Intractable OCD and depression cause tremendous suffering in those affected and 
in their families. The impaired ability to function of those affected imposes a 
heavy burden on society as a whole. Existing data suggest that lesion procedures 
offer benefit to a large proportion (ranging from about 35%-70%) of patients 
with intractable OCD and depression. The literature also suggests that although 
serious long-term adverse events have occurred, these are relatively infrequent 
overall. Methodologic limitations of the earlier reports on any of these 
procedures were described previously in this article. The major academic centers 
conducting this work have since been obtaining systematic prospective data using 
modern assessment tools. Nevertheless, even with improved methodologies, more 
recent studies confront some remaining issues that have been difficult to 
overcome fully. First, the number of patients who have received any one 
procedure has been relatively small, constraining statistical power. This limits 
the ability of researchers to enhance patient selection based on clinical 
characteristics. This is important, because patients with intractable OCD and 
depression referred for neurosurgery have high rates of comorbid Axis I 
diagnoses, personality disorders, and functional impairments, which may have 
value in predicting response. Other features, such as age of onset, chronicity, 
and symptom subtypes, may be likewise useful. Another key factor in response may 
be postoperative management, which has varied most over time but also across 
patients enrolled in trials. As noted previously, randomized controlled trials 
of neurosurgical treatment for intractable psychiatric illness have not been 
reported, although one has been proposed for gamma knife capsulotomy in 
intractable OCD [23]. The development of deep brain stimulation has also made 
sham-controlled studies possible and also allows within-patient designs to be 
considered. Bearing these problems in mind, the literature does provide 
important guidance on a number of key points, including approaches to referral, 
patient selection, and the need for long-term prospective follow-up and 
postoperative management. Nevertheless, important gaps in knowledge remain in 
all these areas. Research is expected to narrow these gaps in a number of ways, 
including patient selection, optimizing the procedures themselves, and 
understanding the mechanisms of therapeutic action. Neuroimaging studies will 
play a key role in achieving these aims (see the article by Rauch in this 
issue). So will cross-species translational research on the anatomy and 
physiology of the pathways implicated in the pathophysiology and response to 
treatment in these disorders. Future research in psychiatric neurosurgery must 
proceed cautiously. A recent editorial statement of the OCD-DBS Collaborative 
Group [26] recommends a minimum set of standards for any multidisciplinary teams 
contemplating work in this domain. The rationale for those standards is found 
throughout this issue and is especially developed in the article by Fins. The 
need for safe and effective therapeutic options for people suffering with these 
severe illnesses is just as clear. The experience over the last several decades 
provides grounds for careful optimism that refined lesion procedures or 
reversible deep brain stimulation may relieve suffering and improve the lives of 
people with these devastating disorders.