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Relationship Between Neuroanatomical and Serotonergic Hypotheses of Obsessive-Compulsive Disorder: A Combined Functional Magnetic Resonance Imaging–Evoked Potential Study

J Clin Psychiatry 2018;79(6):17m11811

Objective: The so-called neuroanatomical hypothesis (with an increased activity of orbitofrontal cortex [OFC]) and the serotonergic hypothesis (with low activity in this system) have been discussed regarding the pathogenesis of obsessive-compulsive disorder (OCD) for decades. This study aimed to look for a relationship between the 2 pathogenetic concepts.

Methods: Nineteen OCD patients (8 female, 11 male, mean ± SD age = 33.37 ± 11.73 years, Yale-Brown Obsessive Compulsive Scale: 21.79 ± 6.59; diagnosed by ICD-10/DSM-IV-TR) were compared to 19 matched healthy controls (8 female, 11 male, mean ± SD age = 31.63 ± 10.79 years) and investigated (2012–2014) with the loudness dependence of auditory-evoked potentials (LDAEP) as a marker of the synaptic serotonergic activity and functional magnetic resonance imaging (fMRI) during the delay discounting paradigm, inducing OFC blood-oxygen level–dependent activity in the 2 groups.

Results: There were significant correlation coefficients between LDAEP (eLORETA right side) and fMRI OFC activities (anatomic region of interest) within the delay discounting paradigm (immediate vs control) in patients with OCD (r = –0.554; P = .014). LDAEP differed between the 2 groups with larger LDAEP at Cz in OCD patients indicating low serotonergic activity (0.28 ± 0.14 vs 0.20 ± 0.10 µV/10 dB, F2,35 = 4.66, P = .016). fMRI activations of dorsolateral and medial prefrontal cortex as well as ventral striatum (functional region of interest) were different between OCD and healthy volunteers.

Conclusions: The 2 main pathophysiologic hypotheses of OCD seem to be related to each other as measured by LDAEP and fMRI OFC activity during the delay discounting task. This could be interpreted as a further hint that low serotonergic activity induces altered OFC responsivity, which has to be treated in each patient with OCD by a serotonin agonist.