Depression as a Network Disorder: Why Precision Approaches are Changing Treatment

Depression affects millions globally. For example, estimates by the World Health Organization (WHO) suggest that an estimated 5.7% of adults worldwide suffer from depression.¹ Data from Gallup suggest that in 2024 and 2025 more than 18% of U.S. adults reported having or being treated for depression.²

Depression can be debilitating because its symptoms can include, among others, persistent sadness, fatigue, loss of interest in daily activities and difficulty concentrating. Depression can result in lost productivity and missed days of work. Statistics from the WHO indicate that “Globally, an estimated 12 billion working days are lost every year to depression and anxiety at a cost of US$ 1 trillion per year in lost productivity.”³ 

Depression remains a leading cause of disability,⁴ in part because it significantly alters communication across the brain’s interconnected networks.⁵ Research shows that in major depressive disorder (MDD), the default mode network (DMN), which governs internal thoughts, becomes hyperactive, while the central executive network (CEN), which is responsible for planning and decision making, loses flexibility.⁶ This imbalance contributes to rumination, low motivation and cognitive fog.^7,8,9 

Functional connectivity studies have also shown impaired communication between the DMN subsystems in people experiencing depressive episodes.¹⁰ These disruptions help to explain why people often describe feeling “stuck,” or unable to shift out of negative thought loops, even when they want to.^11,12

Salma Health’s approach begins with a thorough evaluation of biological, psychological and neurological factors. This may include cognitive assessments, biomarker panels, and when indicated, imaging-based review to understand how depression is affecting your personal brain-network functioning.

Treatment plans often include psychotherapy, medication management and evidence-based neuromodulation. For people with treatment-resistant depression, accelerated fMRI-guided SAINT® therapy has shown rapid and profound improvements. In a pivotal double-blinded randomized controlled trial (RCT), 79% of participants achieved remission from depression after just five days of SAINT therapy, with an average time to remission of 2.6 days.¹³  

For others, Spravato® (esketamine) may be appropriate. Spravato targets multiple neurotransmitter systems, including glutamatergic signaling, and supports synaptic repair, improving network flexibility in ways that traditional antidepressants often cannot achieve as quickly.^14,15

Depression is not merely a chemical imbalance.^16,17 It is a complex network disorder, yet it is one that can be treated effectively when care is informed by science, precision and continuous support.

‍

‍

<sup>1. https://www.who.int/news-room/fact-sheets/detail/depression
2.  https://news.gallup.com/poll/694199/u.s.-depression-rate-remains-historically-high.aspx
3.  https://www.who.int/news-room/fact-sheets/detail/mental-health-at-work
4.  https://doi.org/10.1016/j.jpsychires.2024.07.054
5.   https://doi.org/10.1111/cns.12998
6.  https://contextualscience.org/sites/default/files/2025-07/Mahdieh%20Jafari%20-%20Default%20Mode%20Network%20%28DMN%29%20Signature%20of%20Depression_Maddie%20Jafari_36x48%20%281%29.pdf
7.  https://doi.org/10.1073/pnas.0812686106
8.  doi: 10.1093/scan/nsq080
9.  doi: 10.1162/netn_a_00056
10.  https://gpsych.bmj.com/content/gpsych/35/6/e100929.full.pdf
11.  doi: 10.1093/scan/nsad032
12.  https://doi.org/10.1146/annurev.clinpsy.121208.131305
13  https://pubmed.ncbi.nlm.nih.gov/34711062/
14.  https://doi.org/10.1038/s41386-023-01629-w
15.  doi: 10.1038/mp.2017.255
16. https://www.psychologytoday.com/us/blog/insight-therapy/202207/depression-is-not-caused-chemical-imbalance-in-the-brain
17.  https://doi.org/10.1038/s41380-022-01661-0</sup>