Metabolic effects of Deep Brain Stimulation in patients with Obsessive Compulsive Disorder.

Deep Brain Stimulation (DBS) is a promising intervention for
treatment-intractable Obsessive Compulsive Disorder (OCD) patients. Currently,
at the AMC Amsterdam, the efficacy of deep brain stimulation (DBS) for
treatment refractory OCD patients targeting the nucleus accumbens is under
investigation in 16 patients. See METC protocol number 04/113-E. In the current
study, we aim to examine the hormonal and metabolic effects of DBS at the
nucleus accumbens target in the same set of 16 OCD patients.

Previous studies have suggested increased activity of the HPA axis in OCD, with
indications of a disturbed functioning at cerebral level. Increasing evidence
points to a relation between the prefrontale cortex (PFC) and the HPA axis.
Dysfunction of the prefrontal cortex, as part of the frontal-striato-thalamic
circuitry, is important in the pathophysiology of OCD. DBS in the nucleus
accumbens may provide an extraordinary paradigm for examining the role of HPA
activity and PFC involvement in OCD.
Recently it has been shown that hypothalamic activity is altered in obese
subjects with type 2 diabetes mellitus compared to healthy controls. Moreover,
result from our own study suggested that disturbances in dopamine metabolism
within the brain might be related to disturbed hepatic glucose metabolism.
Since food intake, satiety and energy expenditure are the major players in the
regulation of body weight, it is not very surprising that quite recently the
nucleus accumbens has become a new area of interest in obesity research.
Dopamine is one of the main neurotransmitters of the nucleus accumbens and is
involved in food intake, satiety and energy expenditure. It has been shown that
dopamine metabolism in the mesoaccumbens system may be altered in obesity with
contradictory results showing either reduced or increased dopamine signaling.
The procedure of DBS in the nucleus accumbens provides an exceptional
opportunity to gain insight in the role of the nucleus accumbens in hepatic
glucose production, energy expenditure and plasma lipids.

1.To relate activity of the HPA axis to OCD symptoms and prefrontal brain
abnormalities, using plasma ACTH and urine cortisol measures.
2. To examine the role of nucleus accumbens activity on changes in endogenous
glucose production, energy expenditure and plasma lipids following nucleus
accumbens DBS.

A total of 16 subjects will be invited to participate in this study, which is
determined by the amount of subjects that are included in our current DBS trial.
HPA-axis activity will be determined by measuring plasma ACTH and cortisol in
two consecutive 24-h urine samples . Endogenous glucose production will be
measured via a hyperinsulinemic euglycemic clamp using stable isotopes.
Furthermore, energy expenditure and plasma lipids will be assessed in on and
off conditions of the stimulator.
Differences in symptoms strength and neuropsychological performance will be
assessed with the Yale Brown Obsessive Compulsive Scale (YBOCS) and with tests
taken from the Cambridge Neuropsychological Test Automated Battery (CANTAB).
Neuroimaging will be performed using fMRI and SPECT, according to protocol MEC
07/330

The inserted infusion needle can cause bruises.
The overall risks are very small, the main burden is that it is time consuming.
The group of subjects we would like to include is unique, because worldwide
there are very few people that have received a neurostimulator. Insight in how
this intervention works can also provide insight in the pathofysiology and
treatment possibilities of OCD.