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Publications (247)
Many bipolar disorder (BD) patients are non-responsive to lithium. The mechanisms underlying lithium (non-)responsiveness are largely unknown. By using gene-set enrichment analysis methods, we found that core clock gene-sets are significantly associated with lithium response. Among the top hits was BHLHE41, a modulator of the molecular clock and ho...
Background
Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the in...
Academic performance plays a crucial role in long-term educational attainment and occupational function. Chronotype refers to an individual's daily tendencies for times for waking, activity, and sleep. Social jetlag reflects the mismatch between an individual's chronotype and their social schedule. Because school typically starts early in the morni...
Bipolar disorder (BD) is characterized by disrupted circadian rhythms and neuronal loss. Lithium is neuroprotective and used to treat BD, but outcomes are variable. Past research identified that circadian rhythms in BD patient neurons are associated with lithium response (Li-R) or non-response (Li-NR). However, the underlying cellular mechanisms re...
The link between bipolar disorder (BP) and immune dysfunction remains controversial. While epidemiological studies have long suggested an association, recent research has found only limited evidence of such a relationship. To clarify this, we performed an exploratory study of the contributions of immune-relevant genetic factors to the response to l...
Lithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extra...
Background: Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the i...
Lithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extra...
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disabling disorder characterized by disrupted daily patterns of activity, sleep, and physiology. Past studies in ME/CFS patients have examined circadian rhythms, suggested that desynchronization between central and peripheral rhythms may be an important pathological feature, and ident...
Bipolar disorder (BD) is characterized by mood episodes, disrupted circadian rhythms and gray matter reduction in the brain. Lithium is an effective pharmacotherapy for BD, but not all patients respond to treatment. Lithium has neuroprotective properties and beneficial effects on circadian rhythms that may distinguish lithium responders (Li-R) from...
Lithium (Li) is one of the most effective drugs for treating bipolar disorder (BD), however, there is presently no way to predict response to guide treatment. The aim of this study is to identify functional genes and pathways that distinguish BD Li responders (LR) from BD Li non-responders (NR). An initial Pharmacogenomics of Bipolar Disorder study...
Background:
Lithium medication is considered to be the first-line treatment for bipolar disorder as a monotherapy, and for treatment-resistant depression with lithium augmentation. However, because of potential toxicity, lithium levels must be monitored frequently. Recent studies have demonstrated a significant correlation between lithium levels m...
Bipolar disorder (BD) is characterized by manic and depressive mood episodes and loss of brain gray matter. Lithium has antimanic and neuroprotective properties, but only 30% BD patients respond to lithium pharmacotherapy. Dopamine signaling has been implicated in BD and may contribute to lithium response. Methamphetamine (METH) stimulates dopamine...
Antipsychotic drugs (AP) are highly efficacious treatments for psychiatric disorders but are associated with significant metabolic side-effects. The circadian clock maintains metabolic homeostasis by sustaining daily rhythms in feeding, fasting and hormone regulation but how circadian rhythms interact with AP and its associated metabolic side-effec...
Bipolar disorder (BD) is characterized by mood episodes, disrupted circadian rhythms and gray matter reduction in the brain. Lithium is an effective pharmacotherapy for BD, but not all patients respond to treatment. Lithium has neuroprotective properties and beneficial effects on circadian rhythms that may distinguish lithium responders (Li-R) from...
Bipolar disorder (BD) is characterized by disrupted circadian rhythms affecting sleep, arousal, and mood. Lithium is among the most effective mood stabilizer treatments for BD, and in addition to improving mood symptoms, stabilizes sleep and activity rhythms in treatment responsive patients. Across a variety of experimental models, lithium has effe...
Background
Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
Aims
To use a combination of transdiagnostic genetic and clinical factors to predict l...
Antipsychotic drugs (AP) are highly efficacious treatments for psychiatric disorders but are associated with significant metabolic side effects. The circadian clock maintains metabolic homeostasis by sustaining daily rhythms in feeding, fasting and hormone regulation but how circadian rhythms interact with AP and its associated metabolic side effec...
Personality traits influence risk for suicidal behavior. We examined phenotype- and genotype-level associations between the Big Five personality traits and suicidal ideation and attempt in major depressive, bipolar and schizoaffective disorder, and schizophrenia patients ( N = 3012) using fixed- and random-effects inverse variance-weighted meta-ana...
Lithium (Li) is one of the most effective drugs for treating bipolar disorder (BD), however, there is presently no way to predict response to guide treatment. The aim of this study is to identify functional genes and pathways that distinguish BD Li responders (LR) from BD Li non-responders (NR). An initial Pharmacogenomics of Bipolar Disorder study...
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a common and disabling disorder primarily characterized by persistent fatigue and exercise intolerance, with associated sleep disturbances, autonomic dysfunction, and cognitive problems. The causes of ME/CFS are not well understood but may coincide with immune and inflammatory responses...
Lithium is the gold standard therapy for Bipolar Disorder (BD) but its effectiveness differs widely between individuals. The molecular mechanisms underlying treatment response heterogeneity are not well understood, and personalized treatment in BD remains elusive. Genetic analyses of the lithium treatment response phenotype may generate novel molec...
Background
Bipolar disorder (BD) is characterized by episodes of depression and mania and disrupted circadian rhythms. Lithium is an effective therapy for BD, but only 30-40% of patients are fully responsive. Preclinical models show that lithium alters circadian rhythms. However, it is unknown if the circadian rhythm effects of lithium are essentia...
Response to lithium varies widely between individuals with bipolar disorder (BD). Polygenic risk scores (PRSs) can uncover pharmacogenomics effects and may help predict drug response. Patients ( N = 2,510) with BD were assessed for long-term lithium response in the Consortium on Lithium Genetics using the Retrospective Criteria of Long-Term Treatme...
Bipolar affective disorder (BD) is a severe psychiatric illness, for which lithium (Li) is the gold standard for acute and maintenance therapies. The therapeutic response to Li in BD is heterogeneous and reliable biomarkers allowing patients stratification are still needed. A GWAS performed by the International Consortium on Lithium Genetics (ConLi...
Objective
The narrow therapeutic window of lithium medications necessitates frequent serum monitoring, which can be expensive and inconvenient for the patient. Compared to blood, saliva collection is easier, non-invasive, requires less processing, and can be done without the need for trained personnel. This study investigated the utility of longitu...
Bipolar disorder (BD) is a neuropsychiatric illness defined by recurrent episodes of mania/hypomania, depression and circadian rhythm abnormalities. Lithium is an effective drug for BD, but 30–40% of patients fail to respond adequately to treatment. Previous work has demonstrated that lithium affects the expression of “clock genes” and that lithium...
Lithium is a first-line medication for bipolar disorder (BD), but only one in three patients respond optimally to the drug. Since evidence shows a strong clinical and genetic overlap between depression and bipolar disorder, we investigated whether a polygenic susceptibility to major depression is associated with response to lithium treatment in pat...
Background
Pharmacotherapies for depression are often ineffective and treatment-resistant depression (TRD) is common across bipolar disorder (BD), major depressive disorder (MDD), and post-traumatic stress disorder (PTSD). Patient genetic information can be used to predict treatment outcomes. Prospective studies indicate that pharmacogenetic (PGX)...
Background
Lithium is regarded as a first line treatment for bipolar disorder (BD), but partial response and non‐response commonly occurs. There exists a need to identify lithium non‐responders prior to initiating treatment. The Pharmacogenomics of Bipolar Disorder (PGBD) Study was designed to identify predictors of lithium response.
Methods
The P...
The narrow therapeutic window of lithium medications necessitates frequent serum monitoring, which can be expensive and inconvenient for the patient. The use of saliva as a biofluid may have advantages over blood, as it is non-invasive, easier to collect, requires less processing, and can be collected without the need for trained personnel. This st...
Bipolar disorder (BD) is characterized by cyclical mood shifts. Studies indicate that BD patients have a peripheral pro-inflammatory state and alterations in glial populations in the brain. We utilized an in vitro model to study inflammation-related phenotypes of astrocytes derived from induced pluripotent stem cells (iPSCs) generated from BD patie...
Bipolar disorder (BD) is a neuropsychiatric disorder with genetic risk factors defined by recurrent episodes of mania/hypomania, depression and circadian rhythm abnormalities. While lithium is an effective drug for BD, 30-40% of patients fail to respond adequately to treatment. Previous work has demonstrated that lithium affects the expression of c...
Circadian rhythm disturbances are frequently described in psychiatric disorders such as major depressive disorder, bipolar disorder, and schizophrenia. Growing evidence suggests a biological connection between mental health and circadian rhythmicity, including the circadian influence on brain function and mood and the requirement for circadian entr...
This study was carried out to develop a prediction model for soluble solid content (SSC) of intact chestnut and to detect internal defects using nuclear magnetic resonance (NMR) relaxometry and magnetic resonance imaging (MRI). Inversion recovery and Carr–Purcell–Meiboom–Gill (CPMG) pulse sequences used to determine the longitudinal (T 1 ) and tran...
The maturity of tomato fruit is normally characterized by external color, and it is often difficult to know when fruit have achieved commercial maturity or become over-mature. The internal structure of tomato fruit changes during development and this study investigates the utility of nondestructive measurement of tomato fruit structure as a functio...
Background
Novel technologies make it possible to incorporate pharmacogenetic testing into the medical management of depression. However, previous studies indicate that there may be a subset of subjects who have concerns about genetic testing and may be psychologically vulnerable. If so, pharmacogenetic testing in depressed subjects could negativel...
Predicting antidepressant response has been a clinical challenge for mood disorder. Although several genome-wide association studies have suggested a number of genetic variants to be associated with antidepressant response, the sample sizes are small and the results are difficult to replicate. Previous animal studies have shown that knockout of the...
Lithium remains the gold standard for the treatment of bipolar disorder (BD); however, its use has declined over the years mainly due to the side effects and the subjective experience of cognitive numbness reported by patients. In the present study, we aim to methodically test the effects of lithium on neurocognitive functioning in the largest sing...
Bipolar disorder (BD) is a neuropsychiatric mood disorder characterized by recurrent episodes of mania and depression in addition to disruptions in sleep, energy, appetite, and cognitive functions-rhythmic behaviors that typically change on daily cycles. BD symptoms can also be provoked by seasonal changes, sleep, and/or circadian disruption, indic...
Antipsychotic drugs (APD) have clinically important, adverse effects on metabolism that limit their therapeutic utility. Pancreatic beta cells produce dopamine and express the D2 dopamine receptor (D2R). As D2R antagonists, APDs alter glucose-stimulated insulin secretion, indicating that dopamine likely plays a role in APD-induced metabolic dysfunc...
Mitochondria have been linked to the etiology of schizophrenia (SZ). However, studies of mitochondria in SZ might be confounded by the effects of pharmacological treatment with antipsychotic drugs (APDs) and other common medications. This review summarizes findings on relevant mitochondria mechanisms underlying SZ, and the potential impact of psych...
Bipolar disorder (BD) is a mood disorder with genetic and neurobiological underpinnings, characterized primarily by recurrent episodes of mania and depression, with notable disruptions in rhythmic behaviors such as sleep, energy, appetite and attention. The chronobiological links to BD are further supported by the effectiveness of various treatment...
Low frequency nuclear magnetic resonance (NMR) is used to noninvasively and nondestructively detect spoiled tomato concentrate stored in >200 L metal‐lined containers. It is shown that longitudinal and transverse NMR relaxation times change as the tomato concentrate spoils. A rapid, viscosity‐dependent spoilage detection method that takes advantage...
Bipolar disorder (BD) is a complex neuropsychiatric disorder characterized by recurrent mania and depression episodes and requiring lifelong treatment with mood stabilizing drugs. Several lines of evidence, including with BD patient iPSC‐derived neurons, suggest that neuronal hyperexcitability may underlie the key clinical symptoms of BD. Indeed, h...
A low cost, portable, high volume, stainless steel pressure reactor is modified to easily perform magnetic resonance relaxometry at industrially relevant pressures. Unlike existing pressurization strategies common to nuclear magnetic resonance (NMR)spectroscopy, this approach is amenable to realistic samples that feature heterogeneity and have trad...
Bipolar disorder (BD) is characterized by recurrent mood episodes, and circadian rhythm disturbances. Past studies have identified calcium channel genes as risk loci for BD. CACNA1C encodes an L-type calcium channel (LTCC) involved in the entrainment of circadian rhythms to light. Another calcium channel, i.e., the ryanodine receptor (RYR), is invo...
Background
Bipolar disorder is a neuropsychiatric disorder that is characterized by fluctuations between manic and depressive phases. Lithium is the original and best mood stabilizing treatment for bipolar disorder. While its mechanism is not well understood, it is believed to have a strong genetic component, as several studies suggest that lithium...
Background
A disrupted circadian clock has been linked to the risk of several neuropsychiatric disorders. Likewise, circadian rhythms have been suggested as mediators of the mechanism of action of lithium in bipolar disorder. Nonetheless the relationship between the ‘clock genes’ that regulate circadian rhythms and lithium treatment response is not...
Circadian rhythm abnormalities have been recognized as a central feature of bipolar disorder (BD) but a coherent biological explanation for them remains lacking. Using genetic mutation of 'clock genes', robust animal models of mania and depression have been developed that elucidate key aspects of circadian rhythms and the circadian clock-mood conne...
Insomnia is a worldwide problem with substantial deleterious health effects. Twin studies have shown a heritable basis for various sleep-related traits, including insomnia, but robust genetic risk variants have just recently begun to be identified. We conducted genome-wide association studies (GWAS) of soldiers in the Army Study To Assess Risk and...
Bipolar disorder (BD) is a serious mood disorder associated with circadian rhythm abnormalities. Risk for BD is genetically encoded and overlaps with systems that maintain circadian rhythms. Lithium is an effective mood stabilizer treatment for BD, but only a minority of patients fully respond to monotherapy. Presently, we hypothesized that lithium...
Antipsychotic drugs cause metabolic abnormalities through a mechanism that involves antagonism of D2 dopamine receptors (D2R). Under healthy conditions, insulin release follows a circadian rhythm and is low at night, and in pancreatic beta-cells, D2Rs negatively regulate insulin release. Since they are sedating, many antipsychotics are dosed at nig...
Purpose of review:
Comorbidity of posttraumatic stress disorder (PTSD) and insomnia, nightmares, and obstructive sleep apnea (OSA) is high. We review recent research on psychotherapeutic and pharmacological interventions for sleep disorders in PTSD.
Recent findings:
PTSD treatments decrease PTSD severity and nightmare frequency, but do not resol...
Objectives
Bipolar disorder (BD) with early disease onset is associated with an unfavorable clinical outcome and constitutes a clinically and biologically homogenous subgroup within the heterogeneous BD spectrum. Previous studies have found an accumulation of early age at onset (AAO) in BD families and have therefore hypothesized that there is a la...
Bipolar disorder (BD) is a common, highly heritable neuropsychiatric disease characterized by recurrent episodes of mania and depression. Lithium is the best-established long-term treatment for BD, even though individual response is highly variable. Evidence suggests that some of this variability has a genetic basis. This is supported by the larges...
Most living organisms maintain cell autonomous circadian clocks that synchronize critical biological functions with daily environmental cycles. In mammals, the circadian clock is regulated by inputs from signaling pathways including glycogen synthase kinase 3 (GSK3). The drug lithium has actions on GSK3, and also on inositol metabolism. While it is...
Importance
Lithium is a first-line mood stabilizer for the maintenance treatment of Bipolar Disorder (BPD). However, the efficacy of lithium varies widely, with a non-response rate of up to 30%. Biological response markers and predictors are lacking.
Objective
Genetic factors are thought to mediate lithium treatment response, and the previously re...
A hybrid multi-scale velocimetry method utilizing
Doppler optical coherence tomography in combination
with either magnetic resonance imaging or ultrasound velocity
profiling is used to investigate pipe flow of four rheologically
different working fluids under varying flow regimes.
These fluids include water, an aqueous xanthan gum solution,
a softw...
Time domain nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) are well-known non-destructive characterization techniques that are used to evaluate food quality. Time domain NMR is primarily based on relaxation and diffusion measurements from the signal coming from the whole sample whereas MRI enables visualization of the interio...
Significance
One-third of bipolar disorder (BPD) patients are lithium-responsive (LiR) for unknown reasons. Were lithium’s target to be identified, then BPD’s pathogenesis might be unraveled. We identified and mapped the “lithium-response pathway,” which governs the phosphorylation of CRMP2 , a cytoskeleton regulator, particularly for dendritic spi...
Antipsychotic drugs are widely prescribed medications, used for numerous psychiatric illnesses. However, antipsychotic drugs cause serious metabolic side effects that can lead to substantial weight gain and increased risk for type 2 diabetes. While individual drugs differ, all antipsychotic drugs may cause these important side effects to varying de...
Major depressive disorder (MDD) is often associated with disturbed circadian rhythms. However, a definitive causal role for functioning circadian clocks in mood regulation has not been established. We stereotactically injected viral vectors encoding short hairpin RNA to knock down expression of the essential clock gene Bmal1 into the brain's master...
Background
A connection between the mechanism of action of lithium in bipolar disorder and circadian rhythms has been suggested. Nonetheless the relationship between the “clock genes“ that regulate circadian rhythms and lithium treatment response is not completely understood. Some studies, based on candidate-gene approaches have attempted to find t...
Introduction:
Circadian alterations are prevalent in Alzheimer's disease (AD) and may contribute to cognitive impairment, behavioral symptoms, and neurodegeneration. Epigenetic mechanisms regulate the circadian clock, and changes in DNA methylation have been reported in AD brains, but the pathways that mediate circadian deregulation in AD are inco...
Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behavior. Genome-wide
association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability.
To identify additional risk loci, we performed a two-stage meta-analysis of >9 million geneti...
Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behavior. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage meta-analysis of >9 million geneti...