In an attempt to reframe the either-or debate over the impact of genetics versus environment on emotional makeup, a panel convened at the American Psychoanalytic Association’s Winter 2005 Meeting in New York City. This article highlights studies presented at the meeting.
In an attempt to reframe the long-standing debate over the either-or impact of genetics versus environment on emotional makeup, a panel titled "Genes-Environment Interactions: Developmental and Psychotherapeutic Implications" convened at the American Psychoanalytic Association's Winter 2005 Meeting in New York City.
Glen O. Gabbard, M.D., Brown Foundation chair of psychoanalysis and professor of psychiatry at the Baylor College of Medicine in Houston, presented data on the gene-environment interaction in antisocial and borderline personality disorders, showing that DNA is both inherited and environmentally modifiable. Gabbard told Psychiatric Times that there is today, in the field of psychiatry, a simplistic thinking that wants everything reduced to the genome.
"Most people do not like complexity, so there's a seductiveness about genetic reductionism," he said. "But genes alone do not determine personality, and we have good data now showing that it is a matter of genes interacting with the environment in the expression of those genes, and the environment making actual changes in that expression."
At the meeting, Gabbard described a long-term, follow-up study of 1,037 children in Dunedin, New Zealand--a birth cohort assessed every two years up to age 26 (Caspi et al., 2002). Measures included degree of maltreatment, monoamine oxidase A (MAOA) gene activity and antisocial behavior. Results showed that males with low MAOA activity who were maltreated in childhood had elevated antisocial scores, whereas males with high MAOA activity did not have the elevated scores even when they had experienced maltreatment. Overall, 85% of the males with both the low MAOA activity genotype and severe maltreatment became antisocial.
"The authors concluded that a functional polymorphism in the MAOA gene moderates the impact of childhood maltreatment on development of antisocial behavior. The point here, against reductionism, is that neither the low-activity gene alone nor the environmental maltreatment alone is enough to create antisocial behavior," explained Gabbard.
Those findings were replicated in a study of 514 male twins (ages 8 to 17), which showed that low MAOA activity increased risk for conduct disorder only in the presence of an adverse childhood environment (Foley et al., 2004). "Once again, the combination had to be present," Gabbard said.
In a study of the effects of differential parenting on antisocial behavior in 708 families with at least two same-sexed adolescent siblings, almost 60% of the variance in adolescent antisocial behavior and 37% of the variation in depressive symptoms were accounted for by conflictual and negative parental behavior directed specifically at the adolescent, not at the sibling (Reiss et al., 1995).
"So there's differential parenting and you can't assume that every kid in a family has the same parenting," said Gabbard. "Non-shared environmental influences appear to have the largest impact on normal versus pathological development."
Inherited traits can produce differential parenting responses that could ameliorate or exacerbate those traits.
"One implication that hasn't been studied in a sophisticated prospective design is that psychotherapeutic interventions with caregivers might actually alter genetic expression in genetically vulnerable children," said Gabbard.
Provocative data confirming this idea comes from a 15-year follow-up of a randomized, controlled trial of the impact of home visitation by a nurse on children's antisocial behavior (Olds et al., 1998). The study found that adolescents born to young, low-income women who received nurse visits indeed had significantly lower rates of antisocial behavior than controls. They also had lower rates of substance abuse and fewer lifetime sex partners.
"So this kind of intervention made quite a difference in what we might expect from these kids," Gabbard said. "So what I am saying so far is that genes and environment are inextricably connected in the pathogenesis of antisocial behavior; a strict dichotomy is specious. Psychotherapy of parents and caregivers may influence genetic vulnerability, and a neglected benefit of psychotherapy in the literature is its impact on offspring of the patient."
Shifting to a discussion of borderline personality disorder (BPD), Gabbard said there are much less genetic data regarding this condition. Some data come from neuroimaging studies that showed smaller hippocampus and amygdala volumes in patients with BPD versus controls (Driessen et al., 2000; Schmahl et al., 2003; Tebartz van Elst et al., 2003). "But the exact relationship between early trauma and decreased volumes in the amygdala is unclear, since 60% to 80% of patients with BPD have substantial childhood trauma," explained Gabbard.
A volumetric study of response to facial expressions found that patients with BPD showed significantly greater left amygdala activation to happy, sad and fearful expressions compared with normal controls, and attributed negative qualities to neutral faces (Donegan et al., 2003).
"A hyperactive amygdala may be involved in the predisposition to be hypervigilant and overreactive to relatively benign emotional expressions," said Gabbard. "Misreading neutral faces is clearly related to transference misreadings that occur in psychotherapy and the creation of bad object experiences linked with projective identification."
Another study found that individuals with one or two copies of the short allele of the serotonin transporter (5-HTT) promoter gene demonstrated greater amygdala neuronal activity in response to fearful stimuli compared to individuals homozygous for the long allele (Hariri et al., 2002).
"There may be a genetic vulnerability that predisposes one to amygdala hyperreactivity in response to trauma," Gabbard said. "We need more data to know that, but we do know from the Dunedin longitudinal study that the short allele moderated the influence of stressful life events on depression, and stressful life events predicted suicidal ideation or attempt among individuals carrying the short allele but not among those with the long variant [Caspi et al., 2003]."
In a study of how social support might moderate depression after mistreatment, 57 maltreated children were compared to 44 controls (Kaufman et al., 2004). "What was ideal here is that there were no differences in short versus long alleles of the serotonin transporter gene between maltreated [participants] and controls," said Gabbard. Results showed that maltreated children with the short allele and no social support had the highest depression ratings, but positive social supports reduced risk of depression associated with maltreated children and the short allele.
"So the environment can moderate the impact of the genetic constellation," said Gabbard. "This is a very provocative study showing that genetic vulnerability can be modified by intensive social support."
It may be more than the presence of trauma that makes the difference in outcome, according to Gabbard. The child's intrapsychic interpretation of the trauma may be highly relevant. Parents and caretakers can contextualize events so that the child can make sense of them in ways that are beneficial. These ideas also relate to the potential for psychoanalysis and other therapies to change the impact of those experiences, added Gabbard.
"Whether or not environmental factors trigger the expression of the gene may depend on the conscious or unconscious meaning attributed to these experiences," stated Gabbard.
The studies on the influence of genes and environment on human development are supported by studies of primates and rats. "The support from laboratories, where you can manipulate genes and environments in ways you can't do with human beings because of ethics, definitely shows that the environment alters genetic expression," explained Gabbard.
One example is a series of lab and field studies of monkeys done by Stephen Suomi, Ph.D., chief of the Laboratory of Comparative Ethology, and his team at the National Institute of Child Health and Development (see Suomi, 2003). Suomi presented data on a group of rhesus monkeys that showed the aggressive and highly impulsive characteristics of antisocial personalities. Such monkeys had deficits in serotonin, a highly heritable characteristic also associated with a tendency to drink an excessive amount of alcohol. But a series of studies showed that these highly heritable characteristics can be modified substantially by a nurturing environment.
Specifically, the studies looked at monkeys with short and long alleles of the serotonin transporter 5-HTT promoter gene, the short version being associated with low serotonin and the long version associated with normal serotonin levels. The two types of monkeys were separated into groups raised by peers and other groups raised by mothers. The mother-raised monkeys of both allele types showed normal 5-HIAA levels, while peer-raised monkeys with short alleles showed much lower levels than either group of normal monkeys. The same pattern was seen with aggression, with short-allele mother-raised monkeys showing the same low level of aggression as normal monkeys in either group, and peer-raised short-allele monkeys showing high levels of aggression. The peer-raised monkeys acted far more anxious, clingy and fearful, no matter what their allele type.
"So good mothering is very important and goes a long way toward protecting these [at-risk] monkeys," said Suomi.
Furthermore, there is a non-genetic transmission of mothering, as the attachment style of monkey mothers--whether foster or not--is usually copied by daughters. Rat studies also support evidence for the gene-environment interaction.
Regina Pally, M.D., assistant clinical professor at the University of California at Los Angeles Neuropsychiatric Institute and chair of the panel, reviewed rat projects conducted by Michael Meaney, Ph.D., and colleagues at McGill University (see Zhang et al., 2004.) She explained that in rats, maternal care runs across a spectrum from highly nurturing mothers to poorly nurturing mothers, and that offspring resemble their mothers as to behavior and emotional temperament.
To address the question of nature versus nurture with regard to these observations, Meaney used an experimental design called "cross-fostering," wherein rats who are inbred to share the same genes are developed into two strains, each at opposite ends of the nurturing spectrum. Right after birth, some of the pups of low-nurturing mothers are placed with high-nurturing mothers, and some of the pups of high-nurturing mothers are likewise switched. Therefore, each mother is rearing both biological and foster pups.
"The mothering environment shaped the genes. Every gene has a promoter region which turns it on or off, and the environment influences the promoter," explained Pally.
Results showed that in terms of emotion and behavior, pups resemble the mother that raised them more than their biological mother. The results were interpreted in terms of gene expression.
"It is in this way that over the course of development, the growth of the brain--in terms of neurons, neurotransmitters, and neurotransmitter receptors--will be affected and will be manifest as behaviors and emotions, such as how that individual responds to stress or how nurturing that individual is," concluded Pally.
Caspi A, McClay J, Moffitt TE et al. (2002), Role of genotype in the cycle of violence in maltreated children. Science 297(5582):851-854 [see comment].
Caspi A, Sugden K, Moffitt TE et al. (2003), Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 301(5631):386-389 [see comment].
Donegan NH, Sanislow CA, Blumberg HP et al. (2003), Amygdala hyperreactivity in borderline personality disorder: implications for emotional dysregulation. Biol Psychiatry 54(11):1284-1293.
Driessen M, Herrmann J, Stahl K et al. (2000), Magnetic resonance imaging volumes of the hippocampus and the amygdala in women with borderline personality disorder and early traumatization. Arch Gen Psychiatry 57(12):1115-1122.
Foley DL, Eaves LJ, Wormley B et al. (2004), Childhood adversity, monoamine oxidase A genotype, and risk for conduct disorder. Arch Gen Psychiatry 61(7):738-744.
Hariri AR, Mattay VS, Tessitore A et al. (2002), Serotonin transporter genetic variation and the response of the human amygdala. Science 297(5580):400-403 [see comment].
Kaufman J, Yang BZ, Douglas-Palumberi H et al. (2004), Social supports and serotonin transporter gene moderate depression in maltreated children. Proc Natl Acad Sci U S A 101(49):17316-17321 [see comment].
Olds D, Henderson CR Jr, Cole R et al. (1998), Long-term effects of nurse home visitation on children's criminal and antisocial behavior: 15-year follow-up of a randomized controlled trial. JAMA 280(14):1238-1244 [see comments].
Reiss D, Hetherington EM, Plomin R et al. (1995), Genetic questions for environmental studies. Differential parenting and psychopathology in adolescence. Arch Gen Psychiatry 52(11):925-936.
Schmahl CG, Vermetten E, Elzinga BM, Bremner DJ (2003), Magnetic resonance imaging of hippocampal and amygdala volume in women with childhood abuse and borderline personality disorder. Psychiatry Res 122(3):193-198.
Suomi SJ (2003), Gene-environment interactions and the neurobiology of social conflict. Ann N Y Acad Sci 1008:132-139.
Tebartz van Elst L, Hesslinger B, Thiel T et al. (2003), Frontolimbic brain abnormalities in patients with borderline personality disorder: a volumetric magnetic resonance imaging study. Biol Psychiatry 54(2):163-171.
Zhang TY, Parent C, Weaver I, Meaney MJ (2004), Maternal programming of individual differences in defensive responses in the rat. Ann N Y Acad Sci 1032:85-103.