NIMH perspectives on future directions in neuroimaging for mental health.

NIMH's mission is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery, and cure. New imaging techniques hold great promise for improving our understanding of the pathophysiology of mental illnesses, stratifying patients for treatment selection, and developing a personalized medicine approach. Here, we highlight emerging and promising new technologies that are likely to be vital in helping NIMH accomplish its mission, the potential for utilizing multimodal approaches to study mental illness, and considerations for data analytics and data sharing.

Key Findings from Mental Health Research During the Menopause Transition for Racially and Ethnically Minoritized Women Living in the United States: A Scoping Review.

Racially and ethnically minoritized (REM) women experience social and structural factors that may affect their response to mental health treatment and menopausal symptoms during the menopause transition (MT). This scoping review on mental health during the MT for REM women in the United States was conducted to characterize factors associated with mental health challenges. Five databases were searched.

Tryptophan challenge in individuals with schizophrenia and healthy controls: acute effects on circulating kynurenine and kynurenic acid, cognition and cerebral blood flow.

Cognitive impairments predict poor functional outcomes in people with schizophrenia. These impairments may be causally related to increased levels of kynurenic acid (KYNA), a major metabolic product of tryptophan (TRYP). In the brain, KYNA acts as an antagonist of the of α7-nicotinic acetylcholine and NMDA receptors, both of which are involved in cognitive processes.

Tryptophan Challenge in Healthy Controls and People with Schizophrenia: Acute Effects on Plasma Levels of Kynurenine, Kynurenic Acid and 5-Hydroxyindoleacetic Acid.

The pivotal tryptophan (TRP) metabolite kynurenine is converted to several neuroactive compounds, including kynurenic acid (KYNA), which is elevated in the brain and cerebrospinal fluid of people with schizophrenia (SZ) and may contribute to cognitive abnormalities in patients. A small proportion of TRP is metabolized to serotonin and further to 5-hydroxyindoleacetic acid (5-HIAA). Notably, KP metabolism is readily affected by immune stimulation.

Linking Salience Signaling With Early Adversity and Affective Distress in Individuals at Clinical High Risk for Psychosis: Results From an Event-Related fMRI Study.

Evidence suggests dysregulation of the salience network in individuals with psychosis, but few studies have examined the intersection of stress exposure and affective distress with prediction error (PE) signals among youth at clinical high-risk (CHR). Here, 26 individuals at CHR and 19 healthy volunteers (HVs) completed a monetary incentive delay task in conjunction with fMRI. We compared these groups on the amplitudes of neural responses to surprising outcomes-PEs without respect to their valence-across the whole brain and in two regions of interest, the anterior insula and amygdala.

Schizophrenia: a disorder of broken brain bioenergetics.

A substantial and diverse body of literature suggests that the pathophysiology of schizophrenia is related to deficits of bioenergetic function. While antipsychotics are an effective therapy for the management of positive psychotic symptoms, they are not efficacious for the complete schizophrenia symptom profile, such as the negative and cognitive symptoms. In this review, we discuss the relationship between dysfunction of various metabolic pathways across different brain regions in relation to schizophrenia.

Relating Glutamate, Conditioned, and Clinical Hallucinations via 1H-MR Spectroscopy.

Background And Hypothesis: Hallucinations may be driven by an excessive influence of prior expectations on current experience. Initial work has supported that contention and implicated the anterior insula in the weighting of prior beliefs.

Study Design: Here we induce hallucinated tones by associating tones with the presentation of a visual cue.

Two Factors, Five Factors, or Both? External Validation Studies of Negative Symptom Dimensions in Schizophrenia.

Objectives: Negative symptom studies frequently use single composite scores as indicators of symptom severity and as primary endpoints in clinical trials. Factor analytic and external validation studies do not support this practice but rather suggest a multidimensional construct. The current study used structural equation modeling (SEM) to compare competing dimensional models of negative symptoms to determine the number of latent dimensions that best capture variance in biological, psychological, and clinical variables known to have associations with negative symptoms.

Relations Among Anhedonia, Reinforcement Learning, and Global Functioning in Help-seeking Youth.

Dysfunction in the neural circuits underlying salience signaling is implicated in symptoms of psychosis and may predict conversion to a psychotic disorder in youth at clinical high risk (CHR) for psychosis. Additionally, negative symptom severity, including consummatory and anticipatory aspects of anhedonia, may predict functional outcome in individuals with schizophrenia-spectrum disorders. However, it is unclear whether anhedonia is related to the ability to attribute incentive salience to stimuli (through reinforcement learning [RL]) and whether measures of anhedonia and RL predict functional outcome in a younger, help-seeking population.

Metabolite Alterations in Adults With Schizophrenia, First Degree Relatives, and Healthy Controls: A Multi-Region 7T MRS Study.

Proton magnetic resonance spectroscopy (MRS) studies in schizophrenia have shown altered GABAergic, glutamatergic, and bioenergetic pathways, but if these abnormalities are brain region or illness-stage specific is largely unknown. MRS at 7T MR enables reliable quantification of multiple metabolites, including GABA, glutamate (Glu) and glutamine (Gln), from multiple brain regions within the time constraints of a clinical examination. In this study, GABA, Glu, Gln, the ratio Gln/Glu, and lactate (Lac) were quantified using 7T MRS in five brain regions in adults with schizophrenia ( = 40), first-degree relatives ( = 11), and healthy controls ( = 38).

Multimodal Neuroimaging Study of Visual Plasticity in Schizophrenia.

Schizophrenia is a severe mental illness with visual learning and memory deficits, and reduced long term potentiation (LTP) may underlie these impairments. Recent human fMRI and EEG studies have assessed visual plasticity that was induced with high frequency visual stimulation, which is thought to mimic an LTP-like phenomenon. This study investigated the differences in visual plasticity in participants with schizophrenia and healthy controls.

Neurotransmitters and Neurometabolites in Late-Life Depression: A Preliminary Magnetic Resonance Spectroscopy Study at 7T.

Background: Magnetic resonance spectroscopy (MRS) methods have quantified changes in levels of neurotransmitters and neurometabolites in patients with major depression across the lifespan. The application of 7T field strengths and greater have not been a major focus of study in patients with late-life depression (LLD).

Methods: Nine LLD patients who met DSM-IV criteria for a current major depressive episode and nine non-depressed, healthy, age-matched controls underwent clinical and neuropsychological assessment and single-voxel 7T H-MRS at baseline and after 10-12 weeks of antidepressant treatment (Citalopram; patients only).

Social Disconnection in Late Life Mental Illness - Commentary From the National Institute of Mental Health.

• Social disconnection – both social isolation as well as social isolation (otherwise known as loneliness) – is a prevalent affliction among older adults, with profound effects on mental health. • Mechanistic understanding of how mental illness contributes to, is exacerbated by, or is otherwise linked to social disconnection remains elusive, and therapeutic interventions which leverage social connection to enhance compliance with or efficacy of mental health treatment, though promising, remain scarce. • The National Institute of Mental Health (NIMH) is committed to transforming the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery, and cure.

White matter alterations and the conversion to psychosis: A combined diffusion tensor imaging and glutamate H MRS study.

Introduction: Widespread white matter abnormalities and alterations in glutamate levels have been reported in patients with schizophrenia. We hypothesized that alterations in white matter integrity and glutamate levels in individuals at clinical high risk (CHR) for psychosis are associated with the subsequent development of psychosis.

Methods: Participants included 33 antipsychotic naïve CHR (Female 7/Male 26, Age 19.

The Role of Hippocampal Functional Connectivity on Multisystem Subclinical Abnormalities in Schizophrenia.

Objective: Schizophrenia is associated with excess medical mortality: patients have an average life expectancy one to two decades shorter than the general population. This study investigates the relationship between aberrant hippocampal resting-state functional connectivity in schizophrenia and cumulative subclinical effects of chronic stress on metabolic, cardiovascular, and immune function using the allostatic load index.

Methods: Cumulative stress was estimated using allostatic load total score (range, 0-13) in 46 patients with schizophrenia and 31 controls matched for age and sex (patients: age = 36.

Hippocampus and cognitive domain deficits in treatment-resistant schizophrenia: A comparison with matched treatment-responsive patients and healthy controls.

Some patients with schizophrenia do not respond to pharmacotherapy. More severe cognitive dysfunctions have been associated with treatment-resistant schizophrenia (TRS). This study examines cognitive functions and hippocampal volumes in 43 patients with TRS and compared them to 43 treatment-responsive patients (NTRS), matched on age, sex and education, as well as 53 healthy controls (HC).

Effects of ketamine and midazolam on resting state connectivity and comparison with ENIGMA connectivity deficit patterns in schizophrenia.

Subanesthetic administration of ketamine is a pharmacological model to elicit positive and negative symptoms of psychosis in healthy volunteers. We used resting-state pharmacological functional MRI (rsPhfMRI) to identify cerebral networks affected by ketamine and compared them to the functional connectivity (FC) in schizophrenia. Ketamine can produce sedation and we contrasted its effects with the effects of the anxiolytic drug midazolam.

Sleep quality is related to brain glutamate and symptom severity in schizophrenia.

Up to 80% of patients with schizophrenia experience sleep disturbances, which negatively impact daytime functioning. Given that the glutamatergic system is involved in the pathophysiology of schizophrenia as well as normal sleep-wake neurobiology, the current project aimed to determine whether sleep quality was related to brain glutamate levels in schizophrenia. The Pittsburgh Sleep Quality Index (PSQI) was used to assess subjective sleep quality and proton magnetic resonance spectroscopy (MRS) was used to quantify glutamate in the bilateral anterior cingulate, left parietal cortex, and left hippocampus.

Choroid Plexus Enlargement and Allostatic Load in Schizophrenia.

Although schizophrenia is a brain disorder, increasing evidence suggests that there may be body-wide involvement in this illness. However, direct evidence of brain structures involved in the presumed peripheral-central interaction in schizophrenia is still unclear. Seventy-nine previously treatment-naïve first-episode schizophrenia patients who were within 2-week antipsychotics initial stabilization, and 41 age- and sex-matched healthy controls were enrolled in the study.

Clinical and genetic validity of quantitative bipolarity.

Research has yet to provide a comprehensive understanding of the genetic basis of bipolar disorder (BP). In genetic studies, defining the phenotype by diagnosis may miss risk-allele carriers without BP. The authors aimed to test whether quantitatively detected subclinical symptoms of bipolarity identifies a heritable trait that infers risk for BP.