Researchers say they've gained a new understanding of the neurophysiological basis of cognitive and emotional symptoms seen in schizophrenia.
Schizophrenics exhibit both positive symptoms including delusions and hallucinations and negative symptoms of cognitive deficits and an impairment of emotional drive.
It's the severity of those negative symptoms that mainly determines the long-term prognosis for a schizophrenia patient, which is why scientists have urgently sought a better understanding of their source and causes, the researchers say.
That lack of understanding is one reason the shortened average life span of about 25 years for schizophrenia patients has remained largely unimproved in recent decades, they say.
Now a German and American team, using a schizophrenia mouse model of the disease, say they've identified reduced electrical activity of certain dopamine neurons in the midbrain crucial for cognitive and emotional processing.
While acute psychotic states of schizophrenia, a severe psychiatric illness that strikes around one percent of the global population, can by successfully treated using antipsychotic drugs, the cognitive deficits and impairment of emotional motivation have not responded well to such drug therapy, the researchers note.
"In order to develop new therapy strategies we need an improved neurobiological understanding of the negative symptoms of schizophrenia" explains Jochen Roeper of the Institute for Neurophysiology of the Goethe University.
To improve that understanding, the researchers created genetically modified mice as a schizophrenia model that displayed typical symptoms of impairment in working memory and corresponding neurochemical changes in dopamine in the brain's prefrontal cortex.
They were able to detect altered patterns and frequencies of electrical activity in the dopamine midbrain neurons responsible for emotional and cognitive processing, they report in the Proceedings of the National Academy of Sciences.
In contrast, dopamine neurons in adjacent brain areas, which are involved in motor control, did not show such affects, they said.
The altered electrical activity of the affected neurons persisted even after the genetic modification was "switched off" in adult mice, the researchers said, which is in line with the long-term persistence seen in cognitive deficits in schizophrenia.
"This result emphasizes the presence of a critical early phase for the development of cognitive deficits in schizophrenia," Roeper says. "Our results show that altered neuronal activity of selective dopamine neurons is crucial for schizophrenia."
