New Mental Health Research: Genetics, Diagnosis, and Treatment

Several new studies published in Science, The Lancet Psychiatry, and JAMA Network Open are expanding understanding of mental health, covering the genetics of neuropsychiatric disorders, the safety of antidepressants in pregnancy, the timing of parental depression, and the reliability of diagnostic interviews.

Many DNA variants linked with neuropsychiatric disorders (NPD) that do not code for proteins depend on neuronal activation, a study in Science suggests. The findings highlight the power of cell stimulation to reveal context-specific "hidden" genetic effects in conditions such as schizophrenia. Genome-wide association studies have revealed hundreds of genetic loci associated with mental illness, with more than 280 identified for schizophrenia alone. Researchers studied gene expression and chromatin accessibility in single neurons derived from induced pluripotent stem cells collected from a hundred human donors, before and after neurons were activated through potassium-induced depolarization. Both the number of detectable expression quantitative trait loci (eQTLs) and chromatin accessibility QTLs (caQTLs) rose after neuronal stimulation. eQTLs after stimulation had substantially weaker overlap with brain eQTL catalogs derived from postmortem tissue compared with eQTLs before stimulation. A higher number of caQTLs were associated with neuropsychiatric disease compared with eQTLs. The researchers identified thousands of cell type-specific and activity-dependent quantitative trait loci, helping prioritize NPD risk variants and genes that manifested functional effects only upon neuronal stimulation.

A review published in The Lancet Psychiatry found that antidepressant use during pregnancy does not cause an increased risk for neurodevelopmental disorders in offspring. Based on 37 studies (648,626 antidepressant-exposed and nearly 25 million unexposed pregnancies), the researchers found that prenatal antidepressant use was associated with a modestly increased risk for neurodevelopmental disorders (relative risk [RR], 1.13), including attention-deficit/hyperactivity disorder (ADHD; RR, 1.35) and autism spectrum disorder (ASD; RR, 1.69). No significant associations were seen for intellectual disabilities, motor disorders, or speech and language disorders. Associations were attenuated or became nonsignificant in sensitivity analyses when adjusting for confounding factors, including maternal mental disorders, familial or genetic influences, and misclassification. As a negative control, paternal antidepressant use during pregnancy was associated with increased ADHD risk (RR, 1.46) and ASD risk (RR, 1.28), suggesting the association reflects parental mental health and genetics rather than the medication itself. "We know many parents-to-be worry about the potential impact of taking medication during pregnancy; our study provides reassuring evidence that commonly used antidepressants do not increase the risk of neurodevelopmental disorders such as autism and ADHD in children," a coauthor from the University of Hong Kong said in a statement.

A study from Yale School of Medicine, published in JAMA Network Open, found that pregnancy is a sensitive period, and exposure to high levels of maternal depression during pregnancy alone is associated with increased risk of psychosis in adult offspring. The effects of maternal depression on adult symptoms of depression were detected across childhood, as well as during pregnancy, while paternal effects emerged from mid-childhood. The findings come from a 30-year study of more than 5,000 participants. The researchers said that earlier intervention is better, and providing adequate mental health support for parents during pregnancy is important.

A study in JAMA Network Open found that diagnostic interviews for substance use and mental disorders vary in reliability from condition to condition. The study's authors used Cohen's kappa coefficient to estimate how reliable diagnostic interviews were for different mental health conditions. The average reliability was generally better for substance use disorders, and highest overall for opioid use disorder. A psychiatry professor at McMaster University said diagnostic interviews are "often treated as a 'gold standard' for assessing mental disorders in both clinical settings and research," but pointed out that these interviews fall short of providing a "definitive benchmark that demonstrates excellent validity and reliability." A psychiatrist and professor at Columbia University raised concerns about how the study lumped "fully structured" and "semi-structured" interviews together, noting that fully structured interviews are more likely to yield the same result when administered more than once. The review included papers on diagnostic tools including the Structured Clinical Interview for DSM-5 (SCID), the Mini International Neuropsychiatric Interview (Mini), and the Clinically Administered PTSD Scale (CAPS). The study's authors suggested that clinicians could "move away from strict diagnostic categories, where a condition is either present or absent, and think about symptoms on a spectrum or continuum."

A mixed-methods study of 93 licensed clinical psychologists in Austria found that clinicians perceived both self- and desired diagnoses as occurring significantly more frequently than in the past. More than 70% of psychologists reported that self-diagnoses occurred "more often" or "much more often" than before, and none of the respondents reported a decrease in desired diagnoses. According to participating psychologists, attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) overwhelmingly dominated both self-diagnosed and desired diagnoses, with nearly 9 of 10 psychologists reporting that patients frequently sought an ADHD diagnosis. The study noted that self-diagnosis may be facilitated by widespread access to online mental health content, including symptom checklists, personal narratives, and social media posts.