Altered amygdala connectivity within the social brain in schizophrenia.

BACKGROUND: Impairments in social cognition have been described in schizophrenia and relate to core symptoms of the disorder. Social cognition is subserved by a network of brain regions, many of which have been implicated in schizophrenia. We hypothesized that deficits in connectivity between components of this social brain network may underlie the social cognition impairments seen in the disorder. METHODS: We investigated brain activation and connectivity in a group of individuals with schizophrenia making social judgments of approachability from faces (n = 20), compared with a group of matched healthy volunteers (n = 24), using functional magnetic resonance imaging. Effective connectivity from the amygdala was estimated using the psychophysiological interaction approach. RESULTS: While making approachability judgments, healthy participants recruited a network of social brain regions including amygdala, fusiform gyrus, cerebellum, and inferior frontal gyrus bilaterally and left medial prefrontal cortex. During the approachability task, healthy participants showed increased connectivity from the amygdala to the fusiform gyri, cerebellum, and left superior frontal cortex. In comparison to controls, individuals with schizophrenia overactivated the right middle frontal gyrus, superior frontal gyrus, and precuneus and had reduced connectivity between the amygdala and the insula cortex. DISCUSSION: We report increased activation of frontal and medial parietal regions during social judgment in patients with schizophrenia, accompanied by decreased connectivity between the amygdala and insula. We suggest that the increased activation of frontal control systems and association cortex may reflect a compensatory mechanism for impaired connectivity of the amygdala with other parts of the social brain networks in schizophrenia.

Lower effective connectivity between amygdala and parietal regions in response to fearful faces in schizophrenia.

Behavioral abnormalities related to processing negative emotions such as fear have been demonstrated in schizophrenia. The amygdala is strongly associated with fear processing, and alterations in amygdala function and structure have been demonstrated in schizophrenia. Further, functional disconnectivity has been attributed as key to the etiology of schizophrenia, with a number of lines of evidence supporting this theory. In the present study, we examine the effective connectivity corresponding to fear processing, from the amygdala to the whole brain, and compare this between patients with schizophrenia and control participants. An implicit facial emotion processing task was performed by 19 patients with schizophrenia and 24 matched controls during fMRI scanning. During the task, participants made gender judgments from facial images with either neutral or fearful emotion. Neural response to fearful images versus neutral was used as contrast of interest to estimate effective connectivity between the amygdala and the whole brain using the psycho-physiological interactions approach. This connectivity was compared between patients with schizophrenia and healthy controls. We show that when looking at fearful compared to neutral faces patients with schizophrenia show significantly reduced effective connectivity from the amygdala to a large cluster of regions including parts of the precuneus and parietal lobe, compared to healthy controls. These regions have been associated with emotion processing and high level social cognition tasks involving self related processing and mental representations about other people. The reduced amygdala connectivity in schizophrenia shown here further illuminates the neural basis for the behavioral abnormalities in emotional and social function found in the disorder.

Effects of the BDNF Val66Met polymorphism on neural responses to facial emotion.

The brain derived neurotrophic factor (BDNF) Val66Met polymorphism has been associated with affective disorders, but its role in emotion processing has not been fully established. Due to the clinically heterogeneous nature of these disorders, studying the effect of genetic variation in the BDNF gene on a common attribute such as fear processing may elucidate how the BDNF Val66Met polymorphism impacts brain function. Here we use functional magnetic resonance imaging examine the effect of the BDNF Val66Met genotype on neural activity for fear processing. Forty healthy participants performed an implicit fear task during scanning, where subjects made gender judgments from facial images with neutral or fearful emotion. Subjects were tested for facial emotion recognition post-scan. Functional connectivity was investigated using psycho-physiological interactions. Subjects were genotyped for the BDNF Val66Met polymorphism and the measures compared between genotype groups. Met carriers showed overactivation in the anterior cingulate cortex (ACC), brainstem and insula bilaterally for fear processing, along with reduced functional connectivity from the ACC to the left hippocampus, and impaired fear recognition ability. The results show that during fear processing, Met allele carriers show an increased neural response in regions previously implicated in mediating autonomic arousal. Further, the Met carriers show decreased functional connectivity with the hippocampus, which may reflect differential retrieval of emotional associations. Together, these effects show significant differences in the neural substrate for fear processing with genetic variation in BDNF.

Overactivation of fear systems to neutral faces in schizophrenia.

BACKGROUND: The amygdala plays a central role in detecting and responding to fear-related stimuli. A number of recent studies have reported decreased amygdala activation in schizophrenia to emotional stimuli (such as fearful faces) compared with matched neutral stimuli (such as neutral faces). We investigated whether the apparent decrease in amygdala activation in schizophrenia could actually derive from increased amygdala activation to the neutral comparator stimuli. METHODS: Nineteen patients with schizophrenia and 24 matched control participants viewed pictures of faces with either fearful or neutral facial expressions, and a baseline condition, during functional magnetic resonance imaging scanning. RESULTS: Patients with schizophrenia showed a relative decrease in amygdala activation to fearful faces compared with neutral faces. However, this difference resulted from an increase in amygdala activation to the neutral faces in patients with schizophrenia, not from a decreased response to the fearful faces. CONCLUSIONS: Patients with schizophrenia show an increased response of the amygdala to neutral faces. This is sufficient to explain their apparent deficit in amygdala activation to fearful faces compared with neutral faces. The inappropriate activation of neural systems involved in fear to otherwise neutral stimuli may contribute to the development of psychotic symptoms in schizophrenia.

Emotional memory in schizophrenia.

Emotionally arousing scenes are better remembered than neutral ones. The biological basis of this emotional memory effect has been studied in lesion and neuro-imaging studies and depends upon an interaction between the amygdala and medial temporal lobe memory systems including the hippocampus. This study sought to investigate whether patients with schizophrenia had performance deficits on emotional memory tasks consistent with abnormal amygdala function. Patients with schizophrenia and matched control subjects were shown scenes with negative, positive and neutral emotional content. Subjects rated the slides according to how emotionally arousing they found them and then performed surprise memory tests at 10 min (recall) and 3 weeks (recall and recognition). Subjects with schizophrenia did not differ from control subjects in their ratings of the slides. However, patients showed a significant loss of the emotional enhancement of recognition memory for both negative and positive scenes. In addition, patients showed an overall deficit in recall memory, with a selective impairment in recall of the most arousing negative slides. These findings are consistent with the view that medial temporal lobe and in particular amygdala function is abnormal in schizophrenia.