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  • Writer's pictureThe OAD Clinic

Connecting Anxiety, Depression and PTSD through Neural Phenotypes

Updated: Jun 16, 2023


Deep research into the grounds of psychopathology has extensively focused on two chief etiologic categories: genetic vulnerability and environmental factors. A crucial role

for heritable/familial factors in the aetiology of a broad range of psychiatric disorders was established well before the modern era of genomic research. In this article, we will focus on the genetic basis of three disorder categories—major depressive disorder (MDD), the anxiety disorders, and posttraumatic stress disorder (PTSD)—for which stress responses and environmental stressors chiefly contribute towards pathogenesis. Each of these disorders runs in families and have been revealed to be moderately heritable. We will also reveal the possible connections between the three disorders based on the neural phenotypes as assessed by the functional MRI of the affected individuals and control population.

What is Anxiety?

Anxiety is your body’s natural response to stress. It’s a feeling of fear or worry regarding what’s to come. Anxiety disorders refer to a group of mental illnesses, and the distress they cause can keep you from carrying on with your life normally. The umbrella includes Generalised Anxiety Disorder, Specific Phobias, and Social Anxiety Disorder.

What is depression?

Depression (major depressive disorder) is a serious psychological disorder that negatively impacts your emotions, how you feel, your thought process and thus, your actions. However, it is treatable in most cases. Depression is characterized by feelings of grief and/or a loss of interest in daily activities (that were once enjoyed). Leading to a variety of physical and emotional symptoms, depression can decrease a person’s ability to function at work and at home.

What is PTSD?

Post-traumatic stress disorder (PTSD) is a mental disorder that's triggered by a terrifying incident — either witnessing it or experiencing it. Symptoms may include nightmares, flashbacks, and severe anxiety, as well as uncontrollable thoughts about the event.

What are Neural Phenotypes? Evaluating the Genetic Basis of Psychiatric Disorders

Psychiatric disorders are prevalent, complex, and severe disorders that affect the core of an individual: their emotions, intellect, and ability to self-regulate.

The diverse research in this topic reflect various opinions and approaches in the field of neuropsychiatric genetics and neurodegeneration and could be understood as innovative responses to the challenges in the research on common complex disorders. Neurogenetics collects aspects from both the studies of neuroscience and genetics, focusing in particular how the genetic code of an organism affects the traits it expresses. Neurological diseases, behaviour and personality are all studied in a neurogenetic context.

There is a significant overlap between the symptoms of post-traumatic stress disorder (PTSD), anxiety disorders, and mood disorders — like major depressive disorder and bipolar disorder. For example, someone with a generalised anxiety disorder might exhibit depressive symptoms, and someone with the major depressive disorder might experience excessive anxious states.

Family Studies

Evaluating the influence of genetics towards psychiatric disorders (as with other complex disorders) typically involves a series of questions and study designs. The first question remains, whether the disorder is inherited in families. Family studies are typically conducted to compare the prevalence of illness among first-degree relatives of affected individuals.

Association Studies

For multifaceted disorders, association studies remain more powerful for recognising risk loci and have become the dominant strategy for genetic studies of psychiatric disorders. Association studies typically utilise a case-control design to determine whether specific genetic variants (alleles) are more common among affected (cases) than among unaffected individuals (controls). Association studies have been used to assess different classes of DNA variation pertinent to psychopathology. The genetic makeup of a phenotype refers to the entire complement of underlying genetic risks factors including their number, allele frequencies, and effect sizes of contributing variants.

Use of Brain Imaging to Connect the Dots Between Anxiety Disorder, PTSD, and Mood Disorders

According to the JAMA study:

"Up to 90% of patients with an anxiety disorder meet criteria for a concurrent mood disorder, and as many as 70% of individuals with mood disorders meet criteria for an anxiety disorder during their lifetime."

The overlap of symptoms in these comorbid conditions infers that there have to be neurological similarities between the two conditions. To elucidate the findings, 9000 functional MRI’s from both diseased and control population were evaluated to unlock inner pathophysiology underlying these interconnected neurological disorders.

Hypoactivation of Inhibitory Areas

The clusters of hypoactivation were found in the following areas:

· Prefrontal cortex/Insula

· Inferior parietal lobule

· Putamen

These regions represent the right-dominant brain system which is chiefly involved in the contextual shifting and stopping of brain impulses and behavioural responses.

The right inferior prefrontal cortex is exceedingly relevant when it comes to inhibition of contextually inappropriate affective, cognitive, and motor responses. This phenomenon is generally known as Salience.

Neurocognitive studies in mood and anxiety disorders also indicate a general disruption in cognitive control because they consistently report deficits of large effect size in stopping and shifting responses in a range of tasks.

These hypoactive areas correspond to the symptoms that we observe in these patients, like the inability to switch between tasks or particular emotions. “Locked in” states may also be explained very well through this finding as this is exactly what lack of salience can lead to.

Clusters of Hyperactivation

3 chief clusters of hyperactivation were found

- The left amygdala/parahippocampal gyrus (involved in emotional memory formation and retrieval)

- The left thalamus,

- The perigenual/dorsal anterior cingulate cortex (involved in regulatory influence for appraisal and emotional experience as well as generation of internal autonomic and their associated expressive emotional responses)

The relative hyperactivation points towards the notion that these individuals have lower thresholds to arousal in response to stress factors. However, it could not be ruled out if these factors can/can't be attributed to the stress related to fMRI scans.


The study concluded that

In this transdiagnostic study for mood disorders, posttraumatic stress disorder, and anxiety disorders, the most consistent abnormalities were found in the task-related brain activity in the regions that are primarily associated with inhibitory control and salience processing.

This revelation regarding significant overlap in functional MRIs of these interconnected psychological disorders gives way for future interventions that can be directed towards these pathways and prevent morbidity in these affective studies.


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