Mechanisms
Though the pathophysiology of schizoaffective disorder remains unclear, studies suggest that dopamine, norepinephrine, and serotonin may be factors in the development of the disorder.White matter and Grey Matter  reductions in the right lentiform nucleus, left superior temporal gyrus, and right precuneus, and other areas in the brain are also characteristic of schizoaffective disorder. Deformities in white matter have also been found to worsen with time in individuals with schizoaffective disorder. Due to its role in emotional regulation, researchers believe that the hippocampus is also involved in the progression of schizoaffective disorder. Specifically, psychotic disorders (such as schizoaffective disorder) have been associated with lower hippocampal volumes. Moreover, deformities in the medial and thalamic regions of the brain have been implicated as contributing factors to the disorder as well. Diagnosis
Psychosis as a symptom of a psychiatric disorder is first and foremost a diagnosis of exclusion. So a new-onset episode of psychosis cannot be considered to be a symptom of a psychiatric disorder until other relevant and known medical causes of psychosis are excluded, or ruled out. Many clinicians improperly perform, or entirely miss this step, introducing avoidable diagnostic error and misdiagnosis.An initial assessment includes a comprehensive history and physical examination. Although no biological laboratory tests exist which confirm schizoaffective disorder, biological tests should be performed to exclude psychosis associated with or caused by substance use, medications, toxins or poisons, surgical complications, or other medical illnesses.
But DSM-IV schizoaffective disorder carries an unnecessarily worse prognosis than a "mood disorder with psychotic features" diagnosis, because long-term data revealed that a significant proportion of DSM-IV schizoaffective disorder patients had 15-year outcomes indistinguishable from patients with mood disorders with or without psychotic features, even though the clinical picture at the time of first diagnosis looked different from both schizophrenia and mood disorders.These problems with the DSM-IV schizoaffective disorder definition result in most people the diagnosis is used on being misdiagnosed; furthermore, outcome studies done 10 years after the diagnosis was released showed that the group of patients defined by the DSM-IV and ICD-10 schizoaffective diagnosis had significantly better outcomes than predicted, so the diagnosis carries a misleading and unnecessarily poor prognosis. The DSM-IV criteria for schizoaffective disorder will continue to be used on U.S. board examinations in psychiatry through the end of 2014; established practitioners may continue to use the problematic DSM-IV definition much further into the future also. DSM-5 research directions
The new schizoaffective disorder criteria continue to have questionable diagnostic validity. Questionable diagnostic validity does not doubt that people with symptoms of psychosis and mood disorder need treatment—psychosis and mood disorder must be treated. Instead, questionable diagnostic validity means there are unresolved problems with the way the DSM-5 categorizes and defines schizoaffective disorder. A core concept in modern psychiatry since DSM-III was released in 1980, is the categorical separation of mood disorders from schizophrenia, known as the Kraepelinian dichotomy.