April 29, 2020

Considering the Biology of Suicide in Autism

By Liz Bell

April is Autism Awareness Month (AAM), a time to showcase the one in 54 Americans living with this neurobiological condition that affects behavior and social communication to widely varying degrees. While AAM is an opportunity to celebrate acceptance and the unique gifts and contributions of people with autism spectrum disorders (ASD), it is also a time to highlight some important challenges and the need to improve outcomes and reduce suffering. One lesser known characteristic of autism is its association with a dramatically reduced life expectancy, including an increased risk of physical and mental health issues and suicide.

Increased Risk

While there was some general awareness of these concerns, a 2016 population based study utilizing national Swedish registries quantified the considerably reduced life expectancy (54 vs. 70 in the general population) and heightened risk of premature death: 2.5 times higher in autism from all categories of cause except infections. This study also revealed that the suicide death rate in ASD is more than seven times that of the general population. Furthermore, while premature death was significantly higher in those with autism and intellectual disability (‘low functioning’), in all other cause categories suicide was shown to be higher (9.4 times the general population) in those with autism and normal IQ (‘high functioning’).  Suicide in females on the spectrum was a dramatic 13 times the general population rate.

In 2019, the publication of a 20-year study based on Utah surveillance data revealed an increasing rate of suicide in the ASD population over the last five years of the study (2012-2017), and a suicide death rate in women that was three times that of the general population. In young people with autism, suicide risk was doubled, and more than half of the ASD suicides occurred in those under the age of 30 (range 14-70).

Other suicidal behaviors are also shown to be increased in ASD. A recent systematic review of studies on suicidal behaviors indicates a heightened risk in individuals with autism, with suicide attempts ranging from 1-35% and ideation in 11 to 66%. In the UK, a study in individuals with Asperger’s Syndrome showed self-reported suicidal ideation in 66% (exceeding both the general population and those with other medical and psychiatric disorders), suicide plans or past attempts in 35%, and depression in 31%.

The scientific and community response to these findings rightfully includes a call for more investigation into the causes for the alarming statistics and guidance on how to reduce them. The 2016 Swedish paper suggested co-existing psychiatric disorders and depression, social and psychological vulnerability, and lack of usual protective factors that support resilience (e.g. social networks, coping skills and life satisfaction) as contributors to suicide risk in autism. As is customary in suicide, the focus on possible explanations and calls for investigation has been on autism’s skill deficits and psychosocial factors such as social anxiety, exclusion, and bullying, well described in Psychology Today, this article in The Atlantic, and this piece from Spectrum News. Spectrum News also reported unpublished research showing a history of self-harm, which occurs at high rates in autism (particularly in females), greatly increases risk of death by suicide.

As these articles highlight, it is critical that suicide be on the radar for individuals with autism and their families, providers, and clinicians. As is true in suicide intervention, inquiry may help to unearth suicidal ideation and plans, and suggested adaptations to screening tools addressing the unique needs of the autism population may be helpful. However, suicide research also highlights that current tools are insufficient in predicting who is at risk, and when. What other potential indicators could be considered in assessing risk in those with autism, and perhaps addressed in reducing that risk in any given individual?

Potential Biological Risk Factors for Suicide and Autism

Physical and/or psychological pain, particularly chronic pain, is a factor associated with suicide risk. The pain response in individuals with autism can be significantly altered, ranging from neurologically excessive, as measured in a ‘high functioning’ population, to variable, and/or insufficient or misunderstood. Chronic pain can affect mental health and sleep, and promote the development of depression and anxiety. Recent research suggests pain, as well as impulsivity, is likely responsible for self-harm common in those with autism.

Some individuals with autism report ongoing pain, and research indicates a likelihood that individuals with autism live with physical pain and illness that is not sufficiently evaluated or treated by the medical system. The 2016 Swedish study showed higher rates of premature death in autism as a result of neurological disorders, congenital malformations, and mental/behavioral disorders, health challenges that might be expected in autism’s related conditions. Additionally, premature death was also higher in those with autism as a result of endocrine, respiratory, digestive, and circulatory systems, as well as cancer. These findings are notable since accidents at a young age (e.g. drownings) also contribute significantly to the reduced average life expectancy in ASD.  This study also referenced another Swedish registry study from 2012 showing lower levels of medical care, lack of treatment, and increased ‘avoidable mortality’ for patients with a psychiatric diagnosis.

Similarly, a 2014 study of adults with autism in the US shows that co-occurring medical conditions are common, and the authors advocate for more research into the social, healthcare access, and biological factors involved. They reported:

‘Adults with autism had significantly increased rates of all major psychiatric disorders including depression, anxiety, bipolar disorder, obsessive-compulsive disorder, schizophrenia, and suicide attempts. Nearly all medical conditions were significantly more common in adults with autism, including immune conditions, gastrointestinal and sleep disorders, seizure, obesity, dyslipidemia, hypertension, and diabetes. Rarer conditions, such as stroke and Parkinson’s disease, were also significantly more common among adults with autism.’

These indicators are significant, since mind and body are connected, and suicide risk is increased by both mental and physical illness. The majority of those who die by suicide have a mental health condition, and while depression features prominently in suicidal ideation, agitation, anxiety, and impulsivity appear to be more highly associated with suicide deaths. As research delves further into the biology of autism, psychiatric illness, and suicide, focusing on shared mechanisms might highlight additional clues into physiological and potentially modifiable factors for suicide prevention. Of increasing interest in the emerging field of suicide biology are certain risk factors that also feature significantly in the characteristics of many individuals with ASD.

  • Sleep is notably disrupted in autism, often starting in early childhood and for many, continuing throughout life. As JKBF recently highlighted, disordered sleep upsets the circadian rhythm that sets myriad body processes in motion and is a risk factor for depression, anxiety, and suicide. Sleep mediates (bi-directionally) the immune system, pain response, and the microbiome. Sleep is also modifiable, but is often dismissed as a by-product of autism behaviors and not treated directly. Help designed for those with autism is available through a Practice Guideline from the American Academy of Neurology.
  • Impulsivity, impaired problem-solving, and aggression are Behavioral Traits gaining attention as risk factors in suicide research, and suicidal behavior can take years or go from idea to action in moments. These characteristics are often associated with executive function deficits in ASD. Cognitive Behavior Therapy (CBT) and other behavior therapies are often utilized in addressing these concerns, and frontal lobe function can also be influenced by diet, medication, sleep, substance use, and stress, as well as genes.
  • While often characterized in suicide as neglect or abuse, early life adversity (ELA) and stress occurs with autism due to communication/cognition/social issues of the disorder and a mismatch between abilities and others’ expectations. Biological investigations show later life changes to the Hypothalamic-Pituitary-Adrenal(HPA) Axis, responsible for the release of neurotransmitters serotonin, dopamine, and norepinephrine that regulate mood, stress, appetite and sleep. Of interest in both research communities, a recent report outlines the role of the HPA axis in anxiety, assessment, and intervention.
  • Inflammation and immune system involvement are of increasing interest in suicide and in autism, both neurological and in gut-brain interactions. Inflammation has been shown to be a downstream effect of ELA in suicide research, but can also be caused by stress (such as might come from chronic pain, or not understanding the world around you), as well as biological contributors such as diet, injury, and infection. A recent study suggests immune activation may be contributory to the anxiety prevalent in ASD.
  • Gastrointestinal (GI) disorders are increasingly recognized as co-occurring in a portion of individuals with autism, contributory to behavioral, social, and anxiety features, and worthy of evaluation and treatment. GI disorders can also exhibit neurologic or psychiatric features in some patients, such as described in this paper on Celiac Disease. The Gut-Brain Axis, operating through the bi-directional vagus nerve, has been under investigation in autism and is of increasing interest in psychiatric research.  Vagal tone reflects differences beginning in infancy, features in autonomic dysfunction in autism, and mediates neuro-endo-immune function as well as effects on sensory, motor, parasympathetic, cardiac, respiratory, inflammatory, mood, and pain regulation systems.  The Microbiomein particular, is of increasing focus in health and disease across many conditions, including psychiatric and developmental disorders and has been shown to influence severity and treatment effects in mental illness. Vagal tone can be influenced by implanted devices (used to treat epilepsy and depression), as well as through meditation, yoga, deep breathing and other stimulants of the parasympathetic nervous system essential to reducing the stress response and creating autonomic balance.  
  • Diet and nutrition are often challenging in autism, due to sensory issues and food selectivity. Chronic health conditions, especially if under-explored and un-treated, may lead to other suicide-associated risk factors including diabetes, low BMI, respiratory disease, hypertension and cancer. Likewise, eating disorders occur at higher rates in autism, may actually predict autistic characteristics prior to diagnosis, are accompanied by auto-immune, inflammatory and altered microbiome conditions, and are a risk factor for suicide.
  • Epilepsy, also tied to vagal function, raises the risk of suicidal behaviors in the general population and occurs in an estimated one-third of those with ASD. It has not been determined whether the suicide risk is from the condition itself or the psychiatric and behavioral effects of anti-epileptic medications, which are also often used as mood stabilizers in ASD and other mental health conditions.
  • Many medications are known to be risk factors for sleep disruption and a host of GI disturbances and disorders, common conditions in those with autism. SSRIs are used in individuals with autism and depression, but a black box warning for suicide is controversial and often ignored, despite recent data supporting the duty to warn and monitor, especially in young adults and during medication introduction and titration. Since individuals with autism have increased rates of allergies it is worth highlighting that seasonal allergies may increase suicide risk, and a popular asthma/allergy medication, Singulair, just received a black box warning for suicidal thoughts or actions. A 2018 study showed that one-third of the US population is on medications that have depression as a known side effect.  Not surprisingly, those individuals are more likely to be depressed, especially when multiple medications are utilized. Increasing consideration and monitoring of side effects of medication, in light of the added challenges of altered metabolism, sensory experiences, and communication in those with autism, appears to be warranted.
  • Metabolic Disturbances such as enzyme deficiencies and Cerebral Folate Disorder, recently found to be a factor in depression and suicide, occur in autism as well. These measurable and potentially modifiable conditions, which may develop as a result of commonly-used medications, are rarely evaluated or treated in either patient population.
  • Gender differences raise the risk of suicide and in autism there appears to be a heightened prevalence of gender variance but more research in this area is needed.

Suicide and Autism in Females

Surveillance data shows twice the rate of death by suicide in women than in men with autism. While statistics for the general population show more ideation and attempts by females, the risk of dying by suicide is significantly higher in men. Of note, the risk of suicide in females with autism tends to increase with cognitive ability. A study in Autism Research identified a doubling of risk for suicidal ideation and behaviors in adolescents with autism who reported they had been bullied, with higher risk in females, those diagnosed with affective disorders, and those with higher intellectual ability.

Females with autism have specific challenges in getting a diagnosis and coping with the social aspects and strain of camouflaging (fitting in) as outlined in this story on The Lost Girls in Spectrum News. These personal stories reveal many of the related challenges, including depression, anxiety, and eating disorders. Disrupted sleep is mentioned, but not described as being addressed, even though it can contribute to a deterioration in mental health. Behavioral changes due to menstrual cycles are described in these girls and the role of hormones is worth consideration, since suicide is correlated with menstrual cycles, hormonal birth control use, the post-partum period, and menopause. And even as the troubling life story and insufficient medical care of Maya is outlined, there is no mention of the fact that the anti-psychotic quetiapine, the medication she was taking at the time of her suicide attempt, has a suicide warning.

Improving Outcomes, Reducing Stigma

Not so many years ago autism was viewed almost exclusively through a psychiatric lens, with researchers and clinicians asserting that parents, ‘refrigerator’ mothers specifically, had caused autism in their offspring due to cold and unloving practices—even as biological causes such as infections (maternal Rubella), toxins (Thalidomide exposure), and certain genetic conditions (Fragile X) were identified. Thankfully, due to biological findings, this view is no longer accepted and the stigma of autism has reduced considerably.

However, even as physiological features continue to emerge with research, autism primarily remains an enigma and much of the treatment framework remains educational and psychological. Gastrointestinal issues, like sleep, are often dismissed as autism’s partners instead of biological processes that might be addressed, and potentially change the course of a person’s learning, behavior, mood, and outlook. There is great opportunity for investigation of the biological factors contributing to suicide in general, as well as suicide in autism, and the possibility of moving both fields farther together, saving lives, and reducing stigma. Research matters. Biology matters.

Reviewed 4/20 by Clara Lajonchere, PhD

Subsequent Publications:

JAMA Network Open, January 12, 2021, Assessment of Suicidal Behaviors Among Individuals With Autism Spectrum Disorder in Denmark