The only evidence-based behavioral treatment for anxiety and stress-related disorders involves desensitization techniques that rely on principles of extinction learning. However, 40% of patients do not respond to this treatment. Efforts have focused on individual differences in treatment response, but have not examined when, during development, such treatments may be most effective. We examined fear-extinction learning across development in mice and humans. Parallel behavioral studies revealed attenuated extinction learning during adolescence. Probing neural circuitry in mice revealed altered synaptic plasticity of prefrontal cortical regions implicated in suppression of fear responses across development. The results suggest a lack of synaptic plasticity in the prefrontal regions, during adolescence, is associated with blunted regulation of fear extinction. These findings provide insight into optimizing treatment outcomes for when, during development, exposure therapies may be most effective. F ear learning is a highly adaptive, evolutionarily conserved process that allows one to respond appropriately to cues associated with danger. In the case of psychiatric disorders, however, fear may persist long after an environmental threat has passed. This unremitting and often debilitating form of fear is a core component of many anxiety disorders, including posttraumatic stress disorder (PTSD), and involves exaggerated and inappropriate fear responses. Existing treatments, such as exposure therapy, are based on principles of fear extinction, during which cues previously associated with threat are presented in the absence of the initial aversive event until cues are considered safe and fear responses are reduced. Extinction-based exposure therapies have the strongest empirical evidence for benefitting adult patients suffering from PTSD (1), yet a comparative lack of knowledge about the development of fear neural circuitry prohibits similarly successful treatment outcomes in children and adolescents (2). Adolescence, in particular, is a developmental stage when the incidence of anxiety disorders peaks in humans (3-6), and it is estimated that over 75% of adults with fear-related disorders met diagnostic criteria as children and adolescents (7, 8). Because of insufficient or inaccurate diagnoses and a dearth of pediatric and adolescent specialized treatments, fewer than one in five children or adolescents are expected to receive treatment for their anxiety disorders (9), leaving a vast number with inadequate or no treatment (2, 10). The increased frequency of anxiety disorders in pediatric and adolescent populations highlights the importance of understanding neural mechanisms of fear regulation from a developmental perspective, as existing therapies directly rely upon principles of fear-extinction learning. Converging evidence from human and rodent studies suggests that insufficient top-down regulation of subcortical structures (11-14), such as the amygdala, may coincide with diminished prototypical extinction learning (15...

Skin sparing mastectomy (SSM) removes the breast, nipple-areolar complex, previous biopsy incisions, and skin overlying superficial tumors. Preservation of the native skin envelope facilitates immediate breast reconstruction. The procedure has been adopted for the treatment of breast cancer. All cases of SSM and immediate breast reconstruction performed by the senior author (G.W.C.) from January 1, 1993, through December 12, 1997, were reviewed. Patient demographics, cancer staging, treatment, types of surgery performed, and postoperative outcomes were examined. Aesthetic outcomes were measured using four 3-point subscales. A total of 100 patients underwent 118 SSMs during the study period. The American Joint Committee on Cancer staging was as follows: stage 0, 27 patients; stage I, 25 patients; stage II, 39 patients; stage III, 7 patients; stage IV, 3 patients; recurrent, 2 patients; and cystosarcoma phylloides, 1 patient. The mean follow-up was 42.7 months. Local recurrence occurred in 2 patients (2.7%). Reconstructive methods included the transverse rectus abdominis musculocutaneous flap (N = 82; pedicled, 73; free, 9), the latissimus flap (N = 18), and tissue expansion (N = 20). Two patients underwent contralateral delayed reconstruction. The aesthetic results achievable with the three methods were similar. The failure rate was higher for expander reconstruction (10%) than those observed for transverse rectus abdominis musculocutaneous (4.9%) and latissimus (5.6%) flaps. SSM can be used in the treatment of invasive breast cancer without compromising local control. The aesthetic results of the three methods were similar, but tissue expander reconstruction had a higher failure rate.

Breast conservation has been associated with poor cosmetic outcome when used to treat breast cancer in patients who have undergone prior augmentation mammaplasty. Radiation therapy of the augmented breast can increase breast fibrosis and capsular contraction. Skin-sparing mastectomy and immediate reconstruction are examined as an alternative treatment.Six patients with prior breast augmentation were treated for breast cancer by skin-sparing mastectomy and immediate reconstruction. One patient underwent a contralateral prophylactic skin-sparing mastectomy. Silicone gel implants had been placed in the submuscular location in five patients and in the subglandular position in one patient a mean of 10.2 years (range, 6 to 20 years) before breast cancer diagnosis. The mean patient age was 41.3 years (range, 33 to 56 years). Four independent judges reviewed postoperative photographs to grade the aesthetic results in comparison with the opposite native or reconstructed breast. The American Joint Committee on Cancer staging was stage 0 in one patient, stage I for four patients, and stage II for one patient. Five of the six patients presented with a palpable breast mass. Latissimus dorsi flap reconstruction was performed in four patients (bilaterally in one) and a transverse rectus abdominis muscle (TRAM) flap was used in two patients. Three patients were treated by skin-sparing mastectomy with preservation of the breast implant (two patients with latissimus flaps, and one patient with a TRAM flap). The tumor location necessitated the removal of implants in two patients (one patient with a latissimus flap and one with a TRAM. A saline implant was placed under the latissimus flap after gel implant removal. The patient who underwent bilateral skin-sparing mastectomies desired explantation and placement of saline implants. No remedial surgery was performed on the opposite breast to achieve symmetry. Complications occurred in two patients at the latissimus dorsi donor site (seroma in one patient, and seroma and infection in one). Five patients underwent complete nipple reconstructions. The mean duration of follow-up was 33.6 months (range, 15.5 to 70.3 months), and there were no recurrences of breast cancer. The aesthetic results were judged to be good to excellent in all cases.Skin-sparing mastectomy and immediate reconstruction can be used in patients with prior breast augmentation, with good to excellent cosmetic results. Depending on the tumor and implant location, the implant may be preserved without compromising local control.