Most people know depression as a condition of low mood, sadness, or loss of interest. But for many, depression also brings something less talked about but just as disabling: a mental “slowing” or brain fog. Research led by Dr. Susannah Murphy and others shows that these thinking problems called Cognitive Dysfunction are a core feature of depression, not just a side effect.

What is Cognitive Dysfunction?

Cognitive dysfunction refers to difficulties with:

• Attention and focus-staying on tasks feel impossible
• Memory-forgetting details or conversations
• Processing speed-thinking, reading or reacting more slowly
• Executive skills-planning, organizing, making decisions

Dr. Murphy’s article “When the Fog Doesn’t Lift: Targeting Cognitive Dysfunction in Depression” highlights that 85-94% of people with major depression experience some cognitive difficulties especially slower thinking and decision making. These problems often persist even after mood symptoms improve.

Why Processing Speed Slows Down

Depression isn’t just a mental state; it changes how the brain works. Chronic stress, low levels of certain neurotransmitters (like serotonin, norepinephrine, dopamine), and even inflammation can disrupt networks in the prefrontal cortex and hippocampus. These areas are essential for fast thinking, attention, and memory. This results in everyday activities such as reading email, doing work tasks, responding to friends take more effort and more time. People may feel “mentally tired” all day, even with adequate sleep.

Medications Can Play a Role Too

SSRIs-common antidepressants like fluoxetine, sertraline, and citalopram are effective at improving mood, but some patients notice lingering or even new problems with mental speed, especially early in treatment.

Research shows SSRI’s can, in some individuals, slightly dampen processing speed or alertness as the brain adapts to changes in serotonin levels. For most people this is temporary, but for some it may persist.

Neurobiological changes

• Inflammation and Oxidative stress: High levels of inflammatory markers, oxidative damage can injure neurons or impair synaptic function.
• Neuroplasticity deficits: Changes in brain derived neurotrophic factors (BDNF), dendritic atrophy (loss of dendrites), especially in hippocampus and prefrontal cortex.

Structural brain changes

• Altered connectivity, reduced volume or function in certain brain areas like the hippocampus, prefrontal cortex.
• Aging and repeated depressive episodes may lead to more entrenched structural changes.

Other contributing/comorbid factors

Sleep disruption, medical conditions (diabetes, thyroid dysfunction, cardiovascular issues, B12 deficiency, menopause, Alzheimer’s, vascular dementia, Lewy body dementia, sleep apnea, brain injury, stroke), Medication side effects (SSRI’s), Psychosocial stressors (chronic stress, social isolation, trauma which increases cortisol and overtimes harms hippocampus and prefrontal cortex, lifestyle factors (poor diet, lack of exercise and substance abuse)

Why This Matters

Cognitive dysfunction isn’t just an inconvenience. It can:

• Make work or school more difficult
• Reduce social connection
• Increase relapse risk (people with lingering cognitive symptoms are more likely to get depressed again)
• Lower overall quality of life
• Depression combined with cognitive impairment increases risk of developing dementia more than alone.

What You Can Do

If you’re experiencing depression and feel mentally slow, talk to your clinician. Ask specifically about your thinking and memory, not just mood.
Together you can:

• Review your medications (some have more cognitive side effects than others)
• Consider therapies or exercises designed to improve thinking skills
• Make lifestyle changes that help the brain (regular exercise, good sleep, balanced diet, and mindfulness)

Targeting Cognition by Dr. Murphy and Colleagues

1. Pharmacologic interventions such as Vortioxetine (Trintellix) and Repurposing drugs such as prucalopride
2. Non-Pharmacological Interventions such as Cognitive remediation/training, TMS (transcranial magnetic stimulation) and Psychotherapy/Behavioral interventions

The Takeaway

Depression is more than sadness; it can literally slow down your brain. Dr. Murphy’s work reminds us that effective depression treatment should target thinking and processing speed as well as mood. With the right combination of treatments and lifestyle support, many people can lift not only their mood but also the mental fog.