Schizophrenia is a common, chronic and debilitating neuropsychiatric syndrome affecting tens of millions of individuals worldwide. While rare genetic variants play a role in the etiology of schizophrenia, most of the currently explained liability is within common variation, suggesting that variation predating the human diaspora out of Africa harbors a large fraction of the common variant attributable heritability. However, common variant association studies in schizophrenia have concentrated mainly on cohorts of European descent. We describe genome-wide association studies of 6152 cases and 3918 controls of admixed African ancestry, and of 1234 cases and 3090 controls of Latino ancestry, representing the largest such study in these populations to date. Combining results from the samples with African ancestry with summary statistics from the Psychiatric Genomics Consortium (PGC) study of schizophrenia yielded seven newly genome-wide significant loci, and we identified an additional eight loci by incorporating the results from samples with Latino ancestry. Leveraging population differences in patterns of linkage disequilibrium, we achieve improved fine-mapping resolution at 22 previously reported and 4 newly significant loci. Polygenic risk score profiling revealed improved prediction based on trans-ancestry meta-analysis results for admixed African (Nagelkerke’s R2 = 0.032; liability R2 = 0.017; P < 10−52), Latino (Nagelkerke’s R2 = 0.089; liability R2 = 0.021; P < 10−58), and European individuals (Nagelkerke’s R2 = 0.089; liability R2 = 0.037; P < 10−113), further highlighting the advantages of incorporating data from diverse human populations.

A multidisciplinary expert review of key issues and future directions from the conference “Controversial labels and clinical uncertainties: psychogenic disorders, conversion disorder, and functional symptoms.” On October 9 and 10, 2015, a conference entitled “Controversial labels and clinical uncertainties: psychogenic disorders, conversion disorder, and functional symptoms” was held at the Center for Ethics, Emory University, Atlanta, GA, USA. This conference brought together a select group of 30 distinguished thought leaders and practitioners, including ethicists, researchers, clinicians, humanities scholars, and advocates to discuss the unique challenges and controversies related to the diagnosis, treatment, and stigma for patients with what is currently recognized as functional (“psychogenic”) neurological disorders. Our group of experts explored the conflicts and ethical tensions within health care that must be addressed in order to advance care for these disorders. What follows is a reflection on the conversations between conference attendees outlining key challenges and value conflicts in the diagnosis and treatment of patients with functional disorders. With this report, we aim to provide a roadmap for reducing stigma and improving care for functional neurological disorders (FND). A path forward would involve (1) setting a multifactorial research agenda that equally prioritized access to effective psychotherapy as well as identification of novel biomarkers; (2) empowering patients with FND to be heard and to drive changes in care; and (3) reducing isolation for clinicians by providing formal training and setting up multidisciplinary care teams and support networks.

Complementary and integrative strategies are widely used by families with children who have mental health diagnoses. The therapies used by these children include herbs, dietary supplements, massage, acupuncture, meditation, and naturopathy. The literature on efficacy of complementary and alternative approaches is of limited value, and studies are needed to test efficacy and safety. Interpretation of complementary and integrative health care studies for symptomatic management of mental health conditions is hampered by study design and methodological limitations. Well-designed, adequately powered, and suitably controlled clinical trials on promising complementary and integrative modalities are needed for children and adolescents with psychiatric conditions.

The Genomic Psychiatry Cohort (GPC) is a longitudinal resource designed to provide the necessary population-based sample for large-scale genomic studies, studies focusing on Research Domain Criteria (RDoC) and/or other alternate phenotype constructs, clinical and interventional studies, nested case-control studies, long-term disease course studies, and genomic variant-to-phenotype studies. We provide and will continue to encourage access to the GPC as an international resource. DNA and other biological samples and diagnostic data are available through the National Institute of Mental Health (NIMH) Repository. After appropriate review and approval by an advisory board, investigators are able to collaborate in, propose, and co-lead studies involving cohort participants.

Background Low-Field Magnetic Stimulation (LFMS) is a novel, non-invasive, sub-threshold neuromodulation technique, shown in preliminary studies to have immediate mood elevating effects in both unipolar and bipolar depressed patients. Objective We aimed to assess the antidepressant augmentation effects at 48 h of LFMS administered on two consecutive days compared to sham treatment in treatment resistant depression (TRD) subjects, using the Sequential Parallel Comparison Design (SPCD). Methods Eighty-four eligible subjects with TRD were randomly assigned to double-blind treatment with LFMS 20 min/day for four days, sham treatment 20 min/day for four days, or sham treatment 20 min/day for 2 days followed by LFMS treatment 20 min/day for two days, using the pre-randomization version of the SPCD (randomization 1:1:1). The SPCD analyses used a repeated measures linear modeling approach with maximum likelihood estimation to use all available data, and using a 60–40 weighting of Stage 1 vs. 2 responses, with the primary outcome being measured after 2 and 4 days. Results Both primary and secondary outcome measures consistently showed no differences between LFMS-treated patients and those treated with sham, with the exception of a slight, non-significantly greater improvement than sham in the visual analogue scale (VAS) sad mood on LFMS-treated patients. LFMS treatment was relatively well tolerated. Conclusions We did not observe a significantly greater, rapid efficacy of LFMS compared to sham therapy. Future studies need to examine the possible therapeutic effects of more intensive forms of LFMS, as other forms of neurostimulation typically require longer duration of exposure.

We performed a genome-wide association study of 6447 bipolar disorder (BD) cases and 12 639 controls from the International Cohort Collection for Bipolar Disorder (ICCBD). Meta-analysis was performed with prior results from the Psychiatric Genomics Consortium Bipolar Disorder Working Group for a combined sample of 13 902 cases and 19 279 controls. We identified eight genome-wide significant, associated regions, including a novel associated region on chromosome 10 (rs10884920; P=3.28 × 10(-8)) that includes the brain-enriched cytoskeleton protein adducin 3 (ADD3), a non-coding RNA, and a neuropeptide-specific aminopeptidase P (XPNPEP1). Our large sample size allowed us to test the heritability and genetic correlation of BD subtypes and investigate their genetic overlap with schizophrenia and major depressive disorder. We found a significant difference in heritability of the two most common forms of BD (BD I SNP-h(2)=0.35; BD II SNP-h(2)=0.25; P=0.02). The genetic correlation between BD I and BD II was 0.78, whereas the genetic correlation was 0.97 when BD cohorts containing both types were compared. In addition, we demonstrated a significantly greater load of polygenic risk alleles for schizophrenia and BD in patients with BD I compared with patients with BD II, and a greater load of schizophrenia risk alleles in patients with the bipolar type of schizoaffective disorder compared with patients with either BD I or BD II. These results point to a partial difference in the genetic architecture of BD subtypes as currently defined.

Introduction: There has long been an interest in the effects of diet on mental health, and the interaction of the two with stress; however, the nature of these relationships is not well understood. Although associations between diet, obesity and the related metabolic syndrome (MetS), stress, and mental disorders exist, causal pathways have not been established. Methods: We reviewed the literature on the relationship between diet, stress, obesity and psychiatric disorders related to stress. Results: Diet and obesity can affect mood through direct effects, or stress-related mental disorders could lead to changes in diet habits that affect weight. Alternatively, common factors such as stress or predisposition could lead to both obesity and stress-related mental disorders, such as depression and posttraumatic stress disorder (PTSD). Specific aspects of diet can lead to acute changes in mood as well as stimulate inflammation, which has led to efforts to assess polyunsaturated fats (PUFA) as a treatment for depression. Bidirectional relationships between these different factors are also likely. Finally, there has been increased attention recently on the relationship between the gut and the brain, with the realization that the gut microbiome has an influence on brain function and probably also mood and behavior, introducing another way diet can influence mental health and disorders. Brain areas and neurotransmitters and neuropeptides that are involved in both mood and appetite likely play a role in mediating this relationship. Conclusions: Understanding the relationship between diet, stress and mood and behavior could have important implications for the treatment of both stress-related mental disorders and obesity.

Background: Vagal Nerve Stimulation (VNS) has been shown to be efficacious for the treatment of depression, but to date, VNS devices have required surgical implantation, which has limited widespread implementation. Methods: New noninvasive VNS (nVNS) devices have been developed which allow external stimulation of the vagus nerve, and their effects on physiology in patients with stress-related psychiatric disorders can be measured with brain imaging, blood biomarkers, and wearable sensing devices. Advantages in terms of cost and convenience may lead to more widespread implementation in psychiatry, as well as facilitate research of the physiology of the vagus nerve in humans. nVNS has effects on autonomic tone, cardiovascular function, inflammatory responses, and central brain areas involved in modulation of emotion, all of which make it particularly applicable to patients with stress-related psychiatric disorders, including posttraumatic stress disorder (PTSD) and depression, since dysregulation of these circuits and systems underlies the symptomatology of these disorders. Results: This paper reviewed the physiology of the vagus nerve and its relevance to modulating the stress response in the context of application of nVNS to stress-related psychiatric disorders. Conclusions: nVNS has a favorable effect on stress physiology that is measurable using brain imaging, blood biomarkers of inflammation, and wearable sensing devices, and shows promise in the prevention and treatment of stress-related psychiatric disorders.

Background: Traumatic stress can have lasting effects on neurobiology and result in psychiatric conditions such as posttraumatic stress disorder (PTSD). We hypothesize that non-invasive cervical vagal nerve stimulation (nVNS) may alleviate trauma symptoms by reducing stress sympathetic reactivity. This study examined how nVNS alters neural responses to personalized traumatic scripts. Methods: Nineteen participants who had experienced trauma but did not have the diagnosis of PTSD completed this double-blind sham-controlled study. In three sequential time blocks, personalized traumatic scripts were presented to participants immediately followed by either sham stimulation (n = 8; 0–14 V, 0.2 Hz, pulse width = 5s) or active nVNS (n = 11; 0–30 V, 25 Hz, pulse width = 40 ms). Brain activity during traumatic scripts was assessed using High Resolution Positron Emission Tomography (HR-PET) with radiolabeled water to measure brain blood flow. Results: Traumatic scripts resulted in significant activations within the bilateral medial and orbital prefrontal cortex, premotor cortex, anterior cingulate, thalamus, insula, hippocampus, right amygdala, and right putamen. Greater activation was observed during sham stimulation compared to nVNS within the bilateral prefrontal and orbitofrontal cortex, premotor cortex, temporal lobe, parahippocampal gyrus, insula, and left anterior cingulate. During the first exposure to the trauma scripts, greater activations were found in the motor cortices and ventral visual stream whereas prefrontal cortex and anterior cingulate activations were more predominant with later script presentations for those subjects receiving sham stimulation. Conclusion: nVNS decreases neural reactivity to an emotional stressor in limbic and other brain areas involved in stress, with changes over repeated exposures suggesting a shift from scene appraisal to cognitively processing the emotional event.

Objectives This study gathers preliminary data about the biologic effects of repeated Swedish massage therapy compared to a light-touch control condition. Design The study design was a 5-week comparison of repeated Swedish massage and light touch on oxytocin (OT), arginine-vasopressin (AVP), adrenal corticotropin hormone (ACTH), cortisol (CORT), circulating phenotypic lymphocyte markers, and mitogen-stimulated cytokine function. Setting The setting was an outpatient research unit in an academic medical center. Participants The study subjects were medically and psychiatrically healthy young adults. Intervention The study comprised 45 minutes of Swedish massage or light touch, using highly specified and identical protocols, either weekly or twice weekly for 5 weeks. Outcome measures The outcome measures were mean differences between massage and light touch on OT, AVP, ACTH, CORT, lymphocyte markers, and cytokine levels. Results Compared to the touch control condition, weekly Swedish massage stimulated a sustained pattern of increased circulating phenotypic lymphocyte markers and decreased mitogen-stimulated cytokine production, similar to what was previously reported for a single massage session, while having minimal effect on hypothalamic–pituitary–adrenal function. Twice-weekly massage produced a different response pattern with increased OT levels, decreased AVP, and decreased CORT but little effect on circulating lymphocyte phenotypic markers and a slight increase in mitogen-stimulated interferon-γ, tumor necrosis factor-α, interleukin (IL)-1b and IL-2 levels, suggesting increased production of pro-inflammatory cytokines. Conclusions There are sustained cumulative biologic actions for the massage and touch interventions that persist for several days or a week, and these differ profoundly depending on the dosage (frequency) of sessions. Confirmatory studies in larger samples are needed.