Tag: depression

Categories : Mental HealthTags :

Walking the Tightrope of Prescribing Benzodiazepines

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Antidepressants and psychotherapy typically are the preferred treatment options for anxiety and depression, although benzodiazepines can be helpful in treating acute or persistent anxiety that does not respond to first-line therapy. In “Walking the Benzodiazepine High Wire,” published in Psychiatric Services, two experts advocate advocate a multipronged strategy for the cautious prescribing of this class of anxiety medications rather than a stringent and exclusively regulatory approach to their use.

Kurt Kroenke, MD, of the Regenstrief Institute and Indiana University School of Medicine, and Matthew E. Hirschtritt, MD, MPH, of Kaiser Permanente Northern California and University of California, San Francisco,

Noting that the number of benzodiazepine prescriptions in the US has substantially increased over the past decade, leading to a parallel rise in rates of misuse and overdose, Dr Kroenke and Dr Hirschtritt counsel that to stem this disquieting tide, provider and patient education, coupled with prescribing surveillance, may be preferable to overly strict governmental regulation of benzodiazepines.

“Benzodiazepines should not be tried first or probably even second, but as with opiates which can be appropriate for acute pain at end of life or following a severe injury or major surgery, there are appropriate reasons for prescribing benzodiazepines for severe anxiety,” said Dr Kroenke.

He is a pioneer in the field of medical symptomology and international leader in the interpretation and treatment of psychological and physical symptoms. He has co-developed brief survey measures in worldwide clinical use to track symptoms of anxiety (GAD-7); depression (PHQ-9); suicide risk (P-4); and other conditions. These tools have been translated into more than 100 languages and assist clinicians around the world in selecting treatments and evaluating their effectiveness.

The authors conclude: “The tightrope between the benefits and risks of prescribing a medication that may be useful for some patients and harmful for others exists not only for controlled drugs but also for treatments such as antibiotics, which continue to be overprescribed, leading to antibiotic resistance. A multipronged strategy for BZD [benzodiazepine] use that includes ongoing education of providers, patients, and the general population; surveillance to optimise selective and appropriate use; and closer oversight of outlier prescribing patterns is preferable to a stringent and exclusively regulatory approach.”

Source: Regenstrief Institute

Categories : Mental HealthTags :

How Ketamine Flips the Brain’s Switch for Depression

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Depression, young man
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Ketamine, an established anaesthetic and increasingly popular antidepressant, dramatically reorganises activity in the brain, as if a switch had been flipped on its active circuits, according to a new study published in a Nature Neuroscience paper.

Researchers observed greatly altered patterns of neuronal activity in the cerebral cortex of animal models after ketamine administration – normally active neurons were silenced while another set that were normally quiet suddenly sprang to action.

This ketamine-induced activity switch in key brain regions tied to depression may impact our understanding of ketamine’s treatment effects and future research in the field of neuropsychiatry.

“Our surprising results reveal two distinct populations of cortical neurons, one engaged in normal awake brain function, the other linked to the ketamine-induced brain state,” said the co-lead and co-senior author Joseph Cichon, MD, PhD, an assistant professor at the University of Pennsylvania. “It’s possible that this new network induced by ketamine enables dreams, hypnosis, or some type of unconscious state. And if that is determined to be true, this could also signal that it is the place where ketamine’s therapeutic effects take place.”

Anaesthesiologists routinely deliver anesthetic drugs before surgeries to reversibly alter activity in the brain so that it enters its unconscious state. Since its synthesis in the 1960s, ketamine has been a mainstay in anaesthesia practice because of its reliable physiological effects and safety profile. One of ketamine’s signature characteristics is that it maintains some activity states across the surface of the brain (the cortex). This contrasts with most anaesthetics, which work by totally suppressing brain activity. It is these preserved neuronal activities that are thought to be important for ketamine’s antidepressant effects in key brain areas related to depression. But, to date, how ketamine exerts these clinical effects remains mysterious.

In their new study, the researchers analysed mouse behaviours before and after they were administered ketamine, comparing them to control mice who received placebo saline. One key observation was that those given ketamine, within minutes of injection, exhibited behavioural changes consistent with what is seen in humans on the drug, including reduced mobility, impaired responses to sensory stimuli, which are collectively termed “dissociation.”

“We were hoping to pinpoint exactly what parts of the brain circuit ketamine affects when it’s administered so that we might open the door to better study of it and, down the road, more beneficial therapeutic use of it,” said co-lead and co-senior author Alex Proekt, MD, PhD, an associate professor at Penn.

Two-photon microscopy was used to image cortical brain tissue before and after ketamine treatment. By following individual neurons and their activity, they found that ketamine turned on silent cells and turned off previously active neurons.

The neuronal activity observed was traced to ketamine’s ability to block the activity of synaptic receptors called NMDA receptors and ion channels called HCN channels. The researchers found that they could recreate ketamine’s effects without the medications by simply inhibiting these specific receptors and channels in the cortex. The scientists showed that ketamine weakens several sets of inhibitory cortical neurons that normally suppress other neurons. This allowed the normally quiet neurons, the ones usually being suppressed when ketamine wasn’t present, to become active.

The study showed that this dropout in inhibition was necessary for the activity switch in excitatory neurons – the neurons forming communication highways, and the main target of commonly prescribed antidepressant medications. More work will need to be undertaken to determine whether the ketamine-driven effects in excitatory and inhibitory neurons are the ones behind ketamine’s rapid antidepressant effects.

“While our study directly pertains to basic neuroscience, it does point at the greater potential of ketamine as a quick-acting antidepressant, among other applications,” said co-author Max Kelz, MD, PhD. “Further research is needed to fully explore this, but the neuronal switch we found also underlies dissociated, hallucinatory states caused by some psychiatric illnesses.”

Source: University of Pennsylvania School of Medicine

Categories : Obstetrics & Gynaecology PaediatricsTags :

No Link between Benzodiazepines Use in Pregnancy and Offspring Autism, ADHD

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A large-scale study published in JAMA Network has found no link between benzodiazepines use in pregnancy and subsequent autism spectrum disorder (ASD) or attention-deficit/hyperactivity disorder (ADHD) diagnoses in offspring. When comparing siblings, benzodiazepines use had no effect on ASD or ADHD risk, indicating that the mother’s genetics partly explained the increased risk.

Some 10–30% of pregnant women experience mental disorders, including mood or anxiety spectrum disorders, for which benzodiazepine agents are sometimes prescribed; this occurs in an estimated 1.9% of pregnancies globally.

The safety of these agents to the developing foetus and newborn has been called into question, since benzodiazepines are able to cross the placenta and have been found to be present in amniotic fluid and breast milk. The US FDA includes in the category of possible harm to the foetus.

While rodents studies have tested benzodiazepine exposure during the first trimester of pregnancy, investigations of neurodevelopmental outcomes in humans, such as ASD and ADHD, have been lacking.

One study found no significantly increased risks of ADHD symptoms or fine or greater motor deficits. Those researchers suggested the disorder resulting in benzodiazepine use might partly explain the increased risks. Maternal depressive and anxiety symptoms in pregnancy have also been linked to increased ADHD risk in children.

From the Taiwanese national health database, of over 1 .5 million children born full term who were younger than 14 years of age and followed up to 2017; 5.0% had been exposed to benzodiazepines in utero.

However, no differences were found with unexposed sibling controls during the same time frame for ADHD or ASD.

The researchers concluded that their results “challenge current assumptions of a potential association of neurodevelopmental disorders with maternal benzodiazepine use before or during pregnancy. Better identification of maternal mental health concerns, as well as possible interventions or provisions of guidance to build better nurturing and raising environments for newborns at risk, may be relevant to the prevention of adverse outcomes of neurodevelopmental disorders.”

Categories : Mental HealthTags :

Psilocybin Shows Promise in Treatment-resistant Depression

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Mushroom
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The largest and most rigorous clinical trial to date of psilocybin (a psychoactive ingredient in magic mushrooms), suggests the possibility that COMP360 psilocybin with psychological support could be a beneficial therapeutic strategy for people with treatment-resistant depression (TRD). The trial results were published in the New England Journal of Medicine.

Prompted by promising preliminary findings, this funded multi-centre, randomised, double-blind, phase 2b clinical trial was launched in 2018 to determine the safety and potential antidepressant effects of a single dose of COMP360 psilocybin (25mg or 10mg), compared to 1mg, with psychological support in people with TRD.

The trial, which included 233 people with TRD across 10 countries who received a single dose of 25mg COMP360 psilocybin experienced a highly statistically and clinically significant rapid reduction in symptoms of depression compared to 1mg at three weeks. This offers hope that COMP360 psilocybin with psychological support could be an effective antidepressant treatment paradigm for some people with TRD, if proven effective and safe in larger studies. COMPASS Pathways, the company that developed the psilocybin formulation., will be running a larger phase 3 programme of COMP360 psilocybin therapy in TRD, which is on schedule to begin in 2022.

KEY RESEARCH FINDINGS

  • 25mg COMP360 psilocybin with psychological support led to a statistically and clinically significantly reduction in symptoms of depression in people with TRD compared to 1mg at week 3.
  • 37% of people with TRD in the 25mg group met criteria for response at week 3 (≥ 50% decrease in depressive symptoms).
  • Approximately 30% of people with TRD in the 25mg group met criteria for remission at week 3 (29.1%).
  • 20% of people with TRD in the 25mg group met criteria for sustained response at week 12.
  • COMP360 psilocybin was generally well-tolerated.

Dr John R. Kelly, Psychiatrist and Clinical Senior Lecturer, Trinity College said: “This is the largest and most rigorous clinical trial of psilocybin to date. It shows a promising antidepressant signal for 25mg COMP360 psilocybin with psychological support and has paved the way for phase 3 clinical trials, which will determine whether it translates into a much-needed complementary treatment strategy in the psychiatry clinic.”

Source: Trinity College Dublin

Categories : Mental HealthTags :

Long Hours Worsen Depression Risk in New Doctors

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As work hours increase, new doctors are at greater risk of depression, according to a study in the New England Journal of Medicine. Working 90 or more hours a week was associated with changes in depression symptom scores three times larger than the change in depression symptoms among those working 40 to 45 hours a week.

Additionally, compared to those working normal hours, those working more hours had greater odds of scores equating to moderate to severe depression.

By means of advanced statistical methods, the researchers emulated a randomised clinical trial using data on more than 17 000 first-year medical residents, accounting for many other factors in the doctors’ personal and professional lives. Less than 5% met the criteria for moderate to severe depression.

They found a “dose response” effect between hours worked and depression symptoms, with an average symptom increase of 1.8 points on a standard scale for those working 40 to 45 hours, ranging up to 5.2 points for those working more than 90 hours. They conclude that, among all the stressors affecting physicians, working a large number of hours is a major contributor to depression.

The data come from the Intern Health Study, based at the Michigan Neuroscience Institute and the Eisenberg Family Depression Center. Each year, the study recruits new medical school graduates to take part in a year of tracking of their depressive symptoms, work hours, sleep and more while they complete the first year of residency, also called the intern year.

The impact of high numbers of work hours

Though the interns in the study reported a wide range of previous-week work hours, the most common work hour levels were between 65 to 80 hours per week.

The authors say their findings point to a clear need to further reduce the number of hours residents work each week on average.

“This analysis suggests strongly that reducing the average number of work hours would make a difference in the degree to which interns’ depressive symptoms increase over time, and reduce the number who develop diagnosable depression,” said Amy Bohnert, PhD, the study’s senior author and a professor at the U-M Medical School. “The key thing is to have people work fewer hours; you can more effectively deal with the stresses or frustrations of your job when you have more time to recover.”

Yu Fang, MSE, the study’s lead author and a research specialist at the Michigan Neuroscience Institute, notes that the number of hours is important, but so are the training opportunities that come from time spent in hospitals and clinics. “It is important to use the time spent at work for supervised learning opportunities, and not low-value clinical service tasks,” she says.

Source: Michigan Medicine – University of Michigan

Categories : Mental Health Obstetrics & GynaecologyTags :

Biological Changes in Mothers Experiencing Postpartum Depression

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Woman with depression
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Newly discovered biological changes in mothers who suffer postpartum depression may help explain the condition, yield long-sought treatments and let doctors identify those at risk even before their babies are born. The findings were published in Molecular Psychiatry.

Postpartum depression strikes up to 20% of new mothers, and roughly 20% of maternal deaths after childbirth are from suicide. Postpartum depression can cause anxiety and irritability, feelings of self-doubt and difficulty bonding with the baby, cognitive impairment, and interfering with sleeping and eating. For the child, maternal postpartum depression can lead to cognitive, emotional and social development problems.

Risk factors for postpartum depression are thought to include the mother’s age at childbirth, diabetes and prior history of mental health issues. But the new discovery suggests a previously unknown biological contributor: an impairment of the body’s ability to clean up old genetic material and other cellular debris.

“The finding that cells aren’t cleaning out old proteins and cellular debris, called autophagy, occurs before women develop depression symptoms, indicating that it could be part of the disease process,” explained Jennifer L. Payne, MD, director of the Reproductive Psychiatry Research Program at the University of Virginia School of Medicine. “There are several medications that promote autophagy in cells, so this finding might open the door to new treatments and to identification of women at risk of postpartum depression before they become ill.”

Understanding Postpartum Depression

Dr Payne and colleagues wanted to determine if ‘extracellular RNA communication’, a newly discovered form of communication among cells, might contribute to postpartum depression. Extracellular RNA communication is heightened during pregnancy and is critical in embryo implantation and in the body’s inflammatory response afterward.

The researchers analysed blood plasma samples from 14 research participants with and without postpartum depression, collected during and after their pregnancies. The researchers found that extracellular RNA communication in immune cells was altered extensively in women who suffered postpartum depression. Further, they determined that this “large and consistent” change significantly limited the women’s bodies’ ability to perform important cellular cleanup – suggesting a potential biological cause for their depression.

“Deficits in autophagy are thought to cause toxicity that may lead to the changes in the brain and body associated with depression,” Dr Payne said. “We have never fully understood the biological basis for postpartum depression, and this finding gets us closer to an understanding.”

Source: University of Virginia Health System

Categories : Mental HealthTags :

Depression Risk Increases with Greater Social Media Use

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A recent study published in the Journal of Affective Disorders Reports has found that young adults who use more social media are significantly more likely to develop depression within six months, regardless of personality type. 

“Previous research has linked the development of depression with numerous factors,” the authors noted. “However, the literature has been lacking in studies that focus on how various personality characteristics may interact with social media use and depression. This new study addressed these important research questions, finding strong and linear associations of depression across all personality traits.”

People with high agreeableness were found to be 49% less likely to become depressed than people with low agreeableness. Additionally, those with high neuroticism were twice as likely to develop depression than those with low neuroticism when using more than 300 minutes of social media per day. More importantly, for each personality trait, social media use was strongly associated with the development of depression.

A 2018 sample of 18–30 year old US adults was analysed with the Patient Health Questionnaire to measure depression. Social media was measured by asking participants how much daily time was spent using popular social media platforms, and personality was measured using the Big Five Inventory, which assessed openness, conscientiousness, extraversion, agreeableness and neuroticism. 

The authors suggest that problematic social comparison can enhance negative feelings of oneself and others, which could explain how risk of depression increases with increased social media use. Engaging primarily in negative content can also enhance these feelings. And lastly, engaging in more social media reduces opportunities for in-person interactions and activities outside of the home.

Depression has been noted as the leading cause of disability and mortality worldwide. This makes these findings even more pronounced for creating health interventions and prevention efforts.

“Findings from this study are important during a time of technology expansion and integration,” said author Renae Merrill said, a doctoral student when writing the paper. “Connecting to people virtually may increase the risk of miscommunication or misperception that leads to relationship difficulties and potential risk for developing mental health problems.” 

“People have innate emotional needs for social connection and understanding,” Merrill added. “For example, social media experiences can be improved by becoming more aware of our emotions and our connection with others in various life circumstances. This awareness helps improve relationship quality by simply reaching shared meaning and understanding through more effective communication and concern for others and ourselves. Despite our differences, we have the ability to create a culture of empathy and kindness.” 

Source: University of Arkansas

Categories : Mental Health Metabolic DisordersTags :

Genes and Environment Bridge Depression and Endocrine-metabolic Disorders

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While endocrine-metabolic disorders and depression are known to co-occur, genetic and environmental factors are known to underlie both. In a study examining the link, published in the American Journal of Psychiatry, analysis revealed the balance of genetic and environmental influences underlying the co-occurrence of depression for a range of endocrine-metabolic disorders.

It is known that there is elevated co-occurrence between endocrine-metabolic disorders and depression, but the relationship between them is still not well understood.

Familial aggregation

The authors identified 2.2 million individuals born in Sweden between 1973 and 1996, as well as their full and half siblings, and followed them up to age 40. A number of medical conditions were studied; depression and various endocrine-metabolic disorders, including three autoimmune diseases (autoimmune hypothyroidism, Graves’ disease, and type 1 diabetes) and three non-autoimmune disorders (type 2 diabetes, obesity, and polycystic ovary syndrome).

Individuals with endocrine-metabolic disorders had 1.4 to 3.5 times the risk of depression compared to people without these diagnoses. Full and half siblings of these individuals also showed some elevated risk for depression, suggesting that genetic and/or environmental risk factors shared between family members play a role in the co-occurrence of these mental and physical disorders.

Genetic and environmental contributions

By comparing pairs of full sibling (who share about half of their genes) to pairs of half siblings (who share about a quarter of their genes), it was possible to calculate the relative contribution of genetic and environmental factors to the co-occurrence of depression and various endocrine-metabolic disorders. 

The results were a mix of these possibilities; the overlap between depression and non-autoimmune conditions was mainly explained by shared genetic influences, while environmental factors were predominantly involved in the association between depression and autoimmune disorders, particularly type 1 diabetes.

This indicates that the link between depression and different endocrine-metabolic disorders may be driven by different mechanisms. For example, shared biological mechanisms, such as immuno-inflammatory and metabolic dysregulations, may underlie the co-occurrence of depression and type 2 diabetes, obesity, and polycystic ovarian syndrome. In contrast, the absence of shared genetics in the association between type 1 diabetes and depression may reflect the existence of environmental factors influencing the risk of both conditions and/or a direct link between these conditions through mediating factors – eg, biological and psychosocial mechanisms connected to type 1 diabetes, including inflammation, cerebral damage, as well as stress of this lifelong condition that is often diagnosed early in life and that requires a complex management regime for both patients and their families.

“Our results underscore that clinicians should be aware of increased risks of depression in individuals with endocrine-metabolic disorders, and vice versa, and be vigilant for shared symptoms. This study also provides a useful foundation for future research aimed at identifying and targeting the biological mechanisms and modifiable risk factors underlying the co-presentation of endocrine-metabolic disorders and depression”, said Marica Leone, first author for the study.

Source: Karolinska Institutet

Categories : Mental Health NeurologyTags :

Unlocking the Complex Neurological Puzzle of Depression

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By studying the brains of fruit flies, which share similar mechanisms to human ones, scientists at Johannes Gutenberg University Mainz (JGU) are attempting to gain a better understanding of depression-like states and thus improve means of treating them. Their findings include the effect of Asian traditional medicine and its mode of preparation, and the effect of timing, such as getting a reward in the evening as opposed to other times of the day. The results were published recently in the journal Current Biology.

One aspect of their research “We have been looking at the effects of natural substances used in traditional Asian medicine, such as in Ayurveda, in our Drosophila fly model,” explained Professor Roland Strauss at JGU. “Some of these could have an anti-depressive potential or prophylactically strengthen resilience to chronic stress, so that a depression-like state might not even develop.”

The researchers intend to demonstrate efficacy, find optimal formulations, and isolate the active substances from the plant, which could lead to new drugs.

“In the Drosophila model we can pinpoint exactly where these substances are active because we are able to analyse the entire signalling chain,” Strauss pointed out. “Furthermore, every stage in the signalling pathway can also be proven.” The researchers subject the flies to a mild form of recurrent stress, such as irregular phases of vibration of the substrate. This treatment results in the development of a depression-like state (DLS) in the flies, ie, they move more slowly, do not stop to examine unexpectedly encountered sugar, and, unlike their more relaxed counterparts, are less willing to climb wide gaps. Whether or not the natural substances have an effect depends on the preparation of each natural substance, eg, whether it has been extracted with water or alcohol.

The research team has also discovered that if they reward the flies for 30 minutes on the evening of a stressful day, by offering them food with a higher sugar content than usual, or by activating the reward signalling pathway, this can prevent DLS developing. Flies have sugar receptors on their tarsi (the lower part of their legs) and their proboscis, while the end of the signalling pathway at which serotonin is released onto the mushroom body (equivalent to the human hippocampus) have also been located.

The researchers’ investigations showed that the pathway was considerably more complex than anticipated. Three different neurotransmitter systems have to be activated until the serotonin deficiency at the mushroom body, which is present in flies in a DLS, is compensated for by reward. One of these three systems is the dopaminergic system, which also signals reward in humans. Humans might obtain a reward through something other than sugar.

Boosting resilience by preventing depression

In addition, the researchers decided to look for resilience factors in the fly genome. The team intends to find out whether and how the genomes of flies that are able to better cope with stress differ from those that develop a DLS in response to exposure to recurrent mild stress. The hope is that in the future it will be possible to diagnose genetic susceptibility to depression in humans – and then treat this with the natural substances that are also being investigated during the project.

Source: Johannes Gutenberg Universitaet Mainz

Categories : Mental Health PaediatricsTags :

Half of Moms of Autistic Children Have High Depressive Symptoms

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About 50% of all mothers of children with autism spectrum disorder (ASD) had raised levels of depressive symptoms over 18 months, while rates were much lower (6% to 13.6%) for mothers with neurotypical children in the same period, according to a new study in Family Process.

Additionally, thought past studies suggest that having a parent with depression increases the child’s risk of mental health and behaviour problems, this study found something different.

“We found mothers’ higher symptoms of depression did NOT predict increases in children’s behaviour problems over time, including among families with a child with autism who experience a lot of stress,” said first author and UCSF Assistant Professor Danielle Roubinov. “That was surprising and good news.”

“Being the parent of a child with special needs is inherently challenging every day,” noted senior author UCSF Professor Elissa Epel. “It is a prototypical example of chronic stress, which is why we have been focusing on caregiving moms in our studies that examine effects of stress on health.”

“We already know from this sample that mothers with more depression tend to have signs of faster biological aging, such as lower levels of the anti-aging hormone klotho and older immune cells, on average,” added Prof Epel. “Here, we wanted to understand the impact of their depression on their child, and vice versa.”

A One-Way Street

Child behaviour problems predicted higher levels of maternal depression down the road, regardless of ASD status. The inverse effect was not seen, ie prior maternal depression didn’t predict later child behaviour problems.

Asst Prof Roubinov said that mothers of children with ASD need not feel guilty over their depressions impact on their children’s behaviours. “We hope these findings will reassure mothers that it’s both common to struggle with some depression in this high-stress situation of chronic caregiving, and that their depression likely isn’t making their child’s behavioural issues worse.”

Self-blame and guilt among parents of ASD children is common and predicts worsening depression and lower life satisfaction over time, the team’s past research shows.

In the current study, the researchers repeatedly measured maternal depression and children’s behaviour problems in 86 mother-child dyads across 18 months. Half of the mothers had children with ASD and half had neurotypical children. The children were aged 2–17 years old, with 75% being primary school age or younger.

Maternal depression was measured using the Inventory of Depressive Symptoms, a self-report scale completed by mothers. Child behaviour was measured through maternal report on the Child’s Challenging Behavior Scale, which focuses on externalising behaviours such as tantrums, aggression and defiance.

Few studies on maternal depression, child behaviour in ASD context

Bidirectional associations between maternal depression and child behaviour problems have been reported in prior research but few studies have examined these relationships in families with autism.

Families with autism tend to experience more marital conflict, lower relationship satisfaction, and many other challenges, said Ass Prof Roubinov, noting that a “stressful family environment may spill over onto family members” and changing their interactions. “We wanted to see whether the link between maternal and child mental health was different in the context of a high-stress family system, such as when a child has autism.”

Although the study acknowledged that families with a child with ASD experience high levels of stress, the authors were cautious to note that stress is not their only defining characteristic.

“Many mothers of children with autism also report high levels of emotional closeness and positive interactions with their children,” Asst Prof Roubinov said. “These are important experiences that supportive programs can build upon.”

The researchers offered mindfulness classes after the study to the participants to help manage parenting stress, and this improved their mental health.

It is important to experience and notice positive emotions and joy, despite having a more challenging life situation, said Prof Epel.

“Given the effects of chronic stress on health and mood, caregiving parents need extraordinary emotional support in addition to the special services for their child,” she said. “It’s as vital to provide support for parents’ mental health as it is for children’s mental health.”

Physicians should be on the lookout for parental distress and ready to offer resources for parents, especially for parents of special needs children, she said. The researchers said future studies should also look at associations between maternal depression and children’s internalising symptoms (eg, withdrawal, anxiety, emotional reactivity).

Source: University of California – San Francisco