Increased amygdala-visual cortex connectivity in youth with persecutory ideation.

BACKGROUND: Subclinical delusional ideas, including persecutory beliefs, in otherwise healthy individuals are heritable symptoms associated with increased risk for psychotic illness, possibly representing an expression of one end of a continuum of psychosis severity. The identification of variation in brain function associated with these symptoms may provide insights about the neurobiology of delusions in clinical psychosis. METHODS: A resting-state functional magnetic resonance imaging scan was collected from 131 young adults with a wide range of severity of subclinical delusional beliefs, including persecutory ideas. Because of evidence for a key role of the amygdala in fear and paranoia, resting-state functional connectivity of the amygdala was measured. RESULTS: Connectivity between the amygdala and early visual cortical areas, including striate cortex (V1), was found to be significantly greater in participants with high (n = 43) v. low (n = 44) numbers of delusional beliefs, particularly in those who showed persistence of those beliefs. Similarly, across the full sample, the number of and distress associated with delusional beliefs were positively correlated with the strength of amygdala-visual cortex connectivity. Moreover, further analyses revealed that these effects were driven by those who endorsed persecutory beliefs. CONCLUSIONS: These findings are consistent with the hypothesis that aberrant assignments of threat to sensory stimuli may lead to the downstream development of delusional ideas. Taken together with prior findings of disrupted sensory-limbic coupling in psychosis, these results suggest that altered amygdala-visual cortex connectivity could represent a marker of psychosis-related pathophysiology across a continuum of symptom severity.

Lessons From Low- and Middle-Income Countries: Alleviating the Behavioral Health Workforce Shortage in the United States.

The United States is facing a mental health workforce shortage, exacerbated by the COVID-19 pandemic. Low- and middle-income countries (LMICs) have historically grappled with even greater shortages. Therefore, LMICs have thought creatively about expanding the mental health workforce and the settings in which to deliver evidence-based and equitable mental health care. The authors introduce some mental health interventions in LMICs, describe evidence of the efficacy of these interventions gleaned from this context, and discuss the applicability of these interventions to the United States. The authors also reflect on the benefits and challenges of implementing these interventions in the U.S. mental health care system to alleviate its current workforce shortage.

The European psychiatric association (EPA) - early career psychiatrists committee survey on trainees' and early-career psychiatrists' attitudes towards therapeutic drug monitoring (TDM) use and utility during antipsychotic treatment.

OBJECTIVES: This survey assessed psychiatry residents'/early-career psychiatrists' attitudes towards the utility of therapeutic drug monitoring (TDM) of antipsychotics. METHODS: A previously developed questionnaire on attitudes on TDM utility during antipsychotic treatment was cross-sectionally disseminated by national coordinators between 01/01/2022-31/12/2023. The frequency of using TDM for antipsychotics other than clozapine was the main outcome in a linear regression analysis, including sex, clinical setting, caseload, and factors generated by an exploratory factor analysis. Comparisons between residents and early-career psychiatrists, respondents working in in- and outpatient settings, and low-/middle- and high-income countries were performed. RESULTS: Altogether, 1,237 respondents completed the survey, with 37.9% having never used TDM for antipsychotics. Seven factors explained 41% of response variance; six of them were associated with frequency of TDM use (p < 0.05). Items with highest loadings for factors included clinical benefits of TDM (factors A and E: 0.7), negative expectations for beliefs of patients towards TDM (factor B: 0.6-0.7), weak TDM scientific evidence (factor C: 0.8), and TDM availability (factor D: -0.8). Respondents from low-/middle-income countries were less likely to frequently/almost always use TDM compared to high-income countries (9.4% vs. 21.5%, p < 0.001). DISCUSSION: TDM use for antipsychotics was poor and associated with limited knowledge and insufficient availability.

Elevated Amygdala Activity in Young Adults With Familial Risk for Depression: A Potential Marker of Low Resilience.

BACKGROUND: Amygdala overactivity has been frequently observed in patients with depression, as well as in nondepressed relatives of patients with depression. A remaining unanswered question is whether elevated amygdala activity in those with familial risk for depression is related to the presence of subthreshold symptoms or to a trait-level vulnerability for illness. METHODS: To examine this question, functional magnetic resonance imaging data were collected in nondepressed young adults with (family history [FH+]) (n = 27) or without (FH-) (n = 45) a first-degree relative with a history of depression while they viewed images of "looming" or withdrawing stimuli (faces and cars) that varied in salience by virtue of their apparent proximity to the subject. Activation of the amygdala and 2 other regions known to exhibit responses to looming stimuli, the dorsal intraparietal sulcus (DIPS) and ventral premotor cortex (PMv), were measured, as well as levels of resilience, anxiety, and psychotic and depressive symptoms. RESULTS: Compared with the FH- group, the FH+ group exhibited significantly greater responses of the amygdala, but not the dorsal intraparietal sulcus or ventral premotor cortex, to looming face stimuli. Moreover, amygdala responses in the FH+ group were negatively correlated with levels of resilience and unrelated to levels of subthreshold symptoms of psychopathology. CONCLUSIONS: These findings indicate that elevated amygdala activity in nondepressed young adults with a familial history of depression is more closely linked to poor resilience than to current symptom state.

Correlation Between Levels of Delusional Beliefs and Perfusion of the Hippocampus and an Associated Network in a Non-Help-Seeking Population.

BACKGROUND: Delusions are a defining and common symptom of psychotic disorders. Recent evidence suggests that subclinical and clinical delusions may represent distinct stages on a phenomenological and biological continuum. However, few studies have tested whether subclinical psychotic experiences are associated with neural changes that are similar to those observed in clinical psychosis. For example, it is unclear if overactivity of the hippocampus, a replicated finding of neuroimaging studies of schizophrenia, is also present in individuals with subclinical psychotic symptoms. METHODS: To investigate this question, structural and pulsed arterial spin labeling scans were collected in 77 adult participants with no psychiatric history. An anatomical region of interest approach was used to extract resting perfusion of the hippocampus, and 15 other regions, from each individual. A self-report measure of delusional ideation was collected on the day of scanning. RESULTS: The level of delusional thinking (number of beliefs [r = .27, p = .02]), as well as the associated level of distress (r = .29, p = .02), was significantly correlated with hippocampal perfusion (averaged over right and left hemispheres). The correlations remained significant after controlling for age, hippocampal volume, symptoms of depression and anxiety, and image signal-to-noise ratio, and they were confirmed in a voxelwise regression analysis. The same association was observed in the thalamus and parahippocampal, lateral temporal, and cingulate cortices. CONCLUSIONS: Similar to patients with schizophrenia, non-help-seeking individuals show elevated perfusion of a network of limbic regions in association with delusional beliefs.

The Genetics of Endophenotypes of Neurofunction to Understand Schizophrenia (GENUS) consortium: A collaborative cognitive and neuroimaging genetics project.

BACKGROUND: Schizophrenia has a large genetic component, and the pathways from genes to illness manifestation are beginning to be identified. The Genetics of Endophenotypes of Neurofunction to Understand Schizophrenia (GENUS) Consortium aims to clarify the role of genetic variation in brain abnormalities underlying schizophrenia. This article describes the GENUS Consortium sample collection. METHODS: We identified existing samples collected for schizophrenia studies consisting of patients, controls, and/or individuals at familial high-risk (FHR) for schizophrenia. Samples had single nucleotide polymorphism (SNP) array data or genomic DNA, clinical and demographic data, and neuropsychological and/or brain magnetic resonance imaging (MRI) data. Data were subjected to quality control procedures at a central site. RESULTS: Sixteen research groups contributed data from 5199 psychosis patients, 4877 controls, and 725 FHR individuals. All participants have relevant demographic data and all patients have relevant clinical data. The sex ratio is 56.5% male and 43.5% female. Significant differences exist between diagnostic groups for premorbid and current IQ (both p<1×10-10). Data from a diversity of neuropsychological tests are available for 92% of participants, and 30% have structural MRI scans (half also have diffusion-weighted MRI scans). SNP data are available for 76% of participants. The ancestry composition is 70% European, 20% East Asian, 7% African, and 3% other. CONCLUSIONS: The Consortium is investigating the genetic contribution to brain phenotypes in a schizophrenia sample collection of >10,000 participants. The breadth of data across clinical, genetic, neuropsychological, and MRI modalities provides an important opportunity for elucidating the genetic basis of neural processes underlying schizophrenia.

Genetic underpinnings of left superior temporal gyrus thickness in patients with schizophrenia.

OBJECTIVES: Schizophrenia is a highly disabling psychiatric disorder with a heterogeneous phenotypic appearance. We aimed to further the understanding of some of the underlying genetics of schizophrenia, using left superior temporal gyrus (STG) grey matter thickness reduction as an endophenoptype in a genome-wide association (GWA) study. METHODS: Structural magnetic resonance imaging (MRI) and genetic data of the Mind Clinical Imaging Consortium (MCIC) study of schizophrenia were used to analyse the interaction effects between 1,067,955 single nucleotide polymorphisms (SNPs) and disease status on left STG thickness in 126 healthy controls and 113 patients with schizophrenia. We next used a pathway approach to detect underlying pathophysiological pathways that may be related to schizophrenia. RESULTS: No SNP by diagnosis interaction effect reached genome-wide significance (5 × 10-8) in our GWA study, but 10 SNPs reached P-values less than 10-6. The most prominent pathways included those involved in insulin, calcium, PI3K-Akt and MAPK signalling. CONCLUSIONS: Our strongest findings in the GWA study and pathway analysis point towards an involvement of glucose metabolism in left STG thickness reduction in patients with schizophrenia only. These results are in line with recently published studies, which showed an increased prevalence of psychosis among patients with metabolic syndrome-related illnesses including diabetes.

A parametric study of fear generalization to faces and non-face objects: relationship to discrimination thresholds.

Fear generalization is the production of fear responses to a stimulus that is similar-but not identical-to a threatening stimulus. Although prior studies have found that fear generalization magnitudes are qualitatively related to the degree of perceptual similarity to the threatening stimulus, the precise relationship between these two functions has not been measured systematically. Also, it remains unknown whether fear generalization mechanisms differ for social and non-social information. To examine these questions, we measured perceptual discrimination and fear generalization in the same subjects, using images of human faces and non-face control stimuli ("blobs") that were perceptually matched to the faces. First, each subject's ability to discriminate between pairs of faces or blobs was measured. Each subject then underwent a Pavlovian fear conditioning procedure, in which each of the paired conditioned stimuli (CS) were either followed (CS+) or not followed (CS-) by a shock. Skin conductance responses (SCRs) were also measured. Subjects were then presented with the CS+, CS- and five levels of a CS+-to-CS- morph continuum between the paired stimuli, which were identified based on individual discrimination thresholds. Finally, subjects rated the likelihood that each stimulus had been followed by a shock. Subjects showed both autonomic (SCR-based) and conscious (ratings-based) fear responses to morphs that they could not discriminate from the CS+ (generalization). For both faces and non-face objects, fear generalization was not found above discrimination thresholds. However, subjects exhibited greater fear generalization in the shock likelihood ratings compared to the SCRs, particularly for faces. These findings reveal that autonomic threat detection mechanisms in humans are highly sensitive to small perceptual differences between stimuli. Also, the conscious evaluation of threat shows broader generalization than autonomic responses, biased towards labeling a stimulus as threatening.