Chronic social defeat stress is a widely used depression model in male mice. Several proposed adaptations extend this model to females with variable, often marginal effects. We examine if the widely used male-defined metrics of stress are suboptimal in females witnessing defeat.

People exhibit an extraordinary capacity to adjust to stressful situations. Here, we argue that the acute stress response is a major driving force behind this adaptive process. In addition to immediately freeing energy reserves, facilitating a rapid and robust neurocognitive response, and helping to reinstate homeostasis, the stress response also critically regulates neuroplasticity. Therefore, understanding

Alterations in the effects of glucocorticoids have been implicated in mediating some of the negative health effects associated with chronic stress, including increased risk for psychiatric disorders and cardiovascular and metabolic diseases. In this study, we investigated how genetic variants influence gene expression and DNA methylation in response to glucocorticoid receptor (GR) activation and their

Allostatic load (AL) is an objective measure of the biological components of chronic stress in clinical practice, which potentially influence depression, anxiety, and suicide. In this study, we investigated the association between AL and these mental disorders.

After acute COVID-19, 5% of people experience persistent depressive symptoms and reduced cognitive function (COVID-DC). Theoretical models propose that astrogliosis is important in long COVID, but measures primarily indicative of astrogliosis have not been studied in the brain of long COVID or COVID-DC. The objective of the current study was to measure [11C]SL25.1188 total distribution volume ([11C]SL25

Despite the significant personal and societal burden of tic disorders (TDs), treatment outcomes remain modest, necessitating a deeper understanding of their etiology. Family history is the biggest known risk factor, and identifying risk genes could accelerate progress in the field.

We previously reported that a single injection of (R,S)-ketamine or its metabolite (2S,6S)-hydroxynorketamine (HNK) prior to stress attenuated learned fear. However, whether these drugs attenuate learned fear through divergent or convergent effects on neural activity remains to be determined.

Aggression exacts a significant toll on human societies and is highly prevalent among neuropsychiatric patients. The neural mechanisms of aggression are unclear and treatment options are limited.

Exposure to stressful life events is associated with a high risk of developing psychiatric disorders with a wide variety of symptoms. Cognitive symptoms in stress-related psychiatric disorders can be particularly challenging to understand, both for those experiencing them and for health care providers. To gain insights, it is important to capture stress-induced structural, epigenomic, transcriptomic

Neuropsychiatric symptoms, such as depression and anxiety, are observed in 90% of patients with Alzheimer’s disease (AD), two-thirds of whom are women. Neuropsychiatric symptoms usually manifest long before AD onset creating a therapeutic opportunity. Here, we examined the impact of anxiety on AD progression and the underlying brainwide neuronal mechanisms.

Impulse control is a critical aspect of cognitive functioning. Intuitively, whether an action is executed prematurely depends on its associated reward, yet the link between value and impulsivity remains poorly understood. Three frameworks for impulsivity offer contrasting views: impulsive behavior may be valuable because it is associated with hidden internal reward (e.g., reduction of mental effort)

The flexibility to adjust actions and attitudes in response to varying social situations is a fundamental aspect of adaptive social behavior. Adaptive social behaviors influence an individual’s vulnerability to social stress. While it has been proposed that oxytocin is a facilitator of active coping behaviors during social stress, the exact mechanisms remain unknown.

Suicide accounts for more than 700,000 deaths annually and is the fourth leading cause of death among individuals aged 15 to 29 years. Despite years of research to understand the etiology and pathophysiology of suicidal behavior, many questions remain unresolved—for example, whether suicidal behavior has a unique genetic or neurobiological basis and how these differ from related psychiatric conditions

Hyperkatifeia, the manifestation of emotional distress or pain, is a conceptual framework gaining traction throughout the alcohol and other substance use fields as an important driver of addiction. It is well known that previous or current negative life experiences can serve as powerful motivators for excessive alcohol consumption and precipitate the development of an alcohol use disorder (AUD). A

Opioid use disorder (OUD) has reached epidemic proportions, with many countries facing high levels of opioid use and related fatalities. Although currently prescribed medications for OUD are considered lifesaving, they inadequately address negative affect and cognitive impairment, resulting in high relapse rates to nonmedical opioid use even years after drug cessation (protracted abstinence). Evidence

Repetitive transcranial magnetic stimulation (rTMS) has the potential to increase the clinical effect of exposure with response prevention psychotherapy for obsessive-compulsive disorder (OCD). We investigated the use of task-based functional magnetic resonance imaging for predicting clinical outcomes to different rTMS protocols combined with exposure with response prevention in OCD.

Postinfectious autoimmune processes have been proposed as potential causal risk factors for obsessive-compulsive disorder (OCD). In this large population-based study, we aimed to clarify the familial coaggregation pattern between severe infections and OCD across clusters of relatives with varying degrees of relatedness.

Social disequilibrium, or disrupted social homeostasis, underlies many behavioral disorders, including problematic drug use. One way to study the relationship between drug use and social homeostasis is to determine whether single doses of psychoactive drugs relieve some of the discomfort of social isolation and promote social connection. In this narrative review, we discuss challenges and opportunities

The mechanisms of psychotic symptoms such as hallucinations and delusions are often investigated in fully formed illness, well after symptoms emerge. These investigations have yielded key insights but are not well positioned to reveal the dynamic forces underlying symptom formation itself. Understanding symptom development over time would allow us to identify steps in the pathophysiological process

Psychotic experiences are thought to emerge from various interrelated patterns of disrupted belief updating, such as overestimating the reliability of sensory information and misjudging task volatility, yet these substrates have never been jointly addressed under one computational framework, and it is not clear to what degree they reflect trait-like computational patterns.

Glutathione (GSH) is a crucial antioxidant in the human brain. Although proton magnetic resonance spectroscopy using the Mescher-Garwood point-resolved spectroscopy sequence is highly recommended, limited literature has measured cortical GSH using this method in major psychiatric disorders.

Abnormalities in structural-functional connectivity (SC-FC) coupling have been identified globally in patients with major depressive disorder (MDD). However, investigations have neglected the variability and hierarchical distribution of these abnormalities across different brain regions. Furthermore, the biological mechanisms that underlie regional SC-FC coupling patterns are not well understood.

Cognitive impairment associated with schizophrenia (CIAS) and related deficits in learning (plasticity) are among the leading causes of disability in schizophrenia. Despite this, there are no Food and Drug Administration–approved treatments for CIAS, and the development of treatments has been limited by numerous phase 2/3 failures of compounds that showed initial promise in small-scale studies. NMDA-type

Rather than a passive reflection of nociception, pain is shaped by the interplay between one’s experiences, current cognitive-affective states, and expectations. The placebo response, a paradoxical yet reliable phenomenon, is postulated to reduce pain by engaging mechanisms shared with active therapies. It has been assumed that mindfulness meditation, practiced by sustaining nonjudgmental awareness

Magnetic resonance–guided focused ultrasound (MRgFUS) trials targeting the anterior limb of the internal capsule have shown promising results. We evaluated the long-term safety and efficacy of MRgFUS capsulotomy in patients with obsessive-compulsive disorder (OCD) and major depressive disorder (MDD).

22q11.2 deletion syndrome (22qDel) is a copy number variant that is associated with psychosis and other neurodevelopmental disorders. Adolescents who are at clinical high risk for psychosis (CHR) are identified based on the presence of subthreshold psychosis symptoms. Whether common neural substrates underlie these distinct high-risk populations is unknown. We compared functional brain measures in

Autism spectrum disorder (ASD) is a lifelong neurodevelopmental condition. Over the past decade, a considerable number of approaches have been developed to identify potential neuroimaging-based biomarkers of ASD that have uncovered specific neural mechanisms that underlie behaviors associated with ASD. However, the substantial heterogeneity among individuals who are diagnosed with ASD hinders the development

The nucleus accumbens (NAc) mediates reward learning and motivation. Despite an abundance of neuropeptides, peptidergic neurotransmission from the NAc has not been integrated into current models of reward learning. The existence of a sparse population of neurons containing corticotropin-releasing factor (CRF) has been previously documented. Here, we provide a comprehensive analysis of their identity

Persisting symptoms and disability remain a problem for an appreciable proportion of people with schizophrenia despite treatment with antipsychotic medication. Improving outcomes requires an understanding of the nature and mechanisms of the pathological processes underlying persistence. Classical features of schizophrenia, which include disorganization and impoverishment of mental activity, are well-recognized

Brain serotonin 4 receptor (5-HT4R) levels are lower in untreated patients with major depressive disorder (MDD) and are linked to verbal memory. Here, we investigated the relationship between 5-HT4R levels, clinical outcomes, and cognitive function in patients with MDD who initiated selective serotonin reuptake inhibitor drug treatment.

Autism and attention-deficit/hyperactivity disorder (ADHD) are heterogeneous neurodevelopmental conditions with complex underlying neurobiology that is still poorly understood. Despite overlapping presentation and sex-biased prevalence, autism and ADHD are rarely studied together and sex differences are often overlooked. Population modeling, often referred to as normative modeling, provides a unified

Evidence regarding metabolic alterations associated with maternal antenatal depression (AD) is limited, and their role as potential biomarkers that improve the prediction of AD and adverse childbirth, neurodevelopmental, and mental health outcomes remains unexplored.

Sleep deprivation (SD) negatively affects brain function. Most brain imaging studies have investigated the effects of SD on static brain function. SD effects on functional brain dynamics and their relationship with molecular changes remain relatively unexplored.

Maternal prenatal depression can affect child brain and behavioral development. Specifically, altered limbic network structure and function is a likely mechanism through which prenatal depression impacts the life-long mental health of exposed children. While developmental trajectories are influenced by many factors that exacerbate risk or promote resiliency, the role of child age and sex in the relationship

Numerous studies have established the presence of gray matter atrophy and brain activation abnormalities during neurocognitive and social cognitive tasks in schizophrenia. Despite a growing consensus that diseases localize better to distributed brain networks than individual anatomical regions, relatively few studies have examined brain network localization of gray matter atrophy and neurocognitive

Repetitive transcranial magnetic stimulation (rTMS) is an emerging treatment for obsessive-compulsive disorder (OCD). The neurobiological mechanisms of rTMS in OCD have been incompletely characterized. We compared clinical outcomes and changes in task-based brain activation following 3 different rTMS protocols, all combined with exposure and response prevention.

Different types of early-life adversity (ELA) have been associated with children’s brain structure and function. However, understanding the disparate influence of distinct adversity exposures on the developing brain remains a major challenge.

Major depressive disorder is a common psychiatric disorder and a leading cause of disability worldwide. Astrocytes play a role in the maintenance of the function of the central nervous system, both physiologically and pathologically. Accumulated evidence indicates that the astrocyte is an important contributor to the pathophysiology of major depressive disorder including blood-brain barrier integrity

Disruptions of axonal connectivity are thought to be a core pathophysiological feature of psychotic illness, but whether they are present early in the illness, prior to antipsychotic exposure, and whether they can predict clinical outcome remain unknown.