Background Neuroimaging studies provide strong evidence that the pathophysiology of obsessive-compulsive disorder (OCD) involves abnormal functioning along specific frontal-subcortical brain circuits.Method A literature search was carried out for all brain imaging studies of patients with OCD. We also reviewed the basic science literature on the functional neuroanatomy of cortico-basal ganglia circuits, and integrated this information with neuroimaging data in OCD to formulate a theoretical model of brain mediation of OCD symptoms and response to treatment.Results At least a subgroup of patients with OCD may have abnormal basal ganglia development. Functional neuroimaging studies indicate that OCD symptoms are associated with increased activity in orbitofrontal cortex, caudate nucleus, thalamus and anterior cingulate gyrus.Conclusions OCD symptoms are mediated by hyperactivity in orbitofrontal-subcortical circuits, perhaps due to an imbalance of tone between direct and indirect striatopallidal pathways. We present a model which describes how frontal-subcortical brain circuitry may mediate OCD symptomatology, and suggest a hypothesis for how successful treatments may ameliorate symptoms, via their effects on circuit activity.

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The major known genetic risk for Alzheimer's disease (AD), apolipoprotein E-4 (APOE-4), is associated with lowered parietal, temporal, and posterior cingulate cerebral glucose metabolism in patients with a clinical diagnosis of AD. To determine cognitive and metabolic decline patterns according to genetic risk, we investigated cerebral metabolic rates by using positron emission tomography in middle-aged and older nondemented persons with normal memory performance. A single copy of the APOE-4 allele was associated with lowered inferior parietal, lateral temporal, and posterior cingulate metabolism, which predicted cognitive decline after 2 years of longitudinal follow-up. For the 20 nondemented subjects followed longitudinally, memory performance scores did not decline significantly, but cortical metabolic rates did. In APOE-4 carriers, a 4% left posterior cingulate metabolic decline was observed, and inferior parietal and lateral temporal regions demonstrated the greatest magnitude (5%) of metabolic decline after 2 years. These results indicate that the combination of cerebral metabolic rates and genetic risk factors provides a means for preclinical AD detection that will assist in response monitoring during experimental treatments.apolipoprotein E ͉ positron emission tomography ͉ cerebral glucose metabolism ͉ age-associated memory impairment A lzheimer's disease (AD) accounts for approximately twothirds of late-life dementias, afflicting an estimated 8% of people age 65 years and older (1). In the United States alone, AD victims total nearly four million, and annual cost estimates, including caregiver productivity losses and costs of medical, long-term, and home care, approach $90 billion (2, 3). The disease's gradual decline in memory, other cognitive functions, behaviors, and daily functions progress until patients eventually require total care from others (4).Mild memory complaints build gradually years before patients develop dementia, and neurofibrillary tangles (5) and neuritic plaques (6), the neuropathological hallmarks of AD, are present in older persons with memory complaints too mild to warrant a diagnosis of dementia. Amyloid deposits have been observed in middle-aged nondemented persons decades before they reach the age at risk for late-onset AD (7). Moreover, diffuse plaques in nondemented elderly persons are associated with an accelerated age-related cortical cholinergic deficit, which could represent a clinical stage preceding dementia (8). Such observations have stimulated interest in ''preclinical'' AD markers aimed at identifying candidates who may benefit from novel antidementia treatments. Randomized, placebo-controlled trials of cholinesterase inhibitors, anti-oxidants, and anti-inflammatory agents are already in progress for such conditions as mild cognitive impairment (9) or age-associated memory impairment (AAMI) (10). These experimental drug trials use standard clinical examination methods to identify subjects and follow cognitive decline (4, 11). Because many people with mild memory c...

Brain regions associated with arousal, compulsive repetitive behaviors, sensory integration, and episodic memory are activated during exposure to cigarette-related cues and cigarette craving. These regional brain activations and associations with craving are similar to findings with other addictive substances.

This article provides a focused review of the literature on compulsive hoarding and presents a number of options and preliminary recommendations to be considered for DSM-V. In DSM-IV-TR, hoarding is listed as one of the diagnostic criteria for obsessive-compulsive personality disorder (OCPD). According to DSM-IV-TR, when hoarding is extreme, clinicians should consider a diagnosis of obsessive-compulsive disorder (OCD) and may diagnose both OCPD and OCD if the criteria for both are met. However, compulsive hoarding seems to frequently be independent from other neurological and psychiatric disorders, including OCD and OCPD. In this review, we first address whether hoarding should be considered a symptom of OCD and/or a criterion of OCPD. Second, we address whether compulsive hoarding should be classified as a separate disorder in DSM-V, weighing the advantages and disadvantages of doing so. Finally, we discuss where compulsive hoarding should be classified in DSM-V if included as a separate disorder. We conclude that there is sufficient evidence to recommend the creation of a new disorder, provisionally called hoarding disorder. Given the historical link between hoarding and OCD/OCPD, and the conservative approach adopted by DSM-V, it may make sense to provisionally list it as an obsessive-compulsive spectrum disorder. An alternative to our recommendation would be to include it in an Appendix of Criteria Sets Provided for Further Study. The creation of a new diagnosis in DSM-V would likely increase public awareness, improve identification of cases, and stimulate both research and the development of specific treatments for hoarding disorder.

IMPORTANCE Few pharmacotherapies have demonstrated sufficient efficacy in the treatment of posttraumatic stress disorder (PTSD), a chronic and disabling condition.OBJECTIVE To test the efficacy and safety of a single intravenous subanesthetic dose of ketamine for the treatment of PTSD and associated depressive symptoms in patients with chronic PTSD. DESIGN, SETTING, AND PARTICIPANTS Proof-of-concept, randomized, double-blind, crossover trial comparing ketamine with an active placebo control, midazolam, conducted at a single site (Icahn School of Medicine at Mount Sinai, New York, New York). Forty-one patients with chronic PTSD related to a range of trauma exposures were recruited via advertisements.INTERVENTIONS Intravenous infusion of ketamine hydrochloride (0.5 mg/kg) and midazolam (0.045 mg/kg). MAIN OUTCOMES AND MEASURESThe primary outcome measure was change in PTSD symptom severity, measured using the Impact of Event Scale-Revised. Secondary outcome measures included the Montgomery-Asberg Depression Rating Scale, the Clinical Global Impression-Severity and -Improvement scales, and adverse effect measures, including the Clinician-Administered Dissociative States Scale, the Brief Psychiatric Rating Scale, and the Young Mania Rating Scale.RESULTS Ketamine infusion was associated with significant and rapid reduction in PTSD symptom severity, compared with midazolam, when assessed 24 hours after infusion (mean difference in Impact of Event Scale-Revised score, 12.7 [95% CI, 2.5-22.8]; P = .02). Greater reduction of PTSD symptoms following treatment with ketamine was evident in both crossover and first-period analyses, and remained significant after adjusting for baseline and 24-hour depressive symptom severity. Ketamine was also associated with reduction in comorbid depressive symptoms and with improvement in overall clinical presentation. Ketamine was generally well tolerated without clinically significant persistent dissociative symptoms. CONCLUSIONS AND RELEVANCEThis study provides the first evidence for rapid reduction in symptom severity following ketamine infusion in patients with chronic PTSD. If replicated, these findings may lead to novel approaches to the pharmacologic treatment of patients with this disabling condition. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00749203

Subjects with MDD had regional brain metabolic abnormalities at baseline that tended to normalize with treatment. Regional metabolic changes appeared similar with the 2 forms of treatment. These results should be interpreted with caution because of study limitations (small sample size, lack of random assignment to treatment groups, and differential treatment response between treatment subgroups).

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