How Are Autoantibodies Linked to Psychiatric Symptoms in Children?

What you need to know

Some psychiatric symptoms in children may be associated with autoantibodies that target brain proteins
Maternal autoantibodies transferred during pregnancy could potentially impact fetal brain development
Autoantibodies have been linked to conditions like psychosis, ADHD, autism, and OCD in children
More research is needed to clarify the clinical significance of these autoantibodies and develop targeted treatments

Maternal-fetal transfer of autoantibodies

Recent research has examined how autoantibodies from mothers can potentially impact fetal brain development when transferred during pregnancy. Three main types of autoantibodies have been studied in this context:

NMDA receptor autoantibodies

N-methyl-D-aspartate (NMDA) receptors are important for normal brain function. Animal studies have found that when pregnant mice are given NMDA receptor antibodies, it can lead to brain changes and behavioral abnormalities in the offspring. For example, one study observed increased hyperactivity in mice exposed to these antibodies before birth. This may be relevant to conditions like attention deficit hyperactivity disorder (ADHD) in humans. However, the effects in humans are still unclear and need more research.

CASPR2 autoantibodies

Contactin-associated protein-like 2 (CASPR2) is involved in brain development. Studies in mice have found that exposure to CASPR2 antibodies during pregnancy can alter brain structure and lead to social deficits and repetitive behaviors in the offspring. These types of behaviors are reminiscent of autism spectrum disorder in humans. Interestingly, the effects seemed to be more pronounced in male mice, which aligns with the higher rates of autism seen in boys. However, the relevance to human autism is still debated.

Fetal brain protein antibodies

One study in monkeys found that exposure to antibodies targeting certain fetal brain proteins during pregnancy led to social interaction deficits and brain structure changes in the offspring. The behavioral changes were similar to some features of autism. While this provides an interesting animal model, more research is needed to determine if similar mechanisms occur in humans.

These animal studies suggest maternal autoantibodies transferred during pregnancy could potentially impact fetal brain development in ways that influence later behavior. However, the effects in humans are still unclear. More research is needed to determine if these autoantibodies play a causal role in neurodevelopmental and psychiatric conditions in children.

Psychiatric disorders linked to autoantibodies in children

Researchers have found associations between certain autoantibodies and psychiatric symptoms in children. However, in most cases, the clinical significance is still uncertain. Here are some of the key findings for different conditions:

Psychosis

About 54% of children experiencing their first episode of psychosis were found to have antibodies against dopamine receptors or NMDA receptors in their blood. Psychosis involves a disconnect from reality, often with hallucinations or delusions. The presence of these antibodies suggests autoimmunity could potentially play a role in some cases of childhood psychosis. However, more research is needed to determine if the antibodies are truly causing the symptoms.

Attention deficit hyperactivity disorder (ADHD)

ADHD involves problems with attention, hyperactivity, and impulsivity. One small study found antibodies against an enzyme called glutamic acid decarboxylase (GAD) in about 27% of children with ADHD. Another study found elevated levels of antibodies against the dopamine transporter in children with untreated ADHD. While interesting, these findings are preliminary and their significance is unclear.

Autism spectrum disorder (ASD)

ASD is characterized by social difficulties and repetitive behaviors. Several studies have found various brain-reactive antibodies in children with ASD. Some of these antibodies correlated with symptom severity. For example, one study found that antibodies against a 45 kDa brain protein were associated with more cognitive impairment in children with ASD. However, the specific targets and effects of most of these antibodies are still unknown.

Obsessive-compulsive disorder (OCD)

OCD involves intrusive thoughts (obsessions) and repetitive behaviors (compulsions). Some studies have found increased levels of antibodies against basal ganglia proteins in children with OCD. The basal ganglia are brain regions involved in movement and behavior. However, the clinical relevance of these antibodies is debated.

Tics and Tourette syndrome

Tics are sudden, repetitive movements or vocalizations. One study found antibodies against certain brain proteins in children with Tourette syndrome, but their significance is unknown.

While these findings are intriguing, in most cases the evidence for autoimmunity in these disorders is still limited. The presence of antibodies alone does not prove they are causing the symptoms. More research is needed to determine if these antibodies play a causal role and to develop potential treatments targeting autoimmune mechanisms.

The “autoimmune priming attack” hypothesis

Based on the evidence linking autoantibodies to psychiatric symptoms in children, the authors propose an “autoimmune priming attack” hypothesis. This suggests that exposure to certain autoantibodies early in life, either through maternal transfer during pregnancy or circulating antibodies in childhood, could potentially set the stage for psychiatric disorders later in life.

The idea is that these antibodies could disrupt normal brain development or function during critical periods, leading to subtle changes that increase vulnerability to mental health conditions. Even if the initial autoimmune process resolves, the early disruption may have lasting effects on brain structure or function.

For example, a child who experiences autoimmune encephalitis (brain inflammation) early in life might have subtle brain changes that increase their risk of developing conditions like autism, ADHD, or psychosis later on. Or maternal antibodies transferred during pregnancy could potentially alter fetal brain development in ways that influence later behavior and mental health.

This hypothesis is still speculative and needs much more research to validate. However, it provides a potential mechanism linking early autoimmune events to later psychiatric symptoms. If supported by further evidence, it could have important implications for prevention and treatment strategies.

Diagnosing autoantibody-associated psychiatric syndromes

The authors propose guidelines for when doctors should consider testing for autoantibodies in children with psychiatric symptoms. They suggest two main categories:

Subacute psychiatric syndrome (aPS): Symptoms lasting less than 3 months
Subchronic psychiatric syndrome (cPS): Symptoms lasting more than 3 months

They recommend considering autoantibody testing if a child has one of these syndromes along with at least two other signs suggesting possible autoimmunity, such as:

Sudden changes in development
Confusion or altered mental state
Seizures
Movement problems
Lack of response to standard psychiatric medications

If antibody tests or other indicators of autoimmunity are positive, they classify this as an autoimmune psychiatric syndrome (APS). This diagnosis can help guide treatment decisions, potentially including immunotherapy in some cases.

However, the authors emphasize that much more research is needed to validate these proposed guidelines and determine the best ways to diagnose and treat autoantibody-associated psychiatric symptoms in children.

Conclusions

Maternal autoantibodies transferred during pregnancy could potentially impact fetal brain development and influence later behavior
Various autoantibodies have been associated with psychiatric symptoms in children, but their clinical significance is often unclear
More research is needed to determine if these antibodies play a causal role in psychiatric disorders
An “autoimmune priming attack” early in life could potentially increase vulnerability to later psychiatric conditions
Proposed diagnostic guidelines may help identify cases where autoimmunity could be contributing to psychiatric symptoms in children

This is an emerging area of research with many open questions. While intriguing, the links between autoantibodies and psychiatric symptoms in children need much more investigation before leading to changes in clinical practice. However, this line of research offers exciting potential for new ways to understand, diagnose, and treat certain psychiatric conditions in the future.