Turhan Canli

Long story short: the serotonin transporter in emotion regulation and social cognition

The gene encoding the serotonin transporter (5-HTT) contains a regulatory variation that has been associated with anxiety-related traits and susceptibility for depression. Here we highlight recent discoveries related to allelic variation of 5-HTT function with respect to emotion regulation and social behavior, drawing from an interdisciplinary perspective of behavioral genetics and cognitive neuroscience. Following a reductionistic path that leads from gene-behavior association studies to neuroimaging and epigenetic studies, we compare two models of 5-HTT-dependent modulation of brain activity and discuss the role of life stress experience in modifying 5-HTT function in the brain. Integration of these findings suggests that the impact of the 5-HTT gene on behavior is much broader than is commonly appreciated and may have a role in social cognition.

Sex differences in the neural basis of emotional memories

Psychological studies have found better memory in women than men for emotional events, but the neural basis for this difference is unknown. We used event-related functional MRI to assess whether sex differences in memory for emotional stimuli is associated with activation of different neural systems in men and women. Brain activation in 12 men and 12 women was recorded while they rated their experience of emotional arousal in response to neutral and emotionally negative pictures. In a recognition memory test 3 weeks after scanning, highly emotional pictures were remembered best, and remembered better by women than by men. Men and women activated different neural circuits to encode stimuli effectively into memory even when the analysis was restricted to pictures rated equally arousing by both groups. Men activated significantly more structures than women in a network that included the right amygdala, whereas women activated significantly fewer structures in a network that included the left amygdala. Women had significantly more brain regions where activation correlated with both ongoing evaluation of emotional experience and with subsequent memory for the most emotionally arousing pictures. Greater overlap in brain regions sensitive to current emotion and contributing to subsequent memory may be a neural mechanism for emotions to enhance memory more powerfully in women than in men.

An fMRI Study of Personality Influences on Brain Reactivity to Emotional Stimuli

Functional imaging studies have examined which brain regions respond to emotional stimuli, but they have not determined how stable personality traits moderate such brain activation. Two personality traits, extraversion and neuroticism, are strongly associated with emotional experience and may thus moderate brain reactivity to emotional stimuli. The present study used functional magnetic resonance imaging to directly test whether individual differences in brain reactivity to emotional stimuli are correlated with extraversion and neuroticism in healthy women. Extraversion was correlated with brain reactivity to positive stimuli in localized brain regions, and neuroticism was correlated with brain reactivity to negative stimuli in localized brain regions. This study provides direct evidence that personality is associated with brain reactivity to emotional stimuli and identifies both common and distinct brain regions where such modulation takes place.

Amygdala Responses to Emotionally Valenced Stimuli in Older and Younger Adults

As they age, adults experience less negative emotion, come to pay less attention to negative than to positive emotional stimuli, and become less likely to remember negative than positive emotional materials. This profile of findings suggests that, with age, the amygdala may show decreased reactivity to negative information while maintaining or increasing its reactivity to positive information. We used event-related functional magnetic resonance imaging to assess whether amygdala activation in response to positive and negative emotional pictures changes with age. Both older and younger adults showed greater activation in the amygdala for emotional than for neutral pictures; however, for older adults, seeing positive pictures led to greater amygdala activation than seeing negative pictures, whereas this was not the case for younger adults.

Hemispheric asymmetry for emotional stimuli detected with fMRI

CURRENT brain models of emotion processing hypothesize that positive (or approach-related) emotions are lateralized towards the left hemisphere, whereas negative (or withdrawal-related) emotions are lateralized towards the right hemisphere. Brain imaging studies, however, have so far failed to document such hemispheric lateralization. In a functional magnetic resonance imaging (fMRI) study, 14 female subjects viewed alternating blocks of emotionally valenced positive and negative pictures. When the experience of valence was equated for arousal, overall brain reactivity was lateralized towards the left hemisphere for positive pictures and towards the right hemisphere for negative pictures. This study provides direct support for the valence hypothesis, under conditions of equivalent arousal, by means of functional brain imaging.

Neural Bases of Social Anxiety Disorder: Emotional Reactivity and Cognitive Regulation During Social and Physical Threat

CONTEXT Social anxiety disorder is thought to involve emotional hyperreactivity, cognitive distortions, and ineffective emotion regulation. While the neural bases of emotional reactivity to social stimuli have been described, the neural bases of emotional reactivity and cognitive regulation during social and physical threat, and their relationship to social anxiety symptom severity, have yet to be investigated. OBJECTIVE To investigate behavioral and neural correlates of emotional reactivity and cognitive regulation in patients and controls during processing of social and physical threat stimuli. DESIGN Participants were trained to implement cognitive-linguistic regulation of emotional reactivity induced by social (harsh facial expressions) and physical (violent scenes) threat while undergoing functional magnetic resonance imaging and providing behavioral ratings of negative emotion experience. SETTING Academic psychology department. PARTICIPANTS Fifteen adults with social anxiety disorder and 17 demographically matched healthy controls. MAIN OUTCOME MEASURES Blood oxygen level-dependent signal and negative emotion ratings. RESULTS Behaviorally, patients reported greater negative emotion than controls during social and physical threat but showed equivalent reduction in negative emotion following cognitive regulation. Neurally, viewing social threat resulted in greater emotion-related neural responses in patients than controls, with social anxiety symptom severity related to activity in a network of emotion- and attention-processing regions in patients only. Viewing physical threat produced no between-group differences. Regulation during social threat resulted in greater cognitive and attention regulation-related brain activation in controls compared with patients. Regulation during physical threat produced greater cognitive control-related response (ie, right dorsolateral prefrontal cortex) in patients compared with controls. CONCLUSIONS Compared with controls, patients demonstrated exaggerated negative emotion reactivity and reduced cognitive regulation-related neural activation, specifically for social threat stimuli. These findings help to elucidate potential neural mechanisms of emotion regulation that might serve as biomarkers for interventions for social anxiety disorder.

Individual differences in emotion processing

Recent functional brain imaging studies of the neurobiology of emotion have investigated how individual differences among subjects modulate neural responses during emotion processing. Differences in personality, dispositional affect, biological sex, and genotype can all substantially modulate the neural bases of emotion processing in prefrontal, limbic, and other brain regions, across a variety of domains including emotional reactions, emotional memory, and emotion perception. Analysis of individual differences provides a new window into the neurobiology of emotion processing that complements traditional approaches.

Emotional conflict and neuroticism: personality-dependent activation in the amygdala and subgenual anterior cingulate.

The amygdala and subgenual anterior cingulate (AC) have been associated with anxiety and mood disorders, for which trait neuroticism is a risk factor. Prior work has not related individual differences in amygdala or subgenual AC activation with neuroticism. Functional magnetic resonance imaging was used to investigate changes in blood oxygen level-dependent signal within the amygdala and subgenual AC associated with trait neuroticism in a nonclinical sample of 36 volunteers during an emotional conflict task. Neuroticism correlated positively with amygdala and subgenual AC activation during trials of high emotional conflict, compared with trials of low emotional conflict. The subscale of neuroticism that reflected the anxious form of neuroticism (N1) explained a greater proportion of variance within the observed clusters than the subscale of neuroticism that reflected the depressive form of neuroticism (N3). Using a task that is sensitive to individual differences in the detection of emotional conflict, the authors have provided a neural correlate of the link between neuroticism and anxiety and mood disorders. This effect was driven to a greater extent by the anxious relative to the depressive characteristics of neuroticism and may constitute vulnerability markers for anxiety-related disorders.

Analysis of DRD4 and DAT polymorphisms and behavioral inhibition in healthy adults: Implications for impulsivity

Impulsivity, a highly prevalent symptom in multiple psychiatric disorders, is a partially heritable trait influenced by specific biological mechanisms. In particular, dopamine is proposed to play a role in impulsive behaviors and recent studies have implicated functional polymorphisms of dopamine‐related genes in impulsive behaviors across different clinical and behavioral classifications. However, most have not isolated the impulsivity construct per se as a biologically based and measurable endophenotype. The present study was therefore undertaken in a sample of healthy adults to investigate the influence of two candidate dopaminergic gene polymorphisms (DRD4 and DAT) on the endophenotype of impulsivity, which we operationalized as behavioral inhibition during the Stop‐signal task. We recruited an ethnically diverse sample of 119 healthy adults to complete a self‐report questionnaire of impulsivity and to perform a Stop‐signal task. We report significant differences in inhibitory control between individuals with at least one 7‐repeat allele of the DRD4 polymorphism, as well as an interaction between DRD4 and DAT genotypes, on inhibitory control. Results of the present study support the influence of dopaminergic variation on impulsive‐related measures, as well as the advantage of using measures which are likely more sensitive to the effects of such genetic variation.

Amygdala responsiveness is modulated by tryptophan hydroxylase-2 gene variation

Summary.The tryptophan hydroxylase-2 gene (TPH2) codes for the enzyme of serotonin (5-HT) synthesis in the brain and variation of TPH2 has been implicated in disorders of emotion regulation. Here, we used functional magnetic resonance imaging (fMRI) to demonstrate that a potentially functional variant of TPH2 modulates amygdala responsiveness to emotional stimuli of both negative and positive valence.