Genetics of antidepressant response and treatment-resistant depression

Chung, Albert E.; Chen, Tzu-Ting

doi:10.1016/bs.pbr.2023.01.002

Cited by 4 publications

(9 citation statements)

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“…The largest meta-analysis of genome-wide association studies (GWASs) to date targeting MDD indicated that single nucleotide variant–related heritability was estimated at approximately 8%. Similarly, the occurrence of antidepressant responses and treatment-resistant phenotype (or treatment-resistant depression [TRD]) may possess a genetic basis and be transmitted within a family . For example, first-degree relatives of patients with depression responded similarly to amin-oxidase inhibitors or imipramine for depression symptoms .…”

Section: Introductionmentioning

confidence: 99%

“…Generally, the definition of TRD is accepted as not having achieved remission after at least 2 adequate trials of antidepressant treatment within the current depressive episode . In recent years, an increasing number of genetic studies have attempted to understand the genetic architecture of antidepressant response or TRD phenotype using diverse methods, such as candidate gene association studies, GWASs, whole genome sequencing, and copy number variation studies . Although the efforts to understand the genetic mechanism behind antidepressant response are promising, these positive results require more replication and must overcome methodological concerns, such as relatively small sample size and diverse definitions of TRD .…”

Section: Introductionmentioning

confidence: 99%

“…Similarly, the occurrence of antidepressant responses and treatment-resistant phenotype (or treatment-resistant depression [TRD]) may possess a genetic basis and be transmitted within a family. [3][4][5] For example, first-degree relatives of patients with depression responded similarly to aminoxidase inhibitors or imipramine for depression symptoms. 4 An early family study 5 found that individuals with depression within a family responded to tranylcypromine but not to several tricyclic antidepressants.…”

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confidence: 99%

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Susceptibility to Treatment-Resistant Depression Within Families

Cheng,

Chen,

Tsai

et al. 2024

JAMA Psychiatry

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ImportanceAntidepressant responses and the phenotype of treatment-resistant depression (TRD) are believed to have a genetic basis. Genetic susceptibility between the TRD phenotype and other psychiatric disorders has also been established in previous genetic studies, but population-based cohort studies have not yet provided evidence to support these outcomes.ObjectiveTo estimate the TRD susceptibility and the susceptibility between TRD and other psychiatric disorders within families in a nationwide insurance cohort with extremely high coverage and comprehensive health care data.Design, Setting, and ParticipantsThis cohort study assessed data from the Taiwan national health insurance database across entire population (N = 26 554 001) between January 2003 and December 2017. Data analysis was performed from August 2021 to April 2023. TRD was defined as having experienced at least 3 distinct antidepressant treatments in the current episode, each with adequate dose and duration, based on the prescribing records. Then, we identified the first-degree relatives of individuals with TRD (n = 34 467). A 1:4 comparison group (n = 137 868) of first-degree relatives of individuals without TRD was arranged for the comparison group, matched by birth year, sex, and kinship.Main Outcomes and MeasuresModified Poisson regression analyses were performed and adjusted relative risks (aRRs) and 95% CIs were calculated for the risk of TRD, the risk of other major psychiatric disorders, and different causes of mortality.ResultsThis study included 172 335 participants (88 330 male and 84 005 female; mean [SD] age at beginning of follow-up, 22.9 [18.1] years). First-degree relatives of individuals with TRD had lower incomes, more physical comorbidities, higher suicide mortality, and increased risk of developing TRD (aRR, 9.16; 95% CI, 7.21-11.63) and higher risk of other psychiatric disorders than matched control individuals, including schizophrenia (aRR, 2.36; 95% CI, 2.10-2.65), bipolar disorder (aRR, 3.74; 95% CI, 3.39-4.13), major depressive disorder (aRR, 3.65; 95% CI, 3.44-3.87), attention-deficit/hyperactivity disorders (aRR, 2.38; 95% CI, 2.20-2.58), autism spectrum disorder (aRR, 2.26; 95% CI, 1.86-2.74), anxiety disorder (aRR, 2.71; 95% CI, 2.59-2.84), and obsessive-compulsive disorder (aRR, 3.14; 95% CI, 2.70-3.66). Sensitivity and subgroup analyses validated the robustness of the findings.Conclusions and RelevanceTo our knowledge, this study is the largest and perhaps first nationwide cohort study to demonstrate TRD phenotype transmission across families and coaggregation with other major psychiatric disorders. Patients with a family history of TRD had an increased risk of suicide mortality and tendency toward antidepressant resistance; therefore, more intensive treatments for depressive symptoms might be considered earlier, rather than antidepressant monotherapy.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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confidence: 99%

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Susceptibility to Treatment-Resistant Depression Within Families

Cheng,

Chen,

Tsai

et al. 2024

JAMA Psychiatry

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“…The term ”treatment-resistant depression” (TRD) describes a medical condition in patients with MDD who do not respond adequately to two schemes of antidepressant drugs at an adequate dose within an expected period, typically around four weeks [ 19 ]. Pharmacological therapy for depression often fails due to genetic variations that affect patient response [ 20 ], highlighting the need for alternative therapies, such as transcranial magnetic stimulation (TMS). TMS offers direct modulation of cortical activity and has been proven effective in cases of TRD, also presenting a favorable safety profile.…”

Section: Introductionmentioning

confidence: 99%

Technical Report: Efficacy and Safety of Low-Intensity Transcranial Magnetic Stimulation in the Remission of Depressive Symptoms in Patients With Treatment-Resistant Depression in Mexico

Rodríguez Hernández,

Medrano Espinosa,

Sampieri-Cabrera

et al. 2024

Cureus

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Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation technique that induces action potentials in the stimulated cortical area and has been approved by the Food and Drug Administration (FDA) for the treatment of major depressive disorder (MDD). The prevalence of MDD in Mexico almost tripled after the COVID-19 pandemic. In this study, we evaluated the safety and therapeutic effects of lowintensity TMS (Li-TMS) -characterized by inducing electric currents below the action potential threshold on the cerebral cortex -in 41 subjects diagnosed with treatment-resistant depression (TRD). A Li-TMS device dispensed repetitive magnetic pulses at 30 mT for 60 minutes during 20 sessions (once daily from Monday to Saturday) with the theta burst pattern. Our results suggest that Li-TMS is a safe therapy with antidepressant effects, demonstrated by the decrease in Beck Depression Inventory (BDI) scores and lessening of depressive symptoms.

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“…Despite evaluation of drug posology selection, there is variation among individuals in drug response as a result of many different parameters associated with different factors including genomic [16][17][18][19][20], immunological [20,21], pharmacological [22,23] and toxicological variations [24,25], as well as interactions with drugs, dietary substances, etc. Similarly, there are also differences among individuals in drug response as a result of many other limitations such as underlying disease pathological complications, variations in organ functioning, idiosyncratic reactions, accessibility to effective drug posology due to high cost and other variations [22][23][24][25][26].…”

Section: Introductionmentioning

confidence: 99%

Drug Selection and Posology, Optimal Therapies and Risk/Benefit Assessment in Medicine: The Paradigm of Iron-Chelating Drugs

Kontoghiorghes

2023

IJMS

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The design of clinical protocols and the selection of drugs with appropriate posology are critical parameters for therapeutic outcomes. Optimal therapeutic protocols could ideally be designed in all diseases including for millions of patients affected by excess iron deposition (EID) toxicity based on personalised medicine parameters, as well as many variations and limitations. EID is an adverse prognostic factor for all diseases and especially for millions of chronically red-blood-cell-transfused patients. Differences in iron chelation therapy posology cause disappointing results in neurodegenerative diseases at low doses, but lifesaving outcomes in thalassemia major (TM) when using higher doses. In particular, the transformation of TM from a fatal to a chronic disease has been achieved using effective doses of oral deferiprone (L1), which improved compliance and cleared excess toxic iron from the heart associated with increased mortality in TM. Furthermore, effective L1 and L1/deferoxamine combination posology resulted in the complete elimination of EID and the maintenance of normal iron store levels in TM. The selection of effective chelation protocols has been monitored by MRI T2* diagnosis for EID levels in different organs. Millions of other iron-loaded patients with sickle cell anemia, myelodysplasia and haemopoietic stem cell transplantation, or non-iron-loaded categories with EID in different organs could also benefit from such chelation therapy advances. Drawbacks of chelation therapy include drug toxicity in some patients and also the wide use of suboptimal chelation protocols, resulting in ineffective therapies. Drug metabolic effects, and interactions with other metals, drugs and dietary molecules also affected iron chelation therapy. Drug selection and the identification of effective or optimal dose protocols are essential for positive therapeutic outcomes in the use of chelating drugs in TM and other iron-loaded and non-iron-loaded conditions, as well as general iron toxicity.

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Genetics of antidepressant response and treatment-resistant depression

Cited by 4 publications

References 146 publications

Susceptibility to Treatment-Resistant Depression Within Families

Susceptibility to Treatment-Resistant Depression Within Families

Technical Report: Efficacy and Safety of Low-Intensity Transcranial Magnetic Stimulation in the Remission of Depressive Symptoms in Patients With Treatment-Resistant Depression in Mexico

Drug Selection and Posology, Optimal Therapies and Risk/Benefit Assessment in Medicine: The Paradigm of Iron-Chelating Drugs

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