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Background: Modulation of nicotinic acetylcholine receptors (nAChRs), specifically those containing the β2 subunit, may be effective in treating patients with major depressive disorder. Using [123I]5-I-A-85380 single photon emission computed tomography (SPECT), the authors studied the availability of β2-subunit-containing nAChRs (β2*-nAChRs) in depressed patients. To understand its molecular basis, the authors also studied β2*-nAChR binding in postmortem brain samples from depressed subjects.Method: The participants were 23 medication-free, nonsmoking subjects with familial, early-onset depression (eight acutely ill and 15 recovered) and 23 age- and gender-matched nonsmoking comparison subjects. Each received one [123I]5-I-A-85380 SPECT scan and an MRI scan. The availability of β2*-nAChRs was quantified as VT/fP. Postmortem analysis of β2*-nAChR binding was conducted with [123I]5-I-A-85380 on prefrontal cortex samples from 14 depressed subjects and 14 age-matched comparison subjects.Results: The β2*-nAChR availability in both the acutely ill and recovered depressed subjects was significantly lower across all brain regions than in the respective comparison subjects, and it was lower in the acutely ill subjects than in those who were recovered. In the depressed patients, β2*-nAChR availability was significantly correlated with lifetime number of depressive episodes, trauma score, and anxiety score. There were no differences in β2*-nAChR number between groups in the postmortem study.Conclusions: Depressed patients have lower β2*-nAChR availability than do healthy subjects. The difference between β2*-nAChR availability in vivo and in post-mortem samples may be analogous to data with dopaminergic PET ligands and dopamine receptor availability; lower receptor availability for the SPECT ligand could be caused by greater endogenous acetylcholine. [ABSTRACT FROM AUTHOR]

Introduction: Attention-deficit/hyperactivity disorder (ADHD) and anxiety are frequently comorbid disorders associated with different types of abnormal performance on neuropsychological tests. Although some studies have shown that comorbid anxiety alters ADHD test performance, results inconsistently show both improvements and worsening of different abilities, with failures to replicate across different anxiety disorders. Alternatively, trait anxiety may reflect a more stable influence on ADHD test performance than various diagnosable anxiety disorders., Method: To better understand the possible enhancing or deleterious effects of anxiety on ADHD cognitive impairments, this study examined the effect of individual differences in trait anxiety measured by the Multidimensional Anxiety Scale for Children (MASC) on a battery of computerized, rapid-performance tests measuring attention and impulsivity-related performance in 98 Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) Combined-Subtype ADHD adolescents and 123 healthy controls. It was hypothesized that trait anxiety would attenuate response inhibition and attention deficits in ADHD., Results: ADHD-diagnosed adolescents with higher trait anxiety performed better on indices of sustained attention, reaction time, and motor variability, and had altered overall test-performance strategy, while response inhibition was affected in both ADHD and non-ADHD., Conclusions: This study provides the first evidence that pathological levels of anxiety are not needed to see differences in ADHD neuropsychological test performance. Instead, mildly elevated trait anxiety confers a protective influence by reducing the degree of impairment seen in ADHD. These findings suggest that better performing ADHD adolescents might have optimized levels of cortical arousal, and raise new questions about how best to identify the neurobiological substrates responsible for the beneficial effects.

The serotonergic (5-HT) system has been widely implicated in the pathophysiology of Major Depressive Disorder (MDD). Although the 5-HT system is a popular target for drug therapy in MDD the role that serotonin plays in MDD is not clearly understood. An abundance of research suggests that several 5-HT receptor subtypes may be dysfunctional in patients with MDD including the 5-HT(1B) receptor. Evidence implicating 5-HT(1B) receptors in the pathophysiology of depression comes from a number of converging lines of research. Two common genetic polymorphisms of 5-HT(1B) receptors, G861C and C129T, have been implicated in affective disorders. Rats predisposed to learned helplessness have exhibited downregulation of 5-HT(1B) receptor messenger ribonucleic acid (mRNA) in dorsal raphe nucleus (DRN). Pharmacological studies have demonstrated augmentation of extracellular 5-HT levels and antidepressant effects following administration of selective serotonin reuptake inhibitors (SSRIs) in the absence or blockade of 5-HT(1B) receptors. 5-HT(1B) receptor agonists administered alone or with antidepressants have been shown to be effective in preclinical models of depression. Recent interest has focused on p11, an s100 EF-hand protein family protein which colocalizes with 5-HT(1B) receptors. P11 plays a central role in the modulation of 5-HT(1B) receptor function and is dysregulated in preclinical models of depression and postmortem MDD samples. A review of the literature provides strong evidence that 5-HT(1B) receptors and related factors such as p11 are involved in the pathophysiology of depression. The following explores possible factors which may render the 5-HT(1B) receptor dysfunctional, resulting in susceptibility to depression. Implications of using the 5-HT(1B) receptor as a biomarker for vulnerability to MDD are discussed.

Major depressive disorder (MDD) is a mood disorder that is not traditionally considered to affect the visual system. However, recent findings have reported decreased cortical levels of the inhibitory neurotransmitter GABA in occipital cortex. To explore possible functional consequences of MDD on visual processing, we applied a psychophysical visual motion processing task in which healthy young adults typically exhibit impaired perceptual discrimination of large high-contrast stimuli. It has been suggested that this phenomenon, spatial suppression, is mediated by GABAergic center-surround antagonism in visual pathways. Based on previous findings linking MDD to occipital GABA dysfunction, we hypothesized that MDD patients would exhibit decreased spatial suppression, leading to the counterintuitive hypothesis of better psychophysical performance. Indeed, motion perception for typically suppressed stimuli was enhanced in patients with MDD compared with age-matched controls. Furthermore, the degree of spatial suppression correlated with an individual's illness load; patients with greater lifetime duration of depression exhibited the least spatial suppression and performed the best in the high-contrast motion discrimination task. Notably, this decrease in spatial suppression persisted beyond recovery and without the confound of acute illness or treatment; all patients had been clinically recovered and unmedicated for several months at the time of testing, suggesting that depression has ubiquitous consequences that may persist long after mood symptoms have receded. This finding raises the possibility that spatial suppression may represent a sensitive endophenotypic marker of trait vulnerability in MDD.