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Contents
Contributors vii
1 Genes, brain and emotions: Introduction 1
Andrei C Miu, Judith R Homberg, and Klaus-Peter Lesch
Part 1 Methods and approaches
2 Twin studies of emotion 5
Megan Flom and Kimberly J Saudino
3 Gene–environment interactions in humans across multiple units of analyses: A focus on psychopathology and imaging 18
Suzanne Vrshek-Schallhorn, Bradley M Avery, and Vaibhav Sapuram
4 Epigenetics and twin studies: A review and applications in human aggressive behavior 32
Jenny van Dongen and Dorret I Boomsma
5 Genome-wide association studies 51
Thomas W Mühleisen and Sven Cichon
6 Gene–environment interactions in animal models of depression and anxiety 63
Daniela Felice, Anand Gururajan, Olivia F O’Leary, and John F Cryan
7 Methods and theoretical approaches: Genetic animal models of emotional disorders and convergence with human data 77
Celine L St Pierre, Kayvon Sharif, Emily Funsten, Abraham A Palmer, and Clarissa C Parker
8 Optogenetic and chemogenetic technologies for advanced functional investigations of the neural correlates of emotions 97 Alexandre Surget and Catherine Belzung
Part 2 Cognitive mechanisms
9 Fear learning and extinction 113
Tina B Lonsdorf
10 Emotional action control: The role of serotonin in health and disease 129
Inge Volman, Hanneke Den Ouden, and Karin Roelofs
11 Genetics of emotion regulation: A systematic review 144
Andrei C Miu and Mirela I Bîlc
12 Emotional memory 170
Mana R Ehlers and Rebecca M Todd
13 Genetics of decision-making 188
Joshua C Gray, Sandra Sanchez-Roige, Abraham A Palmer, Harriet de Wit, and James MacKillop
Part 3
Biological mechanisms
14 Missing heritability in studies of trait anxiety and amygdala function: Is the solution in plain sight? 205
Turhan Canli
15 Electrocortical endophenotypes of anxiety 216
Erik M Mueller
16 Imaging genetics in depression 235
Ulrich Rabl and Lukas Pezawas
17 Psychosocial stress and telomere regulation 247
Idan Shalev and Waylon J Hastings
18 Genetic effects on peripheral psychophysiological measures of emotion processing 262
Annette Conzelmann, Paul Pauli, Alexander Prehn-Kristensen, and Tobias Renner
Part 4 Disorders and therapy
19 The genetics of personality/psychopathology: A brief review of constructs, results, approaches, and implications 275
Thomas J Bouchard, Jr, Wendy Johnson, and Irving I Gottesman
20 Resilience 286
Rebecca Alexander and Justine Megan Gatt
21 Understanding risk and resilience in maltreated children: Emerging findings from translational, genetic, neuroimaging, and treatment studies 304
Joan Kaufman, Janitza L Montalvo-Ortiz, and Richard S Lee
22 Animal models of post-traumatic stress disorder: Towards understanding of individual differences 324
Lisa Heltzel and Judith R Homberg
23 Genetics of impulsivity, anger, and aggression as risk factors for suicidal behavior 343
Dan Rujescu and Ina Giegling
24 Causes of distress-induced emotional eating 366
Tatjana van Strien
25 Genetics of obsessive–compulsive disorder and Tourette’s syndrome 380
Nuno R Zilhão, Dorret I Boomsma, Dirk JA Smit, and Danielle C Cath
26 Therapygenetics: Predicting psychological treatment response from genetic markers 396
Jonathan RI Coleman, Kathryn J Lester, and Thalia C Eley
27 The role of pharmacogenetics in the treatment of depression 421
Airiss R Chan, Ilona Gorbovskaya, and Daniel J Müller
Index 433
Contributors
Rebecca Alexander
Research School of Psychology, ANU College of Health and Medicine, Australian National University, Australia; Neuroscience Research Australia (NeuRA), Australia
Bradley M Avery Department of Psychology, University of North Carolina at Greensboro, USA
Catherine Belzung
UMR 1253, iBrain, Université de Tours, Inserm, Tours, France
Mirela I Bîlc
Cognitive Neuroscience Laboratory, Department of Psychology, Babeș-Bolyai University, Romania
Dorret I Boomsma Department of Biological Psychology, Vrije Universiteit Amsterdam, The Netherlands
Thomas J Bouchard Jr Department of Psychology, University of Minnesota, USA
Turhan Canli
Department of Psychology Stony Brook University, USA
Danielle C Cath UMC Groningen, Department of Psychiatry and Rijksuniversiteit Groningen, The Netherlands
Airiss R Chan
Centre for Addiction and Mental Health, University of Toronto, Canada
Sven Cichon
Department of Biomedicine, University of Basel, Switzerland and Institute of Neuroscience and Medicine (INM-1), Research Center Jülich, Germany
Jonathan RI Coleman King’s College
London, Institute of Psychiatry, Psychology and Neuroscience, UK; Institute of Neuroscience and Medicine (INM-1), Research Center Jülich, Germany
Annette Conzelmann
Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Tübingen, Germany
John F Cryan
Department of Anatomy and Neuroscience, University College Cork, Ireland
Harriet de Wit
Department of Psychiatry and Behavioural Neuroscience, University of Chicago, USA
Hanneke Den Ouden
Donders Institute for Brain, Cognition and Behaviour, Centre for Cognitive Neuroimaging, Radboud University Nijmegen, The Netherlands
Mana R Ehlers
Department of Psychology, University of British Columbia, Canada
Thalia C Eley King’s College
London, Institute of Psychiatry, Psychology and Neuroscience, UK
Daniela Felice
Department of Anatomy and Neuroscience, University College Cork, Ireland
Megan Flom
Department of Psychological and Brain Sciences, Boston University, USA
Emily Funsten
Program in Neuroscience, Middlebury College, USA
Justine Megan Gatt
School of Psychology, University of New South Wales, Australia; Neuroscience Research Australia (NeuRA), Australia
Ina Giegling
Department of Psychiatry, Psychotherapy and Psychosomatics, Martin Luther University Halle-Wittenberg, Germany
Ilona Gorbovskaya Centre for Addiction and Mental Health, Canada
Irving I Gottesman (deceased), Department of Psychology, University of Minnesota, USA
Joshua C Gray
Department of Medical and Clinical Psychology, Uniformed Services University, USA
Anand Gururajan
Department of Anatomy and Neuroscience, University College Cork, Ireland
Waylon J Hastings Department of Biobehavioral Health, Pennsylvania State University, USA
Lisa Heltzel
Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Centre, The Netherlands
Judith R Homberg
Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Centre, The Netherlands
Wendy Johnson
Department of Psychology, University of Edinburgh, UK
Joan Kaufman
Center for Child and Family Traumatic Stress, Kennedy Krieger Institute, USA, and Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, USA
Richard S Lee
Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, USA
Klaus-Peter Lesch
Division of Molecular Psychiatry, Center of Mental Health, University of Würzburg, Germany
Kathryn J Lester School of Psychology, University of Sussex, UK
Tina B Lonsdorf Department of Systems Neuroscience, University Medical Center
Hamburg-Eppendorf, Hamburg, Germany
James MacKillop
Peter Boris Centre for Addictions Research, McMaster University, Canada
Andrei C Miu
Cognitive Neuroscience Laboratory, Department of Psychology, Babeș-Bolyai University, Romania
Janitza L Montalvo-Ortiz Department of Psychiatry, Yale University School of Medicine, USA
Erik M Mueller
Department of Psychology, University of Marburg, Germany
Thomas W Mühleisen Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Germany; C. and O. Vogt Institute for Brain Research, Medical Faculty, Heinrich Heine University Düsseldorf, Germany
Daniel J Müller
Department of Psychiatry, University of Toronto, Canada
Olivia F O’Leary Department of Anatomy and Neuroscience, University College Cork, Ireland
Abraham A Palmer
Department of Psychiatry, University of California San Diego, USA
Clarissa C Parker
Department of Psychology and Program in Neuroscience, Middlebury College, USA
Paul Pauli
Department of Biological Psychology, Clinical Psychology and Psychotherapy, University of Würzburg, Germany
Lukas Pezawas
Department of Psychiatry and Psychotherapy, Medical University of Vienna, Austria
Alexander Prehn-Kristensen
Department of Child and Adolescent Psychiatry and Psychotherapy, Center for Integrative Psychiatry, School of Medicine, Christian Albrechts University, Kiel, Germany
Ulrich Rabl
Department of Psychiatry and Psychotherapy, Medical University of Vienna, Austria
Tobias Renner
Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Tübingen, Germany
Karin Roelofs
Donders Institute for Brain, Cognition and Behaviour, Centre for Cognitive Neuroimaging, Radboud University Nijmegen, The Netherlands
Dan Rujescu
Department of Psychiatry, Psychotherapy and Psychosomatics Martin Luther University Halle-Wittenberg, Germany
Sandra Sanchez-Roige Department of Psychiatry, University of California San Diego, USA
Vaibhav Sapuram
Department of Psychology, University of North Carolina at Greensboro, USA
Kimberly J Saudino
Department of Psychological & Brain Sciences, Boston University, USA
Idan Shalev
Department of Biobehavioral Health, Pennsylvania State University, USA
Kayvon Sharif Program in Neuroscience, Middlebury College, USA
Dirk JA Smit
Department of Psychiatry, Amsterdam University Medical Center at Meibergdreef, The Netherlands
Celine L St Pierre Department of Genetics, Washington University in St. Louis, USA
Alexandre Surget
UMR 1253, iBrain, Université de Tours, Inserm, Tours, France
Rebecca M Todd
Department of Psychology, University of British Columbia, Canada
Jenny van Dongen
Department of Biological Psychology, Vrije Universiteit Amsterdam, The Netherlands
Tatjana van Strien
Department of Clinical Psychology, Radboud University Nijmegen, The Netherlands
Inge Volman
FMRIB Centre, University of Oxford, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, UK
Suzanne Vrshek-Schallhorn
Department of Psychology, University of North Carolina at Greensboro, USA
Nuno R Zilhão Vrije Universiteit Amsterdam, The Netherlands
Twin studies of emotion
Megan Flom and Kimberly J Saudino
2.1 Introduction to genetic and environmental influences on emotions
People are different in their experience and expression of emotion, and as indicated in other chapters in this volume, these differences are related to a variety of outcomes. This, then, begs the question as to what factors explain these differences. The twin design can address this question at the level of etiology by exploring the relative contributions of genetic and environmental influences on individual differences in emotion, and links between emotion and outcomes. After providing an overview of the twin methodology, the present chapter will summarize findings from twin studies that inform on basic emotions (e.g. fear, anger, sadness, happiness, and emotionality), complex emotions, emotion processes, and mechanisms underlying the relations between emotion and psychopathology.
2.2 The twin design
The classic twin design compares the resemblances of identical (monozygotic, MZ) twins with fraternal (dizygotic, DZ) twins to decompose the phenotypic (i.e. observed) variance of a behavior or trait into genetic, shared, and nonshared environmental components. Heritability, the genetic effect size, is the proportion of phenotypic variance that can be attributed to genetic factors. If genetic influences are important to a behavior, then MZ twins who share 100% of their genes should be more similar for that behavior than DZ twins who share, on average, 50% of their segregating genes. Shared environmental variance is familial resemblance that is not explained by genetic variance and comprises environmental influences that are shared by family members (e.g. socioeconomic status (SES), neighborhood, friends, or even such things as the number of TVs or books in the house). If relevant to the behavior under study, shared environmental influences will make family members more alike. Nonshared environmental variance includes environmental influences that are unique to each individual in a family. These unique environmental influences operate to make members of the same family different from one another. Possible sources of nonshared environmental variance include differential parental treatment; relationships with friends, peers, and teachers; and non-systematic factors such as accidents, illness, and measurement error (1).
2.2.1 How can twins inform research on emotions?
The twin design can be applied to the study of emotion in a variety of ways. First, and most basically, it can provide estimates of the extent to which individual differences in emotions and related constructs are due to genetic and environmental influences (e.g. how heritable is sadness, or emotion regulation?). Second, twins can be used to explore genetic and environmental links between different emotions, thus providing information on the etiology underlying the structure
of emotions. Third, when applied to longitudinal data, twin methodology can identify genetic and environmental sources of stability and change in emotions across age. Finally, it can examine sources of genetic and environmental overlap between emotions and psychopathology (e.g. do fear and anxiety share common genes?). Taken together, these applications of the twin design to the study of emotion have implications for intervention and molecular genetic work.
2.3 Basic emotions
Perhaps the largest contribution twin studies have made to our understanding of emotion is through the study of temperament. The conceptualization of temperament as individual differences in the expression of primary emotions is widely accepted by temperament researchers, and often includes emotion-related traits such as anger, fear, sadness, happiness, and emotionality (2, 3). Although twin studies on emotion have now expanded beyond the context of temperament, the study of temperament has been the foundation for such work and hence will be the focus of much of the research reviewed on basic emotions.
2.3.1 Genetic and environmental influences on basic emotions
With few exceptions, twin studies find that basic emotions are heritable. The specific etiological pattern does, however, vary somewhat by emotion domain and measurement method. Anger, fear, and sadness are heritable in infancy and childhood when assessed via parent report (4–8) and observers (6, 9–11). Overall, heritabilities range from 0.50 to 0.70 indicating that genetic factors explain somewhere between 50 and 70% of variation in these emotions. In most cases, the remaining variance is due to the nonshared environment, but there have been some studies that also find modest shared environmental influences on anger and sadness in childhood (6, 8, 10, 12, 13).
Although observer- and parent-report measures of behavioral sadness are genetically influenced, this was not the case in a functional Magnetic Resonance Imaging (fMRI) study of neural activation associated with sadness. In a sample of eight-year-old twins who were shown sad film clips, there was no familial resemblance in neural activation in brain regions associated with sadness for either MZ or DZ twins (14). Hence, variation in neural activation was influenced only by the nonshared environment. While it is possible that this neural activation is due solely to individual-specific experiences, the lack of genetic influences may also be due to the small sample size (104 twin pairs) or measurement error.
Anger and fear are also genetically influenced in adults (15–19). Heritability estimates generally fall within a similar range of magnitude as for younger twins. Sadness as a discrete emotion has not been investigated in adult twins, most likely because the focus is often on the more clinical expression of the emotion (e.g. depression) and/or as a component of the personality trait of neuroticism.
These discrete basic emotions are often subsumed under broader concepts of negative and positive emotionality. In children, adolescents, and adults, negative emotionality is moderately to highly heritable (e.g. 0.40–0.64), with remaining variance explained by the nonshared environment (11, 20–23). Positive emotionality—or as it is sometimes referred, positive affect—tends to be less heritable than negative emotionality (11, 13, 24, 25). In fact, positive affect and related behaviors (e.g. smiling, interest in others) display little or no genetic influences and moderate shared environmental influences during infancy and early childhood (11, 13, 25, 26). However, in middle childhood and beyond, positive emotionality is moderately to highly heritable (0.33–0.79) and the influence of shared environments is negligible (27–32). It is possible that shared environmental influences in early, but not later, childhood reflects the influence of maternal personality and attachment security on positive affect in young children (11).
Interestingly, while measures of overall negative and positive affect are substantially heritable past middle childhood, momentary measures of these two emotion dimensions (i.e. assessed using the experience sampling method (ESM)) have demonstrated little to no genetic effects in adults (33 ,34). This raises the possibility that general perceptions of negative or positive affect assessed retrospectively have different etiologies than the immediate emotions tapped by momentary affect measures (34). However, as Menne-Lothmann and colleagues note, it is also possible that these results may reflect noise in the dynamic nature of ESM data. More research is needed. Overall, with few exceptions, familial resemblance in basic emotions is nearly always a result of shared genes and not shared environments, particularly in adults. Cross-cultural twin studies find a similar pattern across multiple countries (Germany and Poland) and multiple ages (adolescence through old age) (35). Despite widespread support for the substantial heritability of basic emotions, the environment is still relevant to variation in discrete emotions. Notably, twin studies not only inform on magnitude of genetic effects, they are also able to inform on environmental influences to individual differences in emotions. As reviewed earlier, it is those environments that differ within families (i.e. nonshared environments), not between families (i.e. shared environments), that are of key importance for most basic emotions. An implication of this is that researchers exploring how specific environments influence emotions might do well to focus on experiences unique to each member of a family.
In addition to informing about the main effects of the environment, twin studies can also explore interactive effects of genes and environments. Although not well studied, there is some evidence that the environment may moderate genetic and environmental influences on basic emotions. For example, the heritability of negative emotionality was higher for children who experienced poorer quality home environments (36). In other words, under a favorable environment genetic factors may play a smaller role in explaining individual differences in negative emotionality.
2.3.2 Using twins to understand development of basic emotions
Emotions are not a static construct, they change across age. Behavioral genetics addresses the question of developmental change in two ways: (i) differential heritability (i.e. whether the magnitude of genetic effects differs across age); and (ii) genetic and environmental contributions to rank-order continuity and change (i.e. the extent to which the same genetic and environmental effects operate across age). With respect to differential heritability, genetic effects for positive emotionality tend to increase across age (27, 29, 37), but this is not the case for negative emotionality or related discrete emotions, such as fear, anger, and sadness (13, 20, 22). This evidence for differential heritability for positive, but not negative, emotionality does not mean that there is change in the genes that influence positive emotionality but not negative emotionality, only that there is a difference in the relative contributions of genetic factors on individual differences in positive emotionality across age. Even when the same genes operate at different ages, their relative influence on individual differences (i.e. heritability estimates) may differ. Similarly, even when estimates of heritability are similar across development, as is the case for negative emotionality, the genes that influence these emotions may differ from one age to the next. Thus, comparing heritability estimates cannot inform about sources of continuity and change and does not address developmental processes.
By exploring genetic and environmental contributions to rank-order stability, twin studies can address the extent to which there are common and unique genetic and environmental effects across age, thereby informing about underlying developmental processes. For example, to what extent do genetic effects persist from one age to the next (i.e. stability) and to what extent are there age-specific genetic effects (i.e. change)? Longitudinal twin analyses suggest that stability in basic emotions is almost always due to genetic factors, whereas change is most often a result
of both genetic and nonshared environmental influences (10, 20, 21, 31, 38). These findings have implications for emotion researchers in other areas. First, the fact that nonshared environmental influences tend to be age-specific and do not persist across age suggests that emotion researchers interested in uncovering specific environments impacting emotions need to consider that the environments that operate at one age will most likely differ from those that operate at another. Second, for researchers interested in identifying specific genes associated with emotions, those emotions that are highly heritable and have high genetic stability across age will make promising candidates for molecular genetic work.
2.3.3 Etiologic links between basic emotions
Twin studies can also inform about genetic and environmental overlap between different emotions, which can elucidate the underlying structure of broad emotion domains such as negative emotionality. Phenotypic factor analyses suggest three underlying components (anger, fear, and sadness) of negative emotionality (39), but twin studies can provide additional information by telling us why these three basic emotions are related. Although this has not been extensively studied, common genetic effects seem to be the mechanism that primarily explains the underlying structure of parent-reported negative emotionality in middle childhood (12). The results are more mixed for observer-rated negative emotionality. When assessed via observation in structured episodes, anger and sadness were significantly associated, and again, this covariation was due to overlapping genetic effects. However, observed fear was not correlated with either anger or sadness, and thus had no genetic or environmental effects in common (12). One reason for the different etiologic pattern may be because the type of fear assessed in the observation episodes is different than what parents see in more naturalistic situations. That said, even for parent reports, it is fear that demonstrates the most genetic independence from other components of negative emotionality (11, 12). Thus, despite support for an overall negative emotionality construct, there are important distinctions between fear, anger, and sadness that should not be ignored.
When exploring the structure of several different self-report measures of fear and fearlessness in adults, both phenotypic and genetically informed biometric factor analyses suggest a bifactor model with a higher-order broad, bipolar fear/fearlessness factor, and three independent secondorder subfactors of distress, stimulation seeking, and sociability (17). The biometric analyses of variation in this bifactor revealed genetic and nonshared environmental contributions to individual differences in the higher-order fear/fearlessness factor. This consistency across phenotypic and biometric factor analyses provides support for the validity of a fear/fearlessness factor in terms of an underlying genetic and environmental architecture.
Despite the abundance of twin research on negative and positive affect/emotionality, less is known about the etiologic overlap between the two domains. Although it may seem intuitive that they are flip sides of the same coin, the two are often treated as distinct dimensions (40) and, perhaps because of this, to our knowledge, only one twin study has explored the etiologic underpinnings common to both. In middle childhood, genetic and nonshared environmental effects on positive and negative affect overlap, though not entirely (27). While there are genetic and environmental influences unique to each domain, the finding of a common genetic component could mean that there may be a genetic liability to a general tendency to experience or display emotions. More research is needed particularly at other ages to further investigate this possibility. Nonetheless, the modest association between positive and negative affect, as well as overlapping and unique etiologic effects, suggest that there is value to treating positive and negative emotionality as related, but distinct, constructs when examining the relation to psychopathology and other outcomes.
2.4 Complex emotions
Unlike basic emotions, which are more automatic in nature, complex emotions are higher-order emotions that require more cognitive processing. Although there are many complex emotions, they have not gained much attention in the twin literature. Two possible exceptions to this are self-conscious shyness and neuroticism. Self-conscious shyness (e.g. feelings of embarrassment), which emerges later than the more basic emotion of fearful shyness, is also highly heritable, with genetic factors explaining as much as 90% of the variation (5). However, despite both being highly heritable, self-conscious shyness and fearful shyness are not associated, which means that they have no common genetic or environmental underpinnings (5).
Neuroticism, “the subjective and stable tendency towards different states of negative affect” (41) encompasses not only the basic set of emotions that comprise negative affect but also the emotional processes of reacting to experiences. Variance in neuroticism is explained largely by genetic and nonshared environmental effects (42–44), a pattern that has been consistently found across multiple countries (e.g. United States, Australia, the Netherlands, Russia). In fact, estimates of genetic and environmental variance explaining individual differences in neuroticism were highly congruent across twin studies from Canada, Germany, and Japan (45).
More recently, researchers have also started to explore genetic and environmental influences on neuroticism as a state, rather than as a trait, which has been the primary focus of behavioral genetic work. When longitudinal trait–state models are applied to studies of neuroticism, trait variance (i.e. stable individual differences) is more genetically influenced than the state component (i.e. occasion-specific variance) (46, 47). Long-term stability is due to both genetic and nonshared environmental influences. In contrast, occasion-specific state variance is mainly influenced by the nonshared environment, which tends to increase over time. The decreases in heritability and increased importance of the environment across age, in addition to increased stability in neuroticism across age, is consistent with the notion of social selection and social influence. That is, people select environments that correlate with their levels of neuroticism and these environments, in turn, produce experiences that influence neuroticism (46, 47). This is related to the concept of an active gene–environment correlation wherein one’s genetically influenced traits, neuroticism in this case, influences their selection of environments that they experience, thus providing support for the transaction between genetics and the environment in neuroticism (46, 47).
Underlying associations between neuroticism as a trait and other affective state measures have also been explored. Research finds that neuroticism and momentary positive affect (a state-based emotion) are negatively associated and that this arises because of overlapping nonshared environments (48). Neuroticism and momentary negative affect, on the other hand, are positively associated due to common genetic and nonshared environmental effects. This suggests that neuroticism may be a useful indicator of environmental risk for decreased daily positive affect and an environmental and genetic indicator of risk for increased daily negative affect (48).
2.5 Emotion processes
Behavior genetic research on emotion processes has largely focused on emotion regulation and related concepts, and to a lesser extent, the neurobiology of emotion processing. Emotion regulation is an important emotion process that encompasses the regulation of internal affect, external expressive behaviors, and emotion-related physiological reactions, attentional processes, cognition and motivation (49, 50). This process is crucial to adaptive functioning across the lifespan, yet has not often been studied using behavior genetic methodology (51). In a study of infant twins, there were modest genetic contributions to variations in infant gaze aversion (an emotion
regulation tactic used by infants) to an unfamiliar model but not to a familiar model (i.e. mother) (52). Hence, nonshared environmental influences explained most of the variance in this emotion regulation strategy as it is just emerging. Genes, however, may play a larger role as emotion regulation develops. For example, in toddlerhood, genetic and nonshared influences accounted for 43% and 48%, respectively, of the variance in individual differences in emotion regulation observed within the lab (51). Genetic influences have also been found on related constructs such as effortful control (53, 54), physiological regulation (55), anger control (19), and affective intensity and lability (56). There are also hints of gene-by-environment interaction as indicated by the finding that cortisol reactivity (a potential physiological marker of emotion regulation) in infants was influenced by genetic and nonshared environmental factors under conditions of low familial adversity, but by only the environment (both shared and nonshared) under conditions of high familial adversity (57). In other words, when infants experience more “risky” environments, the impact of genes on physiological stress regulation is overshadowed by the environment. This research raises the possibility of finding gene-by-environment interactions in more traditional measures of emotion regulation.
The two twin studies that have explored emotional processes related to reward experience (i.e. the degree to which positive affect increases in response to pleasurable events) and stress sensitivity/perception (i.e. the degree to which negative affect increases in response to unpleasurable events) have mixed findings. When assessed by questionnaires tapping general tendencies related to these two processes, genetic factors explained roughly half of the variation (58). However, ESM measures of reward experience and stress sensitivity showed no familial resemblance (34). The authors suggest that the small sample may have resulted in an underpowered test of genetic effects. However, the fact that there was so little co-twin resemblance for either MZ or DZ twins raises the possibility of measurement issues. Ten assessments per day over five days may not be enough to capture reward experience and stress sensitivity fully. It may also be that ESM measures get at different aspects of these two constructs. More research using ESM methodology in larger samples over more extended periods of time is needed to inform about these possibilities.
As previously indicated, negative emotionality as a basic emotion category is genetically influenced. Negative urgency, an emotion process that reflects the tendency to engage in rash action in response to negative affect, is also genetically influenced, though less so than negative affect as an emotion. Specifically, in adults, genetic factors explained roughly 35% of the variation in negative urgency, with the nonshared environment explaining remaining variance. Overlap between negative urgency and negative affect was primarily due to genetic effects, although there were also genetic factors unique to each (59). Thus, the two are related, but distinct, constructs at the level of underlying etiology.
Neurobiological methods are starting to be applied to the study of emotion processing in twins. A common assumption of researchers interested in emotion processing is that variation in neural responses to emotional stimuli (e.g. response to affective stimuli such as faces and complex emotional scenes) is heritable, but this has only recently been examined empirically. When investigated in adult twins using affect-modulated event-related potentials, P300 neural responses to complex emotional scenes displayed modest to moderate genetic influences (heritabilities ranging from 0.22 to 0.30) with, once again, the nonshared environment explaining most of the remaining variance (60). Genetic influences have also been found for neural responses to emotionally salient facial stimuli (61). By integrating twin methodology and neurobiology, this research strengthens the notion of a neurobiological marker of emotional neural responsivity.
Although not a traditional twin study, neural and behavioral differences between MZ twins have also been studied. By examining differences between MZ twins, it is possible to get a better understanding of nonshared environmental influences on neurobiological measures. For example,
behavioral, psychophysiological, and fMRI measures were assessed in a pair of MZ twins with amygdala dysfunction (62). Despite having the same pathology, one twin was more behaviorally and psychophysiologically “normal” (e.g. had a normal-sized social network, and an acoustic startle response). When examining neurological functioning using fMRI, the more “normal” twin showed responses to fearful faces in areas of the brain relevant to the cortical mirror-neuron systems, thereby highlighting the potential of this system to compensate adaptively for amygdala dysfunction in regard to social information. This finding based on a single pair of twins offers novel support for targeting mirror-neuron systems to help compensate for impaired emotion processing.
2.6 Links between emotion and psychopathology
There is an abundance of evidence showing genetic contributions to emotion-related psychopathology such as depression (63), anxiety (64), fears and phobias (65), and childhood behavior problems (66, 67). In addition to simply estimating genetic and environmental variances of emotion-related psychopathology, behavior genetic methods can also be used to explore genetic and environmental sources of covariance between emotion and psychopathology. That is, to what extent are there common genetic and environmental influences across the two domains?
Research looking at the overlap between negative emotionality and psychopathology has examined the genetic and environmental links between negative emotionality/affect and major depressive disorder and conduct disorder (23); internalizing and externalizing problems (68–70); attention and aggression problems (71); a general internalizing/externalizing bifactor (72); depressive symptoms, attachment-related anxiety and attachment-related avoidance in romantic relationships (73); and dysregulated eating (59). With regard to specific negative emotions, research has looked at links between anger and aggression (4), conduct problems (9), stressful life events (19), and borderline disorder (16). Fear and sadness have been etiologically linked with anxiety (7); and neuroticism with anxiety (74, 75), depression (76, 77), perceived stress (78), and obsessive compulsive symptoms (79). The overall pattern of results is similar across studies. That is, the links between negative emotion and psychopathology are almost always primarily due to genetic factors. When the environment does contribute to links between negative emotionality and psychopathology, it tends to be modest and of the nonshared variety. Common genetic influences suggest pleiotropic effects on psychopathology and negative emotion across development and highlights the potential of negative emotionality as a broad vulnerability factor that underlies various dimensions of psychopathology. As such, this research provides novel support for the view of psychopathology as a continuum. Furthermore, the genetic overlap between negative emotionality and dimensions of psychopathology, the high heritability of negative emotionality, and its relation to psychopathology in the general population, makes it a possible endophenotype for molecular research (22). Indeed, the utility of using temperament rather than psychopathology as the target behavior or trait in molecular genetic work has been previously suggested (80).
The pattern of genetic overlap between negative emotionality and psychopathology is so pervasive that it is most interesting when etiologic links between the two are not explained by genetic factors. This is the case with fear and sadness, and separation anxiety. Although genetic factors explained the association between over-anxious symptoms and both fear and sadness in infancy and early childhood, separation anxiety was entirely environmentally linked with fear and sadness (7). In other words, the shared and nonshared environments explained the phenotypic association between separation anxiety and fear and sadness, suggesting that intervening on separation anxiety in infancy and early childhood may be a way to begin addressing nascent emotional
problems. This research also highlights that similar dimensions of psychopathology can have different underlying etiologic associations with emotion.
While most research on links between emotion and psychopathology has focused on negative emotionality, this does not provide a complete picture of how psychopathology maps onto emotion. This is particularly true given that we know negative and positive emotionality have, at least to a certain extent, unique etiologic underpinnings. By investigating positive emotionality in this context, research can provide novel implications for how we conceptualize and intervene on different dimensions of psychopathology. To our knowledge, only two twin studies have looked at links between positive affect or subjective well-being with psychopathology. In both cases, there was a negative association suggesting that positive emotionality may buffer against psychopathology. A benefit of using twins is the ability to elucidate the extent to which this protective aspect of positive emotionality is due to protective genes or environments. In contrast to research finding genetic links between negative emotionality and behavior problems, in early childhood positive affect showed only environmental links with internalizing problems (81). That is, it was common shared and nonshared environmental factors that increased positive affect and decreased internalizing problems. Although in early childhood the association between positive affect and psychopathology is due to the environment, in adolescence the overlap between subjective well-being and psychopathology was mainly genetic (82). Together these studies suggest that while positive emotionality may serve as a buffer for psychopathology, the mechanisms by which this works may differ across age.
2.7 Conclusion and future directions
Twin studies clearly indicate the importance of both genes and the environment in emotion across development. Nearly all emotions and emotion processes are heritable, and overlap amongst emotions and between emotions and psychopathology is primarily a result of shared genetic factors. Future work should continue exploring the etiologic overlap between different discrete and complex emotions to improve understanding of underlying structures and interrelations amongst them. Additional research on genetic and environmental links between psychopathology and emotion, particularly emotion processes and positive emotionality, is also needed.
The application of the twin design to the study of temperament has provided us with a foundation for understanding the etiology of emotion, and has since been expanded to inform on complex emotions, emotion processes, and links between emotion and psychopathology. However, there are a number of gaps in the literature. The bulk of twin research on emotion has relied on questionnaires. More lab-based methods with large samples are required to improve the definition of phenotypes. A greater focus on behavioral and neurological measurement in twin studies would allow for a more complex understanding of the genetic and environmental etiology of the trait versus state aspects of emotion and emotion processes, as well as increase our understanding of genetic liabilities to emotion-related neurobiological processes. In other words, using these lab-based behavioral and neurological approaches is crucial in moving beyond a questionnairefocused research of emotion to one concentrating on more emotional complexities (e.g. emotion regulation; emotion processing). This will be particularly relevant to our understanding of the overlap between emotion and psychopathology, as well as the overlap with neurobiology. In fact, the necessity and vast potential of a thoughtful approach to integrating behavioral genetics and neuroscience has been advocated (83). Despite this, few twin studies have taken a neurobiological approach. This is most likely due to the high cost of the lab-based twin studies, as well as the lack of cohesion between an individual differences approach (twin studies) and the, until recently, primarily group differences approach of neurobiology. Future research should make a concerted effort to merge the two perspectives. Researchers in both realms will benefit.
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