Individuals with schizoaffective disorder have schizophrenia alongside a mood disorder. It has been suggested that these two similar disorders may have a similar root cause: a chemical imbalance in the brain. Dopamine is an inhibitory neurotransmitter that is involved in the diagnostics of schizophrenia. The dopamine hypothesis states that abnormalities of dopamine in the prefrontal and mesolimbic parts of the brain occur in schizophrenia. Dopamine is created in the ventral tegmental and substantia nigra sections of the brain. Positive symptoms of schizophrenia (such as delusions and hallucinations) are caused by an increased subcortical release of dopamine. Negative schizophrenia symptoms (anhedonia, speech impediments) result from reduced dopamine receptor activation in the prefrontal cortex, as well as decreased activity in the nucleus caudatus.

The role of dopamine in schizophrenia (and how it relates to schizoaffective disorder)

A neurological disease (and an autoimmune disease) where the body forms antibodies against the brain's NMDA receptors. The antibodies produced disrupt normal brain activity, causing swelling in the brain (encephalitis). Some patients also have a tumor that is correlated with this disease; most commonly an ovarian teratoma. Symptoms of anti-NMDA receptor encephalitis are as follows: behavior (hallucinations, paranoia), cognition, speech disorder, memory deficit, movement disorder (abnormal movements), seizures, autonomic dysfunction, and loss of consciousness. It is not known exactly what causes this disease, but it is likely environmental and genetic factors that can cause individuals to be more susceptible to this disease. 

anti-NMDA Receptor Encephalitis

A study of brain structural changes analyzed schizoaffective disorder, and how similar they are to those seen in schizophrenia and bipolar disorder. A group of healthy control subjects was compared with each patient group and discovered that patients with schizophrenia and schizoaffective disorder had coinciding and widespread volume reduction in the brain. Other patients with bipolar disorder did not have these significant reductions in volume. Further analysis uncovered that patients with schizoaffective disorder tended to show a widespread area of gray matter reduction similar to the schizophrenia patient observations. Observed gray matter reductions were more extreme in patients with schizoaffective disorder and schizophrenia than those with bipolar disorder. This suggests that schizoaffective disorder more closely resembles schizophrenia than bipolar disorder (in terms of structural gray matter brain imbalances and abnormalities).

Brain structural alterations in schizoaffective disorder compared to schizophrenia and bipolar disorder

The original dopamine hypothesis proposes the idea that schizophrenia is caused by hyperactive dopamine transmission. The positive symptoms of schizophrenia are caused by increased subcortical dopamine release,  and the negative symptoms are caused by reduced dopamine (D1) receptor activation in different areas of the brain. The new revised dopamine hypothesis also suggests hyperactive dopamine transmission in mesolimbic areas and hypoactive dopamine transmission in the prefrontal cortex. Further examinations of the brain (positron emission tomography) show the variations of dopamine in various areas of the brain (hippocampus, prefrontal cortex, cingulate cortex, etc). 

History of the Dopamine Hypothesis of Schizophrenia

There is a broad spectrum of disorders similar to schizophrenia (SSDs), with schizophrenia and schizoaffective disorder being the most frequent and consequential. They tend to develop in early adulthood, causing detrimental damage during an important growth period. Auditory verbal hallucinations shared by schizophrenia and schizoaffective disorder describe verbal inputs in the "absence of appropriate external stimuli".  Increased activity in the right rostral prefrontal cortex and left primary auditory cortex was associated with AVH symptoms (Auditory verbal hallucinations). Furthermore, patients with AVHs have been found to have negative correlations between experienced hallucinations and the volume of the superior temporal gyrus. 

Brain differences in patients with schizophrenia spectrum disorders

Schizoaffective disorder is a mental illness with symptoms similar to schizophrenia. This condition occurs when an individual has schizophrenia and other mood disorders. Similarly to schizophrenia, experts believe that this disorder may be caused by a chemical imbalance in the brain (dopamine, norepinephrine, or serotonin). Furthermore, genetic susceptibility may be a factor as well, as this schizoaffective disorder runs in families. Individuals who use psychoactive drugs (like LSD) have also developed schizophrenia/psychosis.

University of Illinois at Chicago

These spectrum disorders tend to be chronic illnesses that cause severe communal and personal side effects. SSDs (schizophrenia spectrum disorders) display symptoms similar to psychotic symptomatology, such as hallucinations, speech changes, and delusions. Out of all these disorders, schizoaffective disorder and  schizophrenia tend to occur the most often (whether it is in adolescence or early adulthood). Both of these disorders display a significant overlap in clinical symptoms, leading some research to question whether they are distinct or not. 

Schizophrenia spectrum disorders

Yale Medicine. (2024, July 16). Schizoaffective disorder. Yale Medicine. https://www.yalemedicine.org/conditions/schizoaffective-disorder#:~:text=Experts%20don’t%20yet%20know,dopamine%2C%20norepinephrine%2C%20or%20serotonin. 

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