Tag: depression

Categories : Mental HealthTags :

Sertraline Improves Core Depressive Symptoms Within Two Weeks

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One of the most common antidepressants, sertraline, contributes to a modest improvement in core depression and anxiety symptoms, including low mood, within two weeks, finds a new analysis of a major clinical trial led by UCL researchers.

The study, published in Nature Mental Health, analysed the findings of the PANDA trial, which first published results in 2019 and found that sertraline may have an earlier impact on anxiety than depressive symptoms.* Researchers have now conducted a network analysis of the results, which is an innovative statistical method that allowed them to explore how specific symptoms respond to treatment.

The analysis revealed an improvement in symptoms such as low mood and suicidal thinking within two weeks of taking sertraline, while side effects of the drug led to symptoms such as low libido, low appetite, and tiredness. These side effects can also be symptoms of depression.

The researchers propose that the effect on all depressive symptoms put together in the initial analysis obscured the benefits of the antidepressants on some of the core depressive symptoms.  

In the new analysis, the early improvements from sertraline were found to be on feelings of sadness, self-loathing, restlessness, and suicidal thoughts.

The PANDA trial was a randomised controlled trial testing the effects of sertraline on people with depressive symptoms, including a wide range of patients in England whose symptoms ranged from mild to moderate. In a paper published in The Lancet Psychiatry in 2019*, scientists reported that within six weeks, sertraline improved anxiety symptoms and people reported an overall improvement in their mental health, but depressive symptoms did not meaningfully improve until participants had been taking the drug for 12 weeks. The new analysis, using data from 571 participants of the trial (those who had complete data for each symptom), suggests that sertraline improves some core depressive symptoms more quickly than previously believed.

The somatic (physical) symptoms that worsened, including libido and poor sleep, can be seen as side effects of antidepressants, but they are also common symptoms of depression, which can complicate interpretation of treatment effects.

Lead author Dr Giulia Piazza (UCL Psychiatry and UCL Psychology & Language Sciences) said: “We have now painted a more complex picture of sertraline’s effects on the different symptoms of depression.

“Instead of thinking of depression and anxiety as each being a single, uniform condition, network analysis considers that they’re each a constellation of symptoms, that can appear in different combinations for different people. These symptoms influence each other over time; for example, poor sleep can lead to problems with concentration, which may then impact self-esteem.

“Our analysis was borne out of this theoretical approach, in order to gain deeper insights and add nuance to the results of the PANDA trial.”

The researchers found that sertraline contributed to improvements in anxiety symptoms and in the emotional symptoms of depression within two weeks, and a modest worsening of somatic symptoms. The effect on somatic symptoms plateaued after six weeks, while the improvements in emotional symptoms and anxiety continued to improve from six weeks to 12 weeks.

Dr Piazza added: “It appears that the adverse effects on somatic symptoms like poor sleep and libido may stabilise after six weeks, which is then counteracted by continued improvements in emotional symptoms, the core symptoms of depression.”

Antidepressants are the standard pharmaceutical treatment for both depression and generalised anxiety disorder. Sertraline is a selective serotonin reuptake inhibitor (SSRI), the most common class of antidepressants.

Co-author Professor Glyn Lewis (UCL Psychiatry), who led the PANDA trial, said: “Our findings provide robust evidence that continues to support the prescription of sertraline for people experiencing depressive and anxiety symptoms. These findings will help patients and clinicians to make more informed decisions about treatment.”

Co-senior author Professor Jean-Baptiste Pingault (UCL Psychology & Language Sciences) said: “We found that the beneficial effects of sertraline can be detected very early on, as soon as two weeks after people start taking the antidepressant.

“Beyond this study, our results highlight the importance of considering symptom-level effects when developing novel drugs and evaluating existing drugs in psychiatry, and how this can help us to understand how these drugs work and how they can help patients.”

Source: University College London

Categories : Mental HealthTags :

Ketamine no Benefit for Patients Hospitalised with Depression

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Researchers from Trinity College, St Patrick’s Mental Health Services, Queen’s University Belfast, Ireland, investigate use of twice-weekly ketamine infusions as an add-on treatment for inpatients with serious depression

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Findings from a randomised and blinded clinical trial investigating repeated ketamine infusions for treating depression have revealed no extra benefit for ketamine when added onto standard care for people admitted to hospital for depression. The paper is published in the journal JAMA Psychiatry.

The KARMA-Dep (2) Trial involved researchers from St Patrick’s Mental Health Services, Trinity College Dublin, and Queens University Belfast, Ireland. It was sponsored by Trinity College Dublin  and led by Declan McLoughlin, Research Professor of Psychiatry at Trinity College Dublin and Consultant Psychiatrist at St Patrick’s Mental Health Services.

Depression has been recognised by the World Health Organization as a leading cause of disability globally.  According to the Health Research Board’s most recent report, there were 15 631 adult admissions to psychiatric services in Ireland in 2023. Similar to previous years, depressive disorders accounted for the highest proportion (about 24%) of all admissions.

Studies show that about 30% of people with depression do not respond sufficiently well to conventional antidepressants, which mostly target monoamine neurotransmitters, for example serotonin, dopamine and noradrenaline.  There is thus a need for new treatments.  One such novel treatment is the dissociative anaesthetic ketamine when given intravenously in low sub-anaesthetic doses. Ketamine works differently to other antidepressants and is believed to mediate its effects in the brain through the chemical messenger glutamate.

Single infusions of ketamine have been reported to produce rapid antidepressant effects, but these disappear within days. Nonetheless, ketamine is increasingly being adopted as an off-label treatment for depression even though the evidence to support this practice is limited. One possibility is that repeated ketamine infusions may have more sustained benefit. However, this has so far been evaluated in only a small number of trials that have used an adequate control condition to mask the obvious dissociative effects of ketamine, e.g. altered consciousness and perceptions of oneself and one’s environment. 

KARMA-Dep 2 is an investigator-led trial, sponsored by Trinity College Dublin and  funded by the Health Research Board. The randomised trial was developed to assess antidepressant efficacy, safety, cost-effectiveness, and quality of life during and after serial ketamine infusions when compared to a psychoactive comparison drug midazolam. Trial participants were randomised to receive up to eight infusions of either ketamine or midazolam, given over four weeks, in addition to all other aspects of usual inpatient care. 

 The trial findings revealed that:

  • There was no significant difference between the ketamine and midazolam groups at the end of the treatment course on the trial’s primary outcome, which was an objective measurement of depression. This was assessed with the commonly used Montgomery-Åsberg Depression Rating Scale (MADRS).
  • There was no significant difference between the two groups at the end of the treatment course on a subjective, patient-rated, scale for depression.  This was assessed with the commonly used Quick Inventory of Depressive Symptoms, Self-Report scale (QIDS-SR-16). 
  • No significant differences were found between the ketamine and midazolam groups on secondary outcomes for cognitive, economic or quality-of-life outcomes. 
  • Despite best efforts to keep the trial patients and researchers blinded about the randomised treatment, the vast majority of patients and raters correctly guessed the treatment allocation. This could lead to enhanced placebo effects.

Speaking about the impact of the findings, Declan McLoughlin, Research Professor of Psychiatry at Trinity College Dublin and Consultant Psychiatrist at St Patrick’s Mental Health Services, said:

“Our initial hypothesis was that repeated ketamine infusions for people hospitalised with depression would improve mood outcomes. However, we found this not to be the case. Under rigorous clinical trial conditions, adjunctive ketamine provided no additional benefit to routine inpatient care during the initial treatment phase or the six-month follow-up period. Previous estimates of ketamine’s antidepressant efficacy may have been overstated, highlighting the need for recalibrated expectations in clinical practice.” 

Lead author of the study, Dr Ana Jelovac, Trinity College Dublin, said:

“Our trial highlights the importance of reporting the success, or lack thereof, of blinding in clinical trials. Especially in clinical trials of therapies where maintaining the blind is difficult, e.g. ketamine, psychedelics, brain stimulation therapies. Such problems can lead to enhanced placebo effects and skewed trial results that can over-inflate real treatment effects.”.

Source: Trinity College Dublin

Categories : Mental Health Substance UseTags :

Poor Mental Health Can Be Worsened by Cannabis Use

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New research from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London, in partnership with the University of Bath, has found that the reasons why a person chooses to use cannabis can increase their risk of developing paranoia.

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The use and potency of cannabis is increasing worldwide, and dependence and cannabis-induced psychosis are also greatly increasing as a result, especially in North America. Two new research papers, both using data from Cannabis & Me – the largest survey of its kind – have identified key risk factors associated with the more severe forms of paranoia in cannabis users.

The first study, published in BMJ Mental Health, explored the relationship between why people first started using cannabis, and how this affected their subsequent use.

3389 former and current cannabis users aged 18 and over responded to a survey examining their reasons for first and continued use, their weekly consumption of cannabis in THC units, and their mental health.

Researchers established several key findings. Respondents who first started using cannabis to self-medicate an illness, including physical pain, anxiety, depression, or because they were experiencing minor psychotic symptoms, all demonstrated higher paranoia scores.

This was in contrast to those respondents who tried cannabis for fun or curiosity, or with their friends, who reported the lowest average paranoia and anxiety scores.

Dr Edoardo Spinazzola, a Research Assistant at King’s IoPPN and the study’s first author said, “This research suggests that using cannabis as a mean to self-medicate physical or mental discomfort can have a negative impact on the levels of paranoia, anxiety, and depression. Most of these subgroups had average scores of depression and anxiety which were above the threshold for referral to counselling.”

Respondents were also asked to provide data on the frequency and strength of the cannabis they were using so that researchers could track their average weekly consumption of Tetrahydrocannabinol (THC) – the principle psychoactive component of cannabis.

The researchers found that the average respondent consumed 206 units of THC a week. This might equate to roughly 10-17 ‘joints’ per week, if the user was consuming an expected 20% THC content that is standard for the most common types of cannabis available in London.

However, respondents who started using cannabis to help with their anxiety, depression, or in cases where they started due to others in their household who were already using cannabis, reported on average 248, 254.7, and 286.9 average weekly THC units respectively.

Professor Tom Freeman, Director of the Addiction and Mental Health Group at the University of Bath and one of the study’s authors said, “A key finding of our study is that people who first used cannabis to manage anxiety or depression, or because a family member was using it, showed higher levels of cannabis use overall.

“In future, standard THC units could be used in a similar way to alcohol units – for example, to help people to track their cannabis consumption and better manage its effects on their health.”

In a separate study, published in Psychological Medicine, researchers explored the relationship between childhood trauma, paranoia and cannabis use.

Researchers used the same data set from the Cannabis & Me survey, with just over half of respondents (52 per cent) reporting experience of some form of trauma.

Analysis established that respondents who had been exposed to trauma as children reported higher average levels of paranoia compared to those who hadn’t, with physical and emotional abuse emerging as the strongest predictors.

Researchers also explored the relationship between childhood trauma and weekly THC consumption. Respondents who reported experience of sexual abuse had a markedly higher weekly intake of THC, closely followed by those who reported experiencing emotional and physical abuse.

Finally, the researchers confirmed that the strong association between childhood trauma and paranoia is further exacerbated by cannabis use, but is affected by the different types of trauma experienced. Respondents who said they had experienced emotional abuse or household discord were strongly associated with increased THC consumption and paranoia scores. Respondents reporting bullying, physical abuse, sexual abuse, physical neglect and emotional neglect on the other hand did not show the same effects.

Dr Giulia Trotta, a Consultant Psychiatrist and Researcher at King’s IoPPN and the study’s first author said, 

“We have not only established a clear association between trauma and future paranoia, but also that cannabis use can further exacerbate the effects of this, depending on what form the trauma takes.

“Our findings will have clear implications for clinical practice as they highlight the importance of early screening for trauma exposure in individuals presenting with paranoia.”

Professor Marta Di Forti, Professor of Drug use, Genetics and Psychosis at King’s IoPPN, Clinical Lead at the South London and Maudsley NHS Foundation Trust’s Cannabis Clinic for Patients with Psychosis, and the senior author on both studies said, “There is extensive national and international debate about the legality and safety of cannabis use.

“My experience in clinic tells me that there are groups of people who start to use cannabis as a means of coping with physical and emotional pain. My research has confirmed that this is not without significant further risk to their health and wellbeing, and policy makers across the world should be mindful of the impact that legalisation , without adequate public education and health support, could have on both the individual, as well as on healthcare systems more broadly.”

Source: King’s College London

Categories : Cardiovascular Disease Mental HealthTags :

A Connection Between Mental Health and Heart Disease, Increased Mortality Risks

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Every 34 seconds, someone in the United States dies from heart disease. As nearly half of the country suffers from some form of cardiovascular disease (CVD), another 1 in 4 adults experience a mental health disorder in their lifetime, signalling an inevitable overlap.

Now, a new report from Emory University shows that certain mental health conditions escalate the risk of developing heart disease by 50–100% – and adverse outcomes from existing heart conditions by 60–170%.

The report, published in The Lancet Regional Health-Europe, summarises cardiovascular health disparities among those diagnosed with depression, anxiety, schizophrenia, bipolar and post-traumatic stress disorders (PTSD). The article is part of a series aiming to raise awareness around disparities in CVD health in four populations: women, the elderly, racial minorities and those with mental health conditions.

Emory University professor Viola Vaccarino, MD, PhD, led this metareview linking mental health conditions to CVD, along with co-authors Amit Shah, MD, and Douglas Bremner, MD, also Emory professors.

The report associated the following conditions and their corresponding risks of developing CVD:

  • Major depression, 72%
  • PTSD, 57%
  • Bipolar disorder, 61%
  • Panic disorder, 50%
  • Phobic anxiety, 70%
  • Schizophrenia, nearly 100%

The research also shows that these conditions are associated with a poorer prognosis, greater risk for readmission and higher mortality from existing heart conditions. For example, major depression more than doubles the mortality rate in those with existing CVD.

Additionally, the report emphasises a bidirectional relationship. “More than 40 percent of those with cardiovascular disease also have a mental health condition,” adds Vaccarino.

The physiology of stress

According to the report, a well-documented relationship exists among depression, schizophrenia, PTSD, and abnormal stress responses in the autonomic nervous system (ANS) and hypothalamic-pituitary adrenal axis (HPA).

The former allows the brain to manage involuntary responses, such as functions of the liver, heart, sweat glands, and eye muscles. ANS also manages both acceleration and deceleration of these functions, regulating inflammatory responses. Since most major organs have ANS nerve endings, this system impacts most bodily functions.

The hypothalamic-pituitary adrenal axis (HPA) also influences immune response and metabolism, which can impact cardiovascular function.

According to the report, dysregulation of these systems creates “adverse downstream effects that can affect cardiovascular risk chronically, including increased inflammation, metabolic abnormalities, high blood pressure, enhanced systemic vascular resistance and autonomic inflexibility.” Inflammation has also been implicated in both the development of heart disease and mental health conditions.

Social determinants and quality of care

The role of social determinants of health in CVD disparities is critical. Those with mental health conditions may face disruptions and barriers in the continuum of care, such as affordability and accessibility. Compromised health literacy or communication can also impede access to health screenings and treatment.

Clinicians could also be challenged to care for patients with certain mental conditions, which can be compounded by stigma and existing models that fragment mental and physical health care. Stigmas are also present in the field of clinical research, where having a mental health condition is often an exclusionary criterion in randomised trials.

Moreover, according to the report, current prediction models don’t account for mental health disorders when forecasting the risk of developing heart disease.

Next steps toward a healthier future

To address the disparities of CVD among people with mental health disorders, the authors recommend an integrated approach with interdisciplinary care encompassing behavioural, mental and cardiovascular health.

“The tight connection between cardiovascular and psychological health warrants changes in the health care system that are more amenable to patients with comorbidities,” says Vaccarino. “A clinical team would be ideal for the care of these patients – a team of specialists, social workers, and nursing staff who work in collaboration to provide multidisciplinary care and resources.” 

The report concludes that closing the health disparity gap upholds the rights of those living with a mental health condition to achieve the highest level of health and fully participate in society. 

Source: Emory University

Categories : Mental HealthTags :

People with High Sensitivity Have Greater Mental Health Risk

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New research, led by Queen Mary University of London and published in Clinical Psychological Science, has revealed that highly sensitive people (HSP) are more likely to experience mental health problems compared to individuals who are less sensitive. 

The meta-analysis of 33 studies, the first of its kind, looked at the relationship between sensitivity and common mental health problems such as depression and anxiety. Researchers found there was a significant, positive relationship between the two, concluding that highly sensitive people are more likely to experience depression and anxiety compared to those who are less sensitive.

In the study, sensitivity was defined as a personality trait that reflects people’s capacity to perceive and process environmental stimuli such as bright lights, subtle changes in the environment and other peoples’ moods. Often overlooked in mental health studies and clinical practice, which tend to focus on neuroticism and its association with mental health conditions, this research shows that understanding a person’s sensitivity level is important and can have therapeutic implications. 

People with sensitive personality traits may benefit from different treatment plans

For example, people with more sensitive personality traits may be more likely to benefit from treatment plans which involve techniques such as applied relaxation and mindfulness, which can also prevent relapse. 

Tom Falkenstein, a psychotherapist and a PhD student at Queen Mary University of London, said: “This is the most extensive systematic review on sensitivity and mental health in adolescents and adults to date, and is the first ever meta-analysis on the topic to estimate the impact of this relationship. We found positive and moderate correlations between sensitivity and various mental health problems such as depression, anxiety, post-traumatic stress disorder, agoraphobia and avoidant personality disorder. Our findings suggest that sensitivity should be considered more in clinical practice which could be used to improve diagnosis of conditions.”

“In addition, our findings could help improve treatment for these individuals. Around 31% of the general population are considered highly sensitive, and, as our findings show, are more likely to respond better to some psychological interventions than less sensitive individuals. Therefore, sensitivity should be considered when thinking about treatment plans for mental health conditions. Our work shows it is crucial that the awareness of sensitivity is improved among mental health care professionals, so clinicians and practitioners can recognise the trait in their patients, and tailor treatment to their sensitivity.”

Michael Pluess, Professor in Developmental Psychology at University of Surrey and Visiting Professor at Queen Mary University of London said: “This is the first meta-analysis providing robust evidence that highly sensitive people are more prone to common mental health problems. However, it is important to remember that highly sensitive people are also more responsive to positive experiences, including psychological treatment. Our results provide further evidence that sensitive people are more affected by both negative and positive experiences and that the quality of their environment is particularly important for their well-being.”

The systematic review and meta analysis of 33 studies was carried out by an academic team from several universities including Queen Mary University and the University of Surrey. 

Source: Queen Mary University London

Categories : Addiction Mental HealthTags :

Teen Smokers and Vapers Have Higher Rates of Depression and Anxiety, Study Finds

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Study analysed data from the US National Youth Tobacco Survey on more than 60 000 middle and high school students.

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Adolescents who use either e-cigarettes or conventional tobacco products (CTP) – like cigarettes, cigars, hookah and pipes – are significantly more likely to report symptoms of depression and anxiety than teens who don’t use tobacco products at all, according to a study published this week in the open-access journal PLOS Mental Health by Noor Abdulhay of West Virginia University, USA, and colleagues.

Tobacco use and mental health challenges are known to have a complex, bidirectional relationship. Understanding the interplay between adolescent tobacco use and mental health is particularly important, since adolescence is a critical developmental period during which many health-related risk-taking behaviors begin. Moreover, there are increasing rates of anxiety, depression, and suicide among adolescents in the U.S. as well as shifting patterns of tobacco use.

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In the new study, researchers used data on tobacco use, depression and anxiety symptoms, among different demographics, from the 2021-2023 National Youth Tobacco Survey. Among the 60,072 middle and high school students who had completed all questionnaires in full, 21.37% had used tobacco products, with 9.94% using only e-cigarettes, 3.61% using only CTPs, and 7.80% using both.

Overall, 25.21% of respondents reported symptoms associated with depression and 29.55% reported anxiety symptoms. Compared to adolescents who had not used any tobacco products, users of e-cigarettes or CTPs displayed a potentially heightened risk of depression and anxiety, whilst those who used both CTPs and e-cigarettes had the highest odds of reporting mental health struggles

The authors conclude that “while causality cannot be determined, the results from this study showed that all forms of tobacco use were significantly associated with mental health issues. There is a need to continue promoting mental health support and implementing tailored interventions to combat all forms of tobacco use among adolescents”.

Provided by PLOS

Categories : Mental Health Neurodegenerative DiseasesTags :

Parkinson’s Drug Effective in Treating Persistent Depression

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In the largest clinical trial to date, pramipexole was found to be substantially more effective than a placebo at reducing the symptoms of treatment resistant depression (TRD) over the course of nearly a year, when added to ongoing antidepressant medication.

The trial, supported by National Institute for Health and Care Research (NIHR) and published in The Lancet Psychiatry, included 150 patients with treatment resistant depression, with equal numbers receiving 48 weeks of pramipexole or a placebo, alongside ongoing antidepressant medication.

Overall, the group taking pramipexole experienced a significant and substantial reduction in symptoms by week twelve of treatment, with the benefits persisting over the course of a year. However, there were also significant side effects, such as nausea, sleep disturbance and dizziness, with around one in five people on pramipexole dropping out of the trial as a result.

Professor Michael Browning, from the Department of Psychiatry, University of Oxford, and workstream lead in Mood Disorders for the NIHR Mental Health-Translational Research Collaboration (MH-TRC) Mission, who led the trial, said: ‘Effectively treating people who have not responded to first-line interventions for depression is a pressing clinical problem and there has long been an urgent need to find new treatments.

‘These findings on pramipexole are a significant breakthrough for patients for whom antidepressants and other treatments and therapies have not worked.

‘Pramipexole is a medicine licensed for Parkinson’s disease and works by boosting the brain chemical dopamine. This differs from the majority of other antidepressant medications which act on brain serotonin and may explain why pramipexole was so helpful in this study.

‘We now need more research focusing on reducing the side effects of pramipexole, evaluating its cost-effectiveness, and comparing it with other add-on treatments.’

Previous research into using the drug for depression had shown promise, but there had been limited data on its long-term outcomes and side effects until now.

Current guidelines for people with treatment resistant depression recommend adding new treatments, such as lithium or antipsychotics, to ongoing antidepressant treatment, but these have limited effectiveness and do not work for everyone.

Phil Harvey, 72, from Oxfordshire, was diagnosed with depression 20 years ago and tried different tablets and counselling but nothing worked. Eventually he had to take a year off work before retiring. He started on the trial in 2022.

He said: ‘Within a few weeks I felt the effects, it was amazing. I kept a diary which they gave us on how my mood was, motivation and how it improved. It was dragging me out of this dark black hole that I’ve been in for years.’

Participants were recruited from across the country, including as part of the NIHR-funded MH-TRC Mission mood disorder clinics, which are hosted at Oxford but located across the country. The clinics efficiently, and largely remotely, assess patients with difficult to treat mood disorders and offer them enrolment in research studies. The network can also support primary care services by providing assessment and treatment advice for patients who have not responded to initial treatment.

Source: University of Oxford

Categories : Immune System Mental HealthTags :

Autoimmune Disease Linked to Doubling in Depression, Anxiety, Bipolar Risks

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Risks higher in women than in men with the same condition
Chronic exposure to systemic inflammation may explain associations, say researchers

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Living with an autoimmune disease is linked to a near doubling in the risk of persistent mental health issues, such as depression, generalised anxiety, and bipolar disorder, with these risks higher in women than in men, finds a large population-based UK study, published in the open access journal BMJ Mental Health.

Chronic exposure to the systemic inflammation caused by the autoimmune disease may explain the associations found, say the researchers.

A growing body of evidence suggests that inflammation is linked to mental ill health, but many of the published studies have relied on small sample sizes, limiting their statistical power, note the researchers.

In a bid to overcome this, they drew on data from 1.5 million participants in the recently established Our Future Health dataset from across the UK. Participants’ average age was 53; just over half (57%) were women; and 90% identified as White.

On recruitment to Our Future Health, participants completed a baseline questionnaire to provide personal, social, demographic, health and lifestyle information.

Health information included lifetime diagnoses–including for their biological parents–for a wide range of disorders, including autoimmune and psychiatric conditions.

Six autoimmune conditions were included in the study: rheumatoid arthritis; Graves’ syndrome (thyroid hormone disorder); inflammatory bowel disease; lupus, multiple sclerosis; and psoriasis.

The mental health conditions of interest were self-reported diagnoses of affective disorders, defined as depression, bipolar, or anxiety disorder.

In all, 37 808 participants reported autoimmune conditions and 1 525 347 didn’t. Those with autoimmune conditions were more likely to be women (74.5% vs 56.5%) and more likely to report lifetime diagnoses of affective disorders for their biological parents:  8% vs 5.5% for fathers; 15.5% vs 11% for mothers.

Chronic and pathogenic immune system activation—including the presence of markers of inflammation—is a hallmark of many autoimmune conditions. And in the absence of direct measurements of inflammatory biomarkers, an autoimmune condition was regarded as a proxy for chronic inflammation in this study.

The lifetime prevalence of any diagnosed affective disorder was significantly higher among people with an autoimmune disorder than it was among the general population: 29% vs 18%.

Similar associations in lifetime prevalence emerged for depression and anxiety: 25.5% vs just over 15% for depression; and just over 21% vs 12.5% for anxiety.

While the overall prevalence of bipolar disorder was much lower, it was still significantly higher among those with an autoimmune disorder than it was among the general population:  just under 1% compared with 0.5%.

The prevalence of current depression and anxiety was also higher among people with autoimmune conditions.

And the prevalence of affective disorders was significantly and consistently higher among women than it was among men with the same physical health conditions: 32% compared to 21% among participants with any autoimmune disorder.

The reasons for this aren’t clear, say the researchers, but “theories suggest that sex hormones, chromosomal factors, and differences in circulating antibodies may partly explain these sex differences,” they write.

“Women (but not men) with depression exhibit increased concentrations of circulating cytokines and acute phase reactants compared with non-depressed counterparts. It is therefore possible that women may experience the compounding challenges of increased occurrence of autoimmunity and stronger effects of immune responses on mental health, resulting in the substantially higher prevalence of affective disorders observed in this study,” they add.

Overall, the risk for each of the affective disorders was nearly twice as high—87-97% higher—in people with autoimmune conditions, and remained high even after adjusting for potentially influential factors, including age, household income, and parental psychiatric history.

No information was available on the time or duration of illness, making it impossible to determine whether autoimmune conditions preceded, co-occurred with, or followed, affective disorders, note the researchers.

No direct measurements of inflammation were made either, and it was therefore impossible to establish the presence, nature, timing or severity of inflammation, they add.

“Although the observational design of this study does not allow for direct inference of causal mechanisms, this analysis of a large national dataset suggests that chronic exposure to systemic inflammation may be linked to a greater risk for affective disorder,” they conclude.

“Future studies should seek to determine whether putative biological, psychological, and social factors—for example, chronic pain, fatigue, sleep or circadian disruptions and social isolation—may represent potentially modifiable mechanisms linking autoimmune conditions and affective disorders.”

And they suggest that it may be worth regularly screening people diagnosed with autoimmune disease for mental health conditions, especially women, to provide them with tailored treatment early on.

Source: BMJ

Categories : Mental HealthTags :

Psilocybin Dose Provides Two Years of Relief from Cancer Depression

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Phase 2 trial reveals that a single dose of psilocybin offers long-term relief from symptoms of depression and anxiety.

Photo by Marek Piwnicki: https://www.pexels.com/photo/macro-photography-of-a-psilocybin-mushroom-13695325/

New results from a clinical trial reveal that a single dose of psilocybin can provide sustained reductions in depression and anxiety in individuals with cancer suffering from major depressive disorder. The findings are published by Wiley online in CANCER, a peer-reviewed journal of the American Cancer Society.

People with cancer often struggle with depression. In this phase 2 trial, 28 patients with cancer and major depressive disorder received psychological support from a therapist prior to, during, and following a single 25mg dose of psilocybin.

During clinical interviews conducted 2 years later, 15 (53.6%) patients demonstrated a significant reduction in depression, and 14 (50%) had sustained depression reduction as well as remission. Similarly, psilocybin reduced anxiety for 12 (42.9%) patients at 2 years.

An ongoing randomised, double-blind trial is currently evaluating up to two doses of 25mg of psilocybin versus placebo as treatment for depression and anxiety in patients with cancer. This study is building on the single-dose study in an effort to bring a larger majority of the patients into remission of depression and anxiety.

“One dose of psilocybin with psychological support to treat depression has a long-term positive impact on relieving depression for as much as 2 years for a substantial portion of patients with cancer, and we’re exploring whether repeating the treatment resolves depression for more than half of the patients,” said lead author Manish Agrawal, MD, of Sunstone Therapies. “If randomised testing shows similar results, this could lead to greater use of psilocybin to treat depression in patients with cancer.”

Source: Wiley

Categories : Mental Health NeurologyTags :

Extending Ketamine’s Relieving Effect on Depression

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For 30% of people with major depressive disorder (MDD), antidepressants don’t work. When infused at a low dose, ketamine shows remarkable efficacy as a rapidly acting antidepressant, with effects observed within hours even in patients who have been resistant to other antidepressant treatments. One drawback is that consistent infusions of ketamine are needed to maintain symptoms at bay, which could result in side effects, such as dissociative behaviours and the possibility of addiction, and stopping treatment can result in relapse.

In a new study published in Science, Lisa Monteggia’s and Ege Kavalali’s labs show that it is feasible to substantially extend the efficacy of a single dose of ketamine from its current duration of up to a week to a longer period of up to two months.

“The premise of this study, which was led by Zhenzhong Ma, a fantastic research assistant professor, was based on a testable mechanistic model that we developed that accounts for ketamine’s rapid antidepressant action,” Monteggia said.

Previously, researchers in the field had determined that ketamine’s antidepressant effect requires the activation of a key signalling pathway called ERK, but only ketamine’s long-term effects – not its rapid effects – are abolished when ERK is inhibited. As a fast-acting antidepressant, ketamine relies on ERK-dependent synaptic plasticity to produce its rapid behavioural effects. Ma and colleagues hypothesised that they could maintain ketamine’s effects for longer periods by enhancing ERK activity. 

In the recent paper, Ma discovered that ketamine’s antidepressant effects could be sustained for up to two months by using a drug called BCI, which inhibits a protein phosphatase and results in increased ERK activity. By inhibiting the phosphatase, the authors retained ERK’s activity and augmented the synaptic plasticity that drives ketamine’s prolonged antidepressant effects. 

lthough the use of BCI makes the application of these results to the clinic difficult, Monteggia said that the results provide a proof of principle that ketamine’s antidepressant action can be sustained by targeting intracellular signaling. She and Kavalali, the William Stokes Professor of Experimental Therapeutics and the chair of the Department of Pharmacology, have worked on the project since its inception and hope that it will foster other studies looking to identify specific molecules to enhance and sustain the action of a single dose of ketamine.

Ultimately, this work will be a stepping stone toward improving MDD patients’ lives by reducing the burden of treatment.

Source: Vanderbilt University