A summary of the Third International Obsessive Compulsive Disorder Conference proceedings on neuroimaging research and neurocircuitry models of obsessive-compulsive disorder (OCD) is presented. This survey of recent and ongoing research indicates that a wide range of modern techniques and experimental strategies are being employed in a complementary fashion to enhance our understanding of OCD. Imaging studies in animal models of OCD are helping to elaborate relevant normal anatomy and neuro-chemistry. Functional imaging methods are being employed in conjunction with behavioral, pharmacologic, and cognitive challenge paradigms. Magnetic resonance spectroscopy as well as radiotracer methods are being utilized to measure neurochemical and neuropharmacologic indices in OCD. Transcranial magnetic stimulation has emerged as a tool for probing neurocircuitry that may also have therapeutic potential. Experimental designs and data-analytic methods are evolving to help elucidate the pathophysiology of OCD and related disorders, delineate neurobiologically meaningful subtypes of OCD, and identify potential predictors of treatment response. Collectively, these efforts promise important advances as we approach the new millennium.

An overview is provided regarding neuroimaging in obsessive-compulsive disorder (OCD). The author emphasizes convergent research results across various experimental paradigms and their implications for neurobiological models of OCD. The article concludes with an outline of future considerations that highlights emerging concepts and techniques. This work was intended to serve as a concise summary of the field, and thus to provide a springboard for discussion about this topic at the upcoming International Obsessive Compulsive Disorder Conference.

Contemporary neuroimaging methods have been used to gather initial data regarding the neural substrates of posttraumatic stress disorder (PTSD). Morphometric magnetic resonance imaging (MRI) studies have reliably shown reduced hippocampal volume in subjects with PTSD vs control cohorts. Functional imaging studies have implicated a network of brain regions in PTSD, comprising the amygdala, hippocampus, and anterior paralimbic territories (including anterior cingulate cortex), as well as Broca's area and visual cortex. Extant relevant neuroimaging data are reviewed, and a tentative heuristic neuroanatomical model of PTSD is provided. In conclusion, emerging strategies for advancement in this field are outlined.

Trichotillomania (TTM, repetitive hair pulling) is a complex underdiagnosed syndrome that often causes considerable psychological distress and physical disfigurement. Although many aspects of hair pulling bear similarity to compulsions of obsessive-compulsive disorder (OCD), TTM lacks obsessions associated with OCD. The phenomenology of TTM also is similar to tics in Tourette Syndrome (TS) and overlaps with TS in both limited structural neuroimaging data and in terms of treatment response to pharmacotherapy with dopamine antagonists.

In order to study potential comorbid relationships between TTM, TS, and OCD, a total of 61 patients with either TS, OCD, or OCD comorbid with TS were assessed using structured interviews as part of a phenomenological study of these groups. Post hoc analyses indicated significantly higher proportions of hair pulling in those subjects with OCD comorbid with TS compared to subjects with either OCD or TS alone.

These data, in conjunction with clinical phenomenology, neuroimaging results, and response to pharmacotherapy suggest the possibility that some forms of TTM may be more closely related to tic disorders than OCD. Futher research is needed to clarify and confirm these observations of putative relationships between TTM and TS and potential treatment implications.

The purpose of this study was to test the hypothesis that orbitofrontal cortical volume would be reduced following anterior cingulotomy for obsessive-compulsive disorder (OCD). Whole brain cortical parcellation was performed on magnetic resonance imaging (MRI) data from nine patients, before and 9(±6) months following anterior cingulotomy. No significant volumetric reductions were found in the orbitofrontal cortex. Exploratory findings of reduced volume in ventral temporo-fusiform and posterior cingulate regions were consistent with chance differences, in the face of multiple comparisons. Therefore, though the circumscribed lesions of anterior cingulotomy have recently been associated with corresponding volumetric reductions in the caudate nucleus, no comparable volumetric reductions are evident in cortical territories. Taken together, these results are most consistent with a model of cingulo-striatal perturbation as a putative mechanism for the efficacy of this procedure. While limitations in sensitivity may have also contributed to these negative findings, the methods employed have previously proven sufficient to detect cortical volumetric abnormalities in OCD. The current results may reflect a relatively diffuse pattern of cortico-cortical connections involving the neurons at the site of cingulotomy lesions. Future functional neuroimaging studies are warranted to assess possible cortical or subcortical metabolic changes associated with anterior cingulotomy, as well as predictors of treatment response.

We review the attributes of inhibited and uninhibited infant temperaments, and their developmental trajectories into early adulthood. Inborn individual differences in infants' propensity to respond to novel people and objects are associated with persistent differences in the responsivity of the amygdala to novelty, as measured with functional magnetic resonance imaging, after more than 20 years of development. Because an inhibited temperament is a risk factor for developing later psychiatric disorders, particularly generalized social anxiety disorder, temperamental differences are confounds in neuroimaging and genetic studies. Longitudinal studies are a unique tool for understanding the developmental and temperamental risk factors for psychiatric disorder.

In the absence of definitive etiological markers of vulnerability or a unitary profile of pathophysiology for obsessive-compulsive disorder (OCD), obsessive-compulsive (OC) symptom dimensions seem to offer a fruitful point of orientation.The complex clinical presentation of OCD can be summarized using a few consistent and temporally stable symptom dimensions. These can be understood as a spectrum of potentially overlapping features that are likely to be continuous with “normal” worries and extend beyond the traditional nosological boundaries of OCD. Although the understanding of the dimensional structure of obsessive-compulsive symptoms (OCS) is still imperfect, this quantitative approach to phenotypic traits has the potential to advance our understanding of OCD and may aid in the identification of more robust endophenotypes. Preliminary data suggest that these dimensional phenotypes may be useful in studies of the natural history, genetics, neurobiology, and treatment outcome of OCD. A dimensional approach is not mutually exclusive of other methods to parse the larger spectrum of disorders related to OCD. Thus far, age-of-onset of OCS and the individual's “tic-related” status seem to be particularly useful categorical distinctions. Finally, existing assessment methods are inadequate and new dimensional scales are needed to take full advantage of a dimensional approach in clinical and population-based studies.

Tourette syndrome (TS) is a complex neurobehavioral disorder principally characterized by motor and vocal tics. However, features of obsessive-compulsive and attention-deficit/hyperactivity disorders are often present. The basal ganglia and associated brain structures have been implicated in the pathophysiology of TS, as well as in these related conditions. Specifically, it is believed that the neuroanatomically and functionally defined basal ganglia thalamocortical loops are involved in TS. These loops are composed of a sequence of connections originating in the cortex and passing in series through the striatum (caudate and putamen), globus pallidus, and thalamus before returning to the cortical areas of origin. This review concentrates on the neuroimaging findings in Ts, particularly as they relate to alterations in components of the basal ganglia thalamocortical circuits. These neuroimaging data suggest that the major abnormalities in TS involve striatal or cortical dysfunction, as well as dysfunction of dopaminergic systems that regulate basas ganglia neurotransmission.

Various schemes have been developed in attempts to define meaningful subtypes of obsessive-compulsive disorder (OCD). A factor analytic approach presumes that the symptom of the disorder can be described by several independent symptom dimensions. The purpose of this study was to explore the neural correlates of three symptom dimensions that were derived from previous factor analyses. Positron emission tomography was used to measure relative regional cerebral blood flow (rCBF) in 14 subjects with OCD while they engaged in a continuous performance task. Clinical indices, including factor scores, we ascertained via structured interviews plus administration of the Yale-Brown Obsessive-Compulsive Scale and checklist. The severity of Factor 1 (religious/aggressive/sexual obsessions and checking) was positively correlated with rCBF in striatum bilaterally. In addition, distinct trends were observed for the other two Factors. These findings provide initial support for a modular neurobiologic model of OCD, where dysfunction within separate component systems may principally mediate independent symptom factors. More important, this nove strategy may represent a powerful new approach to interpreting brain imaging studies of neuropsychiatric diseases.

In this article, we discuss the use of venlafaxine, an antidepressant with predominant effects at both noradrenergic and serotonergic reuptake sites, in the treatment of trichotillomania (TTM), a complex psychiatric condition manifested by chronic, severe hair pulling. We review case examples of 10 consecutive patients exhibiting moderately severe TTM symptoms, as judged by self-report, extent of hair loss, and duration of remission, and discuss our observations regarding the effects of venlafaxine therapy (mean dose, 274 mg/day) on these patients over the course of several months (mean, 15.1 weeks). The Massachusetts General Hospital Hair Pulling Scale, Massachusetts General Hospital Trichotillomania Impact Scale (MGH TIS), Psychiatric Institute Trichotillomania Scale (PITS), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and Clinical Global Improvement (CGI) scale were used to appraise the patients' condition during routine clinical visits. A retrospective chart review of clinical data demonstrated significant improvement in TTM symptoms from baseline to last clinical visit in both behavioral (MGH HPS, P=.02; PITS, P=.02) and psychosocial (MGH TIS, P=.009) terms. Mean improvement on the CGI scale was 2.38±1.51, between “much improved” (2) and “slightly improved” (3). There were no significant differences from baseline to endpoint scores on the BDI or BAI. This retrospective treatment review indicates that short-term treatment with venlafaxine improved TTM symptoms; however, longer controlled trials with extended baseline periods are needed for optimal assessment of pharmacologic treatment of TTM. We look to future studies to confirm and supplement our initial positive findings.

White matter fiber pathways are key structural components of the brain and its functional organization. The limbic system carries a great deal of its anatomic connectivity via the cingulum bundle. By allowing the in vivo delineation of the stem of the major fiber pathway systems, diffusion tensor magnetic resonance imaging has opened a new window into the detailed structure of the white matter in health and disease. Topographic, biophysical, and volumetric information about fiber tracts will provide a more complete understanding of the brain. By appreciating its interconnections, the precise anatomical knowledge of the cingulum bundle will improve our understanding of the limbic system and may enable improvements in the assessment and treatment of neuropsychiatric disorders. In this study, the stem of the cingulum bundle was investigated and defined in terms of its trajectory, anisotropy, and volume, in four normal human subjects, using diffusion tensor imaging.

Introduction: Recently, human studies using exposure therapy to treat anxiety have demonstrated that pretreatment with D-cycloserine (DCS) enhances fear reduction in anxiety disorders. However, the underlying brain mechanisms mediating this fear reduction have yet to be determined.

Methods: The effects of orally administered DCS on amygdala activity during the processing of repeated facial expressions were examined in this double-blind study. Fourteen healthy males (30.0±8.7 years of age) randomly received DCS 500 mg or placebo prior to 3.0 Tesla functional magnetic resonance imaging acquisition. All participants viewed four separate runs, consisting of a single block of a repeated facial expression (happy or fearful) bracketed by fixation blocks.

Results: Anatomic region-of-interest analyses showed that the placebo group exhibited amygdala activation and response habituation, while the DCS group displayed blunted amygdala responses to emotional faces across the experiment, whereby habituation was not detected.

Conclusion: This finding may have relevance for testing treatments of anxiety and depression.

Background. Studies measuring the effects of psychotherapy on brain function are under-represented relative to analogous studies of medications, possibly reflecting historical biases. However, psychological constructs relevant to several modalities of psychotherapy have demonstrable neurobiological correlates, as indicated by functional neuroimaging studies in healthy subjects. This review examines initial attempts to measure directly the effects of psychotherapy on brain function in patients with depression or anxiety disorders.

Method. Fourteen published, peer-reviewed functional neuroimaging investigations of psychotherapy were identified through a MEDLINE search and critically reviewed. Studies were compared for consistency of findings both within specific diagnostic categories, and between specific modalities of psychotherapy. Results were also compared to predicted neural models of psychotherapeutic interventions.

Results. Behavioral therapy for anxiety disorders was consistently associated with attenuation of brain-imaging abnormalities in regions linked to the pathophysiology of anxiety, and with activation in regions related to positive reappraisal of anxiogenic stimuli. In studies of major depressive disorder, cognitive behavioral therapy and interpersonal therapy were associated with markedly similar changes in cortical–subcortical circuitry, but in unexpected directions. For any given psychiatric disorder, there was only partial overlap between the brain-imaging changes associated with pharmacotherapy and those associated with psychotherapy.

Conclusions. Despite methodological limitations, initial neuroimaging studies have revealed convergent and mechanistically sensible effects of psychotherapy on brain function across a range of psychiatric disorders. Further research in this area may take advantage of emerging neuroimaging techniques to explore a broader range of psychotherapies, with the ultimate goal of improving clinical decision-making and treatment.