High-impact rare genetic variants in severe schizophrenia.

Extreme phenotype sequencing has led to the identification of high-impact rare genetic variants for many complex disorders but has not been applied to studies of severe schizophrenia. We sequenced 112 individuals with severe, extremely treatment-resistant schizophrenia, 218 individuals with typical schizophrenia, and 4,929 controls. We compared the burden of rare, damaging missense and loss-of-function variants between severe, extremely treatment-resistant schizophrenia, typical schizophrenia, and controls across mutation intolerant genes. Individuals with severe, extremely treatment-resistant schizophrenia had a high burden of rare loss-of-function (odds ratio, 1.91; 95% CI, 1.39 to 2.63; P = 7.8 × 10-5) and damaging missense variants in intolerant genes (odds ratio, 2.90; 95% CI, 2.02 to 4.15; P = 3.2 × 10-9). A total of 48.2% of individuals with severe, extremely treatment-resistant schizophrenia carried at least one rare, damaging missense or loss-of-function variant in intolerant genes compared to 29.8% of typical schizophrenia individuals (odds ratio, 2.18; 95% CI, 1.33 to 3.60; P = 1.6 × 10-3) and 25.4% of controls (odds ratio, 2.74; 95% CI, 1.85 to 4.06; P = 2.9 × 10-7). Restricting to genes previously associated with schizophrenia risk strengthened the enrichment with 8.9% of individuals with severe, extremely treatment-resistant schizophrenia carrying a damaging missense or loss-of-function variant compared to 2.3% of typical schizophrenia (odds ratio, 5.48; 95% CI, 1.52 to 19.74; P = 0.02) and 1.6% of controls (odds ratio, 5.82; 95% CI, 3.00 to 11.28; P = 2.6 × 10-8). These results demonstrate the power of extreme phenotype case selection in psychiatric genetics and an approach to augment schizophrenia gene discovery efforts.

Treatment of depression, anxiety, and trauma-related disorders during the perinatal period: A systematic review.

Women with psychiatric disorders during pregnancy and the postpartum period (i.e., perinatal period) are at increased risk for adverse maternal and child outcomes. Effective treatment of psychiatric disorders during the perinatal period is imperative. This review summarizes the outcomes of 78 studies focused on the treatment of depression, anxiety, and trauma-related disorders during the perinatal period. The majority of studies focused on perinatal depression (n = 73). Of the five studies focused on anxiety or trauma-related disorders, only one was a randomized controlled trial (RCT). The most studied treatment was cognitive behavioral therapy (CBT; n = 22), followed by interpersonal psychotherapy (IPT; n = 13). Other interventions reviewed include other talk therapies (n = 5), collaborative care models (n = 2), complementary and alternative medicine approaches (n = 18), light therapy (n = 3), brain stimulation (n = 2), and psychopharmacological interventions (n = 13). Eleven studies focused specifically on treatment for low-income and/or minority women. Both CBT and IPT demonstrated a significant benefit over control conditions. However, findings were mixed when these interventions were examined in low-income and/or minority samples. There is some support for complementary and alternative medicine approaches (e.g., exercise). Although scarce, SSRIs demonstrated good efficacy when compared to a placebo. However, SSRIs did not outperform another active treatment condition (e.g., CBT). There is a tremendous need for more studies focused on treatment of perinatal anxiety and trauma-related disorders, as well as psychopharmacological effectiveness studies. Limitations and future directions of perinatal treatment research, particularly among low-income and/or minority populations, are discussed.

Mobile Health Apps in OB-GYN-Embedded Psychiatric Care: Commentary.

This paper explores the potential benefits of the use of mobile health (mHealth) apps in obstetrician-gynecologist (OB-GYN)-embedded psychiatric clinics in the United States. First, we highlight the increasing trend of integrating mental health care within the OB-GYN context. Second, we provide examples of successful uses of mHealth in the global health context and highlight the dearth of available research in the United States. Finally, we provide a summary of the shortcomings of currently available apps and describe the upcoming trial of a novel app currently underway at the Mother-Child Wellness Clinical and Research Center at Boston Medical Center.