This document discusses biomarkers involved in obsessive-compulsive disorder (OCD) and their relationship to psychosis. It notes that OCD is a heterogeneous disorder characterized by intrusive thoughts and compulsions, with median onset at age 19. Common comorbidities include depression, anxiety, and eating disorders. OCD may influence or be influenced by psychosis. Researchers have identified some genetic biomarkers associated with OCD, such as differences in glutamate transporter genes and serotonin receptor genes. However, biomarkers can be difficult to consistently detect due to limitations like small sample sizes. Neuroimaging has also found differences in brain structure and activity in OCD patients compared to healthy controls. Future research directions include exploring environmental factors, larger genetic studies, and developing new treatment

1. BIOMARKERS INVOLVED IN
OBSESSIVE-COMPULSIVE DISORDER
AND THEIR RELATIONSHIP TO PSYCHOSIS
Sarah Och
Center for Early Detection, Assessment and Response to Risk (CEDAR) Clinic
and the Commonwealth Research Center
Beth Israel Deaconess Medical Center
Harvard Medical School
Massachusetts Mental Health Center

2. BACKGROUND OF OCD
Heterogeneous psychiatric disorder characterized by recurrent
thoughts which are disruptive or intrusive, usually
accompanied by compulsions or rituals [6]
Median onset age: 19yrs [4], [6]
Pathogenesis influenced by both genetic and environmental
factors [6]
Clients usually have insight to abnormality of behavior [7]

3. OCD AND PSYCHOSIS
Common comorbidities:
 Major depression, anxiety, social phobia, eating disorders, personality disorders, and
Tourette’s syndrome [7]
OCD may influence the development of psychosis, or vice versa [8]
 Presence of either may exacerbate presence of the other [9]
OCD co-occurs with psychotic disorders at a higher rate when compared to
frequency in general population [6]
Patients with co-morbid OCD exhibited more depressive symptoms and suicidal
ideology
Biological factors
 Genetic overlaps
 OCD and depression share common genes, which may help to explain why OCD and
depression commonly co-exist
 OCD is etiologically related to both schizophrenia spectrum and bipolar disorders [11]

4. TREATING OCD
Therapy:
• CBT (cognitive behavioral therapy)
• ACT (acceptance and commitment therapy)
• Some of these treatment methods are also utilized in treatment for
psychosis
Neurosurgery and neurological treatments
• DBS (deep brain stimulation)
• TMS (transcranial magnetic stimulation)
Medication: Prozac, Zoloft, Paxil

5. POTENTIAL APPLICATIONS OF BIOMARKERS
Help clinicians make more precise diagnoses [1]
Useful in monitoring the progress of treatment [1]
Serve as an observable, biological indicator or process that can be
identified before the onset of psychosis
• Target early-intervention programs: including a genetic screener could help
clinicians to identify CHR clients

6. HOW DO RESEARCHERS IDENTIFY BIOMARKERS?
Family-association studies [4]
 Using genetic information from relatives as controls, usually first through third
generation
Genome-wide linkage analysis
 Examination of common genetic variations across populations in order to determine
if a specific variant is associated with a trait
Allelic association studies
 Do specific alleles correlate with the manifestation of a certain trait?
Segregation analyses
 Helps to determine whether a major gene is associated with a specific trait and also
whether that trait is dominant, recessive, or codominant

7. IDENTIFIED BIOMARKERS IN OCD
Molecular genetic research: genes in the serotonin and dopaminergic
neurotransmitter systems
 Dopamine: inhibitory; reward pathways
 Serotonin: inhibitory; emotion and mood
 Glutamate: excitatory; memory
Suggestive evidence for linkage on chromosome 10p15
SLC1A1 (glutamate transporter gene) and EAAC1 (regulates flow of glutamate)
have been consistently associated with OCD [5]
 Differences in the glutamate systems of clients and healthy controls
Difference in frequencies of the A allele of the 5-HT2A receptor gene
 Serotonin receptor group; also used in antipsychotic medication for bipolar, MDD, and
schizophrenia

8. LIMITATIONS OF BIOMARKERS
Validity: not 100% proven or reliable, and vary among individuals
[1]
Difficult to consistently detect genes in complex disorders like
OCD [4]
Small sample sizes limit applicability [4], [5]

9. NEUROLOGIC CHARACTERISTICS IN CLIENTS WITH OCD
Significantly more gray matter and less white matter in clients
with OCD compared to healthy controls
Consistent differences in reginal brain activity in patients than
healthy controls
 Normal activity is usually restored with serotonin-reuptake inhibitors and
therapy [7]
 Looking at the biological linkage studies to determine a genetic
predisposition

10. DISCUSSION
Importance of considering the environmental with the biological
factors
Future treatment techniques
• DBS (deep brain stimulation) for more severe cases
Future avenues of research
 Include larger sample size for better applicability
 Considering the stage of research on genetics

11. REFERENCES
[1] Freedman et al. (2005). Early biomarkers of psychosis. Dialogues in clinical neuroscience. 7(1):17-29.
[2] Miguel et. Al (2005). Obsessive-compulsive disorder phenotypes: implications for genetic studies. Molecular Psychiatry, 10. 258
– 275.
[3] Koutsouleris et al. (2014). Detecting the psychosis prodrome across high-risk populations using neuroanatomical biomarkers.
Schizophrenia Bulletin, 10. doi:10.1093/schbul/sbu078
[4] Hanna et. al (2007). Evidence for a susceptibility locus on chromosome 10p15 in early-onset obsessive-compulsive disorder.
Biological Psychiatry, 62. 856-862.
[5] Hagen, K., Hansen, B., Joa, I.,and Larsen, TK. (2013). Prevalence and clinical characteristics of patients with obsessive-
compulsive disorder. BMC Psychiatry, 13(156)
[6] Walitza et al. (2010). Genetics of early-onset obsessive-compulsive disorder. Eur Child Adolescent Psychiatry, 19: 227-235.
[7] About OCD. Obsessive-Compulsive and Related Disorders, Stanford University School of Medicine.
[8] Gangdev, P. (2002). The relationship between obsessive-compulsive disorder and psychosis. Australian Psychiatry, 10. 65-80.
doi: 10.1046/j.1440-1665.2002.00505.x
[9] Dowling, F., Pato, M., and Pato, C. (1995). Comorbidity of Obsessive-Compulsive and Psychotic Symptoms: A Review. Harvard
Review of Psychiatry, 3 (2), 75-83.
[10] Bolhuis, K. et. al (2014). Aetiological overlap between obsessive-compulsive disorder and depressive symptoms: a longitudinal
twin study in adolescents and adults. Psychological Medicine, 44. 1439-1449.
[11] Cederlof, M. et al. (2015). Obsessive-compulsive disorder, psychosis, and bipolarity: a longitudinal cohort and
multigenerational family study. Schizophrenia Bulletin, 1-8. doi: 10.1093/schbul/sbu169
[12] Stewart, S. and Pauls, D. (2010). The genetics of obsessive-compulsive disorder . Genetics and Genomics, 8, 350-357. doi:
10.1176/foc.8.3.foc350
[13] Hasler et al. (2005). Obsessive-compulsive disorder symptom dimensions show specific relationships to psychiatric
comorbidity. Psychiatry Research, 135, 121-132. DOI: 10.1016/j.psychres.2005.03.003
[14] Shin et al. (2014). The effects of pharmacological treatment on functional brain connectome in obsessive-
compulsive disorder. Biological Psychiatry, 75, (8). 606-614. doi: 10.1016/j.biopsych.2013.09.002.