Janet L Cunningham

Uppsala University | UU

Higher stress during pregnancy associates with negative outcomes and elevated inflammation. The gut microbiota, reflecting environment and social interactions, alongside host immune responses have the potential to better understand perceived stress and identify when stress is excessive in pregnancy. Two U.S. cohorts of 84 pregnant individuals, comp...

Obsessive-compulsive disorder (OCD) is a highly disabling mental illness that can be divided into frequent primary and rarer organic secondary forms. Its association with secondary autoimmune triggers was introduced through the discovery of Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infection (PANDAS) and Pediatric...

Objective: Physiological parameters that predict electroconvulsive therapy (ECT) effectiveness may reflect propagation of the induced epileptic seizure. As an indication of seizure propagation to the diencephalon, we here examined the correlation between prolactin increase after ECT and clinical seizure evaluation parameters, focusing on peak hear...

Abrupt onset of severe neuropsychiatric symptoms including obsessive–compulsive disorder, tics, anxiety, mood swings, irritability, and restricted eating is described in children with Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS). Symptom onset is often temporally associated with infections, suggesting an underlying autoimmune/autoinflamma...

Background: Neurological and psychiatric manifestations related to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection are widely recognised. Standard magnetic resonance imaging (MRI) investigations are normal in 40-80% of symptomatic patients, eventually delaying appropriate treatment when MRI is unrevealing any structural chan...

Background Higher stress during pregnancy associates with negative outcomes and elevated inflammation. The gut microbiota reflects the environment, lifestyle, and the perinatal period. The gut microbiota, alongside host immune responses, has the potential to aid in identifying when stress is excessive. Methods Two U.S. cohorts, of 84 pregnant indi...

Background Autoimmune psychosis may be caused by well-characterized anti-neuronal autoantibodies, such as against the N-methyl-D-aspartate receptor. However, the presence of additional anti-central nervous system (CNS) autoantibodies in these patients has not been systematically assessed. Methods Serum and cerebrospinal fluid (CSF) from patients w...

This study explores potential associations between the methylation of promoter-associated CpG sites of the toll-like receptor (TLR)-family, plasma levels of pro-inflammatory proteins and depressive symptoms in young female psychiatric patients. Ratings of depressive symptoms and blood samples were obtained from 92 young women seeking psychiatric ca...

Objective: Short chain fatty acids (SCFAs) are produced by the gut microbiota and may reflect health. Gut symptoms are common in individuals with depressive disorders and recent data indicates relationships between gut microbiota and psychiatric health. We aimed to investigate potential associations between SCFAs and self-reported depressive and g...

Exploration of photoplethysmography (PPG), a technique that can be translated to the clinic, has the potential to assess the autonomic nervous system (ANS) through heart rate variable (HRV) in pregnant individuals. This novel study explores the complexity of mental health of individuals in a clinical sample responding to a task in late pregnancy; f...

High neuroticism is related to cardiovascular morbidity. Early detection of metabolic and cardiovascular risk is important in high-risk groups to enable preventive measures. The aim of this study was therefore to explore if neuroticism is associated with early biomarkers for cardiovascular and metabolic disease in young adults from a psychiatry coh...

Antibody responses to SARS-CoV-2 in serum and CSF from 16 COVID-19 patients with neurological symptoms were assessed using two independent methods. IgG specific for the virus spike protein was found in 81% of cases in serum and in 56% in CSF. SARS-CoV-2 IgG in CSF was observed in two cases with negative serology. Levels of IgG in both serum and CSF...

Growing evidence implies interactions between infections, the immune system and vulnerability for psychiatric disease. This study applies an affinity proteomic-based method to investigate potential disease associated autoantibody signatures in serum from patients from the “Young Adults” section of the Department of General Psychiatry at Uppsala Uni...

Objective: To identify serum proteins associated with MS and affected by interferon beta treatment. Methods: Plasma samples from 29 untreated relapsing-remitting MS patients and 15 healthy controls were investigated with a multiplexed panel containing 92 proteins related to inflammation. Follow-up samples were available from 13 patients at 1 and...

Background Neurological symptoms have been frequently reported in hospitalized patients with coronavirus disease 2019 (COVID‐19) and biomarkers of CNS injury are reported to be increased in plasma but not extensively studied in CSF. This study examines CSF for biomarkers of CNS injury and other pathology in relation to neurological symptoms and dis...

In recent years, studies have shown higher prevalence of autoantibodies in patients with schizophrenia compared to healthy individuals. This study applies an untargeted and a targeted affinity proteomics approach to explore and characterize the autoantibody repertoire in brain tissues from 73 subjects diagnosed with schizophrenia and 52 control sub...

Importance Screening for anxiety and depression is important but especially difficult during pregnancy. Identification and quantification of the variation of maternal biologic dimensions during the dynamic pregnancy period, e.g. immune and microbiome profiles, have the potential to greatly improve mental heath screening and patient stratification....

Background >Patients with functional gastrointestinal disorders have a high psychiatric co-morbidity. This study aimed to investigate and characterise gastrointestinal symptoms in relation to depressive symptoms and trait anxiety in a well-defined population of young adult psychiatric outpatients and healthy controls. Methods Gastrointestinal symp...

Acute malignant catatonia with autonomic instability developed in a previously healthy man with PCR-verified SARS-CoV-2. CT and MRI were normal, EEG showed slowing and cerebrospinal fluid showed a subtle indication of inflammation. There were no signs of pathology in other organs. 18F-FDG-PET conveyed high bilateral uptake in the striatum. While co...

Gut dysbiosis has been implicated in the pathophysiology of a growing number of non-communicable diseases. High through-put sequencing technologies and short chain fatty acid (SCFA) profiling enables surveying of the composition and function of the gut microbiota and provide key insights into host-microbiome interactions. However, a methodological...

Lithium is widely used to treat bipolar disorder. However, the efficacy and vulnerability as to its side effects are known to differ. Although the specific biochemical mechanism of action is still elusive, lithium may influence mitochondrial function, and consequently, metabolism. Lithium exposure in this study was conducted on a unique set of mito...

Background: Patients with functional gastrointestinal disorders have a high psychiatric co-morbidity. This study aimed to investigate and characterise gastrointestinal symptoms in relation to depressive symptoms and trait anxiety in a well-defined population of young adult psychiatric outpatients and healthy controls. Methods: Gastrointestinal symp...

Background: Patients with functional gastrointestinal disorders have a high psychiatric co-morbidity. This study aimed to investigate and characterise gastrointestinal symptoms in relation to depressive symptoms and trait anxiety in a well-defined population of young adult psychiatric outpatients and healthy controls. Methods: Gastrointestinal symp...

Background: Patients with functional gastrointestinal disorders have a high psychiatric co-morbidity. This study aimed to investigate and characterise gastrointestinal symptoms in relation to depressive symptoms and trait anxiety in a well-defined population of young adult psychiatric outpatients and healthy controls. Methods: Gastrointestinal symp...

Here we report a case of Covid-19-related acute necrotizing encephalopathy (ANE) where SARS-CoV-2 RNA was found in cerebrospinal fluid (CSF) 19 days after symptom onset after testing negative twice. Even though monocytes and protein levels in CSF were only marginally increased, and our patient never experienced a hyperinflammatory state, her neurol...

Objective Short chain fatty acids (SCFAs) are produced by the gut microbiota and may reflect health. Gut symptoms are common in individuals with depressive disorders and recent data indicates relationships between gut microbiota and psychiatric health. We aimed to investigate potential associations between SCFAs and self-reported depressive and gut...

Gut dysbiosis has been implicated in the pathophysiology of a growing number of non-communicable diseases. High through-put sequencing technologies and short chain fatty acid (SCFA) profiling enables surveying of the composition and function of the gut microbiota and provide key insights into host-microbiome interactions. However, a methodological...

Immunomodulation is increasingly being recognised as a part of mental diseases. Here, we examined whether levels of immunological protein markers changed with depression, age, or the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). An analysis of plasma samples from patients with a major depressive episode and control blood donors (CBD)...

Background: The bidirectional interaction between melatonin and the immune system has largely gone unexplored in a clinical context and especially in a psychiatric population. This study explored the association between melatonin during the day and inflammatory cytokines in young adult patients seeking psychiatric care. Methods: Samples and data...

Background: Meaningful and generalizable research depends on patients' willingness to participate. Studies often fail to reach satisfactory representativeness. Objective: This paper aims to investigate reasons for not participating in research among young adult patients with psychiatric illness. Method: A quantitative cross-sectional study was...

Background: Laboratory tests to assist in the diagnosis and monitoring of neuroinflammatory diseases are scarce. The soluble form of the CD27 molecule (sCD27) is shed in high concentrations by activated T cells and can be detected in the cerebrospinal fluid. The aim of this study was to investigate whether CSF quantitation of sCD27 could discrimin...

Immunomodulation is increasingly being recognised as a part of mental diseases. Here, we examined if levels of immunological protein markers altered with depression, age or by the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Analysis of plasma samples from patients with major depressive episode and control blood donors (CBD) revealed...

Purpose: Childhood trauma in an important public health concern, and there is a need for brief and easily administered assessment tools. The Early Trauma Inventory (ETI) is one such instrument. The aim of this paper is to test the psychometric properties of the Swedish translation of the short, self-rated version (ETISR-SF), and to further validate...

Compared with major depressive disorder, postpartum depression and its relation to immune activation and inflammation is less studied. Postpartum, after vast adaptations of the immune system during pregnancy, the immune system needs to return to a non-pregnant state, during a period of immune challenging events, such as wound healing, sleep loss, a...

Circulating levels of adipokines are known to be associated with depression. This study aimed to investigate a possible association between leptin, adiponectin and dimensional measures of depressive symptoms in young adults with and without psychiatric illness. Total plasma adiponectin and leptin levels were measured in 194 young adults seeking psy...

Objective: The pathophysiology of irritable bowel syndrome (IBS) is not completely understood, although we do know that patients with IBS have a high prevalence of psychiatric comorbidity (mainly depression and anxiety disorders). Melatonin, produced in the gastrointestinal tract, influences gut motility. Psychiatric conditions are associated with...

Postpartum depression (PPD) is a devastating disorder affecting not only more than 10% of all women giving birth, but also the baby, the family, and the society. Compiling evidence suggests the involvement of the immune system in the pathophysiology of major depression; yet, the immune response in perinatal depression is not as well studied. The ai...

Background: Treatment of Hepatitis C virus (HCV) infection has evolved from interferon (IFN)-based treatments to direct-acting antivirals (DAAs). Patients with HCV have an elevated psychiatric morbidity (including substance abuse) and patients with such comorbidity have often been excluded from treatment with IFN. To date, little is known about ps...

Background Numerous studies have shown a correlation between high autoantibody titers and subsequent autoimmune disease in patients with psychiatric disorders compared to healthy individuals. In this study we used a targeted affinity proteomics approach to investigate these autoantibody repertoires. We therefore obtained serum samples from patients...

The genetics behind predisposition to small intestinal neuroendocrine tumors (SI-NETs) is largely unknown, but there is growing awareness of a familial form of the disease. We aimed to identify germline mutations involved in the carcinogenesis of SI-NETs. The strategy included next-generation sequencing of exome- and/or whole-genome of blood DNA, a...

Background: Antenatal depression and use of serotonin reuptake inhibitors (SSRI) in pregnancy have both been associated with an increased risk of poor pregnancy outcomes, such as preterm birth and impaired fetal growth. While the underlying biological pathways for these complications are poorly understood, it has been hypothesized that inflammatio...

Background Research in vulnerable individuals must insure voluntariness and minimize negative reactions caused by participation. This study aimed to describe consent and completion rate in young psychiatric patients in relation to study components, degree of disability and to compare response to research participation in patients and controls. Meth...

Background: Bulimia nervosa (BN) is characterized by dysregulated eating behaviour and present data suggest adipokines may regulate food intake. We investigated a possible association between BN and adipokine levels and hypothesized that plasma (P)-adiponectin would be elevated and P-leptin and P-leptin-adiponectin-ratio would be reduced in women...

Background/Aims Small intestinal neuroendocrine tumours (SI-NETs) are derived from enterochromaffin cells. After demonstrating melatonin in enterochromaffin cells, we hypothesized that SI-NETs may express and secrete melatonin, which may have an impact on clinical factors and treatment response. Methods Tumour tissue from 26 patients with SI-NETs,...

Melatonin antibody neutralisation test. Melatonin immunohistochemistry of normal human rectal epithelium stained using rabbit-anti melatonin antibody 0100–0203 (A). Melatonin immunohistochemistry of a consecutive section where antibody was pre-incubated with 0.1 mg/mL melatonin to ensure antibody specificity (B). (TIF)

Intensity scoring for melatonin immunohistochemistry. Representative examples of melatonin immunohistochemistry intensities of tumour tissue scored using both manual and computerised methods, weak (A), moderate (B) and strong (C). (TIF)

Melatonin antibody cross-reactivity with serotonin. Melatonin immunohistochemistry of normal ileal epithelium stained using rabbit-anti melatonin antibody 0100–0203 (A). Melatonin immunohistochemistry of a consecutive section where antibody was pre-incubated with 0.1 mg/mL serotonin to ensure antibody specificity (B). Serotonin immunohistochemistry...

Melatonin receptor 1 (MT1) antibody neutralisation test. Immunohistochemistry of normal ileal epithelium tissue stained using MT1 antibody sc13179 (A). Immunohistochemistry of a consecutive section where the antibody was pre-incubated with the corresponding peptide sc-13179P (B). (TIF)

Different staining patterns for melatonin and serotonin on consecutive sections. Melatonin immunohistochemistry of small intestinal neuroendocrine tumour stained using rabbit-anti melatonin antibody 0100–0203 (A). Serotonin immunohistochemistry of a consecutive section stained using anti-serotonin antibody 5HT-H209 (B). Arrowheads indicate cluster...

Melatonin receptor 2 (MT2) antibody neutralisation test. Immunohistochemistry of normal ileal epithelium tissue stained using MT2 antibody ABIN122307 (A). Immunohistochemistry of a consecutive section where the antibody was pre-incubated with the corresponding peptide SP4391CP (B). (TIF)

Background: Migraine is a prevalent disorder characterised by recurrent headache attacks preceded or accompanied by aura in a subgroup of patients. Migraine often occurs together with major depressive disorder (MDD). Alterations of adipokine levels have been reported both in migraine and in MDD. In this cross-sectional study, we aimed to assess th...