Antipsychotic Use During Pregnancy Generally Not Associated With Neurodevelopmental Risks

Exposure to most antipsychotics in the womb does not appear to increase the risk of neurodevelopmental disorders in children after controlling for other factors, such as the mother’s illness and lifestyle behaviors, according to a report published today in JAMA Internal Medicine.

“These findings provide much needed clarity regarding NDD [neurodevelopmental disorders] risk and may help to inform treatment decision-making in pregnancy, which is a sophisticated trade-off between benefits and risks,” wrote Loreen Straub, M.D., M.S., of Harvard Medical School and colleagues. “Although the observed 2-fold increase in risk of [neurodevelopmental disorders] is not causally related with in utero exposure to antipsychotic drugs, it does highlight the importance of closely monitoring the neurodevelopment of the offspring of women with mental illness to ensure that early intervention and support can be instituted when needed.”

Straub and colleagues made use of national health insurance databases, both public and private, to compile information on mothers who filled a prescription for any antipsychotic medication during the second half of pregnancy and their children. (The researchers focused on antipsychotic use in the second half of pregnancy because it marks a period of significant brain development for a fetus.) They compared the rates of the following neurodevelopmental disorders in the children exposed to antipsychotics in the womb with those who were not exposed: autism spectrum disorder, attention-deficit/hyperactivity disorder, learning disability, speech or language disorder, developmental coordination disorder, intellectual disability, and behavioral disorder.

By age 8, 37.3% of publicly insured children and 24.5% of privately insured children whose mothers took antipsychotics during the second half of pregnancy had been diagnosed with at least one neurodevelopmental disorder; in comparison, 23.7% of publicly insured children and 11.0% of privately insured children with no antipsychotic exposure were diagnosed with a neurodevelopmental disorder.

The researchers calculated that antipsychotic exposure during pregnancy was associated with a 1.9-fold increased risk of any neurodevelopmental disorders, with similar risks seen for first-generation antipsychotics, such as haloperidol, or second-generation antipsychotics, such as olanzapine. After adjusting for such variables as the mother’s underlying illness and comorbidities, sociodemographic factors, and lifestyle behaviors (such as smoking or drinking), most antipsychotics were no longer associated with any increased risk of neurodevelopmental disorders. The one exception was in children whose mothers who took aripiprazole in the second half of pregnancy; this population had a 1.36-fold increased risk of neurodevelopmental disorders.

Straub and colleagues noted that aripiprazole is a newer antipsychotic that exerts slightly different effects on dopamine receptors. “This action can result in lactation problems owing to prolactin reduction. Therefore, a potential hypothesis is that aripiprazole’s association with [neurodevelopmental disorders] may be mediated through a reduction in breastfeeding. Our data did not include information on breastfeeding, which may be an important avenue to explore in future studies,” they wrote.

Straub and colleagues also noted that the potential risks identified for aripiprazole require replication in other data sources before causality can be assumed.

To read more on this topic, see the Psychiatric News article “Taking Some Antipsychotics During Pregnancy May Raise Risk of Gestational Diabetes.”

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Safest Course to Prevent Fetal Alcohol Syndrome: No Drinking in Pregnancy

Prenatal exposure to alcohol is the leading preventable cause of birth defects and intellectual and neurodevelopmental disabilities, according to a report from the American Academy of Pediatrics. The article, which appeared online this week in the journal Pediatrics, notes that no amount of alcohol should be considered safe and that there is no safe trimester in which to drink.

Children born with fetal alcohol spectrum disorder (FASD) or its variants are more likely than the general population to develop concurrent psychiatric, emotional, and behavioral problems, according to the lead authors Janet Williams, M.D., of the University of Texas Health Science Center in San Antonio and Vincent Smith, M.D., M.P.H., of Boston Children’s Hospital.

“Children and adolescents with FASD have a 95% lifetime likelihood to experience mental health issues, and among the most prevalent are anxiety and mood disorders, particularly depression, as well as ADHD, substance use, addiction, and suicide,” they wrote.

The structural and functional effects of prenatal exposure to alcohol on the brain may also be accompanied by problems in other organ systems, including the heart, kidneys, eyes, ears, and musculoskeletal system.

“Multimodal symptom treatments that improve long-term outcomes [for FASD] include optimizing environmental modifications, parenting strategies, social support, and developmental and educational interventions that address the neurologically based problems related to FASDs,” wrote the authors. Far better than treatment, the experts note, is prevention, however.

“The research suggests that the smartest choice for women who are pregnant is to just abstain from alcohol completely,” Williams said in a press release.

For more information about fetal alcohol syndrome, see the Psychiatric News article “Growing Recognition of Prevalence of Disorders Brought on by Prenatal Alcohol Exposure.”

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People With Schizophrenia May Be at Higher Risk of Developing Dementia

People with schizophrenia may be at a higher risk for dementia with an earlier age at onset than those without the condition, according to a study published last week in JAMA Psychiatry.

By some estimates people with schizophrenia will die, on average, 15 to 20 years earlier than the general population. Although schizophrenia is associated with several age-related disorders and considerable cognitive impairment, studies comparing the risk of dementia among people with schizophrenia versus those without have produced mixed results.

Using nationwide registers in Denmark, researchers from Aarhus University in Denmark and the University of Washington tracked the outcomes of more than 2.8 million people aged 50 and older—20,683 of whom had or developed schizophrenia over the course of the study—for up to 18 years. Overall, 136,012 individuals developed dementia, including 944 individuals with a history of schizophrenia.

After adjusting for age and sex, schizophrenia was found to be associated with a more than two-fold higher risk of dementia when compared with persons without schizophrenia. The relative risk of dementia was almost four-fold higher among individuals younger than 65 years. In absolute numbers, 7.4 of 100 people with schizophrenia developed dementia before the age of 80 years compared with 5.8 of 100 people without schizophrenia.

The risk of dementia in people with schizophrenia was only slightly reduced when adjusting for substance abuse disorder but was unaffected by adjustment for medical comorbidities including cardiovascular disease and diabetes.

“It is clear that individuals with schizophrenia develop dementia at a higher-than-expected rate and at younger ages than those without schizophrenia,” wrote Constantine Lyketsos, M.D., M.H.S., and Matthew Peters, M.D., both of Johns Hopkins University in a related editorial. Still, they noted, “[t]he majority do not undergo cognitive decline, suggesting that this heterogeneous syndrome belies a subgroup with a condition that is both neurodevelopmental and degenerative. … Focusing on the individuals who develop progressive dementia could be a successful approach that will provide clues to the etiology of this diverse condition.”

For related information, see the Psychiatric News article “Neuropsychiatric Symptoms Implicated in Conversion From MCI to Dementia.”

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Study Finds High Prevalence of Prenatal Alcohol Exposure Disorders Among Patients of Chicago Clinic

Over 38 percent of the patients who attended a family medicine clinic in Chicago’s Southside had a neurodevelopmental disorder associated with prenatal alcohol exposure (ND-PAE).

While national surveys has estimated that disorders due to fetal alcohol exposure may affect 2% to 5% of individuals, this new report, published yesterday in Psychiatric Services in Advance, shows how pervasive this problem can get in certain communities.

The article assessed the records of 590 adult and 21 youth psychiatric patients--almost entirely African-American--who attended the Family Medicine Clinic at Jackson Park Hospital.

Of the 611 patients, 237 (226 adults and 11 children) had clinical profiles consistent with ND-PAE, now recognized as an emerging condition in DSM-V; in contrast, only 53 patients presented with a “classical” DSM-V neurodevelopmental disorder such as ADHD or autism. The higher ND-PAE prevalence among the child patients (57 percent) may suggest that this problem is becoming more pronounced, though the sample size was small.

“Fetal alcohol exposure is at the root of much of the violence, abuse, incarceration, special education, and poor adaptability that plague these underserved African-American communities,” said lead author Carl Bell, M.D., a clinical professor of psychiatry and public health at the University of Illinois School of Medicine. “Hopefully these results will bring more attention to the problem of ND-PAE, which is the most common preventable form of intellectual disability.”

To read more about the addition of ND-PAE to DSM-V, see the Psychiatric News viewpoint article, "New DSM Code Should Benefit Clinicians, Researchers."

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Series on DSM-5 Launched Today; Preorder Your Manual Now

The issue of Psychiatric News posted today launches a series of articles on the major differences between DSM-IV and DSM-5; the series will conclude in May, coinciding with the publication of the manual. Today’s installment consists of two articles that outline the broad concepts that have guided the organization of the text and information on changes impacting the diagnosis of neurodevelopmental disorders. The articles can be accessed here:

"Continuity and Changes Mark New Text"
"DSM-5 Provides New Take on Developmental Disorders"

Also, beginning today, DSM-5 may be preordered from American Psychiatric Publishing; preorders will be fulfilled beginning on the manual’s publication date of May 22. Those attending APA’s 2013 annual meeting, which is being held in San Francisco May 18 to 22, have another purchase option: they will have an exclusive opportunity to buy the manual before it goes on sale to the public. Click here to register for the meeting; early-bird rates are in effect until January 24.

In an interview with Psychiatric News, DSM-5 Task Force Chair David Kupfer, M.D., explained that those overarching conceptual ideas include incorporation of a developmental approach to psychiatric disorders, recognition of the influence of culture and gender on how psychiatric illness presents in individual patients, a move toward the use of dimensional measures to rate severity and disaggregate symptoms that tend to occur across multiple disorders, harmonization of the text with ICD, and integration of genetic and neurobiological findings by grouping clusters of disorders that share genetic or neurobiological substrates.

With regard to the chapter on neurodevelopmental disorders, a major change to the description and organization of criteria for autism and related disorders tops the major revisions clinicians can expect to see. The chapter also includes the addition of a new “social communication disorder,” reorganization of criteria for learning disorders, and changes to the criteria for intellectual disability (known in DSM-IV as mental retardation).