Depression during pregnancy: the potential impact of increased risk for fetal aneuploidy on maternal mood.

Depression during pregnancy can have serious consequences for families. Indications of fetal aneuploidy can induce maternal stress, a risk factor for depression. Few studies have assessed symptoms of depression in pregnant women soon after they receive results indicating increased risk for fetal aneuploidy. We compared symptoms of depression in women who had increased risks for fetal aneuploidy with two other groups of pregnant women at similar gestational ages: controls, and women taking antidepressant medications (MEDS). Eighty-one women attending the British Columbia (BC) Medical Genetics (MG) Program regarding positive maternal serum screens or ultrasound soft marker findings completed the Edinburgh Postnatal Depression Scale (EPDS). Control (n = 41) and MEDS (n = 41) groups were recruited from the community or the BC Reproductive Mental Health program. A threshold score of 12 on the EPDS was used to calculate percentages of women likely to be depressed. Mean EPDS scores were compared using anova, followed by post-hoc tests. In the control, MG, and MEDS groups, 2.4%, 35%, and 52.4% of women, respectively, scored above 12. Mean EPDS score was significantly higher in the MG group than in the control group (p < 0.0001). These results suggest a place for depression screening in prenatal genetic counseling.

Telomeres, histone code, and DNA damage response.

Genomic stability is maintained by telomeres, the end terminal structures that protect chromosomes from fusion or degradation. Shortening or loss of telomeric repeats or altered telomere chromatin structure is correlated with telomere dysfunction such as chromosome end-to-end associations that could lead to genomic instability and gene amplification. The structure at the end of telomeres is such that its DNA differs from DNA double strand breaks (DSBs) to avoid nonhomologous end-joining (NHEJ), which is accomplished by forming a unique higher order nucleoprotein structure. Telomeres are attached to the nuclear matrix and have a unique chromatin structure. Whether this special structure is maintained by specific chromatin changes is yet to be thoroughly investigated. Chromatin modifications implicated in transcriptional regulation are thought to be the result of a code on the histone proteins (histone code). This code, involving phosphorylation, acetylation, methylation, ubiquitylation, and sumoylation of histones, is believed to regulate chromatin accessibility either by disrupting chromatin contacts or by recruiting non-histone proteins to chromatin. The histone code in which distinct histone tail-protein interactions promote engagement may be the deciding factor for choosing specific DSB repair pathways. Recent evidence suggests that such mechanisms are involved in DNA damage detection and repair. Altered telomere chromatin structure has been linked to defective DNA damage response (DDR), and eukaryotic cells have evolved DDR mechanisms utilizing proficient DNA repair and cell cycle checkpoints in order to maintain genomic stability. Recent studies suggest that chromatin modifying factors play a critical role in the maintenance of genomic stability. This review will summarize the role of DNA damage repair proteins specifically ataxia-telangiectasia mutated (ATM) and its effectors and the telomere complex in maintaining genome stability.

Infant serotonin transporter (SLC6A4) promoter genotype is associated with adverse neonatal outcomes after prenatal exposure to serotonin reuptake inhibitor medications.

Reduced Apgar scores and birth weight, increased risk of respiratory distress, jitteriness and increased tone have been reported in up to 30% of neonates with prenatal exposure to serotonin reuptake inhibitor (SRI) antidepressant medications. In adults, effects of these medications may be related to the genotype for the serotonin transporter (SLC6A4) promoter. In this study we investigated whether SLC6A4 genotype influences the risk for adverse outcomes in neonates with prenatal SRI exposure. Neonatal outcomes including Apgar scores, birth weight, gestational age at birth, symptoms of poor neonatal adaptation and genotype for SLC6A4 were determined in 37 prenatally SRI exposed neonates and compared with 47 non-exposed neonates. Reduced 5 min Apgar scores were observed in exposed neonates and this was moderated by the ss genotype (P<0.001). Birth weight was lower in exposed ls neonates (P=0.008). Risk for respiratory symptoms (respiratory distress and rapid breathing) was higher in exposed neonates with the ll genotype compared to non-exposed neonates (P<0.05) and risk for neuromotor symptoms increased in exposed ss neonates (P<0.026). These relationships remained when controlling for maternal mood during pregnancy, length of gestational medication exposure and gestational age at birth and cesarean section rate. Prenatal SRI exposure was associated with adverse neonatal outcomes and these effects were moderated by infant SLC6A4 genotype. Relationships between polymorphisms and specific outcomes varied during the neonatal period, suggesting that beyond apparent gene-medication interactions, multiple mechanisms contribute to adverse neonatal outcomes following prenatal SRI exposure.

Paroxetine levels in postpartum depressed women, breast milk, and infant serum.

BACKGROUND: The purpose of this study was to determine the concentrations of paroxetine in maternal serum, breast milk, and infant serum samples and to estimate infant exposure through breastfeeding. METHOD: A total of 25 sample sets was obtained: I sample set each from 23 mother-infant dyads and 2 sample sets from 1 mother-infant dyad. All mothers met DSM-IV criteria for major depressive disorder. The maternal fixed dosage of paroxetine was 10, 20, or 40 mg/day for a minimum of 30 days before the samples were drawn. Samples were collected 6 hours after dose intake, and the concentration of paroxetine in each sample was determined using gas chromatography/mass spectrometry. The analytic method employed in this study is the most sensitive to date, with the ability to detect drug concentrations as low as 0.1 ng/mL. RESULTS: Detectable levels of paroxetine were present in all maternal serum samples and in 24 of the 25 breast milk samples. In all of the infant serum samples, the paroxetine concentrations were below the lower limit of quantification. No unusual adverse effects were reported in any of the infants. CONCLUSION: The results of this study demonstrate that paroxetine, like the other selective serotonin reuptake inhibitors studied to date, is excreted into the breast milk of nursing mothers. The mean infant dose of paroxetine was 1. 1% of the maternal dose. Although no short-term adverse effects were reported in any of the infants in this study, future studies are needed to address a more systematic method for observing and recording any adverse effects. In addition, future studies should incorporate follow-up studies in order to evaluate possible long-term effects of paroxetine exposure.

The impact of partner support in the treatment of postpartum depression.

OBJECTIVE: To determine the impact of partner support in the treatment of mothers suffering from postpartum depression (PPD). METHOD: Patients underwent a comprehensive psychiatric assessment and were enrolled in the study only if they met the DSM-IV criteria for major depressive disorder with postpartum onset. Patients with PPD (n = 29) were assigned randomly to 2 treatment groups: group 1 (control group) consisted of patients only (n = 13), while group 2 (support group) consisted of patients (n = 16) and their partners. The patients in both groups were seen for 7 psychoeducational visits each. In group 2, partners participated in 4 of the 7 visits. Patients in both groups were administered a set of questionnaires that included the Edinburgh Postnatal Depression Scale (EPDS), the Kellner Symptom Questionnaire, the Dyadic Adjustment Scale (DAS), and the Parental Bonding Instrument (PBI). In addition, during visits 1 and 7, all patients underwent assessment using the Mini International Neuropsychiatric Instrument (MINI), section A (major depressive episode). The partners in both groups completed the DAS and the General Health Questionnaire (GHQ). RESULTS: Relative to the control-group patients, the support-group patients displayed a significant decrease in depressive symptoms and other psychiatric conditions. Relative to the support group, the general health of the partners in the control group deteriorated. CONCLUSION: Partner support has a measurable effect on women experiencing PPD.

The use of selective serotonin reuptake inhibitors during pregnancy and lactation: current knowledge.

This article reviews the effects of the selective serotonin reuptake inhibitor (SSRI) class of antidepressants in pregnant and lactating women for the treatment of depression and anxiety disorders. An examination of the literature was conducted using Medline (1966 to present). Despite methodological concerns and the scarcity of data on this important subject, the majority of recent investigations demonstrate safety of the fetus exposed to SSRIs during pregnancy. All of the SSRIs reported in the studies are excreted into breast milk, and low levels have been found in infant serum. The implications of this for practice include identifying the effects of treatment versus nontreatment on the mother-infant dyad. Further research must examine long-term neurobehavioural teratogenicity in exposed infants.

Are SSRIs safe for pregnant and breastfeeding women?

OBJECTIVE: To summarize the literature on use of the selective serotonin reuptake inhibitor (SSRI) class of antidepressants for pregnant and breastfeeding women. DATA SOURCES AND STUDY SELECTION: MEDLINE was searched over the past 9 years. An examination of the literature over the last 8 years was included in this review. Primary studies consist of prospective investigations and case studies. Evidence for the safety of SSRIs is limited, but some good studies describe the effects of untreated depression. SYNTHESIS: All studies report that infants are exposed to SSRIs; the drugs can be measured in their plasma and urine. Some evidence shows an increase in minor perinatal complications among infants exposed to SSRIs late in gestation or while nursing. No studies, however, have found an increase in major fetal malformations or pregnancy-related complications. The only investigation of long-term neurodevelopmental outcomes found no negative outcomes among infants exposed to SSRIs during pregnancy. Data are scarce, and readers are cautioned to take into consideration the limitations of the studies reviewed before making definite treatment decisions. CONCLUSIONS: Major fetal malformations and exposure to SSRIs during pregnancy and lactation do not appear to be associated. Some minor perinatal complications have been reported. Data on the long-term developmental outcomes of children exposed to SSRIs in utero and during breastfeeding are limited.

A controlled study of light therapy in women with late luteal phase dysphoric disorder.

Previous studies suggest that light therapy, as used to treat seasonal affective disorder, may be beneficial for pre-menstrual depressive disorders. We conducted a six-menstrual cycle randomized, double-blind, counter-balanced, crossover study of dim vs. bright light therapy in women with late luteal phase dysphoric disorder (LLPDD). Fourteen women who met DSM-III-R criteria for LLPDD completed two menstrual cycles of prospective baseline monitoring of pre-menstrual symptoms, followed by two cycles of each treatment. During the 2-week luteal phase of each treatment cycle, patients were randomized to receive 30 min of evening light therapy using: (1) 10000 lx cool-white fluorescent light (active condition); or (2) 500 lx red fluorescent light (placebo condition), administered by a light box at their homes. After two menstrual cycles of treatment, patients were immediately crossed over to the other condition for another two cycles. Outcome measures were assessed at the mid-follicular and luteal phases of each cycle. Results showed that the active bright white light condition significantly reduced depression and pre-menstrual tension scores during the symptomatic luteal phase, compared to baseline, while the placebo dim red light condition did not. These results suggest that bright light therapy is an effective treatment for LLPDD.

Seasonality of symptoms in women with late luteal phase dysphoric disorder.

OBJECTIVE: Both late luteal phase dysphoric disorder (LLPDD) and seasonal affective disorder are cyclical disorders often manifested by "atypical" depressive features. The goal of this study was to determine whether patients with LLPDD demonstrate substantial seasonal variation in symptoms. METHOD: Consecutive female patients attending a subspecialty clinic in a university teaching hospital were assessed by means of DSM-III-R criteria. All subjects completed the Seasonal Pattern Assessment Questionnaire, modified to include items on the seasonality of premenstrual symptoms. The results were compared with those of a group of female nonclinical subjects (N = 50). RESULTS: One hundred patients met the DSM-III-R criteria for LLPDD. Compared to the nonclinical group, the LLPDD patients had a significantly higher mean global seasonality score (an index of seasonality of mood and vegetative symptoms) and a significantly higher rate of seasonal affective disorder (38% versus 8%) as determined by Seasonal Pattern Assessment Questionnaire criteria. Twenty-five percent of the LLPDD group rated their seasonal variation in premenstrual symptoms as marked or severe, while 30% considered seasonal changes in overall symptoms to be a marked or severe problem. CONCLUSIONS: These results suggest that patients with LLPDD have substantial seasonal patterns in mood and premenstrual symptoms. These seasonal patterns have implications for the clinical assessment and treatment of LLPDD. For example, light therapy may be beneficial for women with seasonal worsening of LLPDD.

Breast-feeding and postpartum depression: is there a relationship?

OBJECTIVE: To study the relationship between breast-feeding cessation and the onset of postpartum depression. METHOD: The association between breast-feeding and depression was retrospectively examined in an obstetrical outpatient sample of 51 postpartum women who were suffering from major depression and who had stopped breast-feeding. Self-report questionnaire data were obtained from the subjects; the severity of the illness and the clinical course of each subject were evaluated. RESULTS: The majority (39 out of 51; 83%) of the women reported that their depression began the cessation of breast-feeding, while only 8 patients (17%) stated that their depression was subsequent to breast-feeding cessation. CONCLUSIONS: In an outpatient sample of depressed postpartum women, the onset of depression preceded the cessation of breast-feeding. The severity of the illness did not appear to influence breast-feeding persistence significantly.

Selective serotonin-reuptake inhibitors in pregnancy and lactation.

We explore the effects on the developing fetus and neonate of selective serotonin-reuptake inhibitors (SSRIs) during pregnancy and lactation, reviewing the relevant animal and human studies published in English from 1976 to the present. Medline was used to search the terms SSRI, fluoxetine, pregnancy, lactation, and teratogenesis. Animal studies were inconclusive: some found that fetal exposure to high doses of fluoxetine produced no congenital anomalies, while others linked the drug to abnormalities such as craniofacial malformations, alterations in serotonergic neurotransmitter systems, birth-related hematomas, and inhibition of the milk-ejection reflex. Human investigations indicated no relationship between in utero exposure to fluoxetine and teratogenic effects, although data are limited, and none have been collected regarding behavioral teratogenesis. However, we found a suggestion of an increased rate of miscarriage, an association with infants large for gestational age, one reported case of perinatal toxicity, and one case of an infant who was colicky while receiving breast milk from a mother taking fluoxetine. Based on these data, controlled prospective studies of exposure to SSRIs during pregnancy and lactation are needed, as is long-term evaluation for behavioral teratogenesis and enduring cognitive effects. Data are lacking on drug levels in breast milk and neonatal serum. Neonatal toxicity and the effect of SSRIs on labor and delivery, the mother-infant interaction, and lactation also merit further study. Clinically, a conservative approach is encouraged, minimizing the use of SSRIs in pregnancy, avoiding such drugs during the first trimester, tapering them prior to delivery, and discouraging breast-feeding during their use.

Postpartum Mood Disorders: Recognizing the symptoms.

Adjusting to the role of mother, a creative and joyous change for most women, combines with simultaneous physiological and psychological changes to develop into psychiatric problems in some women. Three common syndromes during the postpartum period are postpartum blues, postpartum depression, and postpartum psychosis. Any postpartum condition should be diagnosed rapidly to prevent short- and long-term disorders.

Tricyclic drugs in pregnancy and lactation: a preliminary report.

The management of severe depression during pregnancy and lactation is a serious concern to both physicians and parents, since the use of tricyclic antidepressant drugs (TCAs) has not been proven to be safe. This is a preliminary report of our ongoing studies of four groups of women treated with tricyclic antidepressants before and during pregnancy and/or lactation. The four groups are women who: became pregnant while on TCAs (n = 9); were prescribed TCAs during pregnancy (n = 9); were prescribed TCAs during lactation (n = 20); or were clinically depressed during lactation, but who refused TCAs (n = 5). Our results to date on the very small number of subjects indicate that there have been no fetal malformations, no greater frequency of complications during labor and delivery than in the normal population, only short-term withdrawal symptoms in the neonate, and no adverse effects on the breast-fed infants of mothers on TCAs. However, all of the lactating mothers who refused TCAs had exacerbation of symptoms; two required treatment in hospital, and all five ultimately had to discontinue nursing and commence treatment with TCAs.

Mental health and immigration.

The author reviews the psychosocial implications of immigration. Immigration is a complex, emotionally charged process which involves leaving behind old values, relationships, security, and resettling in an unknown culture with a new set of norms and boundaries. Some studies report a higher incidence of psychiatric illness in a migrant population than among the native born. Preventive and early therapeutic intervention is mandatory. In order to facilitate acculturation and eventual adaptation, the host society should promote easy access to the health-care systems, educational facilities, housing requirements and community organizations.

The use of psychotropic drugs in pregnancy and lactation.

The decision to use drugs during pregnancy can be complicated by many factors. The concerns of congenital malformation, the effects of drugs during labour, withdrawal effects on the newborn, and the exposure of the breast-fed newborn to drugs are some of the issues every physician is faced with when treating a pregnant woman. Drugs should be used during pregnancy only in situations where anticipated benefits far outweigh the possible risks. Approximately 20%-30% of women of childbearing age reportedly use antidepressants. It is absolutely essential that physicians know the effects of psychotropics on pregnancy and lactation before they issue a prescription. In this paper I have reviewed the effects of different classes of psychotropics on women during pregnancy and lactation.

A comparison of the safety and efficacy of bupropion HCL and amitriptyline hcl in depressed outpatients.

1. Thirty adult outpatients diagnosed with depressive illness were treated with either bupropion HCL or amitriptyline HCL. 2. Weekly ratings of efficacy and safety were undertaken using the Hamilton Depression, Hamilton Anxiety, Clinical Global Improvement, and Treatment Emergent Symptom Scales. Periodic physical investigations were also performed. 3. After 4 weeks of active treatment patients in both drug groups showed significant improvement on all rating scales. 4. The side effect profile of each drug was clinically different from one another with a notable absence of anticholinergic side effects characteristic of the bupropion group. 5. No significant laboratory or physical changes were found although slight changes in weight were noted with bupropion patients having a slight weight loss and amitriptyline patients a slight weight gain. There were no withdrawal effects from discontinuing either drug.