Painting by Stephen Magrath

In 2013, about two weeks before the APA released the Diagnostic and Statistics Manual’s 5th Edition (DSM-5; a $25 million dollar project), Tom Insel, then Director of the National Institute of Mental Health (NIMH), announced that the government’s largest funding agency for mental health research was slashing funding for projects that used DSM criteria for classifying mental illness. It was a few months after he delivered a TED talk outlining the failings of the mental health world and about two years before Insel left the NIMH and public research completely to head mental health efforts at Google. It was a pretty epic mic drop in terms of career departures by any standard, but this resulted in heated op-eds calling him a “rat”, a shill, and basically a brain fetishist both during and after his tenure.

The DSM is the bible for mental health practitioners and researchers in the US. It informs how patients are diagnosed and treated as well as how insurance claims are handled. While it’s helped to develop some effective interventions, it is fundamentally unreliable, kind of arbitrary, and confusing. The latest edition of the DSM includes about 15 additional diagnoses to the existing 300 outlined in the previous edition, as well as a dozen or three revisions to existing disorders. These changes influence how clinicians communicate (or fail to communicate) with each other and can lead to treatment-delaying bureaucratic gridlock between insurers and providers. As a side note, the manual switched from using Roman to Arabic numerals in its title because the editors wanted to prepare for even more changes going forward; made a big announcement about it like this was a good thing; and then got pissed at Tom Insel for not taking them seriously.

Contemporary researchers and well-meaning DSM editors aren’t to blame for this mess. In the early 20th Century, US psychiatrists and psychologists splintered from the rest of medicine because — unlike heart disease and Alzheimer’s disease, for example — mental illness was not clearly seen in the body in-vivo or postmortem. While other fields of medicine have made major breakthroughs in the past 100 years, progress in mental health has crawled. Clear medical markers of syndromes like depression didn’t reliably appear until advancements in neuroimaging (e.g., DTI and fMRI) in the 2000s, so the best that early practitioners could do was to come up with some kind of symptom-based classification system that unified the field. From there, practitioners could experiment with psychotherapies and medical treatments and hope that they maintained their patients’ and the publics’ trust.

One of the biggest limitations of the DSM is that the symptoms that characterize distinct DSM diagnoses appear across disorders. For instance, “concentration difficulty” appears as a clinical symptom of depression, anxiety, ADHD, PTSD, and so on. Depending on the clinician’s training, this symptom can mean different things in different contexts (when all you have is a hammer, as the saying goes, everything looks like a nail).

Consider the overlap between anxiety and depression. These are distinct diagnoses according to the DSM; however, they are considered highly comorbid, meaning that people are often diagnosed with both. However, comorbidity rates in anxiety and depression are at least in part due to overlapping symptoms and not to true comorbidity.

If this looks out of focus to you, it’s because it is

In fact, about 50% of psychiatry patients are diagnosed with more than one DSM disorder, and when you diagram all the other DSM diagnoses that map on to anxiety and depression symptoms you end up with something like this:

Ironically, Will Durant’s contributions are skipped in this diagram

Does this mean that anxiety and depression never co-occur? No. It makes sense that someone with a life history of feeling anxious might also develop a sense of worthlessness which would then classify them as as comorbidly depressed-anxious, but the two diagnoses have different risks and it’s important to catch people before those risks become reality. For instance, depression without comorbid anxiety is linked to a higher risk of suicide (which may seem obvious given the above symptoms), so it doesn’t help suicide prevention efforts when the two diagnoses are so enmeshed. Recruitment for depression research is often based on open calls for out-patient volunteers, who have typically been diagnosed by clinicians outside of the research project. They volunteer because they were told they were depressed even though they may also have shown signs of anxiety, PTSD, psychosis, etc. Because of a lack of standardized screening tools and adequate resources during the enrollment process, these patients can be included in depression studies and some studies don’t even bother to control for comorbid symptoms. As my dear friend, the conflict researcher, would say: it’s kind of a balagan.

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Insel’s main point was that successively adding diagnoses to the DSM was a misguided approach — it erodes trust in mental health research and practice, and the best we could do is break psychiatric syndromes down to specific symptoms, study them closely, and try to identify their biological roots. And, in fact when you do this, really interesting and helpful patterns begin to emerge.

Attention and Emotion in Depression and Anxiety

In addition to the DSM criteria above, really important and distinguishing behaviors and symptoms are observed in people with anxiety and depression, respectively. For instance, multiple studies have shown that people with anxiety are more sensitive to threatening subliminal information than non-anxious people. This is measured in a number of ways, but a classic example involves masking pictures of emotional faces at different thresholds of perception (e.g., present an image for a few seconds and then flash a picture of an emotional face for 10–50ms which most people cannot perceive) and then measuring biological reactivity (fMRI signals, heart rate, etc.) or recognition for these faces. Studies have reliably shown that anxious people are more sensitive to subliminal information than non-anxious adults, whereas in depression the findings are less reliable: sometimes that sensitivity is observed, sometimes it’s not.

This small behavior has a really interesting signature in the brain. Basically we’ve evolved to absorb massive amounts of information that may or may not be worthy of our awareness and attention, but we are wired to register it regardless. For example, many people are familiar with the feeling of walking into a room and immediately sensing tension without being able to identify the source. What’s likely happening in that moment is that your brain and thought processes were in an entirely different state prior to walking into the room (maybe you were planning on how to greet someone or rehearsing the argument you wanted to have with them, etc). Upon entering the room, a secondary visual system — one that bypasses brain areas linked to visual awareness and which connects directly to emotional areas (see arrow bonanza below) — has likely picked up enough threatening cues from the environment to produce feelings of destabilization and anxiety.

On the left: The eyeball parts connect to the traffic director part who sends info to the seeing parts. On the right? Eyeball parts connect to the traffic director who tells the gang over at emotions there’s a fire.

People with anxiety don’t have the luxury of a warm-up period or a visual awareness shield to protect them from all the signs of threat in the world. Their intuition system is naturally on high alert and when they walked into that room they were primed to pick up ambient anger and tension, causing a lot of distress. This hypersensitivity can disrupt a person’s ability to stay present and may be at the root of concentration difficulties in anxiety.

In people with depression, the patterns of awareness and attention look a little different. I say this cautiously because the neuroscience research findings around depression and anxiety are just beginning to come into focus. It appears that people with depression aren’t as sensitive to subtle cues of threat — but once they do perceive them it’s like they are locked in. They spend more time looking at negative information and when asked to focus their attention on information that is relevant to their goals, they can’t seem to disengage. This little behavior might be the source of a cascade of problems that develop into “depression”. While we currently don’t know the pattern of influence between symptoms, it’s possible that staring at an angry face for long enough builds semantic connections in the brain…leading to elaborate, dysfunctional beliefs…which are reinforced by rumination…which keeps the person awake at night…causing them to feel sluggish….and then they forget to eat…et cetera (for the record, this is slightly a hand-wavy but not-totally-inaccurate model of how depression develops). Once this constellation of symptoms develops, it’s hard to stop. Depression is progressive meaning that one episode of depression increases the likelihood of future episodes and the more episodes one has, the harder it is to treat. Again, narrowing the focus to pivotal behaviors that distinguish depression from other syndromes early can yield the best treatment outcomes and prevent future episodes from developing.

In fact, there’s a little cushion-like substructure of the thalamus (the traffic director in the above schematic) called the pulvinar, which is hyperactive and bigger in people with a life history of — and genetic vulnerability for — depression. (In ancient Rome, a pulvinar was an empty throne meant to symbolize departed heroes and gods.) Recent research has shown that the pulvinar is particularly responsive to medical interventions in depression which is great news! Basically, what the pulvinar is thought to do is synchronize brain networks that govern attention, emotion regulation, and self-reflection. In a non-depressed person, the pulvinar regulates these systems: through attention, that person can filter the ubiquitous, irrelevant crap in the world and the self-defeating noise and suddenly the world isn’t as overwhelming. But in those with dysfunctional pulvinar activity, thoughts, emotions, and attention crash into each other causing unnecessary suffering and confusion. By targeting the pulvinar and its functions, practitioners just might free themselves from playing whack-a-mole with downstream DSM symptoms and treat core issues that underpin big syndromes like depression.

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This is a cursory pass at two DSM diagnoses among the 300+ that the mental health world needs to unpack. Could Tom Insel stand to work on his delivery? Perhaps. Without the contributions of the DSM, we may have never discovered the relationship between attention and mood — it is important to track how symptoms relate to each other. But I also think that the sooner the mental health world stops defining and re-defining big syndromes, and aims to identify key behaviors and brain structures with jurisdiction over the most maladaptive symptoms, the sooner we’ll be able to heal our (pulvinar) heroes. This is not a wholesale endorsement for the pharmaceutical industry; in most cases efficacy of Mindfulness-based therapies is on par with drugs, which may be because they inherently target key issues like awareness and attention.

At its most basic, this is an appeal to stay clear and focused, and to not be afraid or disheartened by what our brain and bodies are trying to tell us.