Individuals with anorexia nervosa (AN) engage in relentless, restrictive eating and often become severely emaciated. Because there are no proven treatments, AN has high rates of relapse, chronicity, and death. Those with AN tend to have childhood temperament and personality traits, such as anxiety, obsessions, and perfectionism, which may reflect neurobiological risk factors for developing AN. Restricted eating may be a means of reducing negative mood caused by skewed interactions between serotonin aversive or inhibitory and dopamine reward systems. Brain imaging studies suggest altered eating is a consequence of dysregulated reward, and/or awareness of homeostatic needs, perhaps related to enhanced executive ability to inhibit incentive motivational drives. Understanding the neurobiology of this disorder is likely to be important for developing more effective treatments.

reatment-resistant depression (TRD) is usually seen as the failure to reach sufficient remission after an Objectives: Very few studies have investigated clinical features associated with treatment-resistant depression (TRD) defined as failure of at least 2 consecutive antidepressant trials. The primary objective of this multicenter study was to identify specific clinical and demographic factors associated with TRD in a large sample of patients with major depressive episodes that failed to reach response or remission after at least 2 consecutive adequate antidepressant treatments.Method: A total of 702 patients with DSM-IV major depressive disorder, recruited from January 2000 to February 2004, were included in the analysis. Among them, 346 patients were considered as nonresistant. The remaining 356 patients were considered as resistant, with a 17-item Hamilton Rating Scale for Depression score remaining greater than or equal to 17 after 2 consecutive adequate antidepressant trials. Cox regression models were used to examine the association between individual clinical variables and TRD.Results: Among the clinical features investigated, 11 variables were found to be associated with TRD. We found anxiety comorbidity (p < .001, odds ratio [OR] = 2.6), comorbid panic disorder (p < .001, OR = 3.2) and social phobia (p = .008, OR = 2.1), personality disorder (p = .049, OR = 1.7), suicidal risk (p = .001, OR = 2.2), severity (p = .001, OR = 1.7), melancholia (p = .018, OR = 1.5), a number of hospitalizations > 1 (p = .003, OR = 1.6), recurrent episodes (p = .009, OR = 1.5), early age at onset (p = .009, OR = 2.0), and nonresponse to the first antidepressant received lifetime (p = .019, OR = 1.6) to be the factors associated with TRD.Conclusions: Our findings provide a set of 11 relevant clinical variables associated with treatment resistance in major depressive disorder that can be explored at the clinical level. The statistical model used in this analysis allowed for a hierarchy of these variables (based on the OR) showing that comorbid anxiety disorder is the most powerful clinical factor associated with TRD.

Individuals who have recovered from anorexia nervosa may have difficulties in differentiating positive and negative feedback. The exaggerated activation of the caudate, a region involved in linking action to outcome, may constitute an attempt at "strategic" (as opposed to hedonic) means of responding to reward stimuli. The authors hypothesize that individuals with anorexia nervosa have an imbalance in information processing, with impaired ability to identify the emotional significance of a stimulus but increased traffic in neurocircuits concerned with planning and consequences.

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