Link between prenatal antidepressant exposure, autism risk called into question

The authors note that, while genetic factors are known to play a substantial role in autism, exactly how that risk may be exacerbated by environmental factors is not well understood. While animal studies and investigations based on health records have suggested an increased risk associated with prenatal antidepressant exposure, others found no such association. Credit: © milosducati / Fotolia

Previous studies that have suggested an increased risk of autism among children of women who took antidepressants during pregnancy may actually reflect the known increased risk associated with severe maternal depression. In a study receiving advance online publication in Molecular Psychiatry, investigators from Massachusetts General Hospital (MGH) report that -- while a diagnosis of autism spectrum disorder was more common in the children of mothers prescribed antidepressants during pregnancy than in those with no prenatal exposure -- when the severity of the mother's depression was accounted for, that increased risk was no longer statistically significant. An increased risk for attention-deficit hyperactivity disorder (ADHD), however, persisted even after controlling for factors relating to a mother's mental health.

"We know that untreated depression can pose serious health risks to both a mother and child, so it's important that women being treated with antidepressants who become pregnant, or who are thinking about becoming pregnant, know that these medications will not increase their child's risk of autism," says Roy Perlis, MD, MSc, MGH Department of Psychiatry, senior author of the report.

The authors note that, while genetic factors are known to play a substantial role in autism, exactly how that risk may be exacerbated by environmental factors is not well understood. 

While animal studies and investigations based on health records have suggested an increased risk associated with prenatal antidepressant exposure, others found no such association. And since discontinuing antidepressant treatment significantly increases the risk of relapse -- including an increased risk of postpartum depression -- the current study was designed to clarify whether or not any increased autism risk could actually be attributed to the medication.

To investigate this possibility, the research team analyzed electronic health record data for children born at MGH, Brigham and Women's Hospital, or Newton Wellesley Hospital -- hospitals belonging to Partners HealthCare System -- for whom a diagnostic code for pervasive developmental disorder, a category that includes autism, was entered at least once between 1997 and 2010. They matched data for almost 1,400 such children with that of more than 4,000 controls with no autism diagnoses, born the same years and matched for a variety of demographic factors.

The children's information was paired with that of their mothers, noting any factors related to the diagnosis and treatment of major depression or other mental illness, including prescriptions for antidepressants and other psychotropic drugs. A similar analysis was done for almost 2,250 children with an ADHD diagnosis, compared with more than 5,600 matched controls with no ADHD diagnoses.

While prenatal exposure to antidepressants did increase the risk for either condition, in the autism-focused comparison, adjusting for factors indicating more severe maternal depression reduced the strength of that association to an insignificant level. Taking antidepressants with stronger action in the serotonin pathway, which has been suspected of contributing to a possible autism risk, did not increase the incidence of the disorder. In addition, the children of mothers who took a serotonin-targeting non-antidepressant drug for severe morning sickness had no increased autism incidence. Prescriptions for antipsychotic drugs sometimes used to treat severe, treatment-resistant depression, as well as psychotic disorders, did appear to increase the risk for autism. For ADHD, however, the increased risk associated with prenatal antidepressant exposure remained significant, although reduced, even after adjustment for the severity of maternal depression.

"There are a range of options -- medication and non-medication -- for treating depression and anxiety in pregnancy," says Perlis, an associate professor of Psychiatry at Harvard Medical School. "But if antidepressants are needed, I hope parents can feel reassured about their safety."

Source: Massachusetts General Hospital

Early results indicate potential for focused ultrasound to treat OCD

Dr. Chang (in sweater) and treatment team with the first patient in the OCD study. Credit: Image courtesy of Focused Ultrasound Foundation

A recently published report in the Journal of Molecular Psychiatry supports the potential of focused ultrasound to treat certain patients with obsessive-compulsive disorder (OCD).

In a study of feasibility, safety and preliminary efficacy, four patients with disabling OCD unresponsive to medical therapy were treated by ablating small targets deep in the brain (anterior internal capsule) using the InSightec ExAblate Neuro MR-guided focused ultrasound system. This proof-of-concept study is being conducted with 12 patients by Jin Woo Chang, MD, PhD, at the Yonsei University Medical Center in Seoul, Korea. The results of the first four patients with six months follow-up were published.

All four patients had the targeted areas of the brain successfully ablated. The procedures were accomplished without complications or side effects and resulted in gradual improvement in obsessive-compulsive thoughts and behaviors as well as showing the nearly immediate and sustained improvement in depression and anxiety over six months.

"There is a need for non-invasive treatment options for patients with OCD that cannot be managed through medication," says Dr. Chang. "Using focused ultrasound, we were able to reduce the symptoms for these patients and help them get some of their life back without the risks or complications of the more invasive surgical approaches that are currently available."

"If these initial results are confirmed in the remaining eight patients in this study as well as in a larger pivotal trial of safety and efficacy, focused ultrasound could emerge as an alternative to surgery for improving quality of life in a cost-effective manner for patients with OCD," said Foundation Chairman Neal F. Kassell, MD. "This could also serve as the predicate for non-invasive therapy for other psychiatric disorders."

Dr. Chang plans to start a study using focused ultrasound to treat depression in 2015.

Current Treatment for OCD

Obsessive-compulsive disorder (OCD) is a psychiatric disorder characterized by recurring anxiety-provoking thoughts (obsessions) that are alleviated only by ritualistic actions (compulsions) such as hand washing. OCD symptoms can be overwhelming and result in severe impairment and dysfunction. Patients also have a high risk for depression, with two-thirds of OCD patients developing major depression.

Although a large portion of OCD patients improve with drug therapy, some patients have debilitating symptoms that are resistant to treatment. For these patients, psychosurgery can be performed to destroy (ablate) a targeted region of the brain (anterior internal capsule) associated with the disorder. The currently available ablative approaches are invasive or involve radiation:

• Radiofrequency ablation requires drilling into the skull and inserting a probe through 
   the brain.

• Stereotactic radiosurgery takes months to achieve an effect and may be associated with
   side effects of radiation.

• Deep brain stimulation has been used as a reversible and adjustable alternative to ablation, but it involves the risks and complications of surgery to implant the system and additional operations for battery changes.

Source: Focused Ultrasound Foundation

Japanese Town: Half the survivors of mega-earthquake, tsunami, have PTSD symptoms

Though just two of Hirono's 5,418 residents lost their lives in Japan's mega-earthquake and tsunami, a new study shows that the survivors are struggling to keep their sanity.

One year after the quake, Brigham Young University professor Niwako Yamawaki and scholars from Saga University evaluated the mental health of 241 Hirono citizens. More than half of the people evaluated experienced "clinically concerning" symptoms of post-traumatic stress disorder. Two-thirds of the sample reported symptoms of depression.

Those rates exceed levels seen in the aftermath of other natural disasters, but what happened in Japan wasn't just a natural disaster. Leaked radiation from nuclear power plants forced residents of Hirono to relocate to temporary housing far from home.

"This was the world's fourth-biggest recorded earthquake, and also the tsunami and nuclear plant and losing their homes -- boom boom boom boom within such a short time," said Yamawaki, a psychology professor at BYU. "The prevalence one year after is still much higher than other studies of disasters that we found even though some time had passed."

Yamawaki got the idea for this study while shoveling mud from a damaged Japanese home one month after the tsunami flooded coastal towns. She had just arrived for a previously scheduled fellowship at Saga University. During her off-time, she traveled to the affected area and volunteered in the clean-up effort. One seemingly stoic homeowner broke down in tears when Yamawaki and her husband thanked her for the chance to help.

"She said 'This is the first time I have cried since the disaster happened,'" Yamawaki said. "She just said 'Thank you. Thank you for letting me cry.'"

Back at Saga University, Yamawaki collaborated with Hiroko Kukihara to conduct a study on the mental health and resilience of survivors. Their report appears in the journal Psychiatry and Clinical Neurosciences.

Participants in the study lived in temporary housing provided by the Japanese government when Hirono was evacuated. With an average age of 58, the people are noticeably older than the populations of normal Japanese towns. Yamawaki suspects that young people were more likely to permanently relocate elsewhere in Japan following the disaster.

The researchers didn't just measure the rates of mental illness; they also performed a statistical analysis to learn what fostered resilience among the survivors. Eating right, exercising regularly and going to work all promoted resilience and served as a buffer against mental illness.

"Having something to do after a disaster really gives a sense of normalcy, even volunteer work," Yamawaki said.

As the researchers got to know survivors, they heard from so many that they missed seeing their former neighbors. The mass relocation outside the radiation zone broke up many neighborhood ties.
"Japanese are very collectivistic people and their identity is so intertwined with neighbors," Yamawaki said. "Breaking up the community has so much impact on them."

While it's hard to fathom the scope of the devastation in the coastal region of Fukushima, most survivors believe something like this will happen again. If so, this new study provides a blueprint for how to help them put their lives back together again.

Source: Brigham Young University
Summary: A new study shows that more than half the survivors in one Japanese town exhibited 'clinically concerning' symptoms of PTSD following the country's mega-earthquake and tsunami. Two-thirds of survivors also reported symptoms of depression. Having work to do has proven important in increasing resilience.