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INFECTIOUS TRIGGERS OF PSYCHIATRIC SYMPTOMS

With mounting evidence, there is a growing appreciation in the scientific community of the ability of bacterial and viral infections to have profound effects on the brain and behavior. In March of 2019 in JAMA Psychiatry (see resources section below), a group of researchers studying Danish medical records for more than 1 million individuals reported that the risk of developing OCD in teenagers increased by a staggering 8-fold following an infection.  As stated in an accompanying editorial, the recent studies demonstrate a definitive link of infections to psychiatric symptoms in children and “bring a sense of urgency to detailing the underlying mechanisms of this association, in particular, because of the possibility that these severe and occasionally permanent neuropsychiatric conditions might be rapidly recognized and treated by pharmacological compounds already in clinical use.” 

PANDAS AND PANS

Two infection-triggered disorders, Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infections (PANDAS) and Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS), were only described in the past 20 years.  For reasons not yet fully understood, some children experience an abrupt onset of obsessive-compulsive behaviors (OCD) and/or motor or vocal tics following infection. In addition, children may develop severe food restriction/anorexia, separation anxiety, frequent urination, deterioration of fine motor skills (often seen as deterioration in handwriting), trouble sleeping, and/or significant mood changes.   

BIOLOGICAL BASIS OF NEUROIMMUNE DISORDERS

Although research into the biological basis of PANDAS is still in its infancy, evidence suggests that an aberrant immune response to the strep infection disrupts normal functioning of the basal ganglia, a region of the brain involved in emotion, cognition, and movement.  Research and clinical experience has confirmed an immune response to infectious pathogens in the onset of a subset of cases of mental illness in children, defining a broader class of post-infectious neuroimmune disorders.  

CRITICAL NEED FOR RESEARCH

There are currently no laboratory tests or biomarkers which aid in the diagnosis of these conditions.  Many children are initially misdiagnosed as having a primary psychiatric illness, which in the best of cases delays access to proper treatment, and in the worst of cases prevents proper treatment entirely. Rigorous scientific study is needed to unravel the mystery of how infections can trigger these psychiatric symptoms given the potential implications for thousands of children.  Understanding the biological mechanism will enable patients to be diagnosed definitively and allow the best therapeutic approaches to be identified.

Influential Scientific Publications

Immunoneuropsychiatry – novel perspectives on brain disorders. By Pape K, Tamouza R, Leboyer M, Zipp F. Jun 2019

Parental Infections Before, During, and After Pregnancy as Risk Factors for Mental Disorders in Childhood and Adolescence: A Nationwide Danish Study. By Lydholm CN, Köhler-Forsberg O, Nordentoft M, Yolken RH, Mortensen PB, Petersen L, and Benros ME. Feb 2019

Recurrent group A Streptococcus tonsillitis is an immunosusceptibility disease involving antibody deficiency and aberrant TFH cells. By Dan JM, Havenar-Daughton C, Kendric K, Al-Kolla R, Kaushik K, Rosales SL, Anderson EL, LaRock CN, Vijayanand P, Seumois G, Layfield D, Cutress RI, Ottensmeier CH, Lindestam Arlehamn CS, Sette A, Nizet V, Bothwell M, Brigger M, and Crotty S. Feb 2019

A Nationwide Study in Denmark of the Association Between Treated Infections and the Subsequent Risk of Mental Disorders in Children and Adolescents.  Köhler-Forsberg O, Petersen L, Gasse C, Mortensen PB, Dalsgaard S, Yolken RH, Mors O, and Benros ME. Dec 2018

Association of Streptoccocal Infections with Mental Disorders: Testing key aspects of the PANDAS Hypothesis in a Nationwide Study. By Orlovska S, Vestergaard CH, Bech BH, Nordentoft M, Vestergaard M, and Benros ME. Jul 2017

MMF Scientific Advisors’ Key Publications

Immunoglobulin A Dysgammaglobulinemia Is Associated with PediatricOnset Obsessive-Compulsive Disorder. By Williams K, Shorser-Gentile L, Sarvode Mothi S, Berman N, Pasternack M, Geller D, and Walter J. May 2019

Psychotic symptoms in youth with Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) may reflect syndrome severity and heterogeneity. By Silverman M, Frankovich J, Nguyen E, Leibold C, Yoon J, Mark Freeman G Jr., Karpel H, and Thienemann M. Mar 2019

Psychometric Evaluation of the Caregiver Burden Inventory in Children and Adolescents With PANS. By Farmer C, Thienemann M, Leibold C, Kamalani G, Sauls B, and Frankovich J. Aug 2018

Clinical Management of Pediatric Acute-Onset Neuropsychiatric Syndrome: Part I-Psychiatric and Behavioral Interventions. By Thienemann M, Murphy T, Leckman J, Shaw R, Williams K, Kapphahn C, Frankovich J, Geller D, Bernstein G, Chang K, Elia J, and Swedo S. Sep 2017

Disordered eating and food restrictions in children with PANDAS/PANS. By Toufexis MD, Hommer R, Gerardi DM, Grant P, Rothschild L, D’Souza P, Williams K, Leckman J, Swedo Se, and Murphy TK. Feb 2015

Clinical evaluation of youth with pediatric acute-onset neuropsychiatric syndrome (PANS): recommendations from the 2013 PANS Consensus Conference. By Chang K, Frankovich J, Cooperstock M, Cunningham MW, Latimer ME, Murphy TK, Pasterrnack M, Thienemann M, Williams K, Walter J, Swedo SE, and the PANS Collaborative Consortium. Feb 2015