Novel Pharmacotherapies for Anxiety Disorders
D-cycloserine (DCS) is an interesting adjunct to the treatment of anxiety disorders because it may enhance or accelerate the efficacy of psychotherapies for anxiety disorders by increasing the “plasticity” of the brain, while having relatively little efficacy when administered outside of the context of psychotherapy. This view of DCS treatment is further supported by a new double-blind, randomized, placebo-controlled study of the treatment of social anxiety disorder by Guastella et al. (pages 544–549). The authors report that 50 mg of DCS enhanced the effectiveness of four group exposure-based therapy sessions and the benefits of DCS were present at the end of treatment and one month later.
Prazosin is a promising experimental treatment for posttraumatic stress disorder (PTSD). In patients diagnosed with PTSD experiencing nightmares and sleep disruption, Taylor et al. (pages 629–632) demonstrated that prazosin significantly increased total sleep time and lengthened mean rapid eye movement (REM) period duration. As in previously reported veteran samples, prazosin reduced trauma-related nightmares and distressed awakenings, and improved overall clinical status.
Biological Distinctions in Anxiety and Emotional Dysregulation
Krain et al. (pages 563–568) provide new insight from functional neuroimaging into how uncertainty raises anxiety levels. During a decision-making task, anxious adolescents who became most distressed by uncertainty showed increased activity in amygdala and orbitofrontal cortex, while anxious individuals who better tolerated uncertainty deactivated these same brain regions.
Neuroticism is a heritable trait that contributes to the risk for mood and anxiety disorders. In a positron emission tomography (PET) study in a large number of healthy subjects, Frokjaer et al. (pages 569–576) show that people with a persisting feeling of vulnerability and anxiety possess a higher density of the serotonin-2A in frontal cortex and associated regions of the limbic system. These data suggest that the serotonin system plays an important role in personality traits that may contribute to the risk for mood and anxiety disorders.
Goldin et al. (pages 577–586) highlight important differences in two different ways of coping with negative emotions, to reappraise their meaning or to suppress one’s emotional response. Using functional magnetic resonance imaging (fMRI), the authors show that both techniques reduce negative emotional experiences. However, the two strategies markedly differed in their impact on brain activity. Reappraisal reduced a rapid component of prefrontal cortical activation and the activation of two brain regions implicated in emotional experience, the amygdala and insula. In contrast, suppression reduced a delayed component of prefrontal cortex activation, but increased the activity of the insula and amygdala. These findings suggest important differences in strategies intended to cope with negative emotions.
Does stress damage the brain? Kasai et al. (pages 550–556) report that, among a sample of Vietnam combat veterans with and without PTSD, and their combat-unexposed identical twins, gray matter density of the pregenual anterior cingulate cortex was reduced in veterans with PTSD, but not in the twins who had not experienced combat. These results suggest that extreme stress exposure contributed to the brain tissue loss in veterans with PTSD.
The Genetics of Fear
Hettema et al. (pages 587–593) question the relationship between the heritability of physiologic arousal measured during fear conditioning and the heritability of self-report fears. The authors report that the variance in arousal during fear conditioning accounted for only 9% of individual differences in self-report fears. These data suggest that physiologic arousal during fear conditioning may not be a useful endophenotype for studying the inheritance of fears and phobias.
Prior studies have identified elevated rates of specific medical conditions including interstitial cystitis, mitral valve prolapse, and migraines among families with panic disorder. This “panic disorder syndrome” may be linked to chromosome 13. Talati et al. (pages 594–601) present data from a new case-control study that replicate earlier clinical findings, and suggest that this syndrome may extend to other anxiety disorders as well.
Impaired Cognition in Non-Psychotic Disorders
Weiser et al. (pages 602–608) utilized the screening performed by the Israeli draft board on all 16–17 year old male adolescents in the country, to examine cognitive functioning of patients diagnosed at the time of testing with non-psychotic disorders (mild depression, anxiety disorders, personality disorders; N = 19,489), and their unaffected siblings. The main findings of the study are that persons with non-psychotic disorders and their unaffected siblings had mildly impaired cognitive abilities, equivalent approximately to 8 and 4 IQ points below population norms, respectively.
Cerebral Markers for Alzheimer’s?
Cognitively normal, middle-aged, individual carriers of the Apolipoprotein E epsilon4 allele with subjective memory complaints showed brain abnormalities consistent with Alzheimer’s disease, such as reductions of cerebral glucose metabolism in brain regions implicated in memory. Mosconi et al. (pages 609–618) also found elevated cerebrospinal fluid levels of a number of proteins associated with the development and progression of Alzheimer’s disease including total (T-Tau) and hyperphosphorylated tau231 (P-Tau), 40 and 42 amino acid forms of β-amyloid (Aβ40 and Aβ42), and F2-isoprostane (IP).
Advances in the Neurobiology and Genetics of OCD
Guehl et al. (pages 557–562) tested the hypothesis that neuronal activity within the caudate nucleus (CN) could be associated with obsessions in patients with obsessive-compulsive disorder (OCD). They performed perioperative recordings of neural activity within the CN in three patients with OCD who were being prepared for deep brain stimulation treatment. The authors report that the frequency of CN neuronal activity and the variability of this activity were abnormally high in the two patients with high levels of obsessive symptoms. These data add to evidence that neural activation in the CN contributes to symptoms of OCD.
Alonso et al. (pages 619–628) implicate the genes coding for brain-derived neurotrophic factor (BDNF) and its receptor NTRK2 in the heritable risk for developing OCD. The authors report haplotypes of both genes that were related to reduced risk for OCD.
Antidepressants for Pain Treatment
Benbouzid et al. (pages 633–636), using knock-out and pharmacological approaches in mice, show that the ability of antidepressant medications to activate endogenous opioid systems leading to the stimulation of delta opioid receptors contributes to their rapid efficacy in reducing chronic pain.
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© 2008 Published by Elsevier Inc. All rights reserved.
