Characterizing the Neural Substrates of Irritability in Women: an Experimental Neuroendocrine Model

What Was Tested

The trial (phase 2) is built around Leuprolide.

The long-term goal of this research is to advance understanding of the neural systems underlying both the triggering of and susceptibility to irritability in women.

It had two arms (groups): Hormone Sensitive Women (HS+) (experimental) and Hormone Insensitive Women (HS-) (experimental).

The registry classes the interventions as drug.

More on the Plan

Irritability, defined as a predisposition to exhibit anger, is a prominent, defining symptom of perinatal depression (PND) and many other neuropsychiatric disorders.

Because women will act as their own controls across time, this study design also allows for a powerful evaluation of state and trait variables that may contribute to irritability, including both threat and reward processing.

Identifying both state and trait markers of irritability, and disentangling them from the effects of reproductive hormones on brain and behavior, will allow for the identification of neural substrates of irritability susceptibility that can be investigated across neuropsychiatric disorders.

The expected outcome of this research is the identification of neural circuits underlying both the susceptibility to and mediation of irritability.

Who Took Part

Enrollment: 23 actual participants took part.

It was open to women only aged from 22 years up to 45 years.

Healthy volunteers could join, not only people with the condition.

Examples of who could join: Has been well for a minimum of one year;. A regular menstrual cycle for at least three months;. Medication free (including birth control pills);. Controls will meet all inclusion criteria specified above except they must not have any past or present Axis I diagnosis or evidence of menstrually related mood disorders.

The full record lists 6 inclusion and 18 exclusion criteria; among the exclusions: current axis i psychiatric diagnosis (based on a structured clinical interview for dsm-v (scid);; undiagnosed enlargement of the ovaries;; liver disease;.

How the Study Was Run

It was run as a non-randomized, parallel-group and double-blind study.

The Leuprolide group and the comparison group ran side by side rather than switching.

As a double-blind Leuprolide study, the assignments were hidden from both participants and investigators until the end.

Those kept unaware of assignments: participant and outcomes assessor.

It started in 2020-01-02 with completion listed for 2022-07-15.

It ran at 1 site in United States.

Its stated primary purpose is basic science.

What Was Measured

Primary outcome: Mean Threat Processing Bias During Visual Dot-probe Paradigm Over Time (time frame: up to 6 weeks). Mean Right Amygdala-medial Prefrontal Cortex BOLD Connectivity During Implicit Emotion Face Processing Task Over Time (time frame: up to 6 weeks). Mean Left Amygdala-medial Prefrontal Cortex BOLD Connectivity During Implicit Emotion Face Processing Task Over Time (time frame: up to 6 weeks).

It also tracked 5 secondary outcomes, for example Correlation Between the Inventory of Depressive and Anxiety Symptoms (IDAS) Ill -0.8Scale and Threat Attention Bias, Correlation Between Irritability and Reactive Aggression During Hormone Addback and Correlation Between Irritability Subcortical Activation in HS+ During Hormone Addback.

What This Means in Plain Language

Put simply, this is a phase 2, non-randomized trial of Leuprolide in 23 people.

Its size is small, so on its own it can only give an early look.

The trial is marked completed; results are posted on the registry, and this page does not restate them.

More context: the Leuprolide compound page, all human trials.