Related Experiment Video

Updated: Nov 17, 2025

An Unpredictable Chronic Mild Stress Protocol for Instigating Depressive Symptoms, Behavioral Changes and Negative Health Outcomes in Rodents
06:55

An Unpredictable Chronic Mild Stress Protocol for Instigating Depressive Symptoms, Behavioral Changes and Negative Health Outcomes in Rodents

Published on: December 2, 2015

23.0K

Mendelian randomization provides no evidence for a causal role in the bidirectional relationship between depression

Adil Harroud1, Ruth Ann Marrie2, Kathryn C Fitzgerald3

  • 1Department of Neurology, University of California San Francisco, San Francisco, CA, USA/Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA.

Multiple Sclerosis (Houndmills, Basingstoke, England)
|February 16, 2021
PubMed
Abstract

Insights

This study found no causal link between major depressive disorder (MDD) and multiple sclerosis (MS) using genetic data. Obesity, however, was linked to increased risk for both MDD and MS.

Area of Science:

  • Neuroscience
  • Genetics
  • Epidemiology

Background:

  • Major depressive disorder (MDD) is frequently observed in patients with multiple sclerosis (MS).
  • The incidence of MDD often precedes an MS diagnosis, raising questions about causality.
  • The bidirectional relationship between MS and MDD requires further investigation.

Purpose of the Study:

  • To investigate the potential causal relationship between MS and MDD.
  • To examine the directionality of the association between MS and MDD using Mendelian randomization.

Main Methods:

  • Utilized two-sample Mendelian randomization (MR) with large genetic datasets for MDD and MS.
  • Employed sensitivity analyses to detect and mitigate pleiotropy.
  • Conducted multivariable MR analyses, adjusting for body mass index (BMI).

Main Results:

  • No evidence supported a causal effect of genetic liability for MDD on MS risk.
  • No evidence supported a causal effect of genetic liability for MS on MDD risk.
  • Genetic predisposition to higher BMI was associated with increased odds of both MS and MDD.

Conclusions:

  • The study does not support a causal association between the genetic liability of MDD and MS susceptibility, or vice versa.
  • Obesity may be a shared genetic factor contributing to the increased incidence of depression observed before MS diagnosis.
Keywords:
Mendelian randomizationMultiple sclerosisgenetic epidemiologymajor depressive disorder

More Related Videos

A Multiple Integrated Social Stress Model for Psychiatric Disorders in Female C57BL/6J Mice06:15

A Multiple Integrated Social Stress Model for Psychiatric Disorders in Female C57BL/6J Mice

Published on: July 15, 2025

884
The Unpredictable Chronic Mild Stress Protocol for Inducing Anhedonia in Mice07:13

The Unpredictable Chronic Mild Stress Protocol for Inducing Anhedonia in Mice

Published on: October 24, 2018

18.2K

Related Concept Videos

Depressive Disorders: Etiology01:27

Depressive Disorders: Etiology

Depressive disorders result from a complex interplay of biological, psychological, and sociocultural factors, each contributing uniquely to the development and persistence of the condition. Understanding these factors provides critical insight into the multifaceted nature of depression.
Biological Factors in Depression
Biological predispositions significantly influence the risk of developing depressive disorders. Genetic studies highlight the role of variations in the serotonin transporter...
270
Human Genetics01:28

Human Genetics

Human genetics provides a profound framework for understanding the interplay between genetic predispositions and human psychology. At the heart of this discipline lies the study of how genes influence physical traits, behaviors, and susceptibility to diseases. Each person carries a unique genetic code that subtly or significantly shapes their psychological and behavioral landscape.
The complex relationship between genetics and psychology is observable through common biological components such...
1.1K
Biological Causes of Schizophrenia01:29

Biological Causes of Schizophrenia

Schizophrenia, a severe psychiatric disorder, arises from a complex interplay of biological factors, including genetic predisposition, structural brain abnormalities, neurotransmitter dysregulation, and developmental irregularities. These factors collectively contribute to the onset and progression of the disorder, which typically manifests in late adolescence or early adulthood.
Genetic Factors in Schizophrenia
The genetic basis of schizophrenia is strongly supported by family and twin...
256
Depression: Overview01:18

Depression: Overview

Depression is a prevalent mental illness marked by persistent sadness and lack of interest in previously enjoyable activities. It can take several forms, including major depression, persistent depressive disorder, and bipolar I and II disorders. Symptoms range from emotional changes like chronic worry to physical changes like sleep disturbances and suicidal thoughts. From a neurobiological perspective, depression is believed to be triggered by abnormalities in the brain's prefrontal cortex,...
556
Psychological and Sociocultural Causes of Schizophrenia01:29

Psychological and Sociocultural Causes of Schizophrenia

Schizophrenia, a complex psychiatric disorder, has been historically misunderstood. Early psychological theories attributed its origins to childhood trauma and unresponsive parenting. However, contemporary research largely rejects these notions, favoring the vulnerability-stress hypothesis. This model proposes that individuals with a genetic predisposition to schizophrenia may develop the disorder following exposure to significant environmental stressors. Notably, studies on high-risk...
296
Regression Toward the Mean01:52

Regression Toward the Mean

Regression toward the mean (“RTM”) is a phenomenon in which extremely high or low values—for example, and individual’s blood pressure at a particular moment—appear closer to a group’s average upon remeasuring. Although this statistical peculiarity is the result of random error and chance, it has been problematic across various medical, scientific, financial and psychological applications. In particular, RTM, if not taken into account, can interfere when...
6.6K