The Disordered Mind

The Disordered Mind: what unusual brains tell us about ourselves - Eric Kandel

What's the angle?
   Kandel is a neuroscientist and writer, whose work on learning and memory led to a Nobel Prize. He's also quite the art buff, and has written extensively about art and creativity. I loved this book, and his writing. It is textbooky: deliberate (he starts each chapter with a brief outline, then finishes with a brief summary), clear syntax and pace, lots of vocabulary - which he defines along the way. Only it isn't 1,000 pages with tiny cramped type, thank goodness. I especially enjoyed his careful combination of psychological and neurological research. The disciplines need each other, he stresses, and need to find some common language.

What is depression?
   Kandel writes that "depression is probably not one but several different disorders, with different degrees of severity and different biological mechanisms." Later in his discussion he describes depression and bipolar disorder as disruptions of the "connections between the brain structures responsible for emotion, thought, and memory." More or less, though, he proceeds without a definition of depression; I guess he basically assumes the DSM criteria. 
   He doesn't spend time trying to distinguish between "normal" down-times and depression episodes, or between grief and depression, or between environmental and biological "triggers." He's interested in a biological analysis of what depression looks like in action, in the brain, and he highlights the research of Helen Mayberg, who has identified a sort-of neural "circuit" for depression. Mayberg focuses on several "nodes" of this circuit, especially "cortical area 25." Kandel also mentions promising research into the stress-response system, the hypothalamic-pituitary-adrenal axis.
   He doesn't specifically hypothesize that one day, doctors will diagnose depression biologically rather than psychologically, but we could assume that would be theoretically possible, based on his vision of a more complete convergence of the two disciplines. More likely, in the nearer future, neuroscientists and geneticists will predict more and more accurately someone's risk for becoming depressed.

What are the genetics of depression?
   He doesn't say much about this, just that the "understanding of the genetics of depression and bipolar disorder is still in the early stages." He does cite some research into the likelihood of depression for an identical twin whose counterpart has depression, (40%) as compared to siblings (less than 8%), as compared to the general likelihood of having depression (6-8%).

How can you treat depression?
    Kandel doesn't recommend anything, but is optimistic about the ability of neuroscience to analyze the efficacy of drugs and therapies with new imaging techniques and animal models. He's also optimistic about the ability of scientists to identify new and better ways to intervene in the neural circuit(s) of depression.


notes

• modern studies of consciousness and its disorders suggest that consciousness is not a single, uniform function of the brain; instead, it is different states of mind in different contexts
• Philippe Pinel (late 18thc) - argued that psychiatric disorders strike people who have a hereditary disposition and who are exposed to excessive social or psychological stress
• Santiago Ramon y Cajal (late 19thc): cell has four parts
• body
• dentrites (receptors)
• axon (long arm)
• presynaptic terminal (synapse is area b/w terminal and dendrite)
• dynamic polarization - info flows only one way (from dendrite to body to axon to terminal)
• action potential - potential voltage between outside (+) and inside (-) cell body 
• when cell "fires" the ion channels open and charge switches
• action potential is all or none
• signal intensity is determined by number or frequency of "fires"
• can divide genetic illnesses into two groups: simple (Mendelian?) or complex
• Identical twins
• autism 90%, bipolar 70%, schiz 50%, depr 40%
• siblings
• 20%, 5-10%, 10%, <8%
• general pop
• 1-3%, 1%, 1%, 6-8%
• copy number variations - sections deleted or copied
• de novo mutations
• arise spontaneously in sperm
• number of mutations increases with paternal age
• 20 yr old - avg of 25 mutations; 40 yr old - avg of 65 mutations
• recent study revealed that teens with autism have too many synapses (not enough synpatic pruning)
• de novo mutations occur more frequently in genes that code for synaptic proteins
• as Darwin first pointed out, emotions are part of a preverbal system of communication that we share with other mammals
• Kraepelin used same diagnostic criteria from general medicine
• what are symptoms?
• what is course of disease?
• what is final outcome?
• he distinguished b/w disorders of thought and disorders of mood; dimentia praecox and manic-depressive illness
• the average length of remission in major depression is about three months
• depression is probably not one but several different disorders, with different degrees of severity and different biological mechanism
• hypothalamic-pituitary-adrenal axis
• excessive concentrations of cortisol destroy synaptic connections between neurons in the hippocampus, the region of the brain that is important in memory storage, and neurons in the prefrontal cortex, which regulates a person's will to live and influences a person's decision making and memory storage
• the amygdala determines what emotion is recruited, and the hypothalamus carries it out
• Helen Mayberg: neural circuit of depression has several nodes, two of which are particularly critical
• cortical area 25 (subcallosal cingulate cortex) - thought, motor control, and drive come together; also rich in neurons that produce serotonin transporters - proteins that remove serotonin from the synapes (these transporters are very active in depressed people)
• right anterior insula - receives info from senses about physiological state and helps generate emotions to respond
• serotonin and dopamine are modulatory transmitters - tunes whole circuits or regions
• mediating neurotransmitter - acts directly on target cell (excitatory or inhibitory)
• modulatory - fine-tunes action of mediating neurotransmitters
• studies of depression suggest that whenever area 25 becomes hyperactive, the components of the neural circuit concerned with emotion are literally disconnected from the thinking brain, leading to a loss of personal identity
• Freud's three key observaions
• children have sexual and aggressive behavioral instincts
• children suppress and render unconscious the conflicts between early needs and prohibitions, as well as early traumas
• the patient's relationship with the therapist reenacts the patient's early relationship (transference), and plays a central role in the therapeutic process
• Mayberg - used electrodes to slow firing rate in area 25
• about 25% of people with major depression go on to experience a manic episode
• differences in the brains of depressed and manic states have been difficult to document
• understanding of the genetics of depression and bipolar disorder is still in the early stages...they disrupt the connections between the brain structures responsible for emotion, thought, and memory
• the emerging view of schizophrenia as a neurodevelopmental disorder that, unlike autism, manifests itself later in life has arise from the considerable genetic research done on the disease
• positive symptoms of sch. - disordered volition and thinking
• negative symptoms - social withdrawal and lack of motivation
• many typical antipsychotics act by blocking dopamine receptors
• may involve problems in serotonergic and histaminergic pathways, as well as in dopaminergic pathways
• in schiz, synaptic pruning appears to go haywire during adolescence (too much pruning going on)
• polymorphism, common variation - more than 1% of world's pop; rare variation, or mutation, is less than 1%
• autism, schiz, and bipolar share some genetic variants
• about 30% with 22q11 deletion syndrome are diagnosed with psychiatric disorders
• overexpressed D2 receptors
• memory is the glue that holds our mental life together
• Larry Squire - two major memory systems
• explicit or declarative - conscious memory
• implicit or non-declarative - motor and perceptual skills, automatic
• both kinds can be stored short term or long term
• alzheimers, parkinsons, huntington - protein folding disorders, protiens clump up, kill neurons
• Alois Riegl - the beholder's share, creative process involved in viewing art
• creativity related to the lifting of inhibitions
• left and right hemispheres inhibit each other; damage to left side can actually enable more creative action of right side
• almost 30% of people on the autism spectrum exhibit special skills in music, memory, numerical and calendar calculations, drawing, or language
• creativity doesn't appear to be related to IQ
• sensory feedback neurons - create internal sense of body and relative position of limbs - proprioception
• in the broadest sense, the task of every circuit in the nervous system is to add up the total excitatory and inhibitory information it receives and determine whether to pass that information along. Sherrington called this principle "the intergrative action of the nervous system."
• prion - misfolded precursor protein - they self-propagate, cause other proteins to misfold
• emotions are states of readiness that arise in our brain in response to our surroundings
• the study of emotions and moods helps reveal the porous boundaries between unconscious and conscious mental processes
• 1st step of emotion - unconsious and outward; 2nd step - subjective and internal
• emotions classified along two axes
• valence - how good or bad something makes us feel on a spectrum from avoidance to approach
• intensity - degree of arousal
• four key areas for emotion
• hypothalamus - executor of emotion; controls instinctive behavior
• amygdala - orchestrates emotion; links unconscious and conscious aspects of an emotional experience
• striatum - habits
• prefrontal cortex - evaluates whether a particular emotional response is appropriate; interacts with and exerts some control over amygdala and striatum
• direct and indirect pathways to the amygdala
• emotion so important in decision making and morality; directs and narrow choices
• all positive or pleasurable emotions traced to dopamine
• a reward is any object or event that produces approach behavior and leads us to sped attention and energy on it
• heritability of addiction moderately high: roughly 50%
• addiction - pleasure decreases while memory/habit conditioning strengthens
• pharmaceutical companies have devoted very little effort to developing drugs to treat addiction
• sex and gender identity are determined separately, at different times in the course of development
• sex
• chromosomal - 23rd pair xy or xx
• anatomical - external genitalia and other visible differences
• gonadal - presence of male or female gonads - testes or ovaries
• gender specific behaviors triggered in different ways - humans particularly sensitive to visual and auditory cues, a fact successfully exploited by the pornography industry
• the neural circuits that control the gender specific behavior of each sex are present in both sexes
• sexual dimorphisms visible in the brain
• greater variation within each sex than between sexes
• since sexual differentiation of the genitals takes place in the first two months of pregnancy and sexual differentiation of the brain starts in the second half of pregnancy, these two processes can be influenced independently, which may result in transsexuality
• those who identify as transgender in adolescence almost always do so permanently
• a nucleus or cluster or neurons in hypothalamus that contains mating neurons and fighting neurons and then some that can be involved in either
• consiousness
• level of arousal
• content of processing
• Searle - three key aspects of consiousness
• qualitative feeling
• subjectivity
• unity of experience
• reticular activating system - wakefulness
• Bernard Baars - global workspace theory; widespread dissemination of previously unconscious info
• without a good psychology of the conscious state we can't make progress in the biology of broadcasting information, and without the biology we will never understand the underlying mechanism of consiousness
• percept - mental representation of an object
• Benjamin Libet - readiness potential (before an action)
• the process of initiating a voluntary action occurs rapidly in an unconscious part of the brain; however, just before the action is begun, consciousness, which comes into play more slowly, approves or vetoes the action
• Kahneman - fast and slow thinking
• neurology and psychiatry will merge into a common clinical discipline that focuses increasingly on the patient as an individual with particular genetic predispositions to health and disease