Biomarkers for Cognitive Control, Response Inhibition, Aggressivity, Impulsivity, and Violence.

Deficits in cognitive control contribute to behavioral impairments across neuropsychiatric disorders. Cognitive control is captured as a construct in the Research Domain Construct (RDoC) matrix and incorporate subdomains of goal selection, response selection, and performance monitoring. Relevant tasks for these subdomains include the "AX" version of the continuous performance task (goal selection) and the Go/NoGo and Stop-Signal reaction time tasks (response selection).

The relationship between COMT, proline, and negative symptoms in clinical high risk and recent psychosis onset.

Individuals at clinical high-risk (CHR) of developing psychosis, as well as patients with recent psychosis onset (RO), experience significant negative symptoms that detrimentally impact daily-life functioning and are associated with poor outcomes, even in those who do not convert to psychosis. Targeting negative symptoms may thus hold promise for the treatment of CHR and RO patients. Building from previous findings we examined whether the catechol-O-methyltransferase (COMT) ValMet functional polymorphism and fasting peripheral proline concentration predicts the severity of negative symptoms experienced by adolescents and young adults at CHR or those with RO.

An analysis of 105 female-perpetrated mass murders.

Most research on mass murderers to date has focused on perpetrators of male sex, while research on perpetrators of female sex has been relegated to case reports and series. We aimed to more fully examine the phenomenon of female-perpetrated mass murder. We analyzed 1715 worldwide incidents of personal-cause mass murder from 1900 to 2019, identifying 105 (6%) events perpetrated by females.

Generalizability and Out-of-Sample Predictive Ability of Associations Between Neuromelanin-Sensitive Magnetic Resonance Imaging and Psychosis in Antipsychotic-Free Individuals.

Importance: The link between psychosis and dopaminergic dysfunction is established, but no generalizable biomarkers with clear potential for clinical adoption exist.

Objective: To replicate previous findings relating neuromelanin-sensitive magnetic resonance imaging (NM-MRI), a proxy measure of dopamine function, to psychosis severity in antipsychotic-free individuals in the psychosis spectrum and to evaluate the out-of-sample predictive ability of NM-MRI for psychosis severity.

Design, Setting, And Participants: This cross-sectional study recruited participants from 2019 to 2023 in the New York City area (main samples) and Mexico City area (external validation sample).

Medial Prefrontal Cortex Dysfunction Mediates Working Memory Deficits in Patients With Schizophrenia.

Background: Schizophrenia (SCZ) is marked by working memory (WM) deficits, which predict poor functional outcome. While most functional magnetic resonance imaging studies of WM in SCZ have focused on the dorsolateral prefrontal cortex (PFC), some recent work suggests that the medial PFC (mPFC) may play a role. We investigated whether task-evoked mPFC deactivation is associated with WM performance and whether it mediates deficits in SCZ.

An Analysis of Motivating Factors in 1,725 Worldwide Cases of Mass Murder Between 1900-2019.

Mass murder, particularly mass shootings, constitutes a major, growing public health concern. Specific motivations for these acts are not well understood, often overattributed to severe mental illness. Identifying diverse factors motivating mass murders may facilitate prevention.

Increased parietal and occipital lobe gyrification predicts conversion to syndromal psychosis in a clinical high-risk cohort.

Background: Local gyrification index (lGI), indicative of the degree of cortical folding is a proxy marker for early cortical neurodevelopmental abnormalities. We studied the difference in lGI between those who do and do not convert to psychosis (non-converters) in a clinical high-risk (CHR) cohort, and whether lGI predicts conversion to psychosis.

Methods: Seventy-two CHR participants with attenuated positive symptom syndrome were followed up for two years.

The association between mental health stigma and face emotion recognition in individuals at risk for psychosis.

Self-stigma has been associated with reduced accuracy of face emotion recognition in individuals at clinical high risk for psychosis (CHR). Stigma may also relate to slowing of performance during cognitive tasks for which a negative stereotype is relevant. This study aimed to investigate the association of mental illness stigma with face emotion recognition among CHR individuals.

Dose-Dependent Augmentation of Neuroplasticity-Based Auditory Learning in Schizophrenia: A Double-Blind, Placebo-Controlled, Randomized, Target Engagement Clinical Trial of the NMDA Glutamate Receptor Agonist d-serine.

Background: Patients with schizophrenia show reduced NMDA glutamate receptor-dependent auditory plasticity, which is rate limiting for auditory cognitive remediation (AudRem). We evaluate the utility of behavioral and neurophysiological pharmacodynamic target engagement biomarkers, using a d-serine+AudRem combination.

Methods: Forty-five participants with schizophrenia or schizoaffective disorder were randomized to 3 once-weekly AudRem visits + double-blind d-serine (80, 100, or 120 mg/kg) or placebo in 3 dose cohorts of 12 d-serine and 3 placebo-treated participants each.

Victimology of Mass Shootings and Mass Murders Not Involving Firearms.

Most research to date has focused on perpetrators of mass murder incidents. Hence, there is little information on victims. We examined 973 mass murders that occurred in the United States between 1900 and 2019 resulting in 5,273 total fatalities and 4,498 nonfatal injuries for a total of 9,771 victims (on average 10 victims per incident).

Mass murders involving firearms and other methods in school, college, and university settings: Findings from the Columbia Mass Murder Database.

While mass murders involving academic settings, especially using firearms, are of grave, growing public concern, identifying consistent patterns to aid prevention has proved challenging. Although some characteristics, such as male sex, have been routinely associated with these events, another hypothesized risk factor, severe mental illness, has been less reliably predictive. We isolated cases of mass murder perpetrated at least in part at schools, colleges, and universities from the Columbia Mass Murder Database (CMDD) and categorized them by location (within or outside of the US), and whether firearms were used.

The neurobiology of duration of untreated psychosis: a comprehensive review.

Duration of untreated psychosis (DUP) is defined as the time from the onset of psychotic symptoms until the first treatment. Studies have shown that longer DUP is associated with poorer response rates to antipsychotic medications and impaired cognition, yet the neurobiologic correlates of DUP are poorly understood. Moreover, it has been hypothesized that untreated psychosis may be neurotoxic.

Illness Phase as a Key Assessment and Intervention Window for Psychosis.

The phenotype of schizophrenia, regardless of etiology, represents the most studied psychotic disorder with respect to neurobiology and distinct phases of illness. The early phase of illness represents a unique opportunity to provide effective and individualized interventions that can alter illness trajectories. Developmental age and illness stage, including temporal variation in neurobiology, can be targeted to develop phase-specific clinical assessment, biomarkers, and interventions.

Smoked Cannabis Effects in Cannabis Users at Clinical High-Risk for Psychosis: A Further Investigation of Cognition and Reward.

Objective: Some adverse cannabis effects are greater in individuals on the psychosis spectrum compared to healthy individuals. We have previously reported that smoked cannabis acutely worsened psychotic- like states and reduced cognitive performance selectively in cannabis users at clinical high-risk (CHR) for psychosis. The objective of the present study was to further investigate the acute effects of cannabis on cognition and reward processing in CHR cannabis users.

Hippocampal Glutamate and Positive Symptom Severity in Clinical High Risk for Psychosis.

This study examines the association between increased hippocampal glutamate and higher total positive symptom severity in converters to psychosis.

Dopamine D1R Receptor Stimulation as a Mechanistic Pro-cognitive Target for Schizophrenia.

Decades of research have highlighted the importance of optimal stimulation of cortical dopaminergic receptors, particularly the D1R receptor (D1R), for prefrontal-mediated cognition. This mechanism is particularly relevant to the cognitive deficits in schizophrenia, given the abnormalities in cortical dopamine (DA) neurotransmission and in the expression of D1R. Despite the critical need for D1R-based therapeutics, many factors have complicated their development and prevented this important therapeutic target from being adequately interrogated.

The neurobiology of auditory and visual perceptual abnormalities in a clinical high-risk for psychosis cohort: A pilot morphometric magnetic resonance imaging study.

Our goal was to examine the neurobiology of auditory and visual perceptual abnormalities in individuals at clinical high-risk for psychosis (CHR) using morphometric magnetic resonance imaging (MRI). We enrolled 72 CHR subjects as delineated by the Structured Interview for Psychosis-Risk Syndromes (SIPS). Greater severity of visual perceptual abnormalities was associated with larger volumes in all regions tested (amygdala, hippocampus, and occipital cortex), while no relationships were observed between auditory perceptual abnormalities and brain volumes.

Experimentally exploring the potential behavioral effects of personalized genetic information about marijuana and schizophrenia risk.

Marijuana use may increase schizophrenia risk, and this effect may be genetically moderated. We investigated how hypothetical genetic test results indicating the presence or absence of heightened schizophrenia risk in reaction to marijuana use would affect attitudes toward marijuana use. In two experiments, participants were randomized to hypothetical scenarios in which genetic testing showed the presence or absence of a predisposition for marijuana use to increase their schizophrenia risk, or to a control condition with no mention of genetic testing.

Deficits in Pre-attentive Processing of Spatial Location and Negative Symptoms in Subjects at Clinical High Risk for Schizophrenia.

Deficits in mismatch negativity (MMN) generation are among the best-established biomarkers for cognitive dysfunction in schizophrenia and predict conversion to schizophrenia (Sz) among individuals at symptomatic clinical high risk (CHR). Impairments in MMN index dysfunction at both subcortical and cortical components of the early auditory system. To date, the large majority of studies have been conducted using deviants that differ from preceding standards in either tonal frequency (pitch) or duration.

Psychotic symptoms in mass shootings . mass murders not involving firearms: findings from the Columbia mass murder database.

Background: Mass shootings account for a small fraction of annual worldwide murders, yet disproportionately affect society and influence policy. Evidence suggesting a link between mass shootings and severe mental illness (i.e.

Stigma and coping experiences in Latinx individuals at clinical high-risk for psychosis.

Aim: The experiences of culturally diverse individuals at clinical high-risk for psychosis (CHR) is not well studied. Exploratory research needs to examine whether differences exist between racial/ethnic groups within the CHR population. Understanding experiences of Latinx patients is of importance, as the Latinx population represents the most rapidly growing paediatric population in the United States and they face significant barriers to mental health treatment.