Exploring associations between perinatal depression, anxiety, and urinary oxytocin levels in Latinas.

Perinatal depression has been associated with lower oxytocin (OT) levels. However, few studies have explored this topic in relation to Latinas who are at high risk of perinatal depression. The objective of this study was to explore these associations in Latinas. A total of 108 Latinas in the third trimester of pregnancy participated in the study. Depression and urinary OT levels were assessed in pregnancy and 6 weeks postpartum. Nonparametric tests were implemented to test the proposed associations. Results revealed that 28% of the participants had probable depression in pregnancy, and 23% at 6 weeks postpartum. OT levels significantly decreased from prenatal to postpartum in the whole sample; however, participants with probable prenatal depression did not exhibit a significant change in OT levels. Participants who were depressed or anxious at 6 weeks postpartum exhibited persistently higher mean OT levels over time. A distinct pattern of higher levels of OT in depressed Latinas suggests that OT levels may be an important neuroendocrine factor contributing to depressive and anxious symptoms.

The effect of intranasal oxytocin on neurocognition in people with schizophrenia: A randomized controlled trial.

Schizophrenia is characterized by persistent cognitive deficits that significantly impact functional outcomes. Despite the current available treatments, these deficits remain inadequately addressed, highlighting the need to explore the effect of more novel treatments on cognition. The current study examined the effect of intranasal oxytocin on cognitive functioning in people with schizophrenia by utilizing data from a 12-week, randomized controlled trial. Sixty-seven participants with schizophrenia or schizoaffective disorder were randomized to receive placebo or intranasal oxytocin. Participants completed a comprehensive neuropsychological battery at baseline and 12 weeks. The results demonstrated that intranasal oxytocin did not significantly improve cognition in people with schizophrenia compared to placebo. These findings suggest that oxytocin does not worsen or enhance cognition in people with schizophrenia. Yet, the current intervention did not standardize the timing of cognitive assessments relative to the timing of oxytocin administration, which may explain our findings. Future studies attempting to clarify this relationship would benefit from employing a more controlled approach to the timing of treatment and assessments.

Intranasal oxytocin blocks alcohol withdrawal in human subjects.

BACKGROUND: The neuropeptide, oxytocin (OT), has been reported to block tolerance formation to alcohol and decrease withdrawal symptoms in alcohol-dependent rodents. Numerous recent studies in human subjects indicate that OT administered by the intranasal route penetrates into and exerts effects within the brain. METHODS: In a randomized, double-blind clinical trial, intranasal OT (24 IU/dose, N = 7) or placebo (N = 4) was given twice daily for 3 days in alcohol-dependent subjects admitted to a research unit for medical detoxification using Clinical Institute Withdrawal Assessment for Alcohol (CIWA) score-driven PRN administration of lorazepam. Subjects rated themselves on the Alcohol Withdrawal Symptom Checklist (AWSC) each time CIWA scores were obtained. Subjects also completed the Penn Alcohol Craving Scale, an Alcohol Craving Visual Analog Scale (ACVAS) and the Profile of Mood States (POMS) on inpatient days 2 and 3. RESULTS: All subjects had drunk heavily each day for at least 2 weeks prior to study and had previously experienced withdrawal upon stopping/decreasing alcohol consumption. OT was superior to placebo in reducing alcohol withdrawal as evidenced by: less total lorazepam required to complete detoxification (3.4 mg [4.7, SD] vs. 16.5 [4.4], p = 0.0015), lower mean CIWA scores on admission day 1 (4.3 [2.3] vs. 11.8 [0.4], p < 0.0001) and day 2 (3.4 [2.2] vs. 11.1 [3.6], p < 0.002), lower AWSC scores on days 1 and 2 (p < 0.02; p = 0.07), and lower ACVAS ratings (p = 0.01) and lower POMS Tension/Anxiety subscale scores on day 2 (p < 0.01). CONCLUSIONS: This is the first demonstration that OT treatment may block alcohol withdrawal in human subjects. Our results are consistent with previous findings in rodents that OT inhibits neuroadaptation to and withdrawal from alcohol. OT could have advantages over benzodiazepines in managing alcohol withdrawal because it may reverse rather than maintain sedative-hypnotic tolerance. It will be important to test whether OT treatment is effective in reducing drinking in alcohol-dependent outpatients.

Racial disparities and predictors of functioning in schizophrenia.

Black Americans are diagnosed with schizophrenia spectrum disorders at more than twice the rate of White individuals and experience significantly worse outcomes following diagnosis. Little research has examined specific factors that may contribute to worse functional outcomes among Black Americans diagnosed with schizophrenia. One approach to understanding why racial disparities emerge is to examine established predictors of functioning in this population: neurocognition, social cognition, and symptom severity. The present study aims to broaden existing literature on racial differences within these domains by (a) examining racial differences in functioning and these established predictors of functioning (i.e., neurocognition, social, and symptom severity) and (b) investigating whether cognition and symptom domains similarly predict functioning between Black and White Americans with schizophrenia. Sixty-six participants' baseline neurocognition, social cognition, symptom severity, and functioning were assessed. Black participants demonstrated lower neurocognition scores and higher levels of disorganized symptoms relative to White participants. No racial differences in functioning or social cognition were observed. Further, race did not moderate the relationship between any of these established predictors and functioning outcomes. The largely nonsignificant differences in known predictors of functioning highlight the need to explore further domains that may be more relevant for understanding racial disparities in schizophrenia. Considering that psychosocial treatments for schizophrenia spectrum disorders often focus on cognition, these results underscore the importance of identifying whether these domains or other treatment targets may be better in addressing racial disparities in functioning. Possible areas of exploration for future work (e.g., structural factors, racism-related stress) are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Associations between Self-Rated Health and Perinatal Depressive and Anxiety Symptoms among Latina Women.

PURPOSE: The objective of this study was to determine whether decreases in or consistently low preconception to pregnancy self-rated health (SRH) were associated with perinatal depressive and anxiety symptoms among Latinas. METHODS: This is a secondary data analysis of 153 perinatal Latinas. Three groups were created to capture SRH from preconception to pregnancy: a decline in ratings, consistently low, and good+ (i.e., good, very good, or excellent). SRH was measured using two questions about their perceived physical health before and during pregnancy. Depressive symptoms and anxiety symptoms were assessed in the third trimester and six weeks postpartum using the Edinburgh Postnatal Depression Scale and State-Trait Anxiety Inventory, respectively. Life stressors were assessed in pregnancy using a modified version of the Life Experiences Survey. Linear regressions tested the associations. RESULTS: Women with consistently low (i.e., fair or poor) SRH reported significantly more prenatal depressive symptoms than women who reported consistently good+ SRH. Women who reported a decline in SRH to fair or poor reported more prenatal anxiety symptoms but decreased postpartum anxiety symptoms than women who reported consistently good+ ratings. Life stressors were positively associated with prenatal depressive and anxiety symptoms. CONCLUSIONS: Healthcare practitioners should assess changes in SRH ratings to identify risks for prenatal depressive and anxiety symptoms among Latinas, who have elevated rates of depressive and anxiety symptoms compared to non-Hispanic White women. Policymakers should provide healthcare providers with mental health resources to support at-risk Latinas during the prenatal period.

Prosocial effects of an oxytocin metabolite, but not synthetic oxytocin receptor agonists, in a mouse model of autism.

Currently, there are no established pharmaceutical strategies that effectively treat social deficits in autism spectrum disorder (ASD). Oxytocin, a neurohormone that plays a role in multiple types of social behaviors, has been proposed as a possible therapeutic against social impairment and other symptoms in ASD. However, from the standpoint of pharmacotherapy, oxytocin has several liabilities as a standard clinical treatment, including rapid metabolism, low brain penetrance, and activity at the vasopressin (antidiuretic hormone) receptors. The present studies describe findings from a preclinical screening program to evaluate oxytocin receptor (OXTR) agonists and oxytocin metabolites for potential clinical use as more optimal treatments. We first investigated two synthetic oxytocin analogs, TC-OT-39 and carbetocin, using in vitro cell-based assays for pharmacological characterization and behavioral tests in the BALB/cByJ mouse model of ASD-like social deficits. Although both TC-OT-39 and carbetocin selectively activate the OXTR, neither synthetic agonist had prosocial efficacy in the BALB/cByJ model. We next evaluated two oxytocin metabolites: OT(4-9) and OT(5-9). While OT(5-9) failed to affect social deficits, the metabolite OT(4-9) led to significant social preference in the BALB/cByJ model, in a dose-dependent manner. The increased sociability was observed at both 24 h and 12 days following the end of a subchronic regimen with OT(4-9) (2.0 mg/kg). Overall, these results suggest that the prosocial effects of oxytocin could be mediated by downstream activity of oxytocin metabolites, raising the possibility of new pathways to target for drug discovery relevant to ASD.

Early Life Abuse Moderates the Effects of Intranasal Oxytocin on Symptoms of Premenstrual Dysphoric Disorder: Preliminary Evidence From a Placebo-Controlled Trial.

Background: Although intranasal oxytocin (OXT) has been proposed to be a promising treatment for some psychiatric disorders, little research has addressed individual difference factors that may predict response to OXT. One such factor is early life abuse (ELA), which has widespread influences on social-emotional processing and behavior. This single-blind, placebo-controlled crossover trial examined the role of ELA in shaping the effects of intranasal OXT (vs. placebo) on daily behavioral symptoms in women with three or more prospectively-diagnosed cycling symptoms of premenstrual dysphoric disorder (PMDD). Methods: Participants were ten women with PMDD (n = 8) or subthreshold PMDD (n = 2), who had experienced ELA prior to age 13 (n = 5) or no ELA (n = 5). They completed two study visits during the late luteal (premenstrual) phase: once following administration of intranasal OXT and once following intranasal placebo (counterbalanced). Participants then self-administered OXT or placebo at home three times per day for 5 days or until menstrual onset, and prospectively rated daily emotional symptoms of PMDD. Power was adequate to detect medium main and interactive effects. Results: Among women with ELA, intranasal OXT (vs. placebo) increased the premenstrual emotional symptoms of PMDD, whereas among women without ELA, OXT decreased symptoms. Conclusion: This study adds to a growing literature highlighting the importance of considering historical social contexts and traits (such as ELA) as moderators of therapeutic response to OXT.

Antenatal thyroid correlates of postpartum depression.

We previously found significantly higher T3-resin uptake and nearly significantly lower total thyroxine concentrations at 38 weeks of pregnancy in women with higher postpartum depression ratings. This study further examined the relationship between thyroid status during late pregnancy and antenatal and postpartum depression scores. Thyroid measures were obtained at 32-35, 36, and 37 weeks of pregnancy in 31 women with normal range thyroid hormone levels. Subjects rated their mood at these antenatal time points and every other week between postpartum weeks 2 and 24 on the Edinburgh Postnatal Depression Scale and the Beck Depression Inventory. Mean antenatal thyroxine concentrations and free thyroxine indices correlated significantly and negatively with mean depression scores during each of three postpartum time periods (postpartum weeks 2-6, 14-18, 20-24). Women with total and free thyroxine concentrations that were, respectively, <10.1 microg/dl and <1.06 ng/dl at all three antenatal time points had significantly higher mean depression scores during all postpartum time periods. The fraction of subjects with pregravid major or minor depression history that was in the low antenatal thyroid group was significantly higher than the fraction of subjects with negative history (5/6 vs. 7/25). Women with antenatal total and free thyroxine concentrations in the lower euthyroid range may be at greater risk of developing postpartum depressive symptoms. Study of the relationships with antenatal thyroid status may provide new insights into the pathophysiology of perinatal mood disturbances.

Repeated long separations from pups produce depression-like behavior in rat mothers.

Long maternal (LMS) versus brief maternal (BMS) daily separations of rat pups from their mothers have contrasting effects on their adult stress responses and maternal behavior by, respectively, decreasing and increasing licking received from their mothers. We hypothesized that LMS decreases pup-licking in mothers by inducing learned helplessness, creating a depression-like state. We subjected postpartum rats to LMS (3 h), BMS (15 min) or no separation (NMS) on postpartum days 2-14. After weaning, mothers were given a forced swim test (FST). LMS mothers exhibited more immobility and fewer escape attempts than BMS or NMS mothers. These results suggest that LMS induces a depression-like state, which may account for the reductions in maternal behavior seen in LMS mothers. Immobility in the FST is recognized as an animal model of depression. Therefore, LMS may be a model of maternal depression.

Persistent alterations in biological profiles in women with abuse histories: influence of premenstrual dysphoric disorder.

OBJECTIVE: To examine dysregulation in biological measures associated with histories of abuse in women and whether women with premenstrual dysphoric disorder (PMDD) differ in their dysregulation. DESIGN: Twenty-five women meeting prospective criteria for PMDD and 42 non-PMDD controls underwent structured interview to determine abuse histories and lifetime Axis I diagnoses, excluding those with current Axis I disorders or using medications. MAJOR OUTCOME MEASURES: Plasma cortisol and norepinephrine (NE), heart rate (HR), blood pressure (BP), and vascular resistance index (VRI) were assessed at rest and in response to mental stress. RESULTS: A greater proportion of PMDD women had prior abuse compared with non-PMDD women. Regardless of PMDD status, all abused women had lower plasma NE and higher HRs and tended to have lower plasma cortisol at rest and during stress. Abused women also reported more severe daily emotional and physical symptoms. Greater VRI and BP at rest and during stress were seen only in PMDD women with abuse. CONCLUSION: There is persistent dysregulation in stress-responsive systems in all abused women that cannot be accounted for by current psychiatric illness or medications, and PMDD women may be differentially more vulnerable to the impact of abuse on measures reflecting alpha-adrenergic receptor function.

Oxytocin, Tolerance, and the Dark Side of Addiction.

Substance use disorders blight the lives of millions of people and inflict a heavy financial burden on society. There is a compelling need for new pharmacological treatments as current drugs have limited efficacy and other major drawbacks. A substantial number of animal and recent clinical studies indicate that the neuropeptide, oxytocin, is a particularly promising therapeutic agent for human addictions, especially alcohol use disorders. In preliminary trials, we found that oxytocin administered by the intranasal route, which produces some neuropeptide penetration into the CNS, potently blocked withdrawal and reduced alcohol consumption in heavy drinkers. A considerable body of earlier animal studies demonstrated that oxytocin inhibits tolerance to alcohol, opioids, and stimulants as well as withdrawal from alcohol and opioids. Based on these preclinical findings and our clinical results, we hypothesize that oxytocin may exert therapeutic effects in substance dependence by the novel mechanism of diminishing established tolerance. A newer wave of studies has almost unanimously found that oxytocin decreases self-administration of a number of addictive substances in several animal models of addiction. Reduction of established tolerance should be included among the potential explanations of oxytocin effects in these studies and changes in tolerance should be examined in future studies in relationship to oxytocin influences on acquisition and reinstatement of self-administration as well as extinction of drug seeking. Oxytocin efficacy in reducing anxiety and stress responses as well as established tolerance suggests it may be uniquely effective in reducing negative reinforcement (Koob's "dark side" of addiction) that maintains chronic substance use.

A 12-week randomized controlled trial of twice-daily intranasal oxytocin for social cognitive deficits in people with schizophrenia.

Social cognition is impaired in people with schizophrenia and these deficits are strongly correlated with social functioning. Oxytocin is a hypothalamic peptide that contributes to maternal infant bonding and has diverse pro-social effects in adults. This study tested the hypothesis that 12weeks of intranasal oxytocin will improve social cognitive function in outpatients with schizophrenia and schizoaffective disorder. Sixty-eight eligible participants were randomized to oxytocin (24IU twice daily) or placebo. Social cognitive function was assessed using the Emotion Recognition-40, Brüne Theory of Mind, Reading the Mind in the Eyes test, Trustworthiness task and Ambiguous Intentions Hostility Questionnaire at baseline, 6weeks and 12weeks. In addition, social function was assessed using the Specific Levels of Functioning Scale and a role-play test, and psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS). Fifty-five participants completed the 12-week trial. The study found no evidence for a differential advantage of oxytocin over placebo on social cognition. Among secondary outcomes, there was a modest advantage for oxytocin over placebo on a component of social functioning, although there was also evidence that the placebo group outperformed the oxytocin group on the role-play task. No between-group differences emerged on measures of psychopathology in pre-specified comparisons, but oxytocin showed significant within-group reduction in PANSS negative symptoms and significant between-group improvement in negative symptoms in the schizophrenia subgroup. Further testing is needed to clarify whether oxytocin has therapeutic potential for social cognitive deficits and/or negative symptoms in people with schizophrenia.

Associations of histories of depression and PMDD diagnosis with allopregnanolone concentrations following the oral administration of micronized progesterone.

Twenty-three women with premenstrual dysphoric disorder (PMDD) and 29 non-PMDD controls were compared for plasma progesterone (P) and its neuroactive steroid metabolite allopregnanolone (ALLO), as well as the ALLO/P ratio following the double-blind, placebo controlled administration of 300 mg oral micronized progesterone. Approximately half of each group had prior depression (DEP) (13 PMDD, 12 non-PMDD), though all were free of current depression. Progesterone and ALLO were sampled 160, 190, 225, and 255 min after progesterone administration. Changes over time in plasma concentrations and the ALLO/P ratio were assessed using area under the curve analyses. Women with prior DEP had lower ALLO levels (p=0.05) and marginally lower P levels (p<0.07) following progesterone administration compared to never depressed women, and this was especially evident in the non-PMDD women (p<0.01). PMDD women with no prior DEP had higher pre-progesterone ALLO/P ratios than all other groups (Ps<0.05) and higher ratios than the never depressed, non-PMDD women following oral progesterone (p<0.05). Results could not be accounted for by group differences in steroid hormone binding protein concentrations. For all women, progesterone administration was associated with increased confusion, fatigue, and with reduced confidence (Ps<0.01), even after controlling for placebo-associated mood change. These results suggest a persistent effect of prior DEP on P and ALLO concentrations following oral progesterone and that PMDD women, especially those with no prior DEP, may have alterations in the metabolic pathways underlying the conversion of P to ALLO.

Histories of depression, allopregnanolone responses to stress, and premenstrual symptoms in women.

Twenty-six women meeting DSM criteria for premenstrual dysphoric disorder (PMDD) and 39 non-PMDD controls were tested for allopregnanolone (ALLO) responses to mental stress. Approximately half of each group had a history of depression (DEP) (14 PMDD, 17 non-PMDD), though all were free of current psychiatric illness. ALLO was sampled in response to venipuncture stress, after an extended baseline, and again 30 and 60 min following the onset of mental stressors. All women with prior DEP, regardless of PMDD status, showed a blunted ALLO stress response at 30 and 60 min (p < 0.05), and also failed to show the expected decrease from venipuncture to baseline rest (p = 0.08) compared to women with no prior DEP. Women with prior DEP did not show the expected correlation between progesterone and ALLO (r = 0.16) that was seen in those with no prior DEP (r = 0.37, p < 0.05). ALLO levels at extended baseline and blunted ALLO reactivity predicted more severe premenstrual symptoms, but only in PMDD women with prior DEP (p values <0.05). These results suggest that a history of DEP is associated with a failure of ALLO to be appropriately responsive to challenge, with alterations in the conversion of progesterone to ALLO, and confirm prior reports linking ALLO to symptoms in PMDD, but only in PMDD women with histories of DEP.

Reversal of social deficits by subchronic oxytocin in two autism mouse models.

Social deficits are a hallmark feature of autism spectrum disorder (ASD) and related developmental syndromes. Although there is no standard treatment for social dysfunction, clinical studies have identified oxytocin as a potential therapeutic with prosocial efficacy. We have previously reported that peripheral oxytocin treatment can increase sociability and ameliorate repetitive stereotypy in adolescent mice from the C58/J model of ASD-like behavior. In the present study, we determined that prosocial oxytocin effects were not limited to the adolescent period, since C58/J mice, tested in adulthood, demonstrated significant social preference up to 2 weeks following subchronic oxytocin treatment. Oxytocin was also evaluated in adult mice with underexpression of the N-methyl-d-aspartate receptor NR1 subunit (encoded by Grin1), a genetic model of autism- and schizophrenia-like behavior. Subchronic oxytocin had striking prosocial efficacy in male Grin1 knockdown mice; in contrast, chronic regimens with clozapine (66 mg/kg/day) or risperidone (2 mg/kg/day) failed to reverse deficits in sociability. Neither the subchronic oxytocin regimen, nor chronic treatment with clozapine or risperidone, reversed impaired prepulse inhibition in the Grin1 knockdown mice. Overall, these studies demonstrate oxytocin can enhance sociability in mouse models with divergent genotypes and behavioral profiles, adding to the evidence that this neurohormone could have therapeutic prosocial efficacy across a spectrum of developmental disorders.

Histories of sexual abuse are associated with differential effects of clonidine on autonomic function in women with premenstrual dysphoric disorder.

In women meeting strict criteria for premenstrual dysphoric disorder (PMDD), we examined whether clonidine, an alpha2-adrenergic receptor (AR) agonist, would have different effects on sexually abused versus non-abused PMDD women for measures of autonomic nervous system function. Twelve women meeting prospective, DSM-IV criteria for PMDD, five of whom had a history of sexual abuse, participated in a randomized, placebo-controlled, double-blind, cross-over design study, comparing 2 months of on oral clonidine (0.3 mg/day) with 2 months on active placebo. During the luteal phase that preceded randomization and following each two-month challenge, women were tested for cardiovascular measures at rest and in response to mental stress, and for resting plasma norepinephrine (NE) concentrations as well as beta1 and beta2-AR responsivity using the isoproterenol sensitivity test. Results revealed that in comparison to placebo, clonidine significantly reduced plasma norepinephrine concentrations, increased both beta1- and beta2-AR responsivity, and reduced resting and stress heart rate (HR) and blood pressure (BP) (p < 0.05) in all PMDD women. With clonidine, sexually abused PMDD women exhibited greater decreases in resting and stress-induced HR (p < 0.01) and stress-induced systolic BP (p < 0.05), while non-abused PMDD women exhibited greater reductions in plasma NE concentration (p = 0.07), and greater increases in beta2-AR responsivity (p < 0.05) than abused PMDD women. These results suggest PMDD women with and without a history of sexual abuse respond differently to a clonidine challenge in measures reflecting autonomic nervous system functioning, indicating that abuse may modify presynaptic alpha2-AR function in PMDD.

The influence of early life sexual abuse on oxytocin concentrations and premenstrual symptomatology in women with a menstrually related mood disorder.

Oxytocin (OT), associated with affiliation and social bonding, social salience, and stress/pain regulation, may play a role in the pathophysiology of stress-related disorders, including menstrually-related mood disorders (MRMD's). Adverse impacts of early life sexual abuse (ESA) on adult attachment, affective regulation, and pain sensitivity suggest ESA-related OT dysregulation in MRMD pathophysiology. We investigated the influence of ESA on plasma OT, and the relationship of OT to the clinical phenomenology of MRMD's. Compared to MRMD women without ESA (n=40), those with ESA (n=20) displayed significantly greater OT [5.39pg/mL (SD, 2.4) vs. 4.36pg/mL (SD, 1.1); t (58)=-2.26, p=0.03]. In women with ESA, OT was significantly, inversely correlated with premenstrual psychological and somatic symptoms (r's=-0.45 to -0.64, p's<0.05). The relationship between OT and premenstrual symptomatology was uniformly low and non-significant in women without ESA. In women with ESA, OT may positively modulate MRMD symptomatology.

Historical sexual abuse and current thyroid axis profiles in women with premenstrual dysphoric disorder.

OBJECTIVE: This study investigated whether women with premenstrual dysphoric disorder (PMDD) who also had histories of sexual abuse differed from women with PMDD with no previous sexual abuse and from women without PMDD in hypothalamic-pituitary-thyroid (axis measures). METHODS: Ten sexually abused women with PMDD were compared with 18 nonabused women with PMDD and 22 nonabused women without PMDD for hypothalamic-pituitary-thyroid axis hormone concentrations during the follicular and luteal phases of confirmed ovulatory cycles. RESULTS: Compared with the women without PMDD, only the group of women with PMDD with sexual abuse showed greater variance in both cycle phases in thyroid-stimulating hormone concentrations and greater luteal phase variance in free and total thyroxine (T4) and reverse tri-iodothyronine (T3). In the group of nonabused women with PMDD, there was greater variance in follicular phase thyroxine-binding globulin concentrations compared with the group without PMDD. Women with PMDD with abuse had greater mean concentrations of total T3 and thyroxine-binding globulin, greater total T3/free T4 and free T3/free T4 ratios, and lower ratios of free T3/total T3 and free T4/total T4 than either of the other 2 nonabused groups. Greater total T3 concentrations and histories of major depression independently predicted premenstrual symptoms in all women with PMDD, together accounting for 31% to 38% of the variance in anxiety, anger, and depression ratings. CONCLUSIONS: These results suggest increased conversion of T4 to T3 and increased binding of thyroid hormones in women with PMDD with previous sexual abuse. Abnormal total T3 concentrations may have pathophysiological significance in PMDD.

Biological correlates of abuse in women with premenstrual dysphoric disorder and healthy controls.

OBJECTIVE: To examine the biological correlates associated with histories of sexual or physical abuse in women meeting DSM criteria for premenstrual dysphoric disorder (PMDD) and in healthy, non-PMDD controls. METHODS: Twenty-eight women with prospectively confirmed PMDD were compared with 28 non-PMDD women for cardiovascular and neuroendocrine measures at rest and in response to mental stressors, and for beta-adrenergic receptor responsivity, during both the follicular and luteal phase of the menstrual cycle. Structured interview was used to assess psychiatric history and prior sexual and physical abuse experiences. All subjects were free of current psychiatric comorbidity and medication use. RESULTS: More PMDD women had prior sexual and physical abuse experiences than controls (20 vs. 10, respectively). Relative to nonabused PMDD women, PMDD women with prior abuse (sexual or physical) exhibited significantly lower resting norepinephrine (NE) levels and significantly greater beta1- and beta2-adrenoceptor responsivity and greater luteal phase NE reactivity to mental stress. For non-PMDD control women, abuse was associated with blunted cortisol, cardiac output, and heart rate reactivity to mental stress relative to nonabused controls. CONCLUSIONS: The results of this initial study suggest that a history of prior abuse is associated with alterations in physiological reactivity to subsequent mental stress in women, but that the biological correlates of abuse may be different for PMDD vs. non-PMDD women.

Biological aspects of social bonding and the roots of human violence.

The brain systems that motivate humans to form emotional bonds with others probably first evolved to mobilize the high-quality maternal care necessary for reproductive success in placental mammals. In these species, the helplessness of infants at birth and their dependence upon nutrition secreted from their mothers' bodies (milk) and parental body heat to stay warm required the evolution of a new motivational system in the brain to stimulate avid and sustained mothering behavior. Other types of social bonds that emerged subsequently in placental mammals, in particular monogamous bonds between breeding pairs, appear to have evolved from motivational brain systems that stimulate maternal behavior. This chapter focuses on aspects of the evolution and neurobiology of maternal and pair bonding and associated behavioral changes that may provide insights into the origins of human violence. The roles of the neuropeptides oxytocin and vasopressin as well as the neurotransmitter dopamine will be emphasized. Maternal and pair bonding are accompanied by increased aggressiveness toward perceived threats to the object of attachment as well as diminished fear and anxiety in stressful situations. The sustained closeness with mother required for the survival of infant mammals opened a new evolutionary niche in which aspects of the mother's care became increasingly important in regulating development in offspring. The quantity and quality of maternal care received during infancy determines adult social competence, ability to cope with stress, aggressiveness, and even preference for addictive substances. Indeed, the development of neurochemical systems within the brain that regulate mothering, aggression, and other types of social behavior, such as the oxytocin and vasopressin systems, are strongly affected by parental nurturing received during infancy. Evidence will be reviewed that the neural circuitry and neurochemistry implicated in studies of lower mammals also facilitate primate/human interpersonal bonding. It is hypothesized that neural bonding systems may also be important for the development in individuals of loyalty to the social group and its culture. Neglect and abuse during early life may cause bonding systems to develop abnormally and compromise capacity for rewarding interpersonal relationships and commitment to societal and cultural values later in life. Other means of stimulating reward pathways in the brain, such as drugs, sex, aggression, and intimidating others, could become relatively more attractive and less constrained by concern about violating trusting relationships. The ability to modify behavior based on negative experiences may be impaired. Unmet needs for social bonding and acceptance early in life might increase the emotional allure of groups (gangs, sects) with violent and authoritarian values and leadership. Social neurobiology has the potential to provide new strategies for treating and preventing violence and associated social dysfunction.