Neuropsychiatric aspects of schizophrenia

Abstract

Cognitive and affective deficits are prominent clinical features of schizophrenia that impact functioning and are a challenge to effective treatment. The integration of functional magnetic resonance imaging (fMRI) with cognitive and affective neuroscience paradigms enables examination of the brain systems underlying domain-specific behavioral deficits manifested in schizophrenia. There has been a marked increase in the number of studies that apply fMRI in neurobiological studies of schizophrenia. This article highlights phenotypic features of schizophrenia that emerge from these studies and provides a neuropsychiatric perspective. Such efforts have helped elucidate potential neural substrates of deficits in cognition and affect in schizophrenia by providing measures of activation to neurobehavioral probes and connectivity among brain regions. Studies have demonstrated abnormalities at early stages of sensory processing that may influence downstream abnormalities in more complex evaluative functioning. The methodology can help bridge integration with neuropharmacologic, genomic, and neurorehabilitation investigations.

Figure 1

The profile of neurocognitive deficits in schizophrenia at intake (Time 1) and 18 months follow‐up (Time 2). ABF, abstraction and mental flexibility; ATT, attention; VMEM, verbal memory; LAN, language; SPA, spatial processing; SEN, sensory; MOT, motor *P < 0.05 **P < 0.01.

Figure 2

Examples of stimuli used in “oddball” studies of attentional processing (top) and contrast images of patients with schizophrenia and comparison subjects for target and novel stimuli. Greater activation in patients is depicted by the blue scale, whereas greater activation in comparison subjects is shown by the red scale. Images are in radiological convention (left hemisphere to viewer's right). (Reprinted with permission from Gur et al. 2007).

Figure 3

The neurobehavioral profile in patients with flat affect (FA), evaluated by the SANS, and no flat affect (NFA). ABF, abstraction and mental flexibility; ATT, attention; VMEM, verbal memory; FME, face memory; LAN, language; SPA, spatial processing; SM, sensory‐motor; EMO, average emotion processing tests. (Reprinted with permission from Gur et al. 2006).

Figure 4

Regions activated for emotion identification task relative to baseline (block analysis) in controls (upper row), patients (middle row), and the controls–patients contrast (bottom row). No patients–controls contrast survived correction. Significance thresholds are based on spatial extent using a height of z≥ 3.1 and a cluster probability of P≤ 0.05. Images are displayed over a Talairach‐normalized template in radiological convention (left hemisphere to viewer's right). The z‐level coordinates are provided. AM indicates amygdala; IF (47), inferior frontal (Brodmann area 47); HI, hippocampus; IF (45), inferior frontal (Brodmann area 45); and TH, thalamus. (Reprinted with permission from Gur et al. 2007).

Figure 5

Association between brain activity and clinical measures. (A) Correlations between event‐related activation for the four emotional expressions in activated regions and severity of clinical ratings for flat affect. (B) Scatterplot of the association between percentage of signal change for the appearance of fear expressions and severity of flat affect. MO, Mid‐occipital; FG, fusiform gyrus. Other abbreviations as in Figure 5. (Reprinted with permission from Gur et al. 2007).