Examining the Psychosis Continuum

The notion that psychosis may exist on a continuum with normal experience has been proposed in multiple forms throughout the history of psychiatry. However, in recent years there has been an exponential increase in efforts aimed at elucidating what has been termed the \u27psychosis continuum\u27. The present review seeks to summarize some of the more basic characteristics of this continuum and to present some of the recent findings that provide support for its validity. While there is still considerable work to be done, the emerging data holds considerable promise for advancing our understanding of both risk and resilience to psychiatric disorders characterized by psychosis

The Practical Approach: How the Roberts Court Has Enhanced Class Action Procedure by Strategically Carving at the Edges

This Article explores the practical impacts of the Court’s class-action jurisprudence from 30,000 feet, observing that, with some notable exceptions, the Court has nibbled away at the rough edges of class-action procedure while passing on chances to dictate more drastic reform. Part II is a chronological summary of notable Roberts Court cases that have come to define its approach toward class litigation. Perhaps surprisingly, the Court eased its way to this point, neglecting to grant certiorari in any significant class-action cases for the first four years after the swearing in of Chief Justice Roberts in 2005. That changed in 2009 when the Court began to grant certiorari over a group of cases that are widely perceived as changing the landscape of class litigation. In Part III, the Article examines the practical impacts of the Court’s class-action decisions and its certiorari denials, concluding that the Court seems to be focused on fine-tuning class-action procedure rather than ending it. The Court’s restrained attitude is reflected by a hesitancy to make broad pronouncements in the class action cases it decides and in its selectivity in choosing cases to begin with. Also in Part III, the Article explores how the Court’s reluctance to issue broad landscape-changing rulings has left breathing room for lower courts to fill in the doctrinal gaps. The Court has undeniably dictated a large amount of change in a few specific areas, especially in the arena of arbitration and class waivers. But the impact of change has been just as overstated regarding topics such as standard of review, federalism, merits consideration, employment, and overbroad classes—all areas that remain friendly enough to class actions that the procedure continues to thrive. Indeed, activity among the lower courts on class-action jurisprudence has often enabled the Court to approve of standards already in place, rather than write new class-action rules. In Part IV, the Article examines the areas of class-action opportunities that the Court either has not addressed yet or simply has overlooked. In some cases, the Court’s lack of action has enabled classaction practice to thrive, whereas in other areas, the Court’s guidance may be needed to provide clearer guidelines, much in the way the Court has done with respect to class waivers in arbitration agreements. The Article concludes by pointing out that this is not a Court that seems intent on ending class litigation or even significantly culling it. Instead, the Court appears quite comfortable pulling, tugging, and shaping the edges of class-action practice. Remarkably, though aggregate litigation looks different in many ways now than it did before the Roberts Court era, much of that change has come from the lower courts. The Supreme Court’s influence is reflected mainly in its endorsement of lower court

Alterations in white matter microstructure in neurofibromatosis-1.

Neurofibromatosis (NF1) represents the most common single gene cause of learning disabilities. NF1 patients have impairments in frontal lobe based cognitive functions such as attention, working memory, and inhibition. Due to its well-characterized genetic etiology, investigations of NF1 may shed light on neural mechanisms underlying such difficulties in the general population or other patient groups. Prior neuroimaging findings indicate global brain volume increases, consistent with neural over-proliferation. However, little is known about alterations in white matter microstructure in NF1. We performed diffusion tensor imaging (DTI) analyses using tract-based spatial statistics (TBSS) in 14 young adult NF1 patients and 12 healthy controls. We also examined brain volumetric measures in the same subjects. Consistent with prior studies, we found significantly increased overall gray and white matter volume in NF1 patients. Relative to healthy controls, NF1 patients showed widespread reductions in white matter integrity across the entire brain as reflected by decreased fractional anisotropy (FA) and significantly increased absolute diffusion (ADC). When radial and axial diffusion were examined we found pronounced differences in radial diffusion in NF1 patients, indicative of either decreased myelination or increased space between axons. Secondary analyses revealed that FA and radial diffusion effects were of greatest magnitude in the frontal lobe. Such alterations of white matter tracts connecting frontal regions could contribute to the observed cognitive deficits. Furthermore, although the cellular basis of these white matter microstructural alterations remains to be determined, our findings of disproportionately increased radial diffusion against a background of increased white matter volume suggest the novel hypothesis that one potential alteration contributing to increased cortical white matter in NF1 may be looser packing of axons, with or without myelination changes. Further, this indicates that axial and radial diffusivity can uniquely contribute as markers of NF1-associated brain pathology in conjunction with the typically investigated measures

Disrupted working memory circuitry and psychotic symptoms in 22q11.2 deletion syndrome.

22q11.2 deletion syndrome (22q11DS) is a recurrent genetic mutation that is highly penetrant for psychosis. Behavioral research suggests that 22q11DS patients exhibit a characteristic neurocognitive phenotype that includes differential impairment in spatial working memory (WM). Notably, spatial WM has also been proposed as an endophenotype for idiopathic psychotic disorder, yet little is known about the neurobiological substrates of WM in 22q11DS. In order to investigate the neural systems engaged during spatial WM in 22q11DS patients, we collected functional magnetic resonance imaging (fMRI) data while 41 participants (16 22q11DS patients, 25 demographically matched controls) performed a spatial capacity WM task that included manipulations of delay length and load level. Relative to controls, 22q11DS patients showed reduced neural activation during task performance in the intraparietal sulcus (IPS) and superior frontal sulcus (SFS). In addition, the typical increases in neural activity within spatial WM-relevant regions with greater memory load were not observed in 22q11DS. We further investigated whether neural dysfunction during WM was associated with behavioral WM performance, assessed via the University of Maryland letter-number sequencing (LNS) task, and positive psychotic symptoms, assessed via the Structured Interview for Prodromal Syndromes (SIPS), in 22q11DS patients. WM load activity within IPS and SFS was positively correlated with LNS task performance; moreover, WM load activity within IPS was inversely correlated with the severity of unusual thought content and delusional ideas, indicating that decreased recruitment of working memory-associated neural circuitry is associated with more severe positive symptoms. These results suggest that 22q11DS patients show reduced neural recruitment of brain regions critical for spatial WM function, which may be related to characteristic behavioral manifestations of the disorder

Altered white matter microstructure is associated with social cognition and psychotic symptoms in 22q11.2 microdeletion syndrome.

22q11.2 Microdeletion Syndrome (22q11DS) is a highly penetrant genetic mutation associated with a significantly increased risk for psychosis. Aberrant neurodevelopment may lead to inappropriate neural circuit formation and cerebral dysconnectivity in 22q11DS, which may contribute to symptom development. Here we examined: (1) differences between 22q11DS participants and typically developing controls in diffusion tensor imaging (DTI) measures within white matter tracts; (2) whether there is an altered age-related trajectory of white matter pathways in 22q11DS; and (3) relationships between DTI measures, social cognition task performance, and positive symptoms of psychosis in 22q11DS and typically developing controls. Sixty-four direction diffusion weighted imaging data were acquired on 65 participants (36 22q11DS, 29 controls). We examined differences between 22q11DS vs. controls in measures of fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD), using both a voxel-based and region of interest approach. Social cognition domains assessed were: Theory of Mind and emotion recognition. Positive symptoms were assessed using the Structured Interview for Prodromal Syndromes. Compared to typically developing controls, 22q11DS participants showed significantly lower AD and RD in multiple white matter tracts, with effects of greatest magnitude for AD in the superior longitudinal fasciculus. Additionally, 22q11DS participants failed to show typical age-associated changes in FA and RD in the left inferior longitudinal fasciculus. Higher AD in the left inferior fronto-occipital fasciculus (IFO) and left uncinate fasciculus was associated with better social cognition in 22q11DS and controls. In contrast, greater severity of positive symptoms was associated with lower AD in bilateral regions of the IFO in 22q11DS. White matter microstructure in tracts relevant to social cognition is disrupted in 22q11DS, and may contribute to psychosis risk

Subcortical modulation in auditory processing and auditory hallucinations

Hearing perception in individuals with auditory hallucinations has not been well studied. Auditory hallucinations have previously been shown to involve primary auditory cortex activation. This activation suggests that auditory hallucinations activate the terminal of the auditory pathway as if auditory signals are submitted from the cochlea, and that a hallucinatory event is therefore perceived as hearing. The primary auditory cortex is stimulated by some unknown source that is outside of the auditory pathway. The current study aimed to assess the outcomes of stimulating the primary auditory cortex through the auditory pathway in individuals who have experienced auditory hallucinations. Sixteen patients with schizophrenia underwent functional magnetic resonance imaging (fMRI) sessions, as well as hallucination assessments. During the fMRI session, auditory stimuli were presented in one-second intervals at times when scanner noise was absent. Participants listened to auditory stimuli of sine waves (SW) (4-5.5kHz), English words (EW), and acoustically reversed English words (arEW) in a block design fashion. The arEW were employed to deliver the sound of a human voice with minimal linguistic components. Patients\u27 auditory hallucination severity was assessed by the auditory hallucination item of the Brief Psychiatric Rating Scale (BPRS). During perception of arEW when compared with perception of SW, bilateral activation of the globus pallidus correlated with severity of auditory hallucinations. EW when compared with arEW did not correlate with auditory hallucination severity. Our findings suggest that the sensitivity of the globus pallidus to the human voice is associated with the severity of auditory hallucination