Journal Digest
Signaling Differences Found in Patients With Schizophrenia
Another step has been made toward demystifying the biological underpinning of schizophrenia, according to a recently published study in the journal Neuron.
Comparing genetic data of 11,355 people with schizophrenia with 16,416 people without the condition, researchers from Cardiff University found that copy number variants—mutations in which large stretches of DNA are either deleted or duplicated—were significantly more likely to disrupt specific sets of genes contributing to glutamatergic (excitatory) and GABAergic (inhibitory) signaling in patients with schizophrenia than in those without the disorder. Several past research efforts have shown that balancing of the two signaling pathways is crucial for healthy brain development and function.
Hugh Perry, Ph.D., the study’s lead author and chair of the MRC Neurosciences and Mental Health Board at Cardiff, said in a press statement that he hopes that current findings could “lead to new ways of predicting an individual’s risk of developing schizophrenia and form the basis of new targeted treatments that are based on an individual’s genetic makeup.”
Pocklington A, Rees E, Walters J, et al. Novel Findings From CNVs Implicate Inhibitory and Excitatory Signaling Complexes in Schizophrenia. Neuron. 2015. 86(5):1203-14.
Psychiatric Drug Combination in Mice Shows Antidepressant-Like Effects
With studies suggesting that 30 percent to 50 percent of patients with depression do not respond adequately to treatment with selective serotonin reuptake inhibitors (SSRIs), scientists continue to search for alternative pharmacotherapies to treat depression. A recent study by researchers at the University of Bath suggests a combination of buprenorphine and naltrexone may be able to decrease symptoms of depression.
Mice administered buprenorphine (1 mg/kg) and naltrexone (1 mg/kg) exhibited antidepressant-like responses in behaviors, measured by the animals’ increased likelihood to intake food in a new environment and their ability to swim for survival as part of the forced swim test.
The drug combination works by buprenorphine stimulating the kappa opioid receptor. Naltrexone works to block the addictive properties of buprenorphine by inhibiting buprenorphine partial stimulation of mu opioid receptors.
Though more work must be done to test the effectiveness of this drug combination, the researchers believe they may be able to reduce the time spent on clinical trials and regulatory approvals since buprenorphine and naltrexone are already licensed for other conditions.
Almatroudi A, Husbands S, Bailey C, et al. Combined Administration of Buprenorphine and Naltrexone Produces Antidepressant-like Effects in Mice. J Psychopharmacol. 2015. 29(7):812-21.
Poison Center Calls Skyrocket for Synthetic Cannabinoid Use
According to an investigation by the Centers for Disease Control and Prevention (CDC), there have been 3,572 calls made to U.S. poison centers for adverse health effects related to synthetic cannabinoid use between January and May of this year—up 229 percent from the 1,085 calls made during this same period in 2014.
The most commonly reported adverse health effects made during these calls were agitation (35.3 percent), tachycardia (29.0 percent), drowsiness or lethargy (26.3 percent), vomiting (16.4 percent), and confusion (4.2 percent).
According to the CDC, 47.5 percent of the large call volume made this year to the poison centers related to synthetic cannabinoid use involved users requiring some form of medical attention, while 11 percent of calls involved users who had a major adverse event, displaying symptoms that were life-threating or resulted in substantial residual disability or disfigurement.
More than 80 percent of the calls to the poison centers concerned male users with a median age of 26 years. Inhalation by smoking was the most common means of consumption at 80 percent, followed by ingestion at 20 percent.
Synthetic cannabinoids are composed of various psychoactive chemicals called cannabimimetics that have affinity for cannabinoid receptor type 1 (CB-1), resulting in a “high.” Manufacturers of synthetic cannabinoids frequently change the formulation to avoid regulation.
The CDC report noted that the current analysis suggests that “synthetic cannabinoids pose an emerging public health threat … [and] a need for greater public health surveillance and awareness, targeted public health messaging, and enhanced efforts to remove these products from the market.”
Law R, Schier J, Martin C, et al. Increase in Reported Adverse Health Effects Related to Synthetic Cannabinoid Use—United States, January–May 2015. Morbidity and Mortality Weekly Report. 2015. 64(22):618-19.
Psychotic Experiences Reported in General Population, Study Finds
Psychotic experiences, such as hallucinations and delusions, are not restricted to individuals with certain mental illnesses—the general population sometimes experiences these symptoms too, according to a study in JAMA Psychiatry.
Researchers from the University of Queensland in Australia and Harvard Medical School analyzed data from the World Health Organization World Mental Health Surveys that included more than 31,000 adults to assess the lifetime prevalence of psychotic experiences among the general population.
The analysis revealed that 5.8 percent of those surveyed reported having at least one psychotic experience in their lifetime, with hallucinatory experience being the most prevalent at 5.2 percent compared with delusional experience at 1.3 percent. The results also showed lifetime prevalence of psychotic experiences was higher among women (6.6 percent) than men (5 percent) and higher among individuals who lived in middle-income (7.2 percent) and high-income (6.8 percent) countries than those in low-income countries (3.2 percent). However, the psychotic experiences were infrequent, with 32.2 percent of respondents with lifetime psychotic experiences reporting only one episode and 31.8 percent reporting having experienced two to five episodes.
“We are interested in learning why some people recover, while others may progress to more serious disorders such as schizophrenia,” John McGrath, M.D., Ph.D., a research professor at the Queensland Brain Institute and lead author of the study, said in a press release. “We can use these findings to start identifying whether the mechanisms causing these hallucinations are the same or different in both situations.”
McGrath J, Saha S, Al-Hamzawi A, et al. Psychotic Experiences in the General Population: A Cross-National Analysis Based on 31 261 Respondents From 18 Countries. JAMA Psychiatry. May 27, 2015 [Epub ahead of print]
Recurrent Depression, Antidepressant Use Linked to Low Bone Density in Men
Women with major depressive disorder (MDD) are not the only ones who are at risk for low bone density: a new study shows that men with MDD are too.
Researchers at the University of Eastern Finland and Deakin University in Australia analyzed data from a large, population-based osteoporosis study in Australia that included over 900 men aged 24 to 98. This analysis revealed that men with recurrent MDD had significantly lower bone mineral density in the forearm and total body when compared with men with no history of MDD.
In addition, the researchers found that antidepressant use—in men with or without recurrent depression—was associated with reduced bone mineral density of the hip in those men who weighed less than 110 kg.
As it relates to the forearm, the association between antidepressants and reduced bone mineral density was observed only in men who weighed under 75 kg.
The findings suggest that the prevention and early detection of depression may be important factors in reducing osteoporosis in some men, according to the study authors. ■
Rauma P, Pasco J, Berk M, et al. The association between major depressive disorder, use of antidepressants and bone mineral density (BMD) in men. J Musculoskelet Neuronal Interact. 2015. 15(2):177-185.
