Schizophrenia Neurobiological correlates

Postmortem and neuroimaging studies have provided evidence of structural and physiological abnormalities in the brains of patients with schizophrenia. Studies using neuroimaging techniques, studies investigating cognitive impairment, genetic investigations and studies of response to treatment have made advancements in identifying the correlates of the neurobiology and symptoms of schizophrenia.

Neuroimaging studies

Neuroimaging has been used to investigate neuroanatomy and neurofunctioning in schizophrenia. Computerized tomography (CT) permitted the first systematic investigations of brain structure in schizophrenia, providing an opportunity to investigate relationships between symptomotology and structure. In this first phase of neuroimaging, investigators attempted to validate the positive and negative subtypes. Enlarged ventricles were associated with more severe negative symptoms as well as more cognitive impairment and greater impairment in premorbid functioning (Johnstone et al. 1976; Weinberger et al. 1980; Andreasen et al. 1982).

Further advancement of technology has provided magnetic resonance imaging (MRI), which allows for high levels of contrast between grey and white matter and cerebrospinal fluid through superior resolution capabilities. Functional neuroimaging allows for the exploration of relationships between symptomatology and dysfunction of specific brain regions. Earlier work used single photon emission computerized tomography (SPECT), while more recent studies utilized positron emission tomography (PET), both of which measure cerebral blood flow. Another method, functional magnetic resonance imaging (fMRI), uses the paramagnetic effects of deoxyhaemoglobin to measure regional blood flow and metabolic activity.

During the second phase of neuroimaging, investigators attempted to identify areas of impaired performance linked with the symptom dimensions in schizophrenia. Liddle et al. examined the three symptom clusters (reality distortion, disorganized symptoms and psychomotor poverty), finding increased cerebral blood flow present in left mesiotemporal structures in patients with hallucinations and delusions as well as increased flow in the right anterior cingulate cortex, left superior temporal gyrus and dorsomedial thalamus. In contrast, a relative decrease in blood flow was observed in the left prefrontal and parietal cortex among patients exhibiting the negative symptom of psychomotor poverty (Friston et al. 1992; Liddle et al. 1992). A number of imaging studies have linked hypofrontality of the frontal lobe with increased negative symptoms in patients with schizophrenia (Volkow et al. 1987; Andreasen et al. 1992, 1994; Wolkin et al. 1992; Schroeder et al. 1995). Other work using PET imaging to assess cerebral blood flow in relation to negative symptom measures was completed by Tamminga et al. (1992), similarly demonstrating decreased cerebral metabolism in frontal and parietal cortex as well as thalamic areas associated with the severity of negative symptoms.