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Emotion processing, the amygdala, and outcome in schizophrenia
Progress in Neuro-Psychopharmacology & Biological Psychiatry 29 (2005) 840 – 845 www.elsevier.com/locate/pnpbp
Review article
Emotion processing, the amygdala, and outcome in schizophrenia Darius K. Shayegana,*, Stephen M. Stahla,b a
b
Department of Clinical Research, Neuroscience Education Institute, 5857 Owens Ave., Suite 102, Carlsbad, CA 92008, United States Department of Psychiatry, University of California San Diego, 9500 Gilman Drive, Mail Code 0603, La Jolla, CA 92037-0603, United States Accepted 1 March 2005 Available online 31 May 2005
Abstract Schizophrenia is a highly complex disorder characterized by multiple independent domains of disease—namely positive, cognitive, and affective symptom clusters. Functional deficits associated with positive and (more recently) cognitive symptoms, as well as the deconstruction of these symptoms into their corresponding neural circuits, are widely discussed in the literature. To the contrary, while a link between affective symptoms and emotion processing circuitry has been hypothesized, it has been considerably less widely discussed in the literature. Here, we review deficits in the processing of emotion in schizophrenia, the role of the amygdala in the context of these deficits, and the functional implications of this relationship upon patient outcome. D 2005 Elsevier Inc. All rights reserved. Keywords: Affect; Amygdala; Emotion; Outcome; Schizophrenia; Social cognition
Contents 1. Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2. Background: deficits in emotion recognition, processing, and social function 3. Affect recognition, and abnormal amygdalar function in schizophrenia . . . 4. Emotion processing and outcomes . . . . . . . . . . . . . . . . . . . . . . 5. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1. Introduction Schizophrenia is a highly complex illness which may be organized discretely into several independent symptom domains– positive, cognitive, and affective – which functionally restrict the participation of affected individuals in
Abbreviations: ACG, anterior cingulate gyrus; AHC, amygdala-hippocampus complex; DLPFC, dorsolateral prefrontal cortex; fMRI, functional magnetic resonance imaging; MRI, magnetic resonance imaging; OFG, orbitofrontal gyrus; PFC, prefrontal cortex. * Corresponding author. Tel.: +1 760 931 8857; fax: +1 760 931 8713. E-mail address: [email protected] (D.K. Shayegan). 0278-5846/$ - see front matter D 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.pnpbp.2005.03.002
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meaningful social engagement (Stahl, 2002). Each of these different symptom clusters may be linked to alterations in different neuroanatomical and neurochemical systems. For example, positive symptoms of psychosis are presumably associated with excessive dopamine neurotransmission at dopamine D2 receptors in the mesolimbic pathway of the brain. Also, a close relationship between neurocognitive function and dopamine signaling in the dorsolateral prefrontal cortex (DLPFC) has been widely reported (Weinberger, 2003; Cannon et al., 2000; Egan et al., 2001) and continues to receive a great deal of research focus. Finally, there is a hypothesized link between affective symptoms, frontal and mediotemporal structures, but it has been less
D.K. Shayegan, S.M. Stahl / Progress in Neuro-Psychopharmacology & Biological Psychiatry 29 (2005) 840 – 845
widely discussed in the literature. Here, we review deficits in the processing of emotion in schizophrenia, the role of the amygdala in the context of these deficits, and the functional implications of this relationship upon patient outcome in an attempt to connect rapidly evolving scientific findings with the potential for enhancing treatment strategies within the clinical realm.
2. Background: deficits in emotion recognition, processing, and social function in schizophrenia As compared to unaffected individuals, patients with schizophrenia often demonstrate a significant impairment in their ability to identify and accurately interpret emotions from overt sources—including facial expressions (Edwards et al., 2001; Whittaker et al., 2001; Kohler et al., 2000) and articulated statements (Kerr and Neale, 1993). Such deficits do not appear to be related to antipsychotic treatment selection or dose, nor do they appear correlated with age or gender (Kline et al., 1992; Salem et al., 1996; Mattes et al., 1995). Although not all studies of affect recognition in schizophrenia report significant differences between affected individuals and controls (Flack et al., 1997), it has been suggested that the inconsistency of such findings may be explained by the diversity of symptom profiles observed to manifest in patients with psychotic illness (Abdi and Sharma, 2004). In addition to having problems identifying emotional information, patients with schizophrenia also demonstrate deficits in emotion processing, emotional experience, and behavior with an apparent emphasis on the decoding and encoding of negative emotions (Bell et al., 1997; Bellack et al., 1996), failure to appropriately interpret overtly fearful stimuli (Edwards et al., 2001) as well as a tendency to recognize ambiguous stimuli as being harmful or threatening (Phillips et al., 2000)—the latter deficit resembling symptoms associated with the decreased fear response threshold observed in anxiety and post traumatic stress disorders theoretically linked to malfunctioning neural circuits involving the amygdala (Kent and Rauch, 2003). Accordingly, impairments in emotion perception and processing have been closely associated with the inability of many schizophrenic patients to interpret various social cues appropriately and in proper context with respect to a given social situation (Mueser et al., 1996). Affected individuals experiencing paranoid symptoms have been reported to exhibit marked distortions in judgment and reasoning, particularly when processing of emotional information is required (Mujica-Parodi et al., 2000; Young and Bentall, 1997). Impairment of these faculties has been described to result in the formation of social cognitive biases, such as the tendency to judge people more negatively, as well as conclude that others hold strong unfavorable impressions of them (Iqbal et al., 2000). These biases in judgment and reasoning are consistent with the
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profile of paranoid symptoms associated with schizophrenia, and are thought to contribute to problems with emotion perception in patients presenting with this subtype of psychotic illness (Peer et al., 2004; Combs and Penn, 2004). Interestingly, in the absence of pronounced paranoia, persecutory delusions, and hallucinations, patients with schizophrenia appear to show considerably better performance in their ability to more accurately recognize and make social judgments from facial expressions—as compared to individuals predominantly experiencing such symptoms (Hall et al., 2004). However, even with the burden of positive symptoms reduced, patients still possess marked difficulty in their ability to derive accurate, corresponding social judgments in common, real-world situations. As a consequence, despite the lack of overwhelming positive symptoms of psychosis – arguably the most treatable symptom domain of schizophrenia at present –affected patients often continue to pilfer contextually inappropriate information from situations that unaffected persons do not. Clues as to the potential sources underlying the aforementioned disability can be found in the emotional machinery of the amygdala.
3. Affect recognition, and abnormal amygdalar function in schizophrenia Brain structures and networks involved in the processing of emotion are numerous and extensive in terms of their connectivity and distribution. Phillips et al. (2003a,b) provide an elaborate characterization of neural structures believed to play a crucial role in a hypothesized, three process model underlying emotion perception—identification of the emotional significance of a stimulus, the production of an affective state, and the effortful regulation of the resulting affective state. In this model, a predominantly ventral system – ventrolateral prefrontal cortex (PFC), orbitofrontal cortex (OFC), ventral anterior cingulate gyrus (ACG), amygdala, insula, thalamus, ventral striatum, and brainstem nuclei – is important for appraisal and identification of emotive stimuli, and generation of an appropriate corresponding emotional response, which may involve autonomic response regulation (Phillips et al., 2003b). This is in contrast to the predominantly dorsal system (i.e. dorsolateral PFC, dorsomedial PFC, dorsal ACG, and hippocampus structures) thought to be responsible for marshaling the necessary cognitive resources employed to maintain the resultant emotional response, including the ability to modulate this behavior effectively to meet contextual demands posed by the environment and one’s internal goals (Phillips et al., 2003a; Lane, 2000). In agreement with predictions of the hypothetical Phillips et al. (2003a,b) model, clinical findings of altered functioning of mediotemporal structures (the amygdala in particular) present in schizophrenia appear to support the hypothesized relationship between such functional abnormalities and the
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emotion perception and processing deficits described previously. Patients with schizophrenia demonstrate marked functional anomalies, failing to activate their amygdala in response to sad, aversive, or threatening stimuli (Takahashi et al., 2004; Schneider et al., 1998; Phillips et al., 1999; Taylor et al., 2002; Williams et al., 2004) (Fig. 1). A recent simultaneous functional magnetic resonance imaging (fMRI) and skin conductance arousal recording study reported a pattern of heightened autonomic responsivity concomitant with amygdala underactivation, predominant in paranoid versus non-paranoid patients, suggesting a potential relationship with disconnectivity between arousal and amygdala-prefrontal circuitry, and the inability of paranoid patients to effectively process fearful or threatening stimuli (Williams et al., 2004). Moreover, patients with schizophrenia experiencing persecutory delusions are shown to misinterpret various social and ambiguous, non-threatening information as threatening signals, though whether or not the amygdala is actively engaged during such responses is presently not well studied (Phillips et al., 2000) (Fig. 2). Patients with anxiety disorders also exhibit abnormal neuronal activation of the amygdala in the processing of fear (Rauch et al., 2003; Kent and Rauch, 2003). This may provide relevant insight into deficits in aversive conditioning observed to manifest as abnormal neuronal activation of the amygdala in schizophrenia as well (Kosmidis et al., 1999; Hofer et al., 2001). Further supporting the hypothesized relationship between abnormal amygdala functioning and affect recognition/ emotion processing deficits present in schizophrenia is a
large body of evidence from individuals who do not have schizophrenia, but who have incurred damage to their amygdala (either complete or partial) and who show similar impairment in their ability to assess basic emotions from facial expressions (Aggleton and Shaw, 1996). In particular, difficulty of interpretation exhibited by these subjects also resembles bias towards (although not limited to) negatively charged emotions, such as sad mood and fear (Adolphs, 2003). Such evidence, for the most part, support findings of structural abnormalities of the amygdala in patients with schizophrenia who have impaired emotion recognition and processing deficits. Specifically, differences in amygdaloid volume –either decreased or increased –have been reported in patients with schizophrenia as compared to normal control subjects (Harrison, 1999; Nelson et al., 1998; Shenton et al., 2001; Wright et al., 2000). It has been suggested that factors such as antipsychotic treatment, illness subtype, chronicity of the illness, handedness, and gender of study participants may play a large role in explaining such differences. Additionally, it has been recently reported by Lawrie et al. (2003), that the size of the amygdala-hippocampus complex (AHC) in individuals considered at high risk for developing schizophrenia is larger than in first episode patients with schizophrenia, yet significantly smaller than in normal subjects (Lawrie et al., 2003). Functional imaging analysis dissociating the AHC complex into its constituent parts also confirm the presence of abnormal amygdaloid volume existing in the early phases of schizophrenia, prior to and in the absence of antipsychotic treatment (Joyal et al., 2003). Significantly decreased
Fig. 1. An artist’s representation of amygdala activation in response to provocative fearful and threatening stimuli. Note that the schizophrenic patient fails to activate their amygdala when presented with the spider. On the contrary, the normal subject appraises and interprets the stimulus as potentially harmful or threatening, activating their amygdala in the processing of this information, as well as portions of their dorsal anterior cingulate cortex in the generation of the corresponding behavior.
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Fig. 2. An artist’s representation of amygdala activation in response to an otherwise ambiguous, or non-emotive stimuli. Notice that the schizophrenic patient interprets a threatening signal in reaction to viewing the chair, hypothetically engaging their amygdala while generating a fear response. The normal subject, however, perceives no threat from the stimulus, and reacts accordingly.
bilateral activation of the AHC has also been associated with affect labeling (Hempel et al., 2003).
4. Emotion processing and outcomes Many psychiatric illnesses are comprised of multiple symptoms, many of which are often observed to manifest differently from one patient to the next. Treatment response and outcomes in patients suffering from these illnesses can also be difficult to predict. Recent advances in science and technology are beginning to provide a more detailed description of associations between complex mental disorders and their potential biological underpinnings. Specifically, participation of the amygdala has been described as ‘‘required for cognitive and behavioral processes to obtain access to the current motivational value of a stimulus.’’ (Adolphs, 2003) It is known for a fact that the amygdala is involved in the processing of motivational properties of stimuli (Adolphs, 2001), and related social characteristics associated with such stimuli (Adolphs, 2003). The importance of the amygdala in one’s ability to appraise and interpret affective qualities belonging to various stimuli (both auditory and visual) is perhaps best represented in the impairment of this ability associated with alterations in amygdalar structure and function as demonstrated in numerous lesion, post-mortem, and magnetic resonance imaging (MRI) studies (Harrison, 1999; Joyal et al., 2003; Wright et al., 2000; Gur et al., 2002; Williams et al., 2004; Takahashi et al., 2004).
Problems with the ability to derive an understanding of the relationship between oneself and others, and to then use this knowledge to modulate one’s corresponding social behavior (i.e. social cognition, (Adolphs, 2001) pierce everyday settings and situations, handicapping both the acutely ill and recovering schizophrenic patients to differing degrees. Together, such deficits in social cognition ultimately interfere with the ability of patients to make appropriate sense of themselves and others in the world around them (Fiske, 1993). For example, it may be considerably less controversial to think that more overtly recognizable social misinterpretations, such as the unanticipated suspicion and disgust expressed by an acutely psychotic patient in reaction to a compliment paid by a family member, may significantly obstruct the return of such patients into the workplace, community, and family life. However, would-be softer consequences of lingering social decoding deficits in stable, recovering patients – the inability to appropriately identify humor in a joke, for example, and the subsequent failure to join fellow coworkers in a bout of laughter, etc. – also appear to take their toll on functional outcome in schizophrenia. Deconstructing the domain of social cognition into its constituent parts allows the parent process to be viewed as the product of various neurocognitive functions operating within social and interpersonal situations (Brekke et al., 2001; Lysaker and Davis, 2004). As the relationship between neurocognitive function and patient outcome becomes clearer, in that those patients who are able to improve aspects of cognition –executive function, working memory, atten-
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tion, verbal learning, among others– ultimately obtain best outcomes in schizophrenia, it may be conceivable, yet controversial, to think that concurrent improvement in social knowledge and functioning contributes to obtaining enhanced outcome to some degree. In fact, recent studies of neurocognitive function in patients with schizophrenia have suggested that improvements in various aspects of cognitive functioning may be linked with better vocational and quality of life outcomes (Green et al., 2000; McGurk and Mueser, 2004; McGurk et al., 2004). It has also been specifically suggested that problems interpreting emotionally charged information in schizophrenia could be attributed to impairment in more basic neurocognitive domains (Bozikas et al., 2004), and that the ability to process emotions is a key determinant of work functioning/independent living for individuals coping with schizophrenia (Kee et al., 2003). Together, these findings suggest that perhaps insight into the neurobiological mechanisms underlying affect recognition and emotion processing in schizophrenia may be an important first step towards gaining a clinical advantage with respect to targeting improvement of neurocognitive and social function, and thus of obtaining best outcomes.
5. Conclusion The impact emotion processing deficits have on outcome in schizophrenia is not yet known. Nevertheless, insight into the relationship between impaired emotion perception, social knowledge and functioning, and patient quality of life continues to grow through accumulating experimental evidence, and clinical recognition. The approach of deconstruction –namely of symptoms into circuits, and complex behaviors into constituent parts – has facilitated the linking of deficits in emotion processing to neurobiology, both functional and structural. Such an approach helps to make potentially relevant clinical connections between such impairments and patient outcome more apparent, if not better accessible for exploration. Interestingly, recent compelling evidence for obtaining enhanced outcome in schizophrenia through the improvement of cognitive deficits may support the hypothesis that similar improvements in impaired affective processes, such as emotion processing and social cognition, might also contribute beneficially upon patient outcome. Whether any such pro-emotion processing improvements actually exist, it is difficult to dispute the potential importance of their additive role in the multimodal treatment approach of schizophrenia—targeting the collective improvement of positive, cognitive, and affective symptom domains.
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Review article
Emotion processing, the amygdala, and outcome in schizophrenia Darius K. Shayegana,*, Stephen M. Stahla,b a
b
Department of Clinical Research, Neuroscience Education Institute, 5857 Owens Ave., Suite 102, Carlsbad, CA 92008, United States Department of Psychiatry, University of California San Diego, 9500 Gilman Drive, Mail Code 0603, La Jolla, CA 92037-0603, United States Accepted 1 March 2005 Available online 31 May 2005
Abstract Schizophrenia is a highly complex disorder characterized by multiple independent domains of disease—namely positive, cognitive, and affective symptom clusters. Functional deficits associated with positive and (more recently) cognitive symptoms, as well as the deconstruction of these symptoms into their corresponding neural circuits, are widely discussed in the literature. To the contrary, while a link between affective symptoms and emotion processing circuitry has been hypothesized, it has been considerably less widely discussed in the literature. Here, we review deficits in the processing of emotion in schizophrenia, the role of the amygdala in the context of these deficits, and the functional implications of this relationship upon patient outcome. D 2005 Elsevier Inc. All rights reserved. Keywords: Affect; Amygdala; Emotion; Outcome; Schizophrenia; Social cognition
Contents 1. Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2. Background: deficits in emotion recognition, processing, and social function 3. Affect recognition, and abnormal amygdalar function in schizophrenia . . . 4. Emotion processing and outcomes . . . . . . . . . . . . . . . . . . . . . . 5. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1. Introduction Schizophrenia is a highly complex illness which may be organized discretely into several independent symptom domains– positive, cognitive, and affective – which functionally restrict the participation of affected individuals in
Abbreviations: ACG, anterior cingulate gyrus; AHC, amygdala-hippocampus complex; DLPFC, dorsolateral prefrontal cortex; fMRI, functional magnetic resonance imaging; MRI, magnetic resonance imaging; OFG, orbitofrontal gyrus; PFC, prefrontal cortex. * Corresponding author. Tel.: +1 760 931 8857; fax: +1 760 931 8713. E-mail address: [email protected] (D.K. Shayegan). 0278-5846/$ - see front matter D 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.pnpbp.2005.03.002
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meaningful social engagement (Stahl, 2002). Each of these different symptom clusters may be linked to alterations in different neuroanatomical and neurochemical systems. For example, positive symptoms of psychosis are presumably associated with excessive dopamine neurotransmission at dopamine D2 receptors in the mesolimbic pathway of the brain. Also, a close relationship between neurocognitive function and dopamine signaling in the dorsolateral prefrontal cortex (DLPFC) has been widely reported (Weinberger, 2003; Cannon et al., 2000; Egan et al., 2001) and continues to receive a great deal of research focus. Finally, there is a hypothesized link between affective symptoms, frontal and mediotemporal structures, but it has been less
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widely discussed in the literature. Here, we review deficits in the processing of emotion in schizophrenia, the role of the amygdala in the context of these deficits, and the functional implications of this relationship upon patient outcome in an attempt to connect rapidly evolving scientific findings with the potential for enhancing treatment strategies within the clinical realm.
2. Background: deficits in emotion recognition, processing, and social function in schizophrenia As compared to unaffected individuals, patients with schizophrenia often demonstrate a significant impairment in their ability to identify and accurately interpret emotions from overt sources—including facial expressions (Edwards et al., 2001; Whittaker et al., 2001; Kohler et al., 2000) and articulated statements (Kerr and Neale, 1993). Such deficits do not appear to be related to antipsychotic treatment selection or dose, nor do they appear correlated with age or gender (Kline et al., 1992; Salem et al., 1996; Mattes et al., 1995). Although not all studies of affect recognition in schizophrenia report significant differences between affected individuals and controls (Flack et al., 1997), it has been suggested that the inconsistency of such findings may be explained by the diversity of symptom profiles observed to manifest in patients with psychotic illness (Abdi and Sharma, 2004). In addition to having problems identifying emotional information, patients with schizophrenia also demonstrate deficits in emotion processing, emotional experience, and behavior with an apparent emphasis on the decoding and encoding of negative emotions (Bell et al., 1997; Bellack et al., 1996), failure to appropriately interpret overtly fearful stimuli (Edwards et al., 2001) as well as a tendency to recognize ambiguous stimuli as being harmful or threatening (Phillips et al., 2000)—the latter deficit resembling symptoms associated with the decreased fear response threshold observed in anxiety and post traumatic stress disorders theoretically linked to malfunctioning neural circuits involving the amygdala (Kent and Rauch, 2003). Accordingly, impairments in emotion perception and processing have been closely associated with the inability of many schizophrenic patients to interpret various social cues appropriately and in proper context with respect to a given social situation (Mueser et al., 1996). Affected individuals experiencing paranoid symptoms have been reported to exhibit marked distortions in judgment and reasoning, particularly when processing of emotional information is required (Mujica-Parodi et al., 2000; Young and Bentall, 1997). Impairment of these faculties has been described to result in the formation of social cognitive biases, such as the tendency to judge people more negatively, as well as conclude that others hold strong unfavorable impressions of them (Iqbal et al., 2000). These biases in judgment and reasoning are consistent with the
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profile of paranoid symptoms associated with schizophrenia, and are thought to contribute to problems with emotion perception in patients presenting with this subtype of psychotic illness (Peer et al., 2004; Combs and Penn, 2004). Interestingly, in the absence of pronounced paranoia, persecutory delusions, and hallucinations, patients with schizophrenia appear to show considerably better performance in their ability to more accurately recognize and make social judgments from facial expressions—as compared to individuals predominantly experiencing such symptoms (Hall et al., 2004). However, even with the burden of positive symptoms reduced, patients still possess marked difficulty in their ability to derive accurate, corresponding social judgments in common, real-world situations. As a consequence, despite the lack of overwhelming positive symptoms of psychosis – arguably the most treatable symptom domain of schizophrenia at present –affected patients often continue to pilfer contextually inappropriate information from situations that unaffected persons do not. Clues as to the potential sources underlying the aforementioned disability can be found in the emotional machinery of the amygdala.
3. Affect recognition, and abnormal amygdalar function in schizophrenia Brain structures and networks involved in the processing of emotion are numerous and extensive in terms of their connectivity and distribution. Phillips et al. (2003a,b) provide an elaborate characterization of neural structures believed to play a crucial role in a hypothesized, three process model underlying emotion perception—identification of the emotional significance of a stimulus, the production of an affective state, and the effortful regulation of the resulting affective state. In this model, a predominantly ventral system – ventrolateral prefrontal cortex (PFC), orbitofrontal cortex (OFC), ventral anterior cingulate gyrus (ACG), amygdala, insula, thalamus, ventral striatum, and brainstem nuclei – is important for appraisal and identification of emotive stimuli, and generation of an appropriate corresponding emotional response, which may involve autonomic response regulation (Phillips et al., 2003b). This is in contrast to the predominantly dorsal system (i.e. dorsolateral PFC, dorsomedial PFC, dorsal ACG, and hippocampus structures) thought to be responsible for marshaling the necessary cognitive resources employed to maintain the resultant emotional response, including the ability to modulate this behavior effectively to meet contextual demands posed by the environment and one’s internal goals (Phillips et al., 2003a; Lane, 2000). In agreement with predictions of the hypothetical Phillips et al. (2003a,b) model, clinical findings of altered functioning of mediotemporal structures (the amygdala in particular) present in schizophrenia appear to support the hypothesized relationship between such functional abnormalities and the
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emotion perception and processing deficits described previously. Patients with schizophrenia demonstrate marked functional anomalies, failing to activate their amygdala in response to sad, aversive, or threatening stimuli (Takahashi et al., 2004; Schneider et al., 1998; Phillips et al., 1999; Taylor et al., 2002; Williams et al., 2004) (Fig. 1). A recent simultaneous functional magnetic resonance imaging (fMRI) and skin conductance arousal recording study reported a pattern of heightened autonomic responsivity concomitant with amygdala underactivation, predominant in paranoid versus non-paranoid patients, suggesting a potential relationship with disconnectivity between arousal and amygdala-prefrontal circuitry, and the inability of paranoid patients to effectively process fearful or threatening stimuli (Williams et al., 2004). Moreover, patients with schizophrenia experiencing persecutory delusions are shown to misinterpret various social and ambiguous, non-threatening information as threatening signals, though whether or not the amygdala is actively engaged during such responses is presently not well studied (Phillips et al., 2000) (Fig. 2). Patients with anxiety disorders also exhibit abnormal neuronal activation of the amygdala in the processing of fear (Rauch et al., 2003; Kent and Rauch, 2003). This may provide relevant insight into deficits in aversive conditioning observed to manifest as abnormal neuronal activation of the amygdala in schizophrenia as well (Kosmidis et al., 1999; Hofer et al., 2001). Further supporting the hypothesized relationship between abnormal amygdala functioning and affect recognition/ emotion processing deficits present in schizophrenia is a
large body of evidence from individuals who do not have schizophrenia, but who have incurred damage to their amygdala (either complete or partial) and who show similar impairment in their ability to assess basic emotions from facial expressions (Aggleton and Shaw, 1996). In particular, difficulty of interpretation exhibited by these subjects also resembles bias towards (although not limited to) negatively charged emotions, such as sad mood and fear (Adolphs, 2003). Such evidence, for the most part, support findings of structural abnormalities of the amygdala in patients with schizophrenia who have impaired emotion recognition and processing deficits. Specifically, differences in amygdaloid volume –either decreased or increased –have been reported in patients with schizophrenia as compared to normal control subjects (Harrison, 1999; Nelson et al., 1998; Shenton et al., 2001; Wright et al., 2000). It has been suggested that factors such as antipsychotic treatment, illness subtype, chronicity of the illness, handedness, and gender of study participants may play a large role in explaining such differences. Additionally, it has been recently reported by Lawrie et al. (2003), that the size of the amygdala-hippocampus complex (AHC) in individuals considered at high risk for developing schizophrenia is larger than in first episode patients with schizophrenia, yet significantly smaller than in normal subjects (Lawrie et al., 2003). Functional imaging analysis dissociating the AHC complex into its constituent parts also confirm the presence of abnormal amygdaloid volume existing in the early phases of schizophrenia, prior to and in the absence of antipsychotic treatment (Joyal et al., 2003). Significantly decreased
Fig. 1. An artist’s representation of amygdala activation in response to provocative fearful and threatening stimuli. Note that the schizophrenic patient fails to activate their amygdala when presented with the spider. On the contrary, the normal subject appraises and interprets the stimulus as potentially harmful or threatening, activating their amygdala in the processing of this information, as well as portions of their dorsal anterior cingulate cortex in the generation of the corresponding behavior.
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Fig. 2. An artist’s representation of amygdala activation in response to an otherwise ambiguous, or non-emotive stimuli. Notice that the schizophrenic patient interprets a threatening signal in reaction to viewing the chair, hypothetically engaging their amygdala while generating a fear response. The normal subject, however, perceives no threat from the stimulus, and reacts accordingly.
bilateral activation of the AHC has also been associated with affect labeling (Hempel et al., 2003).
4. Emotion processing and outcomes Many psychiatric illnesses are comprised of multiple symptoms, many of which are often observed to manifest differently from one patient to the next. Treatment response and outcomes in patients suffering from these illnesses can also be difficult to predict. Recent advances in science and technology are beginning to provide a more detailed description of associations between complex mental disorders and their potential biological underpinnings. Specifically, participation of the amygdala has been described as ‘‘required for cognitive and behavioral processes to obtain access to the current motivational value of a stimulus.’’ (Adolphs, 2003) It is known for a fact that the amygdala is involved in the processing of motivational properties of stimuli (Adolphs, 2001), and related social characteristics associated with such stimuli (Adolphs, 2003). The importance of the amygdala in one’s ability to appraise and interpret affective qualities belonging to various stimuli (both auditory and visual) is perhaps best represented in the impairment of this ability associated with alterations in amygdalar structure and function as demonstrated in numerous lesion, post-mortem, and magnetic resonance imaging (MRI) studies (Harrison, 1999; Joyal et al., 2003; Wright et al., 2000; Gur et al., 2002; Williams et al., 2004; Takahashi et al., 2004).
Problems with the ability to derive an understanding of the relationship between oneself and others, and to then use this knowledge to modulate one’s corresponding social behavior (i.e. social cognition, (Adolphs, 2001) pierce everyday settings and situations, handicapping both the acutely ill and recovering schizophrenic patients to differing degrees. Together, such deficits in social cognition ultimately interfere with the ability of patients to make appropriate sense of themselves and others in the world around them (Fiske, 1993). For example, it may be considerably less controversial to think that more overtly recognizable social misinterpretations, such as the unanticipated suspicion and disgust expressed by an acutely psychotic patient in reaction to a compliment paid by a family member, may significantly obstruct the return of such patients into the workplace, community, and family life. However, would-be softer consequences of lingering social decoding deficits in stable, recovering patients – the inability to appropriately identify humor in a joke, for example, and the subsequent failure to join fellow coworkers in a bout of laughter, etc. – also appear to take their toll on functional outcome in schizophrenia. Deconstructing the domain of social cognition into its constituent parts allows the parent process to be viewed as the product of various neurocognitive functions operating within social and interpersonal situations (Brekke et al., 2001; Lysaker and Davis, 2004). As the relationship between neurocognitive function and patient outcome becomes clearer, in that those patients who are able to improve aspects of cognition –executive function, working memory, atten-
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tion, verbal learning, among others– ultimately obtain best outcomes in schizophrenia, it may be conceivable, yet controversial, to think that concurrent improvement in social knowledge and functioning contributes to obtaining enhanced outcome to some degree. In fact, recent studies of neurocognitive function in patients with schizophrenia have suggested that improvements in various aspects of cognitive functioning may be linked with better vocational and quality of life outcomes (Green et al., 2000; McGurk and Mueser, 2004; McGurk et al., 2004). It has also been specifically suggested that problems interpreting emotionally charged information in schizophrenia could be attributed to impairment in more basic neurocognitive domains (Bozikas et al., 2004), and that the ability to process emotions is a key determinant of work functioning/independent living for individuals coping with schizophrenia (Kee et al., 2003). Together, these findings suggest that perhaps insight into the neurobiological mechanisms underlying affect recognition and emotion processing in schizophrenia may be an important first step towards gaining a clinical advantage with respect to targeting improvement of neurocognitive and social function, and thus of obtaining best outcomes.
5. Conclusion The impact emotion processing deficits have on outcome in schizophrenia is not yet known. Nevertheless, insight into the relationship between impaired emotion perception, social knowledge and functioning, and patient quality of life continues to grow through accumulating experimental evidence, and clinical recognition. The approach of deconstruction –namely of symptoms into circuits, and complex behaviors into constituent parts – has facilitated the linking of deficits in emotion processing to neurobiology, both functional and structural. Such an approach helps to make potentially relevant clinical connections between such impairments and patient outcome more apparent, if not better accessible for exploration. Interestingly, recent compelling evidence for obtaining enhanced outcome in schizophrenia through the improvement of cognitive deficits may support the hypothesis that similar improvements in impaired affective processes, such as emotion processing and social cognition, might also contribute beneficially upon patient outcome. Whether any such pro-emotion processing improvements actually exist, it is difficult to dispute the potential importance of their additive role in the multimodal treatment approach of schizophrenia—targeting the collective improvement of positive, cognitive, and affective symptom domains.
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