In a small proof-of-concept study, researcher Stephen J. Kanes and colleagues showed that injections of allopregnanolone could nearly eliminate symptoms of post-partum depression.
Allopregnanolone is the main metabolite of the hormone progesterone. Rapid changes in hormone levels following delivery are thought to cause post-partum depression.
In the study, four women with post-partum depression were given injections of SAGE-547, a proprietary solution of allopregnanolone. The dose was adjusted over 12 hours until it approximated prenatal levels of allopregnanolone. This level was maintained for 36 hours, and then the women were weaned off the SAGE-547 over another 12 hours. As soon as the women began injections of SAGE-547, their depression began to improve, and this lasted after they stopped receiving the injections. By 84 hours after beginning treatment, depression scores had improved by 81%.
Kanes and colleagues, who presented this research at the 2016 meeting of the Society of Biological Psychiatry, will follow up this study with placebo-controlled trials of SAGE-547.
A 2016 article by Heli Malm and colleagues in the Journal of the American Academy of Child and Adolescent Psychiatry suggests that in utero exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants may increase the risk of depression in adolescence. However, the study included potentially confounding factors. It is possible that women who took SSRIs during pregnancy had more severe depression than those who went unmedicated during pregnancy. The mothers in the study who took SSRIs also had more comorbid conditions such as substance abuse.
Editor’s Note: Women should balance the risks and benefits of antidepressant use during pregnancy, since depression itself can have adverse effects on both mother and fetus. It has recently been established that SSRI use during pregnancy does not cause birth defects, so women with depression that has not responded to non-pharmaceutical interventions such as psychotherapy, omega-3 fatty acid supplementation, exercise, mindfulness, and repeated transcranial magnetic stimulation (rTMS) may still want to consider SSRIs.
A new study suggests that women can continue using antipsychotic medications during the first trimester of pregnancy without meaningfully increasing the risk of birth defects in their offspring.
The study, by Krista F. Huybrechts and colleagues in the journal JAMA Psychiatry, looked at Medicaid users who filled at least one prescription for an antipsychotic medication during their first trimester of pregnancy, when an embryo’s vital organs are formed, and went on to have a live birth. Birth defects, including cardiac malformations, in these children were identified in the first 90 days after delivery and compared to the number of such abnormalities in the children of women on Medicaid who did not receive a prescription for an antipsychotic drug during the first trimester of pregnancy. The number of abnormalities was slightly higher in the children of women who had received atypical antipsychotics than in those who had not, and slightly lower in the children of women who had received a typical antipsychotic than in those who had not.
Huybrechts and colleagues concluded that taking an antipsychotic medication during the first trimester of pregnancy does not meaningfully increase the risk of birth defects in the offspring.
The children of women who took the antipsychotic risperidone did have a small increased risk of birth defects, including cardiac malformations. The researchers called for additional study of risperidone use during pregnancy.
In the study, published by Jesse D. Eclarinel and colleagues in The FASEB Journal, pregnant mother rats were placed in cages that each contained an exercise wheel. One group had access to a working wheel on which they could run. The other group had the same wheel, but it was locked so that they couldn’t use it for running. Daughters of the rats who ran during pregnancy ran more in adulthood (both at 60 days and 300 days after birth) than daughters of the rats who couldn’t run during pregnancy.
While it is a mystery why this occurs, it is consistent with other data about the ways that a parent’s experiences can influence the next generation, even when the offspring don’t grow up with the parents.
For example, father rats conditioned to associate a specific smell with fear of an electric shock have offspring that also fear that smell (but not other smells).
Drug use is another example. Father rats given access to cocaine have offspring that are less interested in cocaine. Interestingly, father rats exposed to marijuana have offspring that are more interested in opiates.
Experiences with drugs or stress are thought to affect the next generation via ‘epigenetic’ marks on ova or sperm. These marks change the way DNA is packaged, with long-lasting effects on behavior and chemistry. Most marks from a mother’s or father’s experiences are erased at the time of conception, but some persist and affect the next generation.
The nature versus nurture debate is getting more and more complicated. Parents can influence offspring in a number of ways: 1) genetics; 2) epigenetics in the absence of contact between parent and offspring after birth; 3) epigenetic effects of behavioral contact—that is, parents’ caring and warmth versus abuse and neglect can affect offspring’s DNA expression too. All these are in addition to any purely behavioral influence a parent may have on their offspring via discipline, teaching, being a role model, etc.
Editor’s Note: The moral of the story is, choose your parents wisely, or behave wisely if you yourself become a parent.
Many psychiatric illnesses, including bipolar disorder, schizophrenia, autism, attention deficit hyperactivity disorder (ADHD), and anxiety disorders may stem from abnormalities in brain development that begin before birth. Researchers are trying to determine whether dietary supplements taken by pregnant mothers or infants can reduce the risk of such illnesses. At a recent scientific meeting, researcher Randal Ross and colleagues reported that compared to placebo, choline supplements reduced problems with a brain process called sensory gating in one-month-old infants and also improved the children’s attention span and social skills at age 3.
Sensory gating is the process by which the brain filters out unimportant information, to avoid flooding higher cortical centers with irrelevant stimuli. Deficits in the way the brain inhibits response to this type of irrelevant information are associated with mental illnesses such as schizophrenia.
In Ross’s study, healthy pregnant mothers received either a placebo or 6300 mg of choline, a nutrient found in liver, egg yolks, and meat. After delivery, the infants also received 700 mg of supplemental choline per day. In children who carried CHRNA7, a risk gene for schizophrenia discovered by Ross’s colleague Robert Freedman, choline reversed the associated risk of sensory gating problems and normalized their behavior at age 3.
A recent study confirms that women who are depressed during pregnancy are more likely to experience adverse pregnancy outcomes such as preterm or cesaerean delivery and small or underweight babies. However, antidepressant treatment improved outcomes for pregnant women with depression.
The 2016 study by Kartik K. Venkatesh and colleagues in the journal Obstetrics & Gynecology included 7,267 women who gave birth after at least 20 weeks of pregnancy. About 11% of the women screened positive for depression during their pregnancy. Depressed mothers-to-be were more likely to give birth before 37 weeks and before 32 weeks compared to nondepressed mothers-to-be. The depressed women were also more likely to deliver small babies or babies weighing under 2500g.
About 7% of the women in the study received antidepressant medication. Compared to nondepressed women, the women taking antidepressants did not have greater rates of early delivery or small babies. However, the authors caution that because so few women received antidepressants, the study does not reveal whether antidepressants improve outcomes for depressed pregnant women.
A Danish working group has released guidelines for prescribing psychotropic drugs to women who are pregnant or breastfeeding. After a comprehensive review of the literature, researchers from several different Danish medical societies reported that sertraline and citalopram are the first choice among selective serotonin reuptake inhibitors (SSRIs) for depression in women who are pregnant or breastfeeding. The working group suggested that women with bipolar disorder who need a mood stabilizer because of frequent relapses could be prescribed lithium, though lithium use is associated with a small risk of cardiac abnormalities in the child. Lamotrigine may also be used, and has not been associated with any congenital abnormalities.
Valproate and carbamazepine are not recommended for use during pregnancy and breastfeeding. Use of valproate among women of child-bearing age should particularly be avoided due to several risks for the potential child. These include spina bifida and other serious congenital problems, but also severe developmental delay and loss of about 9 IQ points. Other possible treatments for bipolar disorder and schizophrenia in pregnant and breastfeeding women include olanzapine, risperidone, quetiapine, and clozapine. The data about the safety of these medications are not extensive.
The working group included members of the Danish Psychiatric Society, the Danish Society of Obstetrics and Gynecology, the Danish Paediatric Society, and the Danish Society of Clinical Pharmacology. The recommendations may be found in an article by E.R. Larsen and colleagues in a 2015 supplement to the journal Acta Psychiatrica Scandinavica.
There is mounting evidence from animal studies and epidemiological research that an infection during pregnancy may increase the risk of schizophrenia in the offspring. A recent study by Alan Brown and colleagues presented at the 2015 meeting of the Society of Biological Psychiatry used a large dataset from the Finnish Prenatal Study of Schizophrenia to compare medical data from the mothers of 777 people with schizophrenia (630 with schizophrenia and 147 with schizoaffective disorder) to data from the mothers of 777 healthy people.
The study’s biobank contained blood samples taken from the mothers in early to mid-pregnancy, which the researchers used to determine the mothers’ levels of C-reactive protein (CRP), an indicator of inflammation. Higher levels of CRP were associated with increased risk of schizophrenia in the offspring. When the researchers analyzed the findings by sex of the offspring, the link between prenatal infection and schizophrenia risk was significant in males, but not females. The effect was also stronger among offspring born after their due date than those born at or before their due date.
A large study of women who took selective serotonin reuptake inhibitor (SSRI) antidepressants in the month before pregnancy and throughout the first trimester suggests that there is a smaller risk of birth defects associated with SSRI use than previously thought, though some risks were elevated in women who took paroxetine or fluoxetine.
The 2015 study, by Jennita Reefhuis and colleagues in the journal BMJ, investigated the drugs citalopram, escitalopram, fluoxetine, paroxetine, and sertraline, and examined birth defects that had previously been associated with SSRI use in smaller studies. The participants were 17,952 mothers of infants with birth defects and 9,857 mothers of infants without birth defects who had delivered between 1997 and 2009.
Sertraline was the most commonly used SSRI among the women in the study. None of the birth defects included in the study were associated with sertraline use early in pregnancy. The study found that some birth defects were 2 to 3.5 times more likely to occur in women who had taken fluoxetine or paroxetine early in their pregnancies.
Five different birth defects, while uncommon, were statistically linked to paroxetine use: anencephaly (undersized brain), heart problems including atrial septal defects and right ventricular outflow tract obstruction defects, and defects in the abdominal wall including gastroschisis and omphalocele. Two types of birth defects were associated with fluoxetine use: right ventricular outflow tract obstruction defects and craniosynostosis (premature fusion of the skull bones). Absolute incidence of these defects was also low.
At the May meeting of the Society of Biological Psychiatry, researcher Deborah Kim gave a talk on the use of repeated transcranial magnetic stimulation (rTMS) for depression in women who are pregnant. In rTMS treatment, an electromagnetic coil is placed against the side of the forehead and magnetic pulses that can penetrate the scalp are converted into small electrical currents that stimulate neurons in the brain. Kim had recently completed an open study of rTMS in pregnant women, in which 70% of the women responded to rTMS. In another controlled randomized study of 30 women (also by Kim), 75% responded to active rTMS and 50% responded to a sham procedure. None of the women included had problems with the fetus or during delivery.
RTMS offers an alternative to women who are reluctant to take antidepressants during pregnancy. Kim cited data by Lee S. Cohen and colleagues in which women taking antidepressants show a 68% relapse rate if they stop taking these medications during pregnancy compared to a 26% relapse rate among those who continue taking antidepressants during pregnancy. Concerns about antidepressants’ potential effects on a fetus may have been overemphasized. Kim summarized the literature on antidepressants in pregnancy, concluding that there is a preponderance of evidence that antidepressants are safe for the mother and fetus, with few serious effects having been observed. Some researchers have been concerned about risks of persistent pulmonary hypertension or autism among offspring of women who took antidepressants during pregnancy, but studies have shown that the absolute risk of either is small. Stay tuned—on Wednesday we’ll discuss a new large and comprehensive study in which most SSRIs showed no link to birth defects, but fluoxetine and paroxetine were associated with risks of certain birth defects.
Editor’s Note: For mild depression during pregnancy, exercise and psychotherapy might be optimal, along with folate and vitamin D3. For moderate depression, omega-3 fatty acids might also be helpful, but it now appears that rTMS would be less risky than electroconvulsive therapy (ECT), which in the past has been a typical recommendation for pregnant women, but which exposes the fetus to the effects of anesthesia and seizure. In her summary Kim recommended that women with a pattern of recurrent depression continue antidepressant treatment, especially since a mother’s depression itself poses non-trivial risks to the fetus.