anxiety | The Mouse Trap

Pathological mental health problems in children and young adults have been classified into externalizing (substance abuse, conduct disorder etc) and internalizing disorders (depression , anxiety etc). Today’s post will try to work out the structure of this internalizing spectrum.

English: An anxious person (Photo credit: Wikipedia)

The first major difference, that is made in say DSM, is between Mood disorders (disturbance in mood) and Anxiety disorders (characterized by anxiety and avoidance behaviors) . However, Watson in this article (pdf) emphasizes that this classification is not proper and in many cases these disorder say depression (say MDD) and Anxiety (say Panic disorder) are co-morbid with each other.

To explain this as well as other genotypical and phenotypical findings, Watson has developed a structure of these ‘distress disorders’ – however the road was long, an intermediate stop was tripartite model of depression/anxiety.

According to this tripartite model (developed by Watson and Clark), both depression (MDD, dysthymia etc) and anxiety disorders (phobia, panic etc) share a common non-specific factor called Negative Affect (NA) which is characterized by things like preponderance of negative emotions like sadness, fear, guilt, anger etc as well as irritability, difficulty concentrating etc.

Depressive disorders meanwhile are specifically characterized by lack of Positive Affect (PA), which means less emotions like happiness, interest etc, but also Anhedonia or inability to derive pleasure from earlier pleasurable experiences. Anxiety disorders, on the other hand, are characterized by physiological hyper arousal (PH) (shortness of breath, dizzyness etc) .

This model however was also found wanting and replaced with an hierarchical integrative model, which posited that there was a generic non-specific factor of NA common to both anxiety and depressive disorders, and a lower order low PA factor characterizing depression and more specific multiple low order factors (instead of one PH hyperarousal factor) associated with the different types of anxiety disorders like panic/ agoraphobia, Phobia-specif stimuli, phobia social etc .

However , Watson further modified the structure and came up with this model shown below: One broad factor of distress/NA; two specific factors of anxious-misery and fear and then further unique factor specific to individual diagnosis.

To summarize and also extending it a a bit,

At top there is an internalizing spectrum and associated with it a non-specific NA factor.
In middle there are four spectrum:- a depressive spectrum , a Fear spectrum and a bipolar spectrum and an Obsessive compulsive spectrum.
each of these can be further divided into discrete diagnosis along two factors/dimensions (I will not eb focusing too much on bipolar or OCD for the purposes of this post) :
1. Depressive spectrum :
  1. group 1: MDD and dysthemia
  2. group 2: GAD and PTSD
2. Fear Sepctrum
  1. group 1: Panic and agarophobia
  2. group 2: Phobia (specific stimuli) and Social Phobia
3. Bipolar spectrum (bipolar I, II and cyclothymia)
4. OCD

Lets focus more closely on Depressive and Fear Spectrum and try to see alignment with ABCD model. MDD/Dysthemia imho are mainly about mood or Affect; GAD/PTSD are more Cognitive (reaming stuck in a thought loop) ; Panic/agorophobia more Physiological or Dynamic in nature and Phobia (both specific and Social) more Behavioral in nature (avoiding people, places and animals).

Each of these in turn splits into four factors; for ex PTSD splits into four factors- Dysphoria (A), Intrusions (C), Hyperarousal(D) and Avoidance (B). Similarly, recent research has shown that MDD is itself heterogeneous made up of four neural subtypes- one way to list those would be – marked primarily by Anhedonia (A), Anxiety (C) , Psychomotor retardation (D) and Fatigue (B) . Similar analysis should be possible for other discrete diagnosis.

For now, we will turn to the structure of Bipolar and OCD spectrum by analogy to dep/anxiety spectrum.

Biploar spectrum:
1. Euphoria (Affective)
2. Flight of ideas (Cognitive)
OCD spectrum
1. Obsessions (Dynamic)
2. Compulsions (Behavioural)

Within this OCD can be seen to be comprising of four factors: Hoarding (A?) , Order and symmetry (C), Obsessions and Checking (D) and Washing and cleaning (B).

Another way to think about the depressive and anxiety spectrum is to say that Depression rgoup 1 is characterized by Low PA, depression group 2 by high PH; Fear group 1 by High PH and Fear group 2 by low PA. What distinguished Fear spectrum from Depression spectrum is the fact that much more variance is explained by High NA for depressive syndromes and only moderate variance explained by NA for Fear syndromes.

What do you think is missing from the above model? Where might it be wrong? where might it be correct? If correct what are the implications?

Regular readers of The Mouse Trap will be familiar with my obsession with knowing how nature is carved at its joints or in other words what are the natural categories or basic kinds.

Anhedonia (The Graduate album) (Photo credit: Wikipedia)

This translates into thinking a lot about what are the fundamental drives, basic emotions and personalty traits and what taxonomic system of mental illness is most reflective of underlying fundamental nosological differences.

While synthesizing the work of others, has great value, and one derives many valuable theoretical insights based on such musings; there is nothing better than finding empirical studies that shed some light on such matters.

For example, I have argued that one set of disorders that arise form emotional polarity of fear/interest is Anxiety disorders and Obsession disorders. When fear is disproportional/ inappropriate to circumstances, it leads to anxiety; when interest is disproportional/ inappropriate it leads to Obsession. Fear and interest though opposed are two separate constructs as per the first tenet of positive psychology that good is not the absence of bad.

Similarly, the set of disorders that arise form sadness/ Joy polarity is depressive disorders and manic disorders. I am deliberately using plural form while defining depressive/ manic disorders as they contain sub-types – as we will soon see in the case of depression.

Now while depression is characterized by excessive low affect (sadness), one way to conceive Mania is as having excessive energy; the opposite of manic symptoms thus might be conceived of as fatigue or anergia. Anxiety is of course marked by excess anxiety while Obsession is too much interest; a possible opposite of obsession may be anhedonia– a sort of disinterest or apathy.

Now, its common to find depression and anxiety disorders comorbid with each other and just like treating bipolar as well as schizophrenia under one umbrella of psychosis, one may conceivably treat depression/ anxiety / anergia and anhedonia under a common nomenclature- in this case that of depression.

But we are perhaps getting ahead of ourselves. Lets backtrack a bit and go straight to this new study that found four neural subtypes of depression.

Basically, Liston and colleagues, used resting state fMRI to look at the functional connectivity of depressed patients and developed an algorithm to predict who has depression and who does not have in a sample consisting of both depressed patients and healthy controls. They found abnormal functional connectivity in frontostraital and limbic systems in teh depressive patients.

They also used clustering techniques to find that their depressive subset of patients clustered around two dimensions- one of which they called anxiety dimension and the other anhedonia. When one takes into account that there could be 2×2 = 4 combinations of anxiety and anhedoinia they found that their patients neatly clustered in those four quadrants.

If you note in the figure 1f accompanying the article,

cluster 1 subjects have low scores on anhedonia and high scores on anxiety
cluster 2 subjects have neither anxiety nor anhedonia
cluster 3 have high anhedonia but low anxiety
cluster 4 have both high anxiety and high anhedonia

The authors note that all subjects had low mood (sadness, hoplessness, helplessness) and that is why they were classified as depressed patients in the first place. The core depressive signature was also associetd with anergia and anhedonia with majority of patients showing these symptoms across all subtypes.

They also found slightly different neural signatures for all the four subtypes. For eg. cluster 1 & 4 characterized by high anxiety had reduced frontoamygdalar connectivity, linking it with fear circuit. Cluster 3 & 4 were associated with hyper connectivity between thalamic and frontostriatal networks and had high anhedonia and psychomotor retardation associated with them. And cluster 1 & 2 had reduced connectivity between anterior cingulate and orbitofrontal coretx involved in reward and incentive salience and guess what they showed anergia or fatigue.

To me it seems apparent that what we are seeing here are different effects of low mood, anxiety, anhedonia and anergia playing out as four clusters.

Cluster 3 I would classify as primarily anehdoina related; cluster 4 as primarily anxiety related; cluster 1 may be thought of as anergia related and clusetr 2 as pure depression or low mood related.

If my hunches are true we should find similar subdivisions in diagnosed anxiety disorders, obsessive disorders , manic disorders too. Of course that is an empirical fact to be proved.