Diminished differentiation of rewards in individuals at clinical high-risk for psychosis.

Reward processing is impaired in people with schizophrenia, which may begin in the clinical high-risk (CHR) for psychosis period. The Monetary Incentive Delay (MID) task has been important in understanding the neural correlates of reward processing deficits in various psychiatric disorders. Previous research has found that CHR individuals have an imprecise mental representation of rewards, which leads to a diminished differentiation between rewards, though this has not been observed behaviorally. A total of 19 CHR individuals and 20 controls were given a novel variant of the MID task, designed to examine how modulating reward context may impact responses to reward cues, a process often referred to as "adaptive coding." Both groups appeared to update their behavior in response to the rewards available in this adaptive task. However, when compared to controls who showed a more graded decrease in response time to increasing reward contexts, CHR individuals appeared to have a sharp decrease in response time in the low reward context that is nearly stable across higher reward contexts. This is largely driven by the exponential component of the response time distribution, which is often interpreted to be more cognitively or effortfully influenced. Response times are related to negative symptoms, but not positive symptoms, disorganized symptoms, or estimated intelligence. Although an adaptive coding effect was not observed, these results provide novel insight into the reward processing mechanisms and volitional processes in the CHR population, as this was the first study to observe the diminished differentiation of rewards behaviorally.

Testing whether implicit emotion regulation mediates the association between discrimination and symptoms of psychopathology in late childhood: An RDoC perspective.

Discrimination has been associated with adverse mental health outcomes, though it is unclear how early in life this association becomes apparent. Implicit emotion regulation, developing during childhood, is a foundational skill tied to a range of outcomes. Implicit emotion regulation has yet to be tested as an associated process for mental illness symptoms that can often emerge during this sensitive developmental period. Youth aged 9-11 were recruited for the Adolescent Brain Cognitive Development (ABCD) study. Associations between psychotic-like experiences, depressive symptoms, and total discrimination (due to race, ethnicity, nationality, weight, or sexual minority status) were tested, as well as associations with implicit emotion regulation measures (emotional updating working memory and inhibitory control). Analyses examined whether associations with symptoms were mediated by implicit emotion regulation. Discrimination related to decreased implicit emotion regulation performance, and increased endorsement of depressive symptoms and psychotic-like experiences. Emotional updating working memory performance partially mediated the association between discrimination and psychotic-like experiences, while emotional inhibitory control did not. Discrimination and implicit emotion regulation could serve as putative transdiagnostic markers of vulnerability. Results support the utility of using multiple units of analysis to improve understanding of complex emerging neurocognitive functions and developmentally sensitive periods.

The utility of an RDoC motor domain to understand psychomotor symptoms in depression.

Despite the clinical impact of motor symptoms such as agitation or retardation on the course of depression, these symptoms are poorly understood. Novel developments in the field of instrumentation and mobile devices allow for dimensional and continuous recording of motor behavior in various settings, particularly outside the laboratory. Likewise, the use of novel assessments enables to combine multimodal neuroimaging with behavioral measures in order to investigate the neural correlates of motor dysfunction in depression. The research domain criteria (RDoC) framework will soon include a motor domain that will provide a framework for studying motor dysfunction in mood disorders. In addition, new studies within this framework will allow investigators to study motor symptoms across different stages of depression as well as other psychiatric diagnoses. Finally, the introduction of the RDoC motor domain will help test how motor symptoms integrate with the original five RDoC domains (negative valence, positive valence, cognitive, social processes, and arousal/regulation).

Reactivity to uncertain threat as a familial vulnerability factor for alcohol use disorder.

BACKGROUND: When sober, problematic drinkers display exaggerated reactivity to threats that are uncertain (U-threat). Since this aversive affective state can be alleviated via acute alcohol intoxication, it has been posited that individuals who exhibit heightened reactivity to U-threat at baseline are motivated to use alcohol as a means of avoidance-based coping, setting the stage for excessive drinking. To date, however, no study has attempted to characterize the dispositional nature of exaggerated reactivity to U-threat and test whether it is a vulnerability factor or exclusively a disease marker of problematic alcohol use. METHOD: The current investigation utilized a family study design to address these gaps by examining whether (1) reactivity to U-threat is associated with risk for problematic alcohol use, defined by family history of alcohol use disorder (AUD) and (2) reactivity to U-threat is correlated amongst adult biological siblings. A total of 157 families, and 458 individuals, participated in the study and two biological siblings completed a threat-of-shock task designed to probe reactivity to U-threat and predictable threat (P-threat). Startle potentiation was collected as an index of aversive responding. RESULTS: Within biological siblings, startle potentiation to U-threat [intraclass correlation (ICC) = 0.35] and P-threat (ICC = 0.63) was significantly correlated. In addition, independent of an individuals' own AUD status, startle potentiation to U-threat, but not P-threat, was positively associated with risk for AUD (i.e. AUD family history). CONCLUSION: This suggests that heightened reactivity to U-threat may be a familial vulnerability factor for problematic drinking and a novel prevention target for AUD.

Orbitofrontal cortex volume and brain reward response in obesity.

BACKGROUND/OBJECTIVES: What drives overconsumption of food is poorly understood. Alterations in brain structure and function could contribute to increased food seeking. Recently, brain orbitofrontal cortex (OFC) volume has been implicated in dysregulated eating but little is known how brain structure relates to function. SUBJECTS/METHODS: We examined obese (n=18, age=28.7±8.3 years) and healthy control women (n=24, age=27.4±6.3 years) using a multimodal brain imaging approach. We applied magnetic resonance and diffusion tensor imaging to study brain gray and white matter volume as well as white matter (WM) integrity, and tested whether orbitofrontal cortex volume predicts brain reward circuitry activation in a taste reinforcement-learning paradigm that has been associated with dopamine function. RESULTS: Obese individuals displayed lower gray and associated white matter volumes (P<0.05 family-wise error (FWE)- small volume corrected) compared with controls in the orbitofrontal cortex, striatum and insula. White matter integrity was reduced in obese individuals in fiber tracts including the external capsule, corona radiata, sagittal stratum, and the uncinate, inferior fronto-occipital, and inferior longitudinal fasciculi. Gray matter volume of the gyrus rectus at the medial edge of the orbitofrontal cortex predicted functional taste reward-learning response in frontal cortex, insula, basal ganglia, amygdala, hypothalamus and anterior cingulate cortex in control but not obese individuals. CONCLUSIONS: This study indicates a strong association between medial orbitofrontal cortex volume and taste reinforcement-learning activation in the brain in control but not in obese women. Lower brain volumes in the orbitofrontal cortex and other brain regions associated with taste reward function as well as lower integrity of connecting pathways in obesity (OB) may support a more widespread disruption of reward pathways. The medial orbitofrontal cortex is an important structure in the termination of food intake and disturbances in this and related structures could contribute to overconsumption of food in obesity.

Updating the research domain criteria: the utility of a motor dimension.

Within the NIMH Research Domain Criteria (RDoC) framework, dimensions of behavior are investigated across diagnoses with the goal of developing a better understanding of their underlying neural substrates. Currently, this framework includes five domains: cognitive, social, arousal/regulatory, negative, and positive valence systems. We argue that the inclusion of a motor systems domain is sorely needed as well. Independent of medication, distinct areas of motor dysfunction (e.g. motor planning/inhibition/learning/coordination, involuntary movements) commonly appear across a number of mental disorders (e.g. schizophrenia, bipolar disorder, autism, attention deficit hyperactivity disorder, Alzheimer's disease, depression) as well as neurological disorders accompanied by significant psychological symptoms (e.g. Parkinson's disease). In addition, motor systems are amenable to study across multiple levels of analysis from the cellular molecular level focusing on cytoarchitechtonics and neurotransmitter systems, to networks and circuits measured using neuroimaging, and finally at the level of overt behavioral performance. Critically, the neural systems associated with motor performance have been relatively well defined, and different circuits have been linked to distinct aspects of motor behavior. As such, they may also be differentially associated with symptoms and motor dysfunction across diagnoses, and be uniquely informative about underlying etiology. Importantly, motor signs can change across stages of illness; they are also often present in the prodromal phases of disease and closely linked with course, suggesting that these behaviors represent a core feature reflective of pathogenic processes. The inclusion of a motor domain would allow researchers to better understand psychopathology more broadly, and may also reveal important contributions to disease processes across diagnoses.

Influence of calcium depletion on iron-binding properties of milk.

We investigated the effects of calcium depletion on the binding of iron in milk. A weakly acidic cation-exchange resin was used to remove 3 different levels (18-22, 50-55, and 68-72%) of calcium from milk. Five levels of iron (5, 10, 15, 20, and 25 mM) were added to each of these calcium-depleted milks (CDM) and the resultant milks were analyzed for particle size, microstructure, and the distribution of protein and minerals between the colloidal and soluble phases. The depletion of calcium affected the distribution of protein and minerals in normal milk. Iron added to normal milk and low-CDM (~20% calcium depletion) bound mainly to the colloidal phase (material sedimented at 100,000 × g for 1 h at 20 °C), with little effect on the integrity of the casein micelles. Depletion of ~70% of the calcium from milk resulted in almost complete disintegration of the casein micelles, as indicated by all the protein remaining in the soluble phase upon ultracentrifugation. Addition of up to ~20 mM iron to high CDM resulted in the formation of small fibrous structures that remained in the soluble phase of milk. It appeared that the iron bound to soluble (nonsedimentable) caseins in high-CDM. We observed a decrease in the aqueous phosphorus content of all milks upon iron addition, irrespective of their calcium content. We considered the interaction between aqueous phosphorus and added iron to be responsible for the high iron-binding capacity of the proteins in milk. The soluble protein-iron complexes formed in high-CDM (~70% calcium depletion) could be used as an effective iron fortificant for a range of food products because of their good solubility characteristics.

Dermatoglyphic asymmetries and fronto-striatal dysfunction in young adults reporting non-clinical psychosis.

OBJECTIVE: Growing evidence indicates that non-clinical psychotic-like experiences occur in otherwise healthy individuals, suggesting that psychosis may occur on a continuum. However, little is known about how the diathesis for formal psychosis maps on to individuals at the non-clinical side of this continuum. Our current understanding of the pathophysiology of schizophrenia implicates certain key factors such as early developmental abnormalities and fronto-striatal dysfunction. To date, no studies have examined these core factors in the context of non-clinical psychosis. METHOD: A total of 221 young adults were assessed for distressing attenuated positive symptoms (DAPS), dermatoglyphic asymmetries (a marker of early developmental insult), and procedural memory (a proxy for fronto-striatal function). RESULTS: Participants reporting DAPS (n = 16; 7.2%) and no-DAPS (n = 205; 92.7%) were split into two groups. The DAPS group showed significantly elevated depression, elevated dermatoglyphic asymmetries, and a pattern of procedural learning consistent with other studies with formally psychotic patients. CONCLUSION: The results indicate that the non-clinical side of the psychosis continuum also shares key vulnerability factors implicated in schizophrenia, suggesting that both early developmental disruption and abnormalities in fronto-striatal function are core aspects underlying the disorder.

The Critical Roles of Early Development, Stress, and Environment in the Course of Psychosis.

Psychotic disorders are highly debilitating with poor prognoses and courses of chronic illness. In recent decades, conceptual models have shaped understanding, informed treatment, and guided research questions. However, these models have classically focused on the adolescent and early adulthood stages immediately preceding onset while conceptualizing early infancy through all of childhood as a unitary premorbid period. In addition, models have paid limited attention to differential effects of types of stress; contextual factors such as local, regional, and country-level characteristics or sociocultural contexts; and the timing of the stressor or environmental risk. This review discusses emerging research suggesting that (a) considering effects specific to neurodevelopmental stages prior to adolescence is highly informative, (b) understanding specific stressors and levels of environmental exposures (i.e., systemic or contextual features) is necessary, and (c) exploring the dynamic interplay between development, levels and types of stressors, and environments can shed new light, informing a specified neurodevelopmental and multifaceted diathesis-stress model.

Using search engine data to gauge public interest in mental health, politics and violence in the context of mass shootings.

Despite significant potential for providing insight to private perceptions and behaviors, search engine data has yet to be utilized as a means of gauging the U.S. public's interest and understanding of mental health in the context of gun violence and politics. An analysis of Google Trends revealed that Mental health searches increased in volume starting in the beginning of the current decade. Notably, both "mental health" and "gun(s)" were searched with greater frequency the week after the mass shooting events occurred. Related searches after the event also observed a significant increase in interest in mental health and gun regulation, legal reform, mass shootings, and gun(s). Results suggest that the American public's perception of mental illness increasingly incorporates associations with themes of violence and politics, which becomes more apparent surrounding mass shooting events. Future studies are needed to determine implications for stigmatization of vulnerable groups, and possible relations to media coverage.

Iron binding to caseins in the presence of orthophosphate.

As adding >5mM ferric chloride to sodium caseinate solutions results in protein precipitation, the effects of orthophosphate (0-64 mM) addition to sodium caseinate solution (2% w/v protein) on iron-induced aggregation of the caseins were studied at pH 6.8. Up to 20mM ferric chloride could be added to sodium caseinate solution containing 32 mM orthophosphate without any protein precipitation. The addition of iron to sodium caseinate solution containing orthophosphate reduced the diffusible phosphorus content in a concentration-dependent manner. Added iron appeared to interact simultaneously with phosphoserine on the caseins and inorganic phosphorus. The relative sizes of the casein aggregates were governed by the concentration of orthophosphate and the aggregates consisted of all casein fractions, even at the lowest level of ferric chloride addition (5mM). It is hypothesised that the addition of iron to caseins in the presence of orthophosphate results in the formation of colloidal structures involving casein-iron-orthophosphate interactions.

A case for partial patellectomy.

The treatment of fractures of the the patella is a subject of controversy. Partial patellectomy with retention of a major fragment and suture of the quadriceps to it, seems reasonable. 18 cases of patella fracture underwent such a procedure. The average age of the patients was 47 years. Maximum recovery took an average of 5 months. There were 6 excellent results, 9 good, 3 fair. Results were assessed on the basis of pain, muscle wasting, quadriceps power, and range of knee motion. Total patellectomy and patella fixation as alternative modes of treatment are discussed. Partial patellectomy, whenever possible, is a good choice.