J. John Mann

J. John Mann
Columbia University | CU · Department of Psychiatry

MD

About

1,308
Publications
152,254
Reads
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89,678
Citations
Citations since 2016
358 Research Items
33002 Citations
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Additional affiliations
July 1994 - present
Columbia University
Position
  • Professor (Full)
July 1994 - present
New York State Psychiatric Institute
Position
  • Managing Director

Publications

Publications (1,308)
Article
Full-text available
Smaller hippocampal volume is reported in Major Depressive Disorder (MDD). We hypothesize it may be related to fewer granule neurons (GN) in the dentate gyrus (DG), a defect possibly reversible with antidepressants. We studied age-, sex-, and postmortem interval-matched groups: no major psychopathology (controls); unmedicated-MDD; and MDD treated w...
Article
Suicide and depression are associated with reduced serotonergic neurotransmission. In suicides, there is a reduction in serotonin transporter (SERT) sites and an increase in postsynaptic 5-HT1A receptors in localized regions of the prefrontal cortex. In depression, there is a diffuse decrease in SERT binding throughout the dorsoventral extent of th...
Article
Although adoption, twin, and family studies have shown that suicidal behavior is familial, the risk factors for familial transmission from parent to child remain unclear. A high-risk family study was conducted comparing the offspring of 2 mood-disordered groups: suicide attempters and nonattempters. Recruited from 2 sites, probands were 81 attempte...
Article
Suicidal behavior is partly heritable. Studies seeking the responsible candidate genes have examined genes involved in neurotransmitter systems shown to have altered function in suicide and attempted suicide. These neurotransmitter systems include the serotonergic, noradrenergic, and dopaminergic systems and the hypothalamic-pituitary-adrenal axis....
Chapter
This chapter reviews the epidemiology and neurobiology of major depressive disorder and suicide. Depression and suicide rates in different countries around the world have changed over the years partly because the onset of major depression is earlier in individuals who are born more recently and partly because of major social changes influencing sui...
Article
Background Resilience represents coping abilities to overcome exposure to psychopathological risk. In the context of risk factors for suicidal behavior, it is unknown if this attribute is deficient in suicide attempters, how it relates to other measures of risk, and where it may overlap with other risk factors associated with suicidal behavior. Me...
Article
Background Soluble epoxide hydrolase (sEH, encoded by EPHX2) and P2X2 (a subtype of ATP receptors) may mediate the antidepressant-like effects of ATP. We sought to determine whether polymorphisms and mRNA expression of EPHX2 and P2X2 are associated with depression and suicidal behavior and how cognition may mediate such associations. Method We exa...
Article
Full-text available
Public health and epidemiologic research have established that social connectedness promotes overall health. Yet there have been no recent reviews of findings from research examining social connectedness as a determinant of mental health. The goal of this review was to evaluate recent longitudinal research probing the effects of social connectednes...
Article
Full-text available
The various functions of the skeleton are influenced by extracellular cues, hormones and neurotransmitters. One type of neuronal regulation favors bone mass accrual by inhibiting sympathetic nervous system activity. This observation raises questions about the transcriptional mechanisms regulating catecholamine synthesis. Using a combination of gene...
Article
Importance: Suicide is a leading cause of death in the United States, having increased more than 30% from 2000 to 2018. An inexpensive, safe, widely available treatment for preventing suicidal behavior could reverse this trend. Objective: To confirm a previous signal for decreased risk of suicide attempt following prescription fills for folic ac...
Article
Full-text available
Depression is disabling and highly prevalent. Intravenous (IV) ketamine displays rapid-onset antidepressant properties, but little is known regarding which patients are most likely to benefit, limiting personalized prescriptions. We identified randomized controlled trials of IV ketamine that recruited individuals with a relevant psychiatric diagnos...
Article
Full-text available
Background Childhood adversity (CA) is linked to suicidal behavior as well as to mood disorders and aggressive traits. This raises the possibility that depression and aggressive traits mediate the relationship of childhood adversity to suicide risk. Moreover, it is not known if they operate independently or interactively. Aims To determine whether...
Article
Background Emotion regulation (ER) processes help support wellbeing, but ineffective ER is implicated in several psychiatric disorders. Engaging ER flexibly by going “online” and “offline” as needs and capacities shift, may be more effective than engaging ER rigidly across time. Here we sought to observe the neural temporal dynamics of an ER proces...
Article
Full-text available
Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with acute and postacute cognitive and neuropsychiatric symptoms including impaired memory, concentration, attention, sleep and affect. Mechanisms underlying these brain symptoms remain understudied. Here we report that SARS-CoV-2-infected hamsters exhibit...
Preprint
Full-text available
Objective: Treatment-resistant depression (TRD), defined as inadequate response to at least one or at least two antidepressant (AD) trials, is common in major depressive disorder (MDD). In this study, electronic health records (EHR) were used to identify clinical associations with TRD. Methods: Using two biobanks, phenomes of patients with at least...
Article
Full-text available
Cellular function in tissue is dependent on the local environment, requiring new methods for spatial mapping of biomolecules and cells in the tissue context ¹ . The emergence of spatial transcriptomics has enabled genome-scale gene expression mapping 2–5 , but the ability to capture spatial epigenetic information of tissue at the cellular level and...
Article
Full-text available
Mood disorders and suicidal behavior have moderate heritability and are associated with altered corticolimbic serotonin 1A receptor (5-HT1A) brain binding. However, it is unclear whether this reflects genetic effects or epigenetic effects of childhood adversity, compensatory mechanisms, or illness stress-related changes. We sought to separate such...
Preprint
Background: Individuals who have lost a loved one to suicide are at increased risk for developing complicated grief (CG). It is unclear why only a subgroup of bereaved develops CG. Vulnerability may be related to the ability to regulate attention toward reminders of the deceased during the acute phase of grief. Using a longitudinal design, we deter...
Preprint
Full-text available
Importance Social determinants of health (SDoH) have well-characterized associations with child mental health outcomes. Their complex, multilevel influences on child mental health are less well understood. Objective To identify patterns across multiple domains of SDoH and estimate their associations with child mental health and suicidality outcome...
Article
Full-text available
Serotonin transporter (5-HTT) binding deficits are reported in major depressive disorder (MDD). However, most studies have not considered serotonin system anatomy when parcellating brain regions of interest (ROIs). We now investigate 5-HTT binding in MDD in two novel ways: (1) use of a 5-HTT tract-based analysis examining binding along serotonergic...
Article
Full-text available
Importance: The COVID-19 pandemic disproportionately affected mental health in socioeconomically disadvantaged children in the US. However, little is known about the relationship of preexisting and time-varying social determinants of health (SDoH) at individual and structural levels, vaccination eligibility/rates, and the racial and ethnic differe...
Article
Purpose: In 1 H MRS-based thermometry of brain, averaging temperatures measured from more than one reference peak offers several advantages including improving the reproducibility, i.e., precision, of the measurement. This paper proposes theoretically and empirically optimal weighting factors to improve the weighted average of temperatures measure...
Preprint
Full-text available
Importance Depression and anxiety are common and highly comorbid, posing a clinical and public health concern because such comorbidity is associated with poorer outcomes. Objective To evaluate association of genetic risk scores with depression and anxiety diagnosis either in isolation or comorbid with each other. Design International Classificati...
Article
Full-text available
The hippocampus is the most common seizure focus in people. In the hippocampus, aberrant neurogenesis plays a critical role in the initiation and progression of epilepsy in rodent models, but it is unknown whether this also holds true in humans. To address this question, we used immunofluorescence on control healthy hippocampus and surgical resecti...
Article
Full-text available
(R,S)-ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist that was originally developed as an anesthetic. Most recently, (R,S)-ketamine has been used as a rapid-acting antidepressant, and we have reported that (R,S)-ketamine can also be a prophylactic against stress in adult mice. However, most pre-clinical studies have been performed in...
Article
Objective: Suicidal ideation (SI) is a risk factor for completed suicide. Our previous resting state functional magnetic resonance imaging (fMRI) study found that higher amplitude of low frequency fluctuation (ALFF) in right hippocampus and thalamus was associated with SI in major depressive disorder (MDD). The present study aimed to evaluate that...
Article
Major depressive disorder (MDD) was previously hypothesized to be a disease of monoamine deficiency in which low levels of monoamines in the synaptic cleft were believed to underlie depressive symptoms. More recently, however, there has been a paradigm shift toward a neuroplasticity hypothesis of depression in which downstream effects of antidepres...
Article
Full-text available
Background (R,S)-ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, is frequently used as an anesthetic and as a rapid-acting antidepressant. We and others have reported that (R,S)-ketamine is prophylactic against stress in adult mice, but have yet to test its efficacy in adolescent or aged populations. Methods Here, we administered sal...
Article
Full-text available
Depression recurrence is debilitating, and there is a pressing need to develop clinical tools that detect the reemergence of symptoms with the aim of bridging patients to treatment before recurrences. At baseline, remitted depressed adults (n = 22) and healthy controls (n = 24) were administered clinical interviews and completed self-report symptom...
Preprint
Full-text available
Mood disorders and suicidal behavior have moderate heritability and are associated with smaller hippocampal volumes. However, it is unclear whether these alterations reflect heritable risk or epigenetic effects of childhood, compensatory mechanisms, or illness-related changes. We sought to separate effects on hippocampal substructure volumes due to...
Article
Full-text available
Clinical and empirical reports suggest that individuals use non-suicidal self-injury (NSSI) not only to ameliorate dysphoria, but to curb suicidal ideation or avoid suicidal behaviour. To date, however, no study has quantitatively assessed whether NSSI leads to short-term reductions in suicidal ideation. Using real-time monitoring over 7 days in a...
Article
Full-text available
Introduction Full quantification of positron emission tomography (PET) data requires an input function. This generally means arterial blood sampling, which is invasive, labor-intensive and burdensome. There is no current, standardized method to fully quantify PET radiotracers with irreversible kinetics in the absence of blood data. Here, we present...
Article
Full-text available
Background: The pathophysiology of bipolar disorder remains largely unknown, despite it causing significant disability and suicide risk. Serotonin signaling may play a role in the pathophysiology, but direct evidence for this is lacking. Treatment of the depressed phase of the disorder is limited. Previous studies have indicated that positron emis...
Article
Purpose: In 1 H MRS thermometry, separately acquired full water and partially suppressed water are commonly used for measuring temperature. This paper compares these two approaches. Methods: Single voxel proton magnetic resonance spectroscopy (1 H MRS) data were collected on a 3T GE scanner from 26 human subjects. Each subject underwent five con...
Article
Objective: Studies demonstrate rapid antidepressant and anti-suicidal ideation effects of subanesthetic ketamine. The specific subcomponents of depression that are most closely tied to reduction of suicidal ideation with ketamine treatment are less explored. Methods: Exploratory, post hoc analysis of data from a randomized clinical trial of ketamin...
Article
Background : During adolescence, suicide risk increases; effective treatments are needed to reduce risk. Methods : Databases were searched (1995-2020) for randomized controlled trials (RCTs) concerning psychosocial treatments for suicide prevention in adolescents (10-18 yrs). Data were extracted from the timepoint closest to 6 months. Cohen's ds w...
Article
Full-text available
Preclinical studies have implicated kappa opioid receptors (KORs) in stress responses and depression-related behaviors, but evidence from human studies is limited. Here we present results of a secondary analysis of data acquired using positron emission tomography (PET) with the KOR radiotracer [ ¹¹ C]GR103545 in 10 unmedicated, currently depressed...
Article
Background Suicidal behavior is moderately heritable and a consequence of a combination of the diathesis traits for suicidal behavior and suicide-related major psychiatric disorders. Here, we sought to examine shared polygenic effects between various psychiatric disorders/traits and suicidal behavior and to compare the shared polygenic effects of v...
Article
Full-text available
Background Several social determinants of health (SDoH) have been associated with the onset of major depressive disorder (MDD). However, prior studies largely focused on individual SDoH and thus less is known about the relative importance (RI) of SDoH variables, especially in older adults. Given that risk factors for MDD may differ across the lifes...
Article
Objective: Subanesthetic ketamine rapidly reduces depressive symptoms and suicidal ideation in some depressed patients. Its effects on neurocognitive functioning in such individuals with significant suicidal ideation is not well understood, even though certain neurocognitive deficits are associated with suicide behavior beyond clinical symptoms. Me...
Article
In many countries suicide rates have been trending upwards for close to twenty years-presenting a public health crisis. Most suicide attempts and deaths are associated with psychiatric illness, usually a depressive disorder. Subanesthetic ketamine is the only FDA-approved antidepressant that works in hours not weeks-thus potentially transforming tr...
Preprint
Full-text available
Infection with the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is associated with onset of neurological and psychiatric symptoms during and after the acute phase of illness¹⁻⁴. Acute SARS-CoV-2 disease (COVID-19) presents with deficits of memory, attention, movement coordination, and mood. The mechanisms of these central nervous sy...
Poster
Full-text available
We examined 3 clinical and 3 neuropsychological risk factors for suicidal behavior cross-sectionally across the lifespan.
Article
Full-text available
Background: Suicide is moderately heritable and also more common in those who report childhood abuse. Previously, it was found that allele A of GABRG2 (GABA A receptor subunit gamma2) polymorphism rs211034 was protective in a suicide attempt (SA). Hence, it was proposed that rs211034 may interact with childhood trauma to influence cognitive deficit...
Article
Full-text available
Background The serotonin 1A (5-HT1A) receptor has been implicated in depression and suicidal behavior. Lower resting cortisol levels are associated with higher 5-HT1A receptor binding, and both differentiate suicide attempters with depression. However, it is not clear whether 5-HT1A receptor binding and cortisol responses to stress are related to f...
Preprint
Serotonin transporter (5-HTT) binding deficits are reported in major depressive disorder (MDD). However, most studies have not considered serotonin system anatomy when parcellating brain regions of interest (ROIs). We now investigate 5-HTT binding in MDD in two novel ways: (1) use of a 5-HTT tract-based analysis examining binding along serotonergic...
Preprint
Full-text available
Introduction: Full quantification of positron emission tomography (PET) data requires an input function. This generally means arterial blood sampling, which is invasive, labor-intensive and burdensome. There is no current, standardized method to fully quantify PET radiotracers with irreversible kinetics in the absence of blood data. Here, we presen...
Article
Full-text available
Suicidal behavior (SB) can be impulsive or methodical; violent or not; follow a stressor or no obvious precipitant. This study tested whether childhood trauma, affective lability, and aggressive and impulsive traits predicted greater SI variability. We also assessed whether affective lability, aggressive or impulsive traits explain childhood trauma...
Article
Full-text available
Glutamate (Glu) and gamma-aminobutyric acid (GABA) are implicated in the pathophysiology of major depressive disorder (MDD). GABA levels or GABAergic interneuron numbers are generally low in MDD, potentially disinhibiting Glu release. It is unclear whether Glu release or turnover is increased in depression. Conversely, a meta-analysis of prefrontal...
Article
Full-text available
Objective: Social determinants of health (SDoH) are non-clinical dispositions that impact patient health risks and clinical outcomes. Leveraging SDoH in clinical decision making can potentially improve diagnosis, treatment planning, and patient outcomes. Despite increased interest in capturing SDoH in electronic health records (EHRs), such informat...
Article
Full-text available
Using magnetic resonance diffusion tensor imaging data from 45 patients with major depressive disorder (MDD) and 41 healthy controls (HCs), network indices based on a 246-region Brainnetcome Atlas were investigated in the two groups, and in the MDD subgroups that were subgrouped based on their duration of the disease. Correlation between the networ...
Article
Full-text available
N-methyl-D-aspartate glutamate-receptor (NMDAR) antagonists such as ketamine have demonstrated efficacy in both major depressive disorder (MDD) and bipolar disorder depression (BP-D). We have previously reported that reduction in Glx (glutamate + glutamine) in the ventromedial prefrontal cortex/anterior cingulate cortex (vmPFC/ACC), measured by pro...
Article
Full-text available
Serotonergic dysfunction is implicated in major depressive disorder (MDD), but the mechanisms of this relationship remain elusive. Serotonin 1A (5-HT1A) autoreceptors regulate brain-wide serotonin neuron firing and are positioned to assert large-scale effects on negative emotion. Here we investigated the relationship between raphe 5-HT1A binding an...
Article
Full-text available
Neuroinflammation and cyclooxygenase-2 (COX-2) upregulation are associated with the pathogenesis of degenerative brain diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), epilepsy, and a response to traumatic brain injury (TBI) or stroke. COX-2 is also induced in acute pain, depression, schizoph...
Article
Objective To identify risk factors for preadolescent onset suicidal behavior compared with adolescent/young adult onset suicidal behavior in a longitudinal sample of youth with parental history of mood disorders. Methods The sample includes 545 youth who were age 21 years or less at the time of their baseline assessment. Participants underwent bas...
Article
Background A COVID-19 pandemic-related rise in suicide rates has been predicted due to social isolation, fear, uncertainty, economic turndown and grief. Detecting an increase in suicide rates is difficult in the absence of real-time data. Alternative data sources for such trends in psychopathology and suicidal behavior must be sought. Methods Data...
Article
Full-text available
There is a public health need for improved suicide risk assessment tools. This pilot methodology study compared the assay sensitivity of computerized adaptive tests (CAT) of depression and suicidal ideation vs. traditional ratings in a randomized trial subgroup. The last 20 persons to enroll in a published ketamine trial in suicidal depression were...