Neuroscience of Personality and Individual Differences
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KeywordsPsychopathic Trait Regional Gray Matter Volume MAOA Genotype Functional Gene Variant Nonshared Environmental Effect
Research aimed at discovery and description of the biological substrate of relatively persistent behavioral traits.
Interindividual differences in personality and behavior must derive from underlying variations in the brain. At present, knowledge on the neurobiological foundation of persistent individual differences consists of highly fragmented pieces of information and does not allow a single coherent theory. The following summary represents a selection of evidence that may be helpful in developing such a theory that had the power of making predictions on future behavior, and points at some significant gaps that research must fill in order to proceed.
Neuroscience embraces the vast complexity of the brain and the large variety of different methods for probing its structure and function, ranging from systems analysis to the molecular level. All this is applied in combination with the multitude of human personality theories or is addressing specific less or more complex traits of particular interest, and can be taxing either healthy mental condition or something out of the variety of mental health pathologies. Furthermore, quite a large number of approaches to study the neural underpinnings of individual differences are carried out in animals, and attempts to translate from other species to humans and vice versa have become the mainstream in neurosciences. Hence, the sheer diversity of the available information is mind-boggling and much of it is unlikely to be the final word on the neural basis of individual differences.
A Neuroanatomical View on Individual Differences Represented in the Brain
Neuroscience operates at a variety of organizational levels. At the macroscopic level of brain regions and their connectivity, recent technological developments have brought research on the living brain to a qualitatively new state and provide excellent tools for the study on neurobiology of human behavioral traits. The findings obtained with methods such as structural and functional magnetic brain imaging and diffusion tensor imaging suggest that major personality traits in humans can be linked to brain structure, metabolic activation, and structural and functional connectivity. For example, the Big Five personality traits have been associated with volume of a number of brain regions (DeYoung et al. 2010), while most of the trait-related areas were cortical or cerebellar. A recent meta-analysis with focus on traits in several personality taxonomies but all representing negative emotionality (Mincic 2015) has suggested that high negative emotionality is associated with lower gray matter volume in left orbitofrontal cortex and perigenual anterior cingulate cortex, but higher gray matter volume in left amygdala and anterior parahippocampal gyrus. Into the realm of negative emotionality also belong the studies on inhibited temperament (Clauss et al. 2015) that have also found hyperreactivity of amygdala to play a central role, as well as altered functional connectivity between prefrontal cortex and basal ganglia.
A contrast to negative emotionality, positive emotionality, has often been viewed as represented in the construct of extraversion, and linked with high dopaminergic function (Depue et al. 1994) of the mesotelencephalic pathway from the ventral tegmental area and substantia nigra to limbic areas such as striatum and nucleus accumbens, and to the frontal cortical areas. Others maintain that dopamine is a necessary but not sufficient factor in experiencing positive emotion and other neurochemical mechanisms in the limbic system, notably several neuropeptides, are implicated (Panksepp 1998).
Variation in the networks of negative and positive affect taken to extreme is reflected in conditions that are considered pathological. Negative emotionality is positively associated with development of mood and anxiety disorders, and there is a genetic common ground for traitwise negative emotionality and these disorders. Studies on patients have yielded in compatible neurobiological findings. Psychopathic traits that are the core of antisocial behavior develop in early age, whereas reduced empathy when others are at distress is based on reduced responsiveness of amygdala to relevant cues; this, however, appears together with alterations in decision-making abilities and behavioural flexibility owing to deficits in function of ventromedial prefrontal cortex and striatum (Blair 2013).
From Genes to Brain Systems
The heritable component of the individual differences is emerging from the genetic information of the individuals, and also the developmental and acquired aspects of persistent traits ought be residing on metastability of gene expression. At the genetic level, systematic review of literature has not detected any strong relationship of variants of a single gene with personality while using models of either Cloninger, Eysenck, or Costa and McCrae (Balestri et al. 2014). Similar systematic approaches to the literature on the level of neurochemistry are missing but also appear to be unlikely to detect any consistent and strong association between personality and a single molecule. This absence of any single simple uncontested association despite of massive research efforts suggests that the persistent aspects in the specific traits under investigation are emerging from a highly complex molecular and cellular arrangement, and within general population any trait can probably raise from many different constellations at the molecular level. Studies on individual differences in intelligence have reached a similar conclusion that while the efficiency of the brain provides a uniform correlate to intelligence and activity in parietal-frontal pathways is important for this, there are many neuronal roads to intelligence (Deary et al. 2010).
Some of the personality models have kept the neurobiological underpinnings in mind since the beginning or have even been conceived after substantial empirical brain research. The approach/avoidance systems research by Gray has led to scales measuring behavioral activation versus inhibition as separate neural systems, and the tridimensional model of Cloninger (Cloninger et al. 1993) was based on the available neurochemical information regarding the three wide-spread monoaminergic systems of the brain, linking novelty seeking to dopamine, harm avoidance to serotonin, and reward dependence to noradrenaline. Further, a powerful attempt of bottom-up personality scale building has been made by compilation of the Affective Neuroscience Personality Scale (ANPS; Davis and Panksepp 2011) that explicitly derives from the predefined emotive systems as discovered in systematic and detailed neurobiological studies on animals (Panksepp 1998). Traits specified and defined in this way have all been characterized in terms of species-specific behavior, neuroanatomical networks, and neurochemical regulation with unprecedented detail, while the chemical neuroanatomy of the model still requires further refinement. Representing six out of seven primary neurobiologically well-defined emotional-motivational systems, SEEKING, FEAR, ANGER, SADNESS, CARING, and PLAY, the ANPS has appeared as a promising tool in human genetic and brain imaging studies (Montag and Reuter 2014), but further investigations remain expected to clarify the eventual value of this approach.
Broad categories of behavior, such as aggressiveness, have been more successfully related to broadly defined neurobiological mechanisms such as serotonergic function.
The vast majority of molecular genetic research of individual differences has been on targets in the dopamine and serotonin systems (Montag and Reuter 2014). Quite a substantial share of this effort is owing to the discovery of a few gene variants that have small but significant effects in meta-analyses but appear to be nominally associated with a large variety of different behavioral measures. An outstanding example is the promoter polymorphism of the serotonin transporter gene, the short variant of the polymorphic region being associated with less efficient transcription of the gene leading to lower expression, and higher levels of neuroticism, anxiety, and depression (Lesch et al. 1996). This promoter polymorphism has remained the most investigated genetic variation in neuroscience, despite the inconsistent association with each of the many personality and behavioral variables it has been linked to, probably owing to certain advantages comprised in hypervigilance produced by the “risk” genotype (Homberg and Lesch 2011) and to gene–environment interactions leading to adaptive changes that compensate for the potential disadvantages carried with the “risk” genotype (Harro 2010).
The behavioral plasticity associated with common gene variants should not lead to underestimation of the potentially major effects that a variation in a single gene with large neurochemical implications can elicit on human behavior. An exemplary case is the Brunner syndrome, resulting from a single nucleotide mutation that was causal to preventing the expression of the monoamine oxidase A (MAOA) gene, with resulting absence of MAO-A enzyme activity throughout life course and expression of borderline mental retardation, limited impulse control, and violent outbursts precipitated by unexpected events in all male subjects who had the mutated variant of this X-chromosomal gene (Brunner et al. 1993). MAO-A is an enzyme with critically important role in breaking down the neurotransmitters such as serotonin, noradrenaline, and dopamine, and by this means has a large effect on real-time neurotransmission but also on brain maturation during the early development of the nervous system. Subsequently, a common variable number of tandem repeat (VNTR) polymorphism was identified in the promoter region of the MAOA gene, with certain alleles leading to higher versus lower expression in vitro. Alleles classified into the low activity MAOA genotype are associated with lower gray matter volume in the limbic regions and carriers of the MAOA-L alleles have diminished responses to angry and fearful faces in the prefrontal cortex but increased responses in the amygdala (Buckholtz and Meyer-Lindenberg 2008). MAOA-L subjects express higher levels of impulsivity, higher aggressiveness upon provocation, and they are more prevalent among subjects who have shown antisocial behavior, including extreme risk-taking and violence. Of note, differences in cerebral responses and higher impulsivity and violence of the MAO-L subjects appears as specific to males.
Neuroscience has paid much attention to the concept of sensation-seeking behavior, and this has been associated with high dopaminergic (Norbury and Husain 2015) and low serotonergic (Zuckerman 1993) function. Especially, the latter has quite consistently been considered a causal factor of impulsivity, even though the large picture is more complex. Impulsivity can be meaningfully subcategorized and the complexity of the serotonergic system (not only are the projection areas and behavioral functions of different serotonergic cell groups distinct, but at least 14 subtypes of 5-HT receptors exist and some act as postsynaptic as well as release-inhibitory receptors) allows for distinct connection between varieties of impulsivity and corresponding aspects of 5-HT neurobiology (Evenden 1999). An indirect measure of the overall capacity of serotonin release in the brain, monoamine oxidase activity in platelets that is likely to reflect the early developmental state of the serotonin system, has quite consistently been found in association with impulse control related complex behaviors (Harro and Oreland 2016). Thus, subjects with low platelet MAO activity and presumably lower capacity of the serotonergic system exhibit higher impulsivity scores, engage more frequently in behaviors associated with high impulsivity and excessive risk-taking, and are overrepresented in groups with serious behavioral deviations. High platelet MAO activity has, in turn, been linked to higher neuroticism.
Impulsivity has emerged as a meaningful construct that can be further dissected into facets and subsequently translationally studied in humans and other species, providing the window to the cellular level and chemical neuroanatomy of the trait. Not unexpectedly, upon close examination the neurobiology underlying impulsive traits has appeared more complex and has besides dopamin- and serotonergic systems included information on other neurochemical systems that use noradrenaline, glutamate, or endocannabinoids (Pattij and Vanderschuren 2008).
Fine-tuning of neural activity is supported by neurochemical systems with lower abundance but high receptor affinity, most prominently by neuropeptides. Personality research has recently implicated neuropeptides such as oxytocin, arginine vasopressin, and neuropeptide Y (Montag and Reuter 2014), but many others are likely to make a significant contribution to individual differences (Panksepp 1998; Harro 2010). Some of the neuropeptides involved in regulation of hormonal regulation via blood or acting as hormones themselves have been found to function as neurotransmitters in the brain within well-defined neuronal circuits. Oxytocin is an example that has received much attention recently: This nonapeptide is released from the posterior lobe of the pituitary gland and acts as a hormone but hypothalamic projections to several brain regions such as prefrontal cortex, amygdala, lateral septum, bed nucleus of stria terminalis, and hippocampus. Oxytocin-mediated neurotransmission may shape the variability in social affiliation related traits but also by moderating dopaminergic function the reward-related behaviors in a more general manner (Love 2014).
Interestingly, both high dopaminergic and low serotonergic function that together may bring about maladaptive behavioral choices are observed in animals after postweaning social isolation (Hall and Perona 2012). Gene–environment interaction studies have become the mainstream in behavioral genetics after the reports by Caspi and coworkers (Caspi et al. 2002, 2003) on the moderating effects of common gene variants on the impact that life events can have on the development of aggressive and antisocial behaviour and depressive traits. How exactly do the impacts of life events and persistent environmental variables become established at the molecular level remains to be clarified but implies the level above the nucleotide sequence of the DNA, referred to as epigenetic changes. Epigenetic mechanisms can include chromatin remodeling, methylation, and acetylation of histone packaging that facilitate gene promotion, and addition of methyl groups to structural DNA and production and binding of micro-RNA-s that silence gene expression. Such regulatory processes have been found to be essential for the development and function of all tissues, including the CNS, are developmentally dynamic, and serve as a basic mechanism for long-term control of gene expression, likely to often overrule the effect of the variations in the coding DNA sequence or in its promoter region. The methylation patterns may well themselves be heritable as well as have random change components, but often are strongly specifically affected by different aspects of environment. For example, methylation of the dopamine D4 receptor gene (DRD4), a gene that has been associated with attention deficit hyperactivity disorder but also with curiosity, was found as largely driven by shared family environment in a twin study, but the methylation of the serotonin transporter promoter was largely dependent on unique, nonshared environmental effects (Wong et al. 2010).
What would be the mediating mechanism from the environment to DNA is also not known, but is likely to involve the known physiological mechanisms of stress response. Animal research has described that maternal care can produce behavioral changes lasting to adulthood by means of epigenetic modification of glucocorticoid receptor gene in the brain (Weaver et al. 2004). This would be likely to affect the reliability of the negative feedback loop that limits the release of cortisol, a hormone released from the adrenal glands as part of an adaptive, homeostatic reaction to a large variety of external and internal challenges. Because hormones, carried in bloodstream, can reach multiple targets almost simultaneously they can serve as universal messengers to many physiological circuits that are involved in trait-wise responses. Several hormones have both rapid effects mediated by membrane targets and more long-term and persistent effects via binding to intracellular receptors and impacting on gene expression. Amongst associations of behavioral traits with hormone secretion, the relationship between aggressiveness and testosterone has received most attention. While the many attempts to show that higher testosterone levels lead to higher aggressiveness have revealed only a very weak positive correlation, this association could be stronger in specific conditions, and surges of testosterone do predict future aggressive behavior and enhance threat-related activation of the amygdala (Carré and Olmstead 2015). The development of social neuroscience has attempted to place testosterone as a source of individual differences into a broader context as playing a role in motivation to achieve and maintain high social status (Eisenegger et al. 2011), this, of course, being well compatible with a nonlinear and time-dependent association of hormone levels with specific complex behaviors such as aggression.
Developmental Aspects and the Sex/Gender Perspective
Many of the genetic effects as well as outcomes of epigenetic programming that are observable throughout life cycle may have occurred already at prenatal and perinatal stage (Harro and Oreland 2016). For example, the MAOA VNTR genotype does not explain MAO-A protein levels in the adult brain as measured by positron emission tomography, and while MAO-B activity in platelets covaries with risk-taking behaviors in adulthood, there is no correlation with MAO-B activity in the brain. Indeed, MAO-B activity levels appear to have little effect on monoamine metabolism if MAO-A activity is preserved. The notion that MAO activity during fetal period is an important contributor to individual differences is supported by animal studies showing the aggressiveness-increasing effect of MAO-A inhibitors if administered during gestation but not in adulthood, and by clinical experience that treatment of depressed patients with MAO inhibitors does not appear to change personality. In the mature brain, MAO-A levels are strongly associated with promoter methylation and hence subject to large variation as the methylation pattern has been found to profoundly change in development (Wong et al. 2010).
Evidence that methylation levels of many key genes of major neurochemical systems changes significantly over a few years already in early childhood, and that methylation profiles are very different even in monozygotic twins owing to the impact of environmental factors (Wong et al. 2010) suggests that environmental factors play a crucial dynamic role in shaping the behavioral traits by influencing gene expression. As several animal studies have revealed, alterations of gene expression are often associated with behavioral stability under environmental pressures (Harro and Oreland 2016). Because the environmental impacts are of different qualitative and quantitative types, the response modes maintaining homeostasis must be manifold.
In this context, it should be acknowledged that male and female individuals differ not only by certain genetically determined biological features but are, in everyday life, confronted by environmental signals that are different within many if not all cultures. At the gene–environment interaction process, the significance of sex as biological and gender as cultural construct become intertwined. Studies on general intelligence have reached the conclusion that in males and females intelligence co-varies with different measures of regional gray matter volume, cortical thickness, and white matter volume and integrity, leading to a conclusion that males and females can achieve similar levels of intelligence by using differently structured neural systems in different ways (Deary et al. 2010). Similar are the findings in studies on behavioral differences and major functional gene variants, most notably with the MAOA VNTR genotype, in which case, quite consistently, aggressive traits are associated with childhood adversity, and with the MAOA-L genotype in males but with the MAOA-H genotype in females (Harro and Oreland 2016). Neuroimaging has revealed compatible distinct patterns in activation of amygdala, hippocampus, and anterior cingulate cortex as early stressful events drive dysfunctional responses in MAOA-L males and MAOA-H females.
It should however be made clear that for the common functional gene variants often labeled as “risk” genotypes, evidence instead supports a role as plasticity genotype: carriers of plasticity alleles would be heavily hit in unfavorable conditions but well equipped to take advantage of supportive environment (Belsky et al. 2009). No biological mechanism that would be universally maladaptive would survive environmental pressure so each variant that can be associated with a trait apparently less adaptive must be either exceedingly rare or permit balanced adaptive responses. Indeed, it may follow that a large share of individual differences are caused by unique, family-specific genetic constellations (Homberg and Lesch 2011). The common genetic “risk” variants such as the s-allele of the serotonin transporter polymorphism promote developmental trajectories that are environmentally shaped to fit in. Nevertheless, if the negative impact of environment can not be compensated for, the common variants can be causally related to maladaptive traits.
Neuroscience has described associations with persistent behavioral traits at different levels from molecular to systems, but currently the landscape of knowledge remains fragmented. It has, however, been found that phenotype is not strictly predicted by the genotype, and that variability of the phenotype from a genotype can be huge, with even opposing solutions if the environmental pressures during development facilitate this (Hall and Perona 2012). Because of the multitude of constructs under investigation, and the many factors that correlate and interact with each other throughout the life course, neurobiology of individual differences should embrace formal modeling that includes the epistatic, hierarchical, dynamic, and homeostatic nature of interaction between genetic factors, environments, endophenotypes, and behaviors (Harro 2010).
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