Ketamine Versus Electroconvulsive Therapy for the Treatment of Depression: A Guide for Clinicians.

The effective treatment of major depressive disorder remains one of the biggest public health challenges globally. For moderate to severe cases, pharmacotherapy often falls short, leading to treatment-resistant depression. Electroconvulsive therapy (ECT) has generally been considered the gold standard for severe cases of treatment-resistant depression.

Deficits in prefrontal metabotropic glutamate receptor 5 are associated with functional alterations during emotional processing in bipolar disorder.

Background: Elucidating biological mechanisms contributing to bipolar disorder (BD) is key to improved diagnosis and treatment development. With converging evidence implicating the metabotropic glutamate receptor 5 (mGlu5) in the pathology of BD, here, we therefore test the hypothesis that recently identified deficits in mGlu5 are associated with functional brain differences during emotion processing in BD.

Methods: Positron emission tomography (PET) with [F]FPEB was used to measure mGlu5 receptor availability and functional imaging (fMRI) was performed while participants completed an emotion processing task.

Synaptic loss and its association with symptom severity in Parkinson's disease.

Parkinson's disease (PD) is the fastest growing neurodegenerative disease, but at present there is no cure, nor any disease-modifying treatments. Synaptic biomarkers from in vivo imaging have shown promise in imaging loss of synapses in PD and other neurodegenerative disorders. Here, we provide new clinical insights from a cross-sectional, high-resolution positron emission tomography (PET) study of 30 PD individuals and 30 age- and sex-matched healthy controls (HC) with the radiotracer [C]UCB-J, which binds to synaptic vesicle glycoprotein 2A (SV2A), and is therefore, a biomarker of synaptic density in the living brain.

Linking resting-state network fluctuations with systems of coherent synaptic density: A multimodal fMRI and C-UCB-J PET study.

Resting-state network (RSN) connectivity is a widely used measure of the brain's functional organization in health and disease; however, little is known regarding the underlying neurophysiology of RSNs. The aim of the current study was to investigate associations between RSN connectivity and synaptic density assessed using the synaptic vesicle glycoprotein 2A radioligand C-UCB-J PET. Independent component analyses (ICA) were performed on resting-state fMRI and PET data from 34 healthy adult participants (16F, mean age: 46 ± 15 years) to identify RSNs of interest (default-mode, right frontoparietal executive-control, salience, and sensorimotor networks) and select sources of C-UCB-J variability (medial prefrontal, striatal, and medial parietal).

Differences in Quantification of the Metabotropic Glutamate Receptor 5 Across Bipolar Disorder and Major Depressive Disorder.

Background: Understanding the neurobiology underlying bipolar disorder (BD) versus major depressive disorder (MDD) is crucial for accurate diagnosis and for driving the discovery of novel treatments. A promising target is the metabotropic glutamate receptor 5 (mGluR5), a modulator of glutamate transmission associated with synaptic plasticity. We measured mGluR5 availability in individuals with MDD and BD for the first time using positron emission tomography.

Imaging synaptic density in depression.

Major depressive disorder is a prevalent and heterogeneous disorder with treatment resistance in at least 50% of individuals. Most of the initial studies focused on the monoamine system; however, recently other mechanisms have come under investigation. Specific to the current issue, studies show synaptic involvement in depression.

Imaging the effect of ketamine on synaptic density (SV2A) in the living brain.

The discovery of ketamine as a rapid and robust antidepressant marks the beginning of a new era in the treatment of psychiatric disorders. Ketamine is thought to produce rapid and sustained antidepressant effects through restoration of lost synaptic connections. We investigated this hypothesis in humans for the first time using positron emission tomography (PET) and [C]UCB-J-a radioligand that binds to the synaptic vesicle protein 2A (SV2A) and provides an index of axon terminal density.

Lower synaptic density is associated with psychiatric and cognitive alterations in obesity.

Obesity is a serious medical condition that often co-occurs with stress-related psychiatric disorders. It is recognized that the brain plays a key role in the (patho)physiology of obesity and that there is a bidirectional relationship between obesity and psychopathology, yet molecular mechanisms altered in obesity have not been fully elucidated. Thus, we investigated relationships between obesity and synaptic density in vivo using the radioligand [C]UCB-J (which binds to synaptic glycoprotein SV2A) and positron emission tomography in individuals with obesity, and with or without stress-related psychiatric disorders.

Identifying brain networks in synaptic density PET (C-UCB-J) with independent component analysis.

Background: The human brain is inherently organized into distinct networks, as reported widely by resting-state functional magnetic resonance imaging (rs-fMRI), which are based on blood-oxygen-level-dependent (BOLD) signal fluctuations. C-UCB-J PET maps synaptic density via synaptic vesicle protein 2A, which is a more direct structural measure underlying brain networks than BOLD rs-fMRI.

Methods: The aim of this study was to identify maximally independent brain source networks, i.

Ketamine Normalizes the Structural Alterations of Inferior Frontal Gyrus in Depression.

Background: Ketamine is a novel fast-acting antidepressant. Acute ketamine treatment can reverse microstructure deficits and normalize functional alterations in the brain, but little is known about the impacts of ketamine on brain volumes in individuals with depression.

Methods: We used 3 T magnetic resonance imaging (MRI) and tensorbased morphological methods to investigate the regional volume differences for 29 healthy control (HC) subjects and 21 subjects with major depressive disorder (MDD), including 10 subjects with comorbid post-traumatic stress disorder (PTSD).

Measuring the effects of ketamine on mGluR5 using [F]FPEB and PET.

The metabotropic glutamate receptor 5 (mGluR5) is a promising treatment target for psychiatric disorders due to its modulatory effects on glutamate transmission. Using [C]ABP688, we previously showed that the rapidly acting antidepressant ketamine decreases mGluR5 availability. The mGluR5 radioligand [F]FPEB offers key advantages over [C]ABP688; however, its suitability for drug challenge studies is unknown.

Lower synaptic density is associated with depression severity and network alterations.

Synaptic loss and deficits in functional connectivity are hypothesized to contribute to symptoms associated with major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). The synaptic vesicle glycoprotein 2A (SV2A) can be used to index the number of nerve terminals, an indirect estimate of synaptic density. Here, we used positron emission tomography (PET) with the SV2A radioligand [C]UCB-J to examine synaptic density in n = 26 unmedicated individuals with MDD, PTSD, or comorbid MDD/PTSD.

Cerebellar and prefrontal cortical alterations in PTSD: structural and functional evidence.

Background: Neuroimaging studies have revealed that disturbances in network organization of key brain regions may underlie cognitive and emotional dysfunction in posttraumatic stress disorder (PTSD). Examining both brain structure and function in the same population may further our understanding of network alterations in PTSD.

Methods: We used tensor-based morphometry (TBM) and intrinsic connectivity distribution (ICD) to identify regions of altered volume and functional connectivity in unmedicated individuals with PTSD (n=21) and healthy comparison (HC) participants (n=18).

Metabotropic Glutamatergic Receptor 5 and Stress Disorders: Knowledge Gained From Receptor Imaging Studies.

The metabotropic glutamatergic receptor subtype 5 (mGluR5) may represent a promising therapeutic target for stress-related psychiatric disorders. Here, we describe mGluR5 findings in stress disorders, particularly major depressive disorder (MDD), highlighting insights from positron emission tomography studies. Positron emission tomography studies report either no differences or lower mGluR5 in MDD, potentially reflecting MDD heterogeneity.

Metabotropic Glutamate Receptor 5 and Glutamate Involvement in Major Depressive Disorder: A Multimodal Imaging Study.

Background: Preclinical and postmortem studies have implicated the metabotropic glutamate receptor 5 (mGluR5) in the pathophysiology of major depressive disorder (MDD). The goal of the present study was to determine the role of mGluR5 in a large group of individuals with MDD compared to healthy controls (HC) with [F]FPEB and positron emission tomography (PET). Furthermore, we sought to determine the role glutamate plays on mGluR5 availability in MDD.

Multimodal Investigation of Network Level Effects Using Intrinsic Functional Connectivity, Anatomical Covariance, and Structure-to-Function Correlations in Unmedicated Major Depressive Disorder.

Converging evidence suggests that major depressive disorder (MDD) affects multiple large-scale brain networks. Analyses of the correlation or covariance of regional brain structure and function applied to structural and functional MRI data may provide insights into systems-level organization and structure-to-function correlations in the brain in MDD. This study applied tensor-based morphometry and intrinsic connectivity distribution to identify regions of altered volume and intrinsic functional connectivity in data from unmedicated individuals with MDD (n=17) and healthy comparison participants (HC, n=20).

Time-dependent neuronal changes associated with craving in opioid dependence: an fMRI study.

Relapse after initially successful treatment is a significant problem facing the treatment of opioid dependence. Evidence suggests craving elicited by re-exposure to drug cues may precipitate relapse. Attempts to identify neural biomarkers of cue-elicited craving have yielded inconsistent findings.

Trajectories of depressive and anxiety symptoms in older adults: a 6-year prospective cohort study.

Objective: Depressive and anxiety symptoms are common in older adults, significantly affect quality of life, and are risk factors for Alzheimer's disease. We sought to identify the determinants of predominant trajectories of depressive and anxiety symptoms in cognitively normal older adults.

Method: Four hundred twenty-three older adults recruited from the general community underwent Aβ positron emission tomography imaging, apolipoprotein and brain-derived neurotrophic factor genotyping, and cognitive testing at baseline and had follow-up assessments.

Altered metabotropic glutamate receptor 5 markers in PTSD: In vivo and postmortem evidence.

Posttraumatic stress disorder (PTSD) is a prevalent and highly disabling disorder, but there is currently no targeted pharmacological treatment for it. Dysfunction of the glutamate system has been implicated in trauma and stress psychopathology, resulting in a growing interest in modulation of the glutamate system for the treatment of PTSD. Specifically, the metabotropic glutamate receptor 5 (mGluR5) represents a promising treatment target.

Neurobiology of Chronic Stress-Related Psychiatric Disorders: Evidence from Molecular Imaging Studies.

Chronic stress accounts for billions of dollars of economic loss annually in the United States alone, and is recognized as a major source of disability and mortality worldwide. Robust evidence suggests that chronic stress plays a significant role in the onset of severe and impairing psychiatric conditions, including major depressive disorder, bipolar disorder, and posttraumatic stress disorder. Application of molecular imaging techniques such as positron emission tomography and single photon emission computed tomography in recent years has begun to provide insight into the molecular mechanisms by which chronic stress confers risk for these disorders.

β-Amyloid, APOE and BDNF Genotype, and Depressive and Anxiety Symptoms in Cognitively Normal Older Women and Men.

Objective: To examine how β-amyloid (Aβ), APOE and BDNF genotypes, and cortisol relate to depressive and anxiety symptoms in cognitively normal older women and men.

Methods: Cross-sectional data were analyzed from 423 older adults from the Australian Imaging Biomarkers and Lifestyle study. Analyses of covariance evaluated associations between Aβ, APOE and BDNF genotype, and cortisol in relation to severity of depressive and anxiety symptoms.

Pre- and postsynaptic serotonergic differences in males with extreme levels of impulsive aggression without callous unemotional traits: a positron emission tomography study using (11)C-DASB and (11)C-MDL100907.

Background: Impulsive aggression (IA) in adults is associated with brain serotonin (5-HT) system abnormalities and is more common following childhood adversity. Within aggressive behavior, IA and callous unemotional (CU) traits are core components of differentiable factors with opposing 5-HT abnormalities. We aimed to investigate 5-HT abnormalities in IA and potential correlations with severity of childhood adversity while controlling for confounding 5-HT effects of high CU traits and mental disorders.