Margaret Altemus

Prolonged institutional rearing is associated with atypically large amygdala volume and difficulties in emotion regulation.

Early adversity, for example poor caregiving, can have profound effects on emotional development. Orphanage rearing, even in the best circumstances, lies outside of the bounds of a species-typical caregiving environment. The long-term effects of this early adversity on the neurobiological development associated with socio-emotional behaviors are not well understood. Seventy-eight children, who include those who have experienced orphanage care and a comparison group, were assessed. Magnetic resonance imaging (MRI) was used to measure volumes of whole brain and limbic structures (e.g. amygdala, hippocampus). Emotion regulation was assessed with an emotional go-nogo paradigm, and anxiety and internalizing behaviors were assessed using the Screen for Child Anxiety Related Emotional Disorders, the Child Behavior Checklist, and a structured clinical interview. Late adoption was associated with larger corrected amygdala volumes, poorer emotion regulation, and increased anxiety. Although more than 50% of the children who experienced orphanage rearing met criteria for a psychiatric disorder, with a third having an anxiety disorder, the group differences observed in amygdala volume were not driven by the presence of an anxiety disorder. The findings are consistent with previous reports describing negative effects of prolonged orphanage care on emotional behavior and with animal models that show long-term changes in the amygdala and emotional behavior following early postnatal stress. These changes in limbic circuitry may underlie residual emotional and social problems experienced by children who have been internationally adopted.

Preliminary Research on Plasma Oxytocin in Normal Cycling Women: Investigating Emotion and Interpersonal Distress

The neurohormone oxytocin is responsible for initiating childbirth and the let-down reflex in lactating women and is released during sexual orgasm. Oxytocin has been thought of as an affiliation hormone because research on nonhuman mammals has demonstrated that it plays a key role in the initiation of maternal behavior and the formation of adult pair bonds. It has been speculated that social stimuli may induce oxytocin release and that oxytocin may make positive social contact more rewarding. Data are presented from an initial study to examine change in plasma oxytocin in response to a standard imagery task that elicits emotion related to attachment. Twenty-five normal cycling, healthy women underwent imagery tasks and completed questionnaires on attachment and interpersonal problems. Blood draws (5 ml) were bone via an indwelling catheter before, during, and after three interventions (massage, positive emotion, and negative emotion) and to establish baselines. Overall, the data showed a tendency for oxytocin levels to be elevated in response to relaxation massage and decreased in response to sad emotion. There were individual differences in response to the interventions. Those who showed evidence of increased oxytocin levels for positive emotion and massage and who maintained oxytocin levels during negative emotion were less likely to report interpersonal problems associated with intrusiveness. Maintaining oxytocin levels during sadness was also correlated with lower anxiety in close relationships. Women who were in a couple relationship had greater increases in oxytocin in response to positive emotion. In contrast, higher basal levels of oxytocin were associated with greater interpersonal distress. These data suggest that peripheral secretion of oxytocin in response to emotional stimuli is associated with the individuals interpersonal characteristics.

Sex differences in depression and anxiety disorders: potential biological determinants.

The phenomenon of higher rates of affective disorders in women illustrates many of the difficulties as well as promises of translating preclinical models to human disorders. Abnormalities in the regulation of the hypothalamic-pituitary adrenal axis and the sympathoadrenomedullary system have been identified in depression and anxiety disorders, and these disorders are clearly precipitated and exacerbated by stress. Despite the striking sex difference in the prevalence of depression and anxiety disorders, attempts to identify corresponding sex differences in stress response reactivity in animal models have met with limited success. Processes which may contribute to increased rates of affective disorders in women are greater fluxes in reproductive hormones across the life span, and increased sensitivity to catecholamine augmentation of emotional memory consolidation.

Association of the serotonin transporter promoter regulatory region polymorphism and obsessive- compulsive disorder

Although modulation of symptoms of obsessive-compulsive disorder (OCD) by serotonergic agents is well established, it is unclear whether an abnormality in the central serotonergic system is involved in its etiology. The serotonin (5-HT) transporter (5-HTT), which is the key modulator of serotonergic neurotransmission, is the target for serotonin reuptake inhibiting drugs (SRIs) that are uniquely effective in the treatment of OCD. In this preliminary study we report an association of a functional polymorphism in the 5-HTT 5′ regulatory-region and OCD. Seventy-five OCD Caucasian patients and 397 ethnically-matched individuals from a non-patient control group were genotyped for the 5-HTTLPR. Population-based association analysis revealed that patients with OCD were more likely to carry two copies of the long allele (l) as compared to controls (46.7% vs 32.3%: χ2 = 5.19, P = 0.023). This finding replicates a recent family-based study of this polymorphism in OCD, and thus indicates that the 5-HTTLPR may be associated with susceptibility to OCD.

Romantic Love and Sexual Desire in Close Relationships

Drawing on recent claims in the study of relationships, attachment, and emotion, the authors hypothesized that romantic love serves a commitment-related function and sexual desire a reproduction-related function. Consistent with these claims, in Study 1, brief experiences of romantic love and sexual desire observed in a 3-min interaction between romantic partners were related to distinct feeling states, distinct nonverbal displays, and commitment- and reproductive-related relationship outcomes, respectively. In Study 2, the nonverbal display of romantic love was related to the release of oxytocin. Discussion focuses on the place of romantic love and sexual desire in the literature on emotion.

Responses to Laboratory Psychosocial Stress in Postpartum Women

Objective Lactation has been associated with attenuated hormonal responses to exercise stress in humans. This study was designed to determine the effect of lactation on hypothalamic-pituitary-adrenal axis, autonomic nervous system, and anxiety responses to psychological stress. Method The Trier Social Stress Test was administered to 24 lactating women, 13 postpartum nonlactating women, and 14 healthy control women in the early follicular phase of the menstrual cycle. Lactating women were stressed at least 40 minutes after last feeding their infant. Results ACTH, cortisol, heart rate, diastolic blood pressure, systolic blood pressure, and subjective anxiety ratings were all significantly increased in response to the psychological stress (all p < .0001). There were no differences among the three groups in any of these responses to the stress. However, postpartum nonlactating women did have a persistently higher systolic blood pressure and lower cardiac vagal tone than the lactating women and control subjects. In addition, the typical negative correlation between cardiac vagal tone and heart rate was consistently higher in lactating women than nonlactating postpartum women and controls, which suggests stronger vagal control of heart rate in lactating women. In addition, there was no change in oxytocin or allopregnanolone in response to the stress, and baseline oxytocin and allopregnanolone levels did not differ among the three groups. Conclusions These results indicate that physiological and subjective responses to social stress are not attenuated in lactating women tested at least one hour after feeding their infant. However, enhanced vagal control of cardiac reactivity was observed in lactating women. In addition, postpartum women who did not lactate showed evidence of increased sympathetic and decreased parasympathetic nervous system tone.

Effects of Estrogen Antagonists and Agonists on the ACTH Response to Restraint Stress in Female Rats

Previous studies have found that female rats are less sensitive than males to hypothalamic-pituitary-adrenal axis feedback inhibition by exogenous glucocorticoid administration. To determine whether estrogen contributes to this sex difference, we examined the effects of the estrogen antagonists tamoxifen and C1628 on the ACTH and corticosterone responses to restraint stress. CI628 increased both the ACTH and corticosterone response to restraint stress, and tamoxifen increased the ACTH response to restraint. Using overiectomized female rats, we also examined the effects of seven days of estradiol and/or progesterone replacement. Low dose estradiol decreased the ACTH but not the corticosterone response to restraint stress while progesterone had no effect on ACTH or corticosterone responses. The combination of estradiol and progesterone also decreased the ACTH response to stress, and the magnitude of the effect did not differ from that found with estradiol treatment alone. These data suggest that in the physiological range estradiol is an important inhibitory factor in the hypothalamic-pituitary-adrenal stress response of females.

Sex differences in anxiety and depression clinical perspectives

Sex differences are prominent in mood and anxiety disorders and may provide a window into mechanisms of onset and maintenance of affective disturbances in both men and women. With the plethora of sex differences in brain structure, function, and stress responsivity, as well as differences in exposure to reproductive hormones, social expectations and experiences, the challenge is to understand which sex differences are relevant to affective illness. This review will focus on clinical aspects of sex differences in affective disorders including the emergence of sex differences across developmental stages and the impact of reproductive events. Biological, cultural, and experiential factors that may underlie sex differences in the phenomenology of mood and anxiety disorders are discussed.

Hippocampal structural changes across the menstrual cycle

Magnetic resonance imaging (MRI) in association with Jacobian‐modulated voxel‐based morphometry (VBM) was used to test for regional variation in gray matter over the menstrual cycle. T1‐weighted anatomical images were acquired using a spoiled gradient recalled acquisition sequence in 21 women. Each subject was scanned twice: once during the postmenstrual late‐follicular phase (Days 10–12 after onset of menses), and once during the premenstrual late‐luteal phase (1–5 days before the onset of menses). Gray matter was relatively increased in the right anterior hippocampus and relatively decreased in the right dorsal basal ganglia (globus pallidus/putamen) in the postmenstrual phase. Verbal declarative memory was increased in the postmenstrual vs. premenstrual phase. This first report of human brain structural plasticity associated with the endogenous menstrual cycle extends well‐established animal findings of hormone‐mediated hippocampal plasticity to humans, and has implications for understanding alterations in cognition and behavior across the menstrual cycle.

Chapter 17 Neuroendocrine and emotional changes in the post-partum period

Abstract As well as having widespread effects on many aspects of mammalian physiology, the hormones of both the reproductive and stress axes can directly and indirectly influence behavior. Here we review possible mechanisms through which centrally active hormones of the female reproductive system and the hypothalamo-pituitary-adrenal stress axis may interact to influence behavior and mood states during the post-partum period. We will focus primarily on the behavioral effects of selected neuropeptide hormones, in particular oxytocin, vasopressin and corticotrophin-releasing hormone. The literature documenting central behavioral effects of these neuropeptides arises almost exclusively from research in experimental animals. In particular, it has been reported that during lactation in rats there are high blood and brain levels of oxytocin. At the same time there is a reduction in corticotrophin-releasing hormone in the brain and in its secretion in response to stress. These changes may contribute to optimal maternal care of the offspring. Correlational studies of peptides and behavior in the post-partum period also support the hypothesis that neuropeptides may influence human physiology and behavior. studies of post-partum women reveal powerful regulatory effects of lactation on the reactivity of the hypothalamo-pituitary-adrenal axis and of autonomic and immune systems, especially in the face of challenge. The integrative function of neural systems that influence both reproduction and the hypothalamo-pituitary-adrenal axis suggests one central mechanism for mediating the effects of environmental challenges.