Online depression intervention tool found effective in adolescent mothers

Researchers from the University of Louisville found that using an Internet-based depression intervention tool program found effective in improving treatment rates of adolescent depressed mothers. This study is published in journal Archives of Women’s Mental Health.

Roughly half of the 400,000 adolescents 18 and younger who give birth annually in the United States experience depressive symptoms, but less than 25 percent follow referrals for depression evaluation and treatment, according to the study.

Internet-based depression tool consisted of a website with videos of mothers describing their experience with management of postpartum depression. Research study involved more than 200 subjects and findings showed that intervention changed attitudes and helped adolescent depressed mothers to seek mental health and depression treatment.

This research was lead by M. Cynthia Logsdon, Ph.D., W.H.N.P.-B.C., University of Louisville School of Nursing professor who said,

Untreated postpartum depression hinders a mother’s relationship with her child, her functioning at work and school, mothering skills and development. The condition also can harm a baby’s development and attachment to the mother.

Reference: Logsdon, M. Cynthia, John Myers, Jeff Rushton, Jennifer L. Gregg, Allan M. Josephson, Deborah Winders Davis, Kyle Brothers, Kristin Baisch, Anissa Carabello, Krista Vogt, Kayla Jones, and Jennifer Angermeier. “Efficacy of an Internet-based Depression Intervention to Improve Rates of Treatment in Adolescent Mothers.” Archives of Womens Mental Health, 2017. doi:10.1007/s00737-017-0804-z.

Research funding: National Institute of Health.

Adapted from press release by the University of Louisville.

Potential treatment for Alzheimer’s dementia using cell therapy

Researchers from Gladstone Institute uncovered the therapeutic benefits of genetically improving interneurons with a voltage-gated sodium channel Nav1.1 and transplanting them into the brain of a mouse model of Alzheimer’s disease. This study is led by Jorge Palop, Ph.D., an assistant investigator at the Gladstone Institutes. The study findings are published in journal Neuron.

Inhibitory interneurons are essential for managing brain rhythms. They regulate the oscillatory rhythms and network synchrony that are required for cognitive functions. Network dysrhythmias in Alzheimer’s disease and multiple neuropsychiatric disorders are associated with hypofunction of Nav1.1, a voltage-gated sodium channel subunit predominantly expressed in interneurons in Alzheimer’s disease (AD).

Researchers found a way to re-engineer inhibitory interneurons genetically boosted by adding protein Nav1.1 to improve their function. They showed that these enhanced interneurons, when transplanted into the abnormal brain of Alzheimer mice, can properly control the activity of excitatory cells and restore brain rhythms.

The researchers then discovered that the interneurons with enhanced function were able to overcome the toxic disease environment and restore brain function. The findings could eventually lead to the development of new treatment options for patients with Alzheimer’s disease.

In addition to examining if the cell therapy could be translated from mice to humans, researchers are working on pharmaceutical drugs to enhance the function of inhibitory interneurons.

Citation: Martinez-Losa, Magdalena, Tara E. Tracy, Keran Ma, Laure Verret, Alexandra Clemente-Perez, Abdullah S. Khan, Inma Cobos, Kaitlyn Ho, Li Gan, Lennart Mucke, Manuel Alvarez-Dolado, and Jorge J. Palop. “Nav1.1-Overexpressing Interneuron Transplants Restore Brain Rhythms and Cognition in a Mouse Model of Alzheimer’s Disease.” Neuron, 2018. doi:10.1016/j.neuron.2018.02.029.

Research funding: National Institutes of Health, Alzheimer’s Association; S.D. Bechtel, Jr. Foundation.

Adapted from press release by Gladstone Institutes.

Researchers find possible link between autism and nuclear receptor protein LXRβ

Research by University of Houston scientists discovered a possible link between nuclear receptor protein LXRβ (Liver X receptor Beta) and autism spectrum disorder. They found that nuclear receptor LXRβ deletion causes poor development of dentate gyrus, a part of brain’s hippocampus. The dentate gyrus, or DG, is responsible for emotion and memory and is known to be involved in autism spectrum disorders (ASD).

This study is led by Margaret Warner and Jan-Åke Gustafsson. The results are published in journal Proceedings of the National Academy of Sciences.”Our findings suggest early changes in dentate gyrus neurogenesis ultimately provide an aberrant template upon which to build the circuitry that is involved in normal social function,” said Warner.

Researchers conducted an animal study using LXRβ-deficient mice. Behavior analysis of these mice showed autistic-like behaviors, including social interaction deficits and repetitive behavior.”Knocking out LXRβ led to autistic behavior and reduced cognitive flexibility,” said Warner. “In this paper, we share our findings that that deletion of the LXRβ (Liver X receptor Beta) causes hypoplasia or underdevelopment in the dentate gyrus and autistic-like behaviors, including abnormal social interaction and repetitive behavior.”

Citation: Cai, Yulong, Xiaotong Tang, Xi Chen, Xin Li, Ying Wang, Xiaohang Bao, Lian Wang, Dayu Sun, Jinghui Zhao, Yan Xing, Margaret Warner, Haiwei Xu, Jan-Åke Gustafsson, and Xiaotang Fan. “Liver X receptor β regulates the development of the dentate gyrus and autistic-like behavior in the mouse.” Proceedings of the National Academy of Sciences, 2018, 201800184. doi:10.1073/pnas.1800184115.

Adapted from press release by the University of Houston.

New target receptor for treating depression GPR158

Researchers from the Scripps Research Institute find a new target receptor called GPR158 for treating depression. Their research shows that individuals with high levels of above receptor may be more susceptible to depression following chronic stress.

“The next step in this process is to come up with a drug that can target this receptor,” says Kirill Martemyanov, Ph.D., co-chair of the TSRI Department of Neuroscience and senior author of the new study, which is published in the journal eLife.

“We need to know what is happening in the brain so that we can develop more efficient therapies,” says Cesare Orlandi, Ph.D., the senior research associate at TSRI and co-first author of the study.

The researchers found elevated GPR158 protein in depressed patients, suspected it could play a major role in the disease process. They then conducted an animal study using male and female mice with and without above receptor. Subsequent behavioral tests showed that mice with elevated levels of GPR158 showed signs of depression following chronic stress and suppressing GPR158 protected them from developing depressive behavior and also resilient to stress.

Next, the researchers examined why GPR158 has these effects on depression. The team demonstrated that GPR158 affects key signaling pathways involved in mood regulation in the region of the brain called prefrontal cortex, though the researchers emphasized that the exact mechanisms remain to be established.

Martemyanov explains that GPR158 is a so-called “orphan receptor” (which gets its name because its binding partner/partners are unknown) with a poorly understood biology and mechanism of action. GPR158 appears to work downstream from other important brain systems, such as the GABA, a major player in the brain’s inhibitory control and adrenergic system involved in stress effects.

Laurie Sutton, Ph.D., a research associate at TSRI and co-first author of the study, says this finding matches what doctors have noticed in people who have experienced chronic stress. “There’s always a small population that is resilient they don’t show the depressive phenotype,” says Sutton.

As the search goes on for additional targets for depression, Martemyanov says scientists are increasingly using new tools in genome analysis to identify orphan receptors like GPR158. “Those are the untapped biology of our genomes, with significant potential for development of innovative therapeutics,” he says.

Citation: Sutton, Laurie P., Cesare Orlandi, Chenghui Song, Won Chan Oh, Brian S. Muntean, Keqiang Xie, Alice Filippini, Xiangyang Xie, Rachel Satterfield, Jazmine D W Yaeger, Kenneth J. Renner, Samuel M. Young, Baoji Xu, Hyungbae Kwon, and Kirill A. Martemyanov. “Orphan receptor GPR158 controls stress-induced depression.” ELife 7 (2018). doi:10.7554/elife.33273.

Research funding: National Institutes of Health, University of Iowa, Max Planck Society, Canadian Institutes of Health Research Fellowship.

Adapted from press release by the Scripps Research Institute.

Diets rich in fruits and vegetables associated with lower depression risk

People who eat vegetables, fruit and whole grains may have lower rates of depression over time, according to a preliminary study that will be presented at the American Academy of Neurology’s 70th Annual Meeting.

Research found that people whose diets adhered more closely to the Dietary Approaches to Stop Hypertension (DASH) diet were less likely to develop depression than people who did not. DASH diet consists of fruit, vegetables, whole grains and fat-free or low fat dairy products. This diet limits intake of foods that contain sugar and saturated fats. Previous research have shown health benefits such as lowering high blood pressure and bad cholesterol (LDL), along with lowering body weight.

“Depression is common in older adults and more frequent in people with memory problems, vascular risk factors such as high blood pressure or high cholesterol, or people who have had a stroke,” said study author Laurel Cherian, MD, of Rush University Medical Center in Chicago and a member of the American Academy of Neurology. “Making a lifestyle change such as changing your diet is often preferred over taking medications, so we wanted to see if diet could be an effective way to reduce the risk of depression.”

For the study, 964 participants with an average age of 81 were evaluated yearly for an average of six-and-a-half years. They were monitored for symptoms of depression and also filled out questionnaires about how often they ate various foods, and the researchers looked at how closely the participants’ diets followed diets such as the Dietary Approaches to Stop Hypertension (DASH) diet, Mediterranean diet and the traditional Western diet.

Participants were divided into three groups based on how closely they adhered to the diets. People in the two groups that followed the Dietary Approaches to Stop Hypertension (DASH) diet most closely were less likely to develop depression than people in the group that did not follow the diet closely. On the other hand, the more closely people followed a Western diet, a diet that is high in saturated fats and red meats and low in fruits and vegetables the more likely they were to develop depression.

Cherian noted that the study does not prove that the Dietary Approaches to Stop Hypertension (DASH) diet leads to a reduced risk of depression; it only shows an association.

“Future studies are now needed to confirm these results and to determine the best nutritional components of the Dietary Approaches to Stop Hypertension (DASH) diet to prevent depression later in life and to best help people keep their brains healthy,” said Cherian.

Adapted from press release by the American Academy of Neurology.

People with depression found to have low arginine levels

Researchers from the University of Eastern Finland have shown that people suffering from major depressive disorder have reduced arginine levels. One of the role of arginine in body is to produce nitric oxide, which in turn have role in vascular regulation and is a nervous system and immune defence mediator. The global arginine bioavailability ratio (GABR) is an indicator of the body’s arginine levels, and the ratio has previously been used to measure the body’s capacity to produce nitric oxide. Previous research shows that educed arginine bioavailability is also known to be an independent risk factor of cardiovascular diseases.

Current research published in Journal of Affective Disorders shows that people suffering from major depressive disorders have reduced arginine bioavailability.

“It is possible that depression-induced inflammatory responses lead to reduced arginine levels. This may result in insufficient production of nitric oxide for the needs of the nervous system and circulation. However, we don’t know yet what exactly causes reduced arginine bioavailability in people with depression,” says Doctoral Student Toni Ali-Sisto, the lead author of the study.

The study carried out by the University of Eastern Finland and Kuopio University Hospital involved 99 adults with diagnosed major depressive disorder and 253 non-depressed controls. The concentrations of three amino acids, namely arginine, citrulline and ornithine, were analysed from their fasting glucose samples, and this data was used to calculate their GABRs. Symmetric and asymmetric dimethylarginine concentrations were also measured, as they both play a role in the production of nitric oxide. The findings were then compared between the depressed and the non-depressed controls. The study also analysed whether these concentrations changed in people with depression during a follow-up of eight months, and whether remission of depression had an effect on the concentrations.

“Although our study shows that people with depression have reduced arginine bioavailability, this doesn’t mean that taking an arginine supplement would protect against depression. That’s an area for further research,” Ali-Sisto says.

People with depression had weaker arginine bioavailability than their non-depressed controls. The study did not find significant differences in the symmetric and asymmetric dimethylarginine concentrations. The use of anti-depressants or anti-psychotics did not affect the concentrations, either.

Contrary to the researchers’ expectations, there were no clear differences in the concentrations measured from people who had recovered from depression and people who remained depressed.

“Arginine bioavailability was slightly higher in people who had recovered from depression than in people who remained depressed. However, a more extensive set of data and a longer follow-up period are necessary for estimating arginine’s role in depression recovery.”

Citation: Ali-Sisto, Toni, Tommi Tolmunen, Heimo Viinamäki, Pekka Mäntyselkä, Minna Valkonen-Korhonen, Heli Koivumaa-Honkanen, Kirsi Honkalampi, Anu Ruusunen, Jatin Nandania, Vidya Velagapudi, and Soili M. Lehto. “Global arginine bioavailability ratio is decreased in patients with major depressive disorder.” Journal of Affective Disorders 229 (2018): 145-51. doi:10.1016/j.jad.2017.12.030.

Adapted from press release by the University of Finland.

Adults with autism spectrum disorder showed good results with cognitive enhancement therapy compared to enriched supportive therapy

While there have been advances in early detection and many studies involving the treatment of children with autism spectrum disorder (ASD), few efforts to date have focused on interventions for adults. These individuals experience significant challenges throughout adulthood, including unemployment, social impairment and poor quality of life. It is believed that the challenges people with autism have in processing and understanding information contribute to these difficulties in adulthood. But treatments to address such problems are virtually non-existent. New research out of the University of signals a potential breakthrough for adults with autism spectrum disorder.

The six-year study, “Cognitive enhancement therapy for adult autism spectrum disorder: Results of an 18-month randomized clinical trial,” involved 54 adults and was led by Shaun Eack, Ph.D., M.S.W., Pitt’s David E. Epperson Professor of Social Work and Psychiatry, and Nancy Minshew, M.D., Pitt professor of psychiatry and neurology. The study tested two treatments, cognitive enhancement therapy (CET) and enriched supportive therapy (EST).

Cognitive enhancement therapy focused on helping adults improve their thinking and social understanding through computer-based exercises designed to improve attention, memory and problem-solving, along with small group exercises designed to help individuals take the perspectives of others and better understand social situations.

The computerized part of the treatment was administered to pairs of adults with autism to help improve their neurocognitive abilities, such as attention and cognitive flexibility which are important precursors to higher-level skills involved in problem-solving, self-regulation and social communication. After several months of computer training, the participant pairs then joined to form a small group focused on social cognition, or thinking abilities involved in understanding others and processing social information. Participants engaged in these computerized and group-based components for approximately three hours a week.

The second treatment tested, enriched supportive therapy, was a one-on-one hour-long session per week in which the participants learned to manage their emotions and stress, improve their social skills, and cope with everyday problems. Enriched supportive therapy builds on traditional psychotherapy practices, such as cognitive behavioral therapy, and uses them to help adults with autism become more aware of their triggers of stress and implement effective strategies to cope with stress and negative emotions. The treatment also provided education to help adults with autism understand their condition, which was an additional focus of the cognitive enhancement therapy group, as many affected adults have not been educated on the nature of autism, its treatment and the challenges it presents in adulthood. Participants were randomly assigned to either the cognitive enhancement therapy or enriched supportive therapy treatment.

The study’s findings, published online in the journal Autism Research, revealed that after 18 months of treatment, adults with autism who received cognitive enhancement therapy had significant increases in neurocognitive function, particularly in attention and their ability to process information quickly. These cognitive gains helped some participants to be much more employable. Further improvements also were seen in social cognition and social understanding. Those treated with enriched supportive therapy showed a marked increase in social-cognitive behaviors, but it took nearly nine months longer for such benefits to emerge compared to adults treated with cognitive enhancement therapy, suggesting that the more intensive training offered in that approach may help speed improvement.

Citation: Eack, Shaun M., Susan S. Hogarty, Deborah P. Greenwald, Maralee Y. Litschge, Shannondora A. Porton, Carla A. Mazefsky, and Nancy J. Minshew. “Cognitive enhancement therapy for adult autism spectrum disorder: Results of an 18-month randomized clinical trial.” Autism Research, 2017. doi:10.1002/aur.1913.

Funding: NIH/National Institute of Mental Health

Adapted from press release by University of Pittsburg.

Role of diet and gut microbiome in the major depressive disorder

An international group of researchers headed by André Carvalho has published in Psychotherapy and Psychosomatic a paper that provides new data and prospects for the links between the intestinal flora and several disorders, notably depression.

Persistent low-grade immune-inflammatory processes, oxidative and nitrosative stress and hypothalamic-pituitary-adrenal axis activation are integral to the pathophysiology of the major depressive disorder. The microbiome, intestinal compositional changes, and resultant bacterial translocation add a new element to the bidirectional interactions of the gut-brain axis. New evidence implicates these pathways in the onset of the major depressive disorder. In addition, abnormalities in the gut-brain axis are associated with several chronic non-communicable disorders, which frequently co-occur in individuals with depression, including but not limited to irritable bowel syndrome, chronic fatigue syndrome, obesity, and type 2 diabetes mellitus.

The composition of the gut microbiota is influenced by several genetic and environmental factors (e.g. diet). Several lines of evidence indicate that gut-microbiota-diet interactions play a significant pathophysiological role in depression and related medical comorbidities. Gut dysbiosis and the leaky gut may influence several pathways implicated in the biology of major depressive disorder, including but not limited to immune activation, oxidative and nitrosative stress, and neuroplasticity cascades. However, methodological inconsistencies and limitations limit comparisons across studies.

Authors conclude that intestinal dysbiosis and the leaky gut may constitute a key pathophysiological link between depression and its medical comorbidities. This emerging literature opens relevant preventative and therapeutic perspectives.

Citation: Slyepchenko, Anastasiya, Michael Maes, Felice N. Jacka, Cristiano A. Köhler, Tatiana Barichello, Roger S. Mcintyre, Michael Berk, Iria Grande, Jane A. Foster, Eduard Vieta, and André F. Carvalho. “Gut Microbiota, Bacterial Translocation, and Interactions with Diet: Pathophysiological Links between Major Depressive Disorder and Non-Communicable Medical Comorbidities.” Psychotherapy and Psychosomatics 86, no. 1 (2016): 31-46. doi:10.1159/000448957.
Adapted from press release by Karger medical and scientific publishers.

Stress, cortisol and perceptual learning process

Neuroscientists of the Ruhr University Bochum found that stress has adverse impact on our learning process. Usually when we train our senses, we sharpen them and thereby improve our perceptual performance. However during stressful situations we produce a hormone called cortisol, which completely blocks this important ability. These findings are reported in Journal “Psychoneuroendocrinology”

Stress by Typographyimages/pixabay

“Previous research has already shown that stress can prevent the retrieval of memories. But now we have discovered that it also has a major effect on our perception and perceptual learning,” explains Dr Hubert Dinse, one of the authors of the study.

In their study, researchers investigated how the sense of touch of 30 study participants could be changed after a training phase. Half of them received a medium dose of the stress hormone cortisol, while the other half received a placebo drug.

To make training comparable across all participants, the researchers employed the well-established approach of passive finger stimulation. Previous studies and several therapy approaches have shown that this method leads to an improved tactile acuity.

Tactile performance was assessed using the so-called “two-point discrimination threshold”. This marker indicates how far apart two stimuli need to be, to be discriminated as two separate sensations the closer they are, the better the sense of touch.

The placebo group improved their tactile acuity, as expected, by about 15 percent. In contrast, the cortisol given to the other group blocked almost all the stimulation-induced improvement. Cognitive psychologist Prof Dr Oliver T. Wolf explains:” Our data show that a single dose of cortisol not only disrupts memory in the hippocampus, but it also has a substantial effect on the plasticity of sensory areas of the brain.”

In previous studies on a cellular level, neuroscientists have demonstrated that cortisol suppresses the strengthening of synaptic connections, and therefore the plasticity of the brain – its ability to learn. The team led by Hubert Dinse therefore suggests, their results could also explain by cortisol-induced suppression of synaptic plasticity.

The results of the study could also affect clinical treatments. Corticosteroids, of which cortisol is one, are often used in the treatment of immunological and neurological diseases. However, the effects on perceptual learning observed in this study may counteract rehabilitation efforts, which rely on just these mechanisms. It is therefore necessary to find out which effects the clinical treatment with these substances has on learning mechanisms in the brain.

Citation: Dinse, Hubert R., J. C. Kattenstroth, M. Lenz, M. Tegenthoff, and O. T. Wolf. “The stress hormone cortisol blocks perceptual learning in humans.” Psychoneuroendocrinology 2017 vol: 77 pp: 63-67.
DOI: 10.1016/j.psyneuen.2016.12.002
Research funding: German Research Foundation (Deutsche Forschungsgemeinschaft, DFG).
Adapted from press release by Ruhr University Bochum.

Research uncovers link between long-term opioid use and preexisting psychiatric and behavioral disease

A wide range of pre-existing psychiatric and behavioral conditions and the use of psychoactive drugs could be important risk factors leading to long-term use of opioid pain medications, reports a study in Journal Pain, the official publication of the International Association for the Study of Pain (IASP).

Using a nationwide insurance database, the researchers identified 10.3 million patients who filed insurance claims for opioid prescriptions between 2004 and 2013. The study looked at whether pre-existing psychiatric and behavioral conditions and use of psychoactive medications were predictors of later opioid use.

“We found that pre-existing psychiatric and behavioral conditions and psychoactive medications were associated with subsequent claims for prescription opioids,” write Patrick D. Quinn, Ph.D., of Indiana University, Bloomington, and colleagues. The association appears stronger for long-term opioid use, and especially for patients with a previous history of substance use disorders.

The results also suggest that some outcomes viewed as harmful outcomes of opioid use substance use disorders, depression, suicidal or self-injuring behavior, and motor vehicle crashes are also predictors of which patients are at risk of long-term use of prescription opioids.

Overall, the results suggested a “modest” increase in any opioid prescriptions for patients with previous psychiatric or behavioral conditions (depression or anxiety disorders, opioid or other substance use disorders, suicide attempts or other self-injury, motor vehicle crashes, and sleep disorders) or use of psychoactive medications.

About 1.7 percent of patients with opioid prescriptions become long-term opioid users (six months or longer). But the risk became substantially higher for patients with mental health conditions or psychoactive medication use. Relative increases in rates of long-term opioid use ranged from 1.5 times for patients taking medications for attention-deficit/hyperactivity disorder, to about 3 times for those with previous substance use disorders other than opioids, to nearly 9 times for those with previous opioid use disorders.

Amid the continuing opioid epidemic, it’s important to understand which patients select (or are selected for) treatment with these pain medications. Previous studies have suggested a pattern of “adverse selection”: patients at greatest risk of harmful outcomes, including those with substance abuse and other psychiatric conditions, may be more likely to be prescribed opioids in higher doses and for longer durations.

Dr. Quinn and coauthors conclude: “Our findings support the ideas that clinical practice has deviated from the ‘careful selection’ under which most clinical trials are conducted and that thorough mental health assessment and intervention should be considered in conjunction with the use of long-term opioid therapy.

Citation: Quinn, Patrick D., Kwan Hur, Zheng Chang, Erin E. Krebs, Matthew J. Bair, Eric L. Scott, Martin E. Rickert, Robert D. Gibbons, Kurt Kroenke, and Brian M. D’onofrio. “Incident and long-term opioid therapy among patients with psychiatric conditions and medications: a national study of commercial health care claims.” Pain 158, no. 1 (2017): 140-148.
DOI: 10.1097/j.pain.0000000000000730
Adapted from press release by Wolters Kluwer publications.