Reactivity to unpredictable threat as a treatment target for fear-based anxiety disorders.

BACKGROUND: Heightened reactivity to unpredictable threat (U-threat) is a core individual difference factor underlying fear-based psychopathology. Little is known, however, about whether reactivity to U-threat is a stable marker of fear-based psychopathology or if it is malleable to treatment. The aim of the current study was to address this question by examining differences in reactivity to U-threat within patients before and after 12-weeks of selective serotonin reuptake inhibitors (SSRIs) or cognitive-behavioral therapy (CBT). METHODS: Participants included patients with principal fear (n = 22) and distress/misery disorders (n = 29), and a group of healthy controls (n = 21) assessed 12-weeks apart. A well-validated threat-of-shock task was used to probe reactivity to predictable (P-) and U-threat and startle eyeblink magnitude was recorded as an index of defensive responding. RESULTS: Across both assessments, individuals with fear-based disorders displayed greater startle magnitude to U-threat relative to healthy controls and distress/misery patients (who did not differ). From pre- to post-treatment, startle magnitude during U-threat decreased only within the fear patients who received CBT. Moreover, within fear patients, the magnitude of decline in startle to U-threat correlated with the magnitude of decline in fear symptoms. For the healthy controls, startle to U-threat across the two time points was highly reliable and stable. CONCLUSIONS: Together, these results indicate that startle to U-threat characterizes fear disorder patients and is malleable to treatment with CBT but not SSRIs within fear patients. Startle to U-threat may therefore reflect an objective, psychophysiological indicator of fear disorder status and CBT treatment response.

Decoupling of the amygdala to other salience network regions in adolescent-onset recurrent major depressive disorder.

BACKGROUND: Recent meta-analyses of resting-state networks in major depressive disorder (MDD) implicate network disruptions underlying cognitive and affective features of illness. Heterogeneity of findings to date may stem from the relative lack of data parsing clinical features of MDD such as phase of illness and the burden of multiple episodes. METHOD: Resting-state functional magnetic resonance imaging data were collected from 17 active MDD and 34 remitted MDD patients, and 26 healthy controls (HCs) across two sites. Participants were medication-free and further subdivided into those with single v. multiple episodes to examine disease burden. Seed-based connectivity using the posterior cingulate cortex (PCC) seed to probe the default mode network as well as the amygdala and subgenual anterior cingulate cortex (sgACC) seeds to probe the salience network (SN) were conducted. RESULTS: Young adults with remitted MDD demonstrated hyperconnectivity of the left PCC to the left inferior frontal gyrus and of the left sgACC to the right ventromedial prefrontal cortex (PFC) and left hippocampus compared with HCs. Episode-independent effects were observed between the left PCC and the right dorsolateral PFC, as well as between the left amygdala and right insula and caudate, whereas the burden of multiple episodes was associated with hypoconnectivity of the left PCC to multiple cognitive control regions as well as hypoconnectivity of the amygdala to large portions of the SN. CONCLUSIONS: This is the first study of a homogeneous sample of unmedicated young adults with a history of adolescent-onset MDD illustrating brain-based episodic features of illness.

Neural response during attentional control and emotion processing predicts improvement after cognitive behavioral therapy in generalized social anxiety disorder.

BACKGROUND: Individuals with generalized social anxiety disorder (gSAD) exhibit attentional bias to salient stimuli, which is reduced in patients whose symptoms improve after treatment, indicating that mechanisms of bias mediate treatment success. Therefore, pre-treatment activity in regions implicated in attentional control over socio-emotional signals (e.g. anterior cingulate cortex, dorsolateral prefrontal cortex) may predict response to cognitive behavioral therapy (CBT), evidence-based psychotherapy for gSAD. METHOD: During functional magnetic resonance imaging, 21 participants with gSAD viewed images comprising a trio of geometric shapes (circles, rectangles or triangles) alongside a trio of faces (angry, fearful or happy) within the same field of view. Attentional control was evaluated with the instruction to 'match shapes', directing attention away from faces, which was contrasted with 'match faces', whereby attention was directed to emotional faces. RESULTS: Whole-brain voxel-wise analyses showed that symptom improvement was predicted by enhanced pre-treatment activity in the presence of emotional face distractors in the dorsal anterior cingulate cortex and dorsal medial prefrontal cortex. Additionally, CBT success was foretold by less activity in the amygdala and/or increased activity in the medial orbitofrontal gyrus during emotion processing. CONCLUSIONS: CBT response was predicted by pre-treatment activity in prefrontal regions and the amygdala. The direction of activity suggests that individuals with intact attentional control in the presence of emotional distractors, regulatory capacity over emotional faces and/or less reactivity to such faces are more likely to benefit from CBT. Findings indicate that baseline neural activity in the context of attentional control and emotion processing may serve as a step towards delineating mechanisms by which CBT exerts its effects.

Attentional bias to threat in social phobia: facilitated processing of threat or difficulty disengaging attention from threat?

There is a growing body of research pointing to the possibility that anxious individuals may have difficulty disengaging their attention from threat-relevant information when this information is task irrelevant (e.g., Amir, N., & Elias, J. (2002). Allocation of attention to threat in social phobia: difficulty in disengaging from task irrelevant cues, Manuscript under review; The Quarterly J. Expo. Psycho. 54A (2001) 665). In the current paper, we report a direct test of this hypothesis in individuals with social phobia. Participants performed a variation of the Posner paradigm (Quart. J. Exp. Psycho. 32 (1980) 3). Social threat, neutral, or positive words cued one of two locations on the computer screen. After the cue disappeared, participants had to detect a probe ("(*)") that appeared in one of the two locations. On some trials the cue was valid (i.e., the probe appeared in the same location as the cue). On other trials the cue was invalid (the probe appeared in a different location than the cue). Yet, on other trials, no cue was presented. All participants were slower in detecting probes following invalid cues than probes following valid cues. Furthermore, individuals with social phobia showed significantly longer response latencies when detecting invalidly cued targets than did controls, but only when the probe followed a social threat word. These results suggest that individuals with social phobia may have difficulty disengaging their attention from socially threatening material.

Age-related decline in central serotonin transporter availability with [(123)I]beta-CIT SPECT.

Postmortem studies have provided limited and conflicting data regarding aging effects on the central serotonin transporter (SERT). The present study investigated the effect of age on SERT availability in the human brainstem and diencephalon with single photon emission computed tomography (SPECT) using the ligand [(123)I]2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane ([(123)I]beta-CIT). Healthy control subjects (n = 126) who ranged in age from 18 to 88 were injected with 6.0 +/- 0.8 (mean +/- SD) mCi [(123)I]beta-CIT and imaged 23.1 +/- 1.9 h later under equilibrium conditions. A ratio of specific to nondisplaceable brain uptake (i.e. , V(3)" = [brainstem-diencephalon -occipital]/occipital), a measure proportional to the binding potential (B(max)/K(D)), was derived. SERT availability (V(3)") showed a significant inverse correlation with age (r = -0.40, P < 0.0001). Linear regression analysis revealed that V(3)" declined by 29.5% over the age range 18 to 88, or approximately 4.2% per decade. These results demonstrate reductions in the availability of central SERT binding sites with age in living human subjects.

[Intestinal triplication--a case report of embryogenesis of tubular and cystic small intestine duplication]. / Die Darmtriplikation--ein kasuistischer Beitrag zur Embryogenese tubulärer und zystischer Dünndarmduplikaturen.

Case report of a triplication of the ileum that has not been described so far in this form, with tubular as well as additional cystic duplication within the first malformation, in a boy of 3 years of age. Due to recurrent massive bleeding per anum and the impossibility of separation, resection of the entire involved intestine was performed. The cause of bleeding was found to be a 10 to 8 mm ulcer within the dystopic gastric mucosa that extended into the submucosa. The theories of pathogenesis are discussed, implying that there is no uniform genesis of this disorder. The clinical pattern, diagnosis and therapy are that of the duplication.

[Eventration of diaphragm on both sides (author's transl)]. / Der seltene Fall einer doppelseitigen Relaxation des Zwerchfells.

There is reported about a patient, who was treated for a complete eventration of diaphragm on the right side and a partial on the left. Diagnostical advancements and operative procedure are discussed.

[Clavicular pseudarthroses in childhood]. / Schlüsselbeinpseudarthrosen im Kindesalter.

Pseudarthrosis of the clavicula in childhood is rare. Beside the congenital forms, especially dysplasia of the skeleton, the cause of acquired pseudarthrosis is often the complete or partial lack of immobilization and poorly performed or not indicated osteosynthesis. Basically firm osteosynthesis with small DC-plates is the therapy indicated, but because of atrophic or short fragments, great defects, or if the relevant parts of the skeleton are too short, a compromise is often necessary, especially for the sake of strength. The autologeous spongiosaplastic, corticospongio bone parts, which strengthen the osteosynthesis procedure, if involved, are basic to undisturbed healing.