risk score.
[35] An example of a well-studied[44] genetic biomarker in schizophrenia is the single nucleotide polymorphism in the HLA-DQB1 gene, which is part of the human leukocyte antigen (HLA) complex.
[56] There is an argument that the underlying issues would be better addressed as a spectrum of conditions[57] or as individual dimensions along which everyone varies rather than by a diagnostic category based on an arbitrary cut-off between normal and ill.[58] This approach appears consistent with research on schizotypy, and with a relatively high prevalence of psychotic experiences, mostly non-distressing delusional beliefs, among the general public.
[62][63][64] Nancy Andreasen has criticized the current DSM-IV and ICD-10 criteria for sacrificing diagnostic validity for the sake of artificially improving reliability.
[57] Neuropsychologist Michael Foster Green went further in suggesting the presence of specific neurocognitive deficits may be used to construct phenotypes that are alternatives to those that are purely symptom-based.
[67] Citing poor interrater reliability, some psychiatrists have totally contested the concept of schizoaffective disorder as a separate entity.
[70][71] The categorical distinction between mood disorders and schizophrenia, known as the Kraepelinian dichotomy, has also been challenged by data from genetic epidemiology.
[72] As clinicians and researchers become increasingly aware of the limitations of the current diagnostic systems, calls for new nosology are being made.
[74] The European Roadmap for Mental Health Research (ROAMER) funding initiative shares many goals with RDoC.
[75] These initiatives encourage researchers to consider diagnosis as dimensional, instead of a clear-cut between patients and healthy subjects, and to cut across diagnostic boundaries.
[77] Initial efforts in this area have been able to stratify patients along the psychosis continuum into genetically distinct sub types based on their symptoms,[76] brain measures such as EEG,[78][79] and serum biomarker profiles.