Biology of anxiety disorders. Rudolph Hoehn Saric, M.D., and Daniel R. McLeod, PhD. American Psychiatric Press, Inc., Washington D.C., 1993, 259 pp, $36.00

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/101825/1/3070010214_ftp.pd

Beyond Anxious Predisposition: Do Padecer de Nervios and Ataque de Nervios Add Incremental Validity to Predictions of Current Distress among Mexican Mothers?

Background Nervios (PNRV) and ataque de nervios (ATQ) are culture-bound syndromes with overlapping symptoms of anxiety, depression, and dissociation, shown to have inconsistent associations to psychiatric disorder. Few studies test the basic assumption that PNRV and ATQ are uniformly linked to distress outcomes across Latina/o immigrant groups. This study examined: (a) the extent to which acculturative stress, Latino/US American acculturation, and anxious predisposition were associated with lifetime history of ATQ and PNRV, and (b) the extent to which ATQ and PNRV add incremental validity in explaining acculturative stress and psychological distress beyond measures of anxious predisposition. Method Participants (n = 82) included Mexican mothers who completed surveys on acculturation, trait anxiety, anxiety sensitivity, lifetime ATQ/PNRV, psychological distress, and acculturative stress. Results Lifetime PNRV, but not lifetime ATQ, was significantly predictive of psychological distress. PNRV was also linked to trait anxiety. Psychometric measures of anxious predisposition (trait anxiety and anxiety sensitivity) were more robust predictors of distress outcomes than lifetime history of ATQ/PNRV. Conclusion Inquiry into lifetime history of nervios may be a useful point of entry in talking to Mexican immigrant mothers about stress and distress. However, standard tools for assessing anxiety sensitivity and trait anxiety appear most useful in identifying and explaining the presence of psychological distress. Further research is needed to determine the cross-cultural relevance of trait anxiety and anxiety sensitivity, and its implications for the development of anxiety treatments that are effective across cultures

Impaired contextual modulation of memories in PTSD: an fMRI and psychophysiological study of extinction retention and fear renewal

Post-traumatic stress disorder (PTSD) patients display pervasive fear memories, expressed indiscriminately. Proposed mechanisms include enhanced fear learning and impaired extinction or extinction recall. Documented extinction recall deficits and failure to use safety signals could result from general failure to use contextual information, a hippocampus-dependent process. This can be probed by adding a renewal phase to standard conditioning and extinction paradigms. Human subjects with PTSD and combat controls were conditioned (skin conductance response), extinguished, and tested for extinction retention and renewal in a scanner (fMRI). Fear conditioning (light paired with shock) occurred in one context, followed by extinction in another, to create danger and safety contexts. The next day, the extinguished conditioned stimulus (CS+E) was re-presented to assess extinction recall (safety context) and fear renewal (danger context). PTSD patients showed impaired extinction recall, with increased skin conductance and heightened amygdala activity to the extinguished CS+ in the safety context. However, they also showed impaired fear renewal; in the danger context, they had less skin conductance response to CS+E and lower activity in amygdala and ventral-medial prefrontal cortex compared with combat controls. Control subjects displayed appropriate contextual modulation of memory recall, with extinction (safety) memory prevailing in the safety context, and fear memory prevailing in the danger context. PTSD patients could not use safety context to sustain suppression of extinguished fear memory, but they also less effectively used danger context to enhance fear. They did not display globally enhanced fear expression, but rather showed a globally diminished capacity to use contextual information to modulate fear expression

Discontinuation of Alprazolam after successful treatment of panic disorder: a naturalistic follow-up study

Low rates of benzodiazepine discontinuation have been seen in long-term outcome studies of alprazolam-treated panic disorder. Discontinuation studies reveal high rates of relapse when alprazolam is stopped. Available data may lack relevance to clinical practice, however, because drug taper rates are often more rapid than those used in many clinical settings. In order to obtain naturalistic data on the long-term course of alprazolam treatment of panic, we obtained follow-up data on 18 of 20 patients who had been enrolled one to two years earlier in a study of alprazolam effects on hypothalamic-pituitary-adrenal (HPA) axis functioning. The HPA protocol provided measures of symptom severity, biological markers, and short-term treatment response (12 weeks). Routine clinical care was then provided, with dosage adjustments dictated by individual clinical needs. The follow-up study repeated clinical measures at a mean of 21 months after initiation of treatment. Alprazolam was discontinued in 78% of patients. Relapse occured in 36% of these. At follow-up, 61% were medication-free. Only 28% were on a benzodiazepine. The four patients remaining on alprazolam were on reduced doses and had maintained clinical gains. HPA axis activity did not predict dose or outcome. Factors related to successful alprazolam discontinuation are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30929/1/0000599.pd

Cortisol pulsatility and its role in stress regulation and health

commentaryOne of the classic characteristics of the human stress response is the wide inter-individual variation. Although there is much current interest in the genetic and environmental contributions to these differences, studies on human subject have been sparse and characterised by methodological problems. The major factor that is rarely taken into account is the intrinsic rhythmicity of hypothalamo–pituitary–adrenal activity, not simply the classic diurnal variation but also the endogenous pulsatility which is similar to, but much less well recognized than, the rhythms found within the reproductive and growth hormone axes. In this review we propose some novel ideas relating to the importance of pulsatility both for the design of human stress-response studies and for their interpretation as well as implications for our understanding of disease.NIMH MH50030 NIMH MH52724Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/49484/2/cortisolpulseLightman.pd

Stimulation of corticotropin release by pentagastrin in normal subjects and patients with panic disorder

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29279/1/0000338.pd

Interaction of Brain Noradrenergic System and the Hypothalamic-Pituitary-Adrenal (HPA) Axis in Man

Background: Numerous interactions between the brainstem locus coeruleus system and the HPA axis have been shown in experimental animals. This relationship is less well characterized in humans and little is known about the influence of psychiatric disorders, which disturb one of these systems, on this relationship. Methods: Untreated subjects with pure MDD (n=13), MDD with comorbid anxiety disorders (n=17), and pure anxiety disorders (n=15) were recruited by advertising. Age and sex matched control subjects were recruited for each subject with a psychiatric diagnosis (n=45). All subjects underwent a social stressor, the Trier Social Stress Test (TSST), and blood was collected for ACTH assay. These same subjects also underwent a clonidine challenge study for assessment of growth hormone release as a marker of tonic noradrenergic activation. Results: Examining log transformed area under the curve response for each hormone, a significant negative relationship (simple regression) was observed between systems in normal subjects. This relationship was preserved in anxiety subjects. However, both pure depressed and comorbid depressed and anxiety subjects demonstrated disruption of this relationship. Conclusions: Under normal circumstances, noradrenergic systems can influence the magnitude of the HPA axis response to stress. However, in subjects with major depression, HPA axis activation appears autonomous of noradrenergic influence.NIMH MH57751 (all authors), MH 01931 to EAY, MO1 RR00042 (General Clinical Research Center (G-CRC) of the University of Michigan),Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/51372/1/Youngintercation.pd

Ptsd Symptoms Across Pregnancy And Early Postpartum Among Women With Lifetime Ptsd Diagnosis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/122410/1/da22465.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/122410/2/da22465_am.pd

Psychological and Environmental Correlates of HPA Axis Functioning in Parentally Bereaved Children: Preliminary Findings

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97514/1/jts21788.pd

Chronic medication does not affect hyperactive error responses in obsessive-compulsive disorder

Patients with obsessive-compulsive disorder (OCD) show an increased error-related negativity (ERN), yet previous studies have not controlled for medication use, which may be important given evidence linking performance monitoring to neurotransmitter systems targeted by treatment, such as serotonin. In an examination of 19 unmedicated OCD patients, 19 medicated OCD patients, 19 medicated patient controls without OCD, and 21 unmedicated healthy controls, we found greater ERNs in OCD patients than in controls, irrespective of medication use. Severity of generalized anxiety and depression was associated with ERN amplitude in controls but not patients. These data confirm previous findings of an exaggerated error response in OCD, further showing that it cannot be attributed to medication. The absence in patients of a relationship between ERN amplitude and anxiety/depression, as was found in controls, suggests that elevated error signals in OCD may be disorder-specific.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79361/1/j.1469-8986.2010.00988.x.pd