Sunday, December 18, 2011

White matter defects, anxiety and a few psychoanalytic observations

Recently I came across a write-up in Psychiatric News (May 20 2011) about a research conducted by Lars Westlye and associates in Norway (Arch of General Psychiatry April 2011) which shows that anxious people have disrupted white matter in amygdala and the areas that are networked with it namely: hippocampus, thalamus, subgenual cingulate and orbitofrontal cortices.

It sparked some thoughts in me which though speculative are worth penning down here.

The excerpt does not tell us what the authors mean by disruptive white matter. Perhaps they left it vague on purpose. And they use the term integrity, an even more ambiguous word, to explain disruption, and in a circular fashion explain disruption as decrease of integrity of the white matter, within and between cortices.

One can assume they are using 'disruption' and 'integrity' interchangeably, and what they mean is that the axonal connections between the gray matter (neuronal cell bodies) of the above mentioned cortices are not very good in anxious people. For the white matter is made up of axons. And the latter are cables of communication between brain cells.

Why is the communication between these brain areas not up to par in anxious?

Are anxious people born that way? Is the pathology inherited with the abnormal genes directing such axonal miswiring?

The authors thinks so, and do wonder whether drugs can be developed which will repair the disintegrity of the white matter. And add that genes responsible for anxiety bring this via defects in the brain white matter.

The excerpt does not tell us the evolutionary advantage/rationale behind such waywardness of axonal wiring.

Does anxiety confer benefits? And if it does what a strange mechanism to achieve this - disruption of neuronal connections!

If we get out of the mindset that anxiety is our enemy, and a precursor of Depression and Schizophrenia, which many claim it is - actually anxiety is precursor of all mental problems - and must be immediately quashed with drugs, we may be able to better understand the factors that generate anxiety and its adaptive functions.

What generates anxiety?

Amygdala of course, one may smartmouth.

But that does not tell us very much. Why did Amygdala evolve in the first place? And hanging the hat upon amygdala, how useful it is in treating anxiety clinically?

Whether anxiety is generated by Amygdala or Hippocampus or Medulla Oblangata or the Spinal Cord or even the liver, it really does not matter, at least not when one is sitting across the patient in the office trying to make sense as to why he is so anxious.T he patient may get very impressed by such tongue twisters, and may give you more respect than you deserve thinking you know some cool stuff, but it will be no more than a shared illusion. Knowing which Brodmann areas of the brain get activated, or go quiescent, when one is anxious is good business for cutting edge PBS documentaries, motivational speakers who invoke half-baked psychological concepts on the strength of MRI slides to raise your self esteem and capture your attention,  and those psychiatrists who think that essence of psychiatry lies in impressing patients with one's knowledge of neurology, but knowing the anatomy of anxiety circuits helps not one whit in dealing with it in practice.  

But instead of digressing in to polemics let us examine what we know about anxiety at the clinical level.

The first thing we notice is that anxiety appears to be more prevalent in those whose nervous system appears to be genetically superior not impaired. Maybe we should start appreciating presence of anxiety more as an indicator of superior genetic inheritance and less as a harbinger of more serious mental illnesses.

And it is not difficult to see why. If you have more neurons [nerves] the more attributes you will have, but also greater liability for the rich store of neuronal networks going haywire and turning you into a bundle of nerves (nervousness). And in fact having more neurons/nerves bestows advantage only in the long run and not always. In the beginning, it is, more often than not, a handicap. For a heavily endowed nervous system is a double edged sword. Failure to find the right developmental environment which would facilitate proper and adequate axonal connections between these rich clusters (nuclei) of neurons can turn the heavily loaded  nervous system in to an organization where its components are more at cross purposes than in harmony.

If you look at children with ADHD, who are very often quite nervous and neurologically awkward in social situations and in class rooms where they have to learn things which allows no motor outlets but listening to  lectures which are boring at that level of maturity, they generally show a wonderfully coordinated and rich nervous system when playing fast-paced sports. As if while playing sports the neuronal nuclei (Gray matter) generally employed for such tasks can find proper connection with each other without difficulty, unlike in situations where the child has to show social etiquette which are more appropriate for the hypocritical world of the adults and in class rooms where essence of the world is distilled for them not directly but by aid of language and other symbolic systems which their impatient system is not yet ready to deal with but reluctantly.

And this may sound counter intuitive but longevity itself appears to be positively associated with anxiety. Most people I see in their Eighties and Nineties, I find they were worry warts all their lives. As if worrying about something happening to them through illness (hypochondriasis/obsessive somatic anxiety) made them take good care of their health to the very last days of their life. Granted many of them did not show overt anxiety - hiding it through binding it with obsessive behaviors and rituals - but there is little doubt that constant anxiety about something harmful happening to them had made them live extra carefully, enabling them to keep their illnesses at bay longer than non-worriers.

Perhaps we can reject the crude assumption that anxious disposition is due to some inherited abnormality in the development of axonal connections arising out of bad genes. In fact it may be quite the reverse: there may be superior genes lying behind sparse connections.

If we go forward with the assumption that anxiety is not an illness, but an affective signal arriving at the consciousness, telling the ego (organized part of the self) to "anticipate harm" and gear up for "fight or flight", which gets pathologically intense in some people, we may be able to shed some light on the problem of why sparse and abnormal connections may exist between different cortical centers, including amygdala, in anxious individuals.

Anxious people are all the time preparing themselves either to run away or fight with some anticipated danger. But what surprises us is the pathological intensity of the fear and about things that are most unlikely to happen.  Depending upon what these dangers symbolize to the worrier in his unconscious, they may worry about such remote things as tornadoes, getting cancer, the family dying with carbon monoxide or food poisoning, financial disaster, taking a business trip to California because of running in to earthquake, skin blemishes that nobody would notice, to name a few. And so the average psychiatrist rightly assumes that such worry warts are out of their mind and deserve to be soaked with drugs and brainwashing - though they euphemistically give the latter the respectable acronym CBT [Cognitive Behavioral Therapy].

What kind of people are those who make mountain out of molehills?

Here we make a gratifying discovery.

Higher the intelligence greater is the perspicacity in seeing the dangerous aspect of things. And one who sees more danger than friendliness in one's universe is compelled to practice greater vigilance and preparedness to bolt from and/or attack the source of danger. And why would it be not so. A rock has no intelligence and hence no readiness to react if someone comes to blow it up with dynamite. The tree has no such preparedness either, despite being living and thus having choices, when they come to cut it down. A multipede on the other hand runs when you try to stomp it, while a lion is likely to attack you back instead of taking off. A monkey may pretend to run from a tiger, go up the tree, and then from behind pull the tiger's tail as I recently saw in a hilarious U-tube posting.

So higher the organism in the evolutionary scale, greater is the preparation to deal with the danger through running away or fighting back with it, even making a game of it.

But why would this superior evolutionary status also makes a person do things that are counter to his interests, in fact, often ruinous to his body? For a sustained fear of harm from things and issues that one can do nothing about keeps the person tense and tight, with sweaty palms, vigilant eyes, and a revved up cardiovascular, glucocorticoid and immune systems.

And how can we look upon the behavior of anxious folks, who to avoid danger are often frozen into inactivity, locked up inside the house, sometimes afraid to the point of leaving their bedroom, as a product of superior genes?

It appears that people with superior neuronal endowment often have a problem in finding proper and sufficient  outlet for their 'bounty' of neuronal masses. For neurons need discharge for a person to rest. So when the time comes for a particular neuronal mass to get activated and be included in the already existing neuronal networks, instead of making orderly entrance and enriching the person's repertoire of behaviours they can easily emerge in a chaotic fashion and as a drag upon the overall functioning, if the handlers of the child are not doing their job right or if the strength of the drives is overwhelming and incompatible with his other drives. It has to be that way because if you have more attributes [drives] then more strongly they will express themselves and try to jostle each other out.

Since neuronal networks often work by strengthening each other if they can make a common cause, and inhibiting each other if they are on cross purposes, the person with a high neuronal load has greater necessity to develop proper networkings - sympathetic harmony - to find sufficient outlets for his drives/needs.

And here the factor of environment comes in to play.

So in genetically predisposed individuals lack of enough or too punitive or too much stimulation during childhood leads to the development of a nervous system where its different parts are in cross purposes; acting independently of each other rather than in sympathetic harmony. And it is this lack of proper connections between different nuclei of the brain, each of them acting more independently than they would have if they had received ideal upbringing, that causes anxiety. For anxiety appears to be a subjective realization that one's nervous system is too revved up. If more neuronal circuits are active and functioning without proper coordination, more will be the subjective sense of anxiety. For anxiety is best conceptualized as highly activated brain nuclei, all ready to go, but with insufficient networking between them to allow a properly coordinated discharge.

Let us see this obtuse theoretical discussion in clinical light.

Let us take a child in throes of Oedipal Conflict. In this highly conflictual phase of development, the networks of neuronal masses that govern child's libidinal attraction towards the mother are in conflict with his libidinal attraction towards his father, both of which are in conflict with the neuronal networks that enforce repression across the board upon all libidinal expression. All three trends are opposed to each other. And they all strive for expression (discharge). For only their expression, and thus discharge, will cause neuronal quiescence and rest and cessation of anxiety.

Now the ideal situation would be for all three neuronal masses to develop rich connections back and forth between them in a manner that will allow maximal expression for each. But such optimal expression - sympathetic harmony between the three subsystems - will occur through mutual compromises (proper inhibitory activities between them), since the three trends are basically opposed to each other.

Now if the environment where the child is being raised is not quite proper, there will be abnormal connections between these three trends; more inhibitions than necessary in some circuitry, while excessive strengthening of others. For example if the parents are emotionally or physically unavailable to the child, or they are in frequent fights with each other, or are excessively punitive or threatening to the child, there will be weak libidinal expression towards both of them, and consequently towards all external objects and auroerotic narcissistic masturbatory activities will become the preferred mode of expression of the libido. The networks connecting the ego (the organized part of the self) with the neuronal substrates (imagos) of parents will become weak (inhibited), while there will be greater activation of the neuronal substrates of one's own ego (narcissism) whenever there is libidinal arousal.

Again taking a different Oedipal scenario. If the mother is too dependent or seductive towards the child then there will be excessive libidinal connections between the child and the mother, and generation of unusually strong hatred towards the father and poor axonal connections between his imago and the self.

In short growing up involves different brain nuclei coming into their prime at different phases of development, and the absolute quantity of their expression depends upon the facilitatory and inhibitory connections that they make with other nuclei. These connections while mostly phylogenetically determined, also depend upon what kind of environment one is growing up in. If the environment is too punitive or too permissive or simply emotionally unavailable then all kinds of abnormalities develop in their interconnections, leaving these nuclei to function more independently instead of in harmony. This results in their inability to find discharge, which causes the person to be in a state of more or less continous alert, which is perceived by consciousness as anxiety.

Perhaps the above discussion is still too theoretical and incomprehensible, so let us examine case history of an actual child.

A four year old child who was happily adjusted to life - though even from an age as early as 11 months he showed a phobia of elevators and closed places and had shown great difficulty in separating from his parents (neophobia)- suddenly developed fears of all kinds, especially of animals.

Analysis showed that he was in an intense Oedipal libidinal longing for his mother, which was generating unbearable hostility towards his father. Besides animals, he showed fear of big vehicles, darkness, large spaces, anything massive and new. They were all displaced fear of his father. The unconscious logic behind fearing these father substitutes was that they were coming to get him for harboring evil intentions: "If my father only got wind of what I am thinking of doing to him, he will come after me with the ferocity of these frightening entities and objects."

Why the Oedipal phase was so strong in this boy?

The genetics of course played a major role. Both the parents were anxiety prone. But there were environmental factors as well. While both his parents loved him very much, they had drifted apart from each other and the mother had been using the boy to fulfill her need to love passionately. She had taken the child as a replacement for her self-absorbed husband. So here was the element of too much facilitation of white matter between the mother and child, setting the stage for too much inhibitions of those axonal connections that were networking libidinal bonding between him and his father.

But the boy's fever pitch hostility could not go on indefinitely. The hatred was generating images in his consciousness that were showing his father getting eaten up by a leopard or meeting some other equally violent fate. Just before the outbreak of his neurosis he had seen a Disney animated Tarzan movie, which showed in graphic details Tarzan locked in mortal combat with a leopard. The scenes were extraordinarily frightening and unpredictable had highly stimulated and scared the child. Few weeks later he had come down with the fear of animals. 

Why the fear had not emerged directly as that of father but of a father substitute the leopard or rather other animals around his house which were again substitutes for the leopard?

This was the result of the inhibitions generated by the neuronal networks of libido between him and his father - for he loved his father very dearly too. So the neuronal masses that generated his love for his father were sending impulses to block the neuronal masses that harbored his hatred for him

Additional inhibitions were sent upon his own ego [the neuronal networks that gave him sense of self] that was producing the motor images of his father getting killed as well, and also upon the neuronal circuits that were generating his libidinal motor impulses towards his mother.

And these inhibitions had a far reaching consequences upon his subsequent development. He lost much of his interest in books and reading, a skill which he had just acquired, because his primary image of his father was of him reading, and he did not want to come in to Oedipal competition with his father on this matter.

A whole range of Tourettian impulses arose in him as well, which were displacement of motor images to attack his father with knives and other objects. These were derived from his suspicion that his father did similar sadistic things to his mother - a reverberation of infantile sexual theories that children make up at that age to solve the riddle of sexuality and childirth.

His phobic fears subsided after he suddenly became obsessed with a Christmas song, "I saw Mommy kissing Santa Cluas." He insisted that the song be played all the time, and his parents had to find as many versions of it as they could from department stores, because his love for the song was insatiable. Santa Claus symbolized the father of course, and it was acknowledgment of his Oedipal defeat and reconciliation with the unpalatable reality that the mother belonged more to father than to him.

The obsession with that Christmas song soon changed into an obsession with numbers and he showed some remarkably precocious abilities with mathematics. The roots of this obsession with numbers at bottom were an attempt to first conjure up images of his father's death and then undo it.

As to his phobias, they changed from specific objects to a generalized fear. Animals were no longer feared, nor was darkness and open spaces and the big sculptures of dinosaurs etc. in the local park. All these symbols of father ceased to be the dreaded objects they had been  for a few months. And with the development of a generalized anxiety his love for his mother and father both showed a dramatic fall, and he became more interested in watching libidinal tendencies of other people - people who were not family. Along with the development of this incest barrier there was also a change in his libidinal expression. Instead of everything  being about him and his parents, he became more interested in the libidinal activities of the world at large. From an actor he became a spectator. 

How all this is connected with inadequate and disrupted white matter connections between amygdala and other nuclei?

In this boy who had a volcanic eruption of the Oedipal phase of sexuality, within a family structure where there was inadequate love between the parents, and where there was too much closeness between him and his mother, the neuronal networks that were forged by Oedipal conflicts were done in less than ideal manner. His hostility towards his father emerged way too strong, and which could be contained only by turning it against his own ego that left whole range of excessive inhibitions in reading and other cognitive tasks and caused mild Tourette's and moderate obsessions.

I will conjecture that it is these kinds of inhibitions that show up in the MRIs of anxious people as disorders of white matter.