In this Issue-February 15th| Volume 65, ISSUE 4, P261-262, February 15, 2009

In this Issue-February 15th

        Deep Brain Stimulation

        Malone et al. (pages 267–275) report on the use of open-label deep brain stimulation (DBS) to treat 15 patients with chronic, severe, highly treatment refractory depression. They observed significant improvements in depressive symptoms as well as global functioning. The treatment was well tolerated overall and may signal a new option for the management of major depression.
        Diffusion tensor imaging and probabilistic tractography were performed in 13 nondepressed subjects to simulate the pattern of connectivity of two brain regions being investigated as DBS targets for treatment resistant depression (TRD): the subcallosal cingulate white matter and anterior limb of the internal capsule. Gutman et al. (pages 276–282) found that differential patterns of connectivity may help explain differences in the safety, efficacy and mechanism of action of DBS of each in the treatment of TRD.

        Novel Approaches to the Treatment of Depression

        Lewitus et al. (pages) show that a brain specific activation of the immune system, via vaccination, ameliorates depressive behavior induced by chronic mild stress in rats. The immunization was also associated with restoration of brain-derived neurotrophic factor expression and neurogenesis. These results indicate that vaccination could be considered as an antidepressant therapy as it may invoke molecular and cellular pathways that are known to be regulated by antidepressant drugs.
        Using magnetoencephalography in patients with major depression and healthy controls, Salvadore et al. (pages 289–295) demonstrated that activity in the anterior cingulate cortex (ACC) predicted rapid antidepressant response to ketamine. Thus, pretreatment rostral ACC activation may be a useful biomarker to identify patients who will respond favorably to ketamine's antidepressant effects.

        The Influence of Interferon-Alpha: Serotonin and Depression

        Accumulating evidence indicates that major depression can be triggered by the inflammatory cytokine interferon-alpha (INF-α). Lotrich et al. (pages 344–348) prospectively followed INF-α-treated, non-depressed patients to evaluate genetic influences on the risk of developing depression. The short or less functional allele of the serotonin transporter gene, a common genetic variant, was associated with higher rates of depression incidence.
        Studies indicate that innate immune cytokines can influence the brain, potentially contributing to the development of depression. Raison et al. (pages 296–303) detected INF-α in the cerebrospinal fluid of all INF-α -treated patients, but in only one control subject. The presence of INF-α activated an immune response that is associated with altered serotonin metabolism, which was, in turn, related to depression. These findings indicate that peripherally administered cytokines access the brain and influence pathways relevant to depression.

        Inflammation Accelerates Neurodegenerative Disease

        Cunningham et al. (pages 304–312) sought to evaluate whether systemic inflammation can accelerate the progression of neurodegenerative disease. Using a mouse model, they show that systemic inflammation causes acute motor and cognitive exacerbations of neurodegenerative disease and accelerates the development of disease symptoms. These data suggest that the control of infection and inflammation could have implications for the treatment of chronic neurodegeneration and associated delirium.

        Inhibition Deficits in Borderline Personality Disorder

        Using transcranial magnetic stimulation, Barnow et al. (pages 313–318) investigated inhibitory and excitatory cortical paradigms in unmedicated females with borderline personality disorder (BPD) and healthy controls. BPD patients showed reduced cortical inhibition in the right cortex, supporting an association between BPD and cortical inhibition deficits.

        Neurotrophins in Suicide Brain Tissue

        In human postmortem brain tissue obtained from suicide subjects, Dwivedi et al. (pages 319–328) found reduced expression and activation of tropomysin receptor kinase (Trk) receptors A, B, and C, and increased expression of p75 neurotrophin receptor (p75NTR). Reduced expression and activation of Trks suggest reduced functioning of Trks in brains of suicide subjects and increased expression ratios of p75NTR to Trks indicate possible activation of pathways that are apoptotic in nature. These findings may be crucial in the pathophysiologic mechanisms of suicide.

        The Histamine System in Anorexia Nervosa

        Histamine, involved in immune system disorders and allergies, also acts in the brain as a neurotransmitter. Using positron emission tomography, Yoshizawa et al. (pages 329–335) have found that the histamine-1 (H1) receptor is increased in the amygdala of patients with anorexia nervosa. These findings suggest that the central histaminergic neuron system may play an important role in the pathophysiology of anorexia nervosa.

        Neural and Physiologic Responses to Fear

        Enhanced glucocorticoid stress responsiveness in patients with social anxiety disorder (SAD) is related to increased social avoidance behavior. Roelofs et al. (pages 336–343) report that patients with SAD show increased cortisol responses to social stress exposure and that elevated cortisol responses are associated with an increased tendency to avoid social threat stimuli on a computerized approach-avoidance task.
        Lau et al. (pages 349–355) explored the relationship between functional polymorphisms in the serotonin transporter gene and brain function in adolescents with anxiety and/or depressive disorders and healthy controls. They sought to determine whether genetic variants would predict amygdala responses when subjects were evaluating subjective fear levels to emotional faces. Results indicated a significant relationship but that the nature of this relationship differed in healthy versus anxious and/or depressed adolescents.