Psychiatric genetics — Does diagnosis matter?

Alda, Martin

doi:10.1503/jpn.170146

Cited by 2 publications

(1 citation statement)

References 15 publications

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“…A huge amount of work across several decades has been done to determine the genetic basis of SZ, bipolar disorder (BD), and major depressive disorder (MDD). However, to date no single causative genetic mutation or polymorphism has been conclusively identified predisposing to these disorders, although some genetic associations have been identified (Alda, 2017; Fabbri & Seretti, 2017). Recently, we invoked abnormalities of epigenetic mechanisms of gene expression to propose an omnigenic model for common psychiatric disorders like SZ, BD, and MDD (Peedicayil & Grayson, 2018).…”

Section: Introductionmentioning

confidence: 99%

Some implications of an epigenetic-based omnigenic model of psychiatric disorders

Peedicayil

Grayson

2018

Journal of Theoretical Biology

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Section: Introductionmentioning

confidence: 99%

Some implications of an epigenetic-based omnigenic model of psychiatric disorders

Peedicayil

Grayson

2018

Journal of Theoretical Biology

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Influence of functional gene polymorphisms on human behaviour: the case of CCR5

Albert

2021

jpn

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The idea that genetic changes can impact behaviour and lead to novel therapeutic approaches for mental illness has been an attractive, yet elusive hypothesis. A couple of recent papers in JPN build the case for the effectiveness of maraviroc in ameliorating depression 1 and reducing the addictive properties of opioids without preventing their analgesic effects. 2 Maraviroc is an antagonist of C-C motif chemokine receptor-5 (CCR5) and has been shown prevent HIV infection by blocking its coreceptor CCR5. These new studies build on the finding that people with a 32-bp deletion mutation that inactivates CCR5 (CCR5-Δ32) and show resistance to HIV also have improved cognitive outcomes after a stroke. 3 The studies also extend a growing literature implicating CCR5 in mental illness and suggest that further clinical studies using maraviroc as a novel treatment or adjuvant, particularly in patients with inflammatory depression involving immune dysregulation, 4 may be warranted. These findings suggest genetic polymorphisms with a strong functional impact (e.g., loss of function) may provide insight into mechanisms underlying certain forms of mental illness and lead to new treatments.Much effort has been directed at studying genetic variants (such as polymorphisms) that can be used to identify risk of major depression or to improve its treatment. Improving diagnosis of depression may help overcome obstacles to treatment response. The first-line treatment for major depression remains the selective serotonin reuptake inhibit or (SSRI) class of antidepressants, 5 even though these medications are effective in only 50% of patients, take several weeks to yield a response, and are associated with many adverse effects. 6,7 Thus, alternative strategies, including augmentation or switching to alternative monoaminetargeting compounds, cognitive behavioural therapy (CBT) and various brain stimulation approaches, are indicated for patients with SSRI-resistant depression. Ultimately, about 30% of patients are treatment resistant, 6 failing to respond to at least 3 treatments; most often electroconvulsive therapy or another form of brain stimulation is indicated, which may help half of these patients. 8,9 Better alternatives are needed to treat major depression, and genetic approaches may reveal new drug targets that could be exploited for treatment-resistant depression.

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Psychiatric genetics — Does diagnosis matter?

Cited by 2 publications

References 15 publications

Some implications of an epigenetic-based omnigenic model of psychiatric disorders

Some implications of an epigenetic-based omnigenic model of psychiatric disorders

Influence of functional gene polymorphisms on human behaviour: the case of CCR5

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