Neural Mechanisms of Negative Symptoms

Abstract

When Kraepelin originally defined and described dementia praecox, he assumed that it was due to some type of neural mechanism. He hypothesised that abnormalities could occur in a variety of brain regions, including the prefrontal, auditory, and language regions of the cortex. Many members of his department, including Alzheimer and Nissl, were actively involved in the search for the neuropathological lesions that would characterise schizophrenia. Although Kraepelin did not use the term ‘negative symptoms', he describes them comprehensively and states explicitly that he believes the symptoms of schizophrenia can be explained in terms of brain dysfunction:“If it should be confirmed that the disease attacks by preference the frontal areas of the brain, the central convolutions and central lobes, this distribution would in a certain measure agree with our present views about the site of the psychic mechanisms which are principally injured by the disease. On various grounds, it is easy to believe that the frontal cortex, which is specially well developed in man, stands in closer relation to his higher intellectual abilities, and these are the faculties which in our patients invariably suffer profound loss in contrast to memory and acquired ability.” Kraepelin (1919, p. 219)

Association of ketamine-induced psychosis with focal activation of the prefrontal cortex in healthy volunteers

“…Perhaps the acute onset of these symptoms is an energy-demanding state reflected in activation in brain imaging studies, whereas chronic symptoms relate to relative decrements in blood flow and glucose utilization. Support for this hypothesis comes from investigations in schizophrenic patients which have demonstrated that prefrontal activation is associated with the acute onset of specific psychotic symptoms (39,43) and from studies indicating that chronic symptoms, such as negative symptoms, are related to prefrontal hypofunction (40,44,45).…”

Gender differences in the incidence of definite schizophrenia and atypical psychosis — focus on negative symptoms of schizophrenia

“…The biological hypothesis has been canvassed by several other authors (1 1, 28, 62, 63), and it has been suggested that women with schizophrenia are more likely to have a familial form and less likely to have suffered a brain insult at birth (1 1,64). Crow's negative syndrome hypothesis (18) was based on the assumption that negative symptoms were caused by a cumulative neuronal loss, but this original formulation has required modification in the light of subsequent research (65), not least because deficit symptoms appear to occur before and not after the first episode (66).…”

Cortical Blood Flow and Negative Symptoms in Schizophrenia

“…Frontal cortex dysfunction has been widely suggested to underlie 'negative' or 'deficit' symptoms of schizophre nia [1][2][3], and several lines of evidence have demon strated correlations of negative symptoms with frontal cortical abnormalities in schizophrenic patients. Recent studies using single-photon emission computed tomogra phy and positron emission tomography have supported a correlation between severity of negative symptoms and decreased activation of the frontal region with different cognitive tasks for frontal cortex activation [4][5][6][7], Various studies using measurement of regional cerebral blood flow (rCBF) with xenon-133 have shown decreased frontal flow in schizophrenic patients compared to normal con trols [5], but none of these studies have investigated the relation of this hypofrontality to negative symptoms.…”