Publications by authors named "Peter P Zandi"

In this case series, we present several examples from participants (2 patients and 1 healthy control) of a 12-week pilot feasibility study to create a digital phenotype of depression (unipolar or bipolar) through active and passive data collection from a smartphone and a wearable device combined with routine clinical care for mood disorders. The selected cases represent real clinical examples that highlight the intrinsic challenges that should be expected when conducting similar studies, including appropriate health data privacy protection, clinical standardization, and interindividual differences in levels of engagement and acceptability of active and passive data collection (ie, self-reported, behavioral, cognitive, and physiological data), particularly with patient-generated data in mobile apps, digital proficiency habituation, and consistent use of wearable devices. In the context of the rapidly growing use of digital technologies in psychiatry, anticipating challenges for the integration of personal mobile devices and smartphone mental health apps as aides to track specific aspects of depressive disorders is critical for a clinically meaningful digital transformation of mood disorders care.

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Genome-wide association studies (GWASs) of major depressive disorder (MDD) have recently achieved extremely large sample sizes and yielded substantial numbers of genome-wide significant loci. Because of the approach to ascertainment and assessment in many of these studies, some of these loci appear to be associated with dysphoria rather than with MDD, potentially decreasing the clinical relevance of the findings. An alternative approach to MDD GWAS is to focus on the most severe forms of MDD, with the hope that this will enrich for loci of larger effect, rendering their identification plausible, and providing potentially more clinically actionable findings.

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  • Concern about clozapine-related neutropenia leads to its underuse, particularly affecting access for individuals of African ancestry who tend to have lower absolute neutrophil counts due to a specific genetic factor.
  • A study at Johns Hopkins Medicine analyzed clozapine usage from 2013-2023, identifying patients and examining neutropenia rates and demographic differences, finding no severe cases among 974 patients but noting some developed mild to moderate neutropenia.
  • The research highlights a potential issue with current ANC monitoring requirements being overly restrictive, which may hinder the effective use of clozapine for patients who could benefit from it, especially within Black populations.
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  • Bipolar disorder (BD) features disrupted sleep patterns and nerve cell loss, with lithium being a common but variably effective treatment.
  • Research focused on how certain circadian genes and their interactions influence cell survival and lithium response using neurons from BD patients and regular controls.
  • Findings indicated that certain gene knockdowns affected cell survival differently between lithium responders and non-responders, suggesting complex roles of circadian rhythms in BD and lithium treatment efficacy.
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  • Lithium is the primary treatment for bipolar disorder (BD), but how it works and predicts outcomes is not fully understood.
  • A previous study identified key cellular pathways linked to lithium response, including focal adhesion and PI3K-Akt signaling.
  • In this new study, researchers confirmed these pathways in a larger group of 2039 patients but found no connection with the extracellular matrix, suggesting that issues with neuronal growth signaling may impact lithium effectiveness.
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The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English.

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  • The study examined the completion rates of telepsychiatry versus in-person psychiatric appointments for patients with depression over five years in an academic health system.
  • Results indicated that telepsychiatry became the primary method for psychiatric care during the COVID-19 pandemic, with completion rates for telepsychiatry appointments being significantly higher than for in-person visits.
  • The authors concluded that maintaining telepsychiatry services post-pandemic could enhance efficiency and patient care outcomes in the psychiatric field.
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Objectives: To understand treatment practices for bipolar disorders (BD), this study leveraged the Global Bipolar Cohort collaborative network to investigate pharmacotherapeutic treatment patterns in multiple cohorts of well-characterized individuals with BD in North America, Europe, and Australia.

Methods: Data on pharmacotherapy, demographics, diagnostic subtypes, and comorbidities were provided from each participating cohort. Individual site and regional pooled proportional meta-analyses with generalized linear mixed methods were conducted to identify prescription patterns.

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Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental health disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores.

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Background: The interaction of polygenic risk (PRS) and environmental effects on development of bipolar disorder (BD) is understudied, as are high-risk offspring perceptions of their family environment (FE). We tested the association of offspring-perceived FE in interaction with BD-PRS on liability for BD in offspring at high or low familial risk for BD.

Methods: Offspring of a parent with BD (oBD;  = 266) or no psychiatric disorders ( = 174), aged 12-21 at recruitment, participated in the US and Australia.

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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 non-responders (Li-NR).

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  • Lithium is recognized as a leading treatment for bipolar disorder, but predicting who will respond to it remains a challenge, leading researchers to investigate the genetic and functional differences between lithium responders and non-responders.
  • A study analyzing iPSC-derived neurons found 41 genes significantly expressed differently between these groups, and further gene prioritization identified over a thousand candidate genes related to lithium response.
  • The research highlighted the role of focal adhesion and the extracellular matrix in response mechanisms, indicating that differences in these areas may have a more significant impact on lithium treatment efficacy than the drug itself.
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  • Genome-wide association studies (GWAS) have identified many risk loci for mood disorders, but understanding the mechanisms is challenging due to small effects of common variants.
  • A study of the Old Order Amish population, with 1,672 participants, found four significant risk loci linked to over 2-fold increased risk of mood disorders.
  • The analysis indicated that these loci contain novel genes interacting with known neuropsychiatric ones, revealing key variants in genes CUX1 and CNOT1 related to neurodevelopment, thus enhancing our understanding of mood disorders' genetic basis.
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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 ( = 2,510) with BD were assessed for long-term lithium response in the Consortium on Lithium Genetics using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score.

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Electroconvulsive therapy (ECT) is a highly therapeutic and cost-effective treatment for severe and/or treatment-resistant major depression. However, because of the varied clinical practices, there is a great deal of heterogeneity in how ECT is delivered and documented. This represents both an opportunity to study how differences in implementation influence clinical outcomes and a challenge for carrying out coordinated quality improvement and research efforts across multiple ECT centers.

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We report results from the Bipolar Exome (BipEx) collaboration analysis of whole-exome sequencing of 13,933 patients with bipolar disorder (BD) matched with 14,422 controls. We find an excess of ultra-rare protein-truncating variants (PTVs) in patients with BD among genes under strong evolutionary constraint in both major BD subtypes. We find enrichment of ultra-rare PTVs within genes implicated from a recent schizophrenia exome meta-analysis (SCHEMA; 24,248 cases and 97,322 controls) and among binding targets of CHD8.

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Recent genetic studies have identified variants associated with bipolar disorder (BD), but it remains unclear how brain gene expression is altered in BD and how genetic risk for BD may contribute to these alterations. Here, we obtained transcriptomes from subgenual anterior cingulate cortex and amygdala samples from post-mortem brains of individuals with BD and neurotypical controls, including 511 total samples from 295 unique donors. We examined differential gene expression between cases and controls and the transcriptional effects of BD-associated genetic variants.

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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 lithium response in patients with bipolar disorder.

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