Recovery Wellness and the Brain Presented by Craig

Recovery, Wellness and the Brain Presented by Craig Strickland, Ph. D, Owner Biobehavioral Education & Consultation https: /sites. google. com/site/bioedcon cstrickland 1977@gmail. com

History “Insanity, when uncomplicated, properly and promptly treated, and having this treatment duly persevered in, may be regarded as curable as most other serious diseases; but its curability mainly depends upon these conditions. Of the class of cases alluded to, it is safe to say that about as many as eighty percent may be expected to recover. ” Thomas Kirkbride (1880)

Initial theories of Mental Illness �Evil spirits �Lack of proper relationship with God(s) �Unbalanced humors: black bile, yellow bile, phlegm and blood �Schizophrenogenic mother

More recent theories of mental illness �Freud and the neuroses �Chemical imbalances �Diathesis Stress Model ◦ Genetic vulnerability ◦ Environmental stressors ◦ A Seesaw

Initial Treatments for Mental Illness �Separation/segregation/imprisonment �Prayer and religious activities �Exorcism �Adjusting the “humors” �Hypothermia �Insulin injections & inducing seizures �Electroconvulsive therapy (ECT) �Psychosurgery

Development of Neuroscience & Psychopharmacology

Development of Neuroscience �More sophisticated techniques ◦ Electron microscope ◦ Brain imaging: MRIs; f. MRIs, etc. ◦ Blood-oxygen Level Dependence (BOLD) studies ◦ Radiographic tracing ◦ Human genome project �Better understanding of neuroanatomy and neurochemistry �Better support for psychopharmacology �Downside: reduction of all experiences to biology (need biopsychosocial!)

Psychopharmacology as a Treatment Choice

What are the goals of Psychopharmacology?

Original purposes of Psychopharmacology �Behavioral control & restraint ◦ Reduce aggression/sedation ◦ Reduce self harm e. g. self-mutilation, suicidality �Stabilize symptoms �Allow for more interpersonal interaction (reduce self-isolation) and…. �Deinstitutionalization �But where is recovery?

Early Psychopharmacology �Use of non-prescribed substances ◦ Psychedelic substances: LSD, psilocybin, etc. ) �Coming back? ◦ ◦ Cocaine (Freud) Alcohol Opium Even noxious substances (hemlock) �Use of sedatives: pills and injectables

More Contemporary Developments � 1952: Thorazine (and other first generation anti-psychotics) �Anti-depressants (to replace/reduce use of ECT): different generations �Mood Stabilizers (starting with Lithium) �Anti-anxiety compounds e. g. benzodiazepines (Valium, etc. )

Research “breakthroughs”? �Again, Thorazine �Anti-convulsant mood stabilizers (alternative to Lithium) �Second generation anti-psychotic medications (starting with Clozaril) �Selective Serotonergic Reuptake Inhibitors (SSRIs, starting with Prozac) �Sleep Aids �Current research: MDMA & Ketamine �But where is recovery?

Changing Brain Structure, Function and Recovery

Changing Brain Activity �Neuroplasticity versus neurogenesis e. g. interactions with the nervous system and the environment ◦ Neurogenesis: the creation of new nerve cells (neurons) ◦ Neuroplasticity: increase (or decrease) in the connections between neurons (next slide)

Neuroplasticity: Classic example

Example: Interaction Between Environment & Genes/Nervous system

Example: Amblyopia: Use it or lose it � Amblyopia (“lazy eye”): cannot see clear image in the affected eye; child “ignores” the vision in the affected eye; note there is no damage to the eye nor the retina ◦ If the eye is not realigned by late childhood, vision becomes dimmed; by adulthood, almost complete suppression of pattern vision in the affected eye ◦ Realignment in adulthood does not restore vision ◦ Suggests that unusual positioning of the eyes during early development changes connections or visual circuits in the brain

�Let’s name some possible sources, situations, etc. which might cause neural changes in the nervous system/brain

Negative Effects on the Brain (Wired for Negativity)

Negative Effects on the Brain �Extreme Stress/Traumatic Exposure �Substance Abuse ◦ In utero: FAE/FAS ◦ As an adult: Korsakoff’s Syndrome �Neglect/environmental deprivation �Malnutrition �Infectious disease e. g. syphilis

Trauma as Environmental Exposure

Trauma as seen on a continuum Acute Stress Disorder PTSD Chronic PTSD Complex Trauma Symptom Duration & Severity

Hippocampu s

Normal Functions of the Hippocampus �The hippocampus is a very complex structure �Is part of the Limbic System �Considered “transitional” tissue �Normal functions include (but may not be limited to) ◦ Memory consolidation: works together with newer cortical brain areas �Integration of “emotional tone” with “higher” cognitive functions �Cortex provides semantic influence to the more episodic (factual) “hippocampal” memories ◦ Behavioral inhibition ◦ Inhibitory influence on brainstem activity

Original Studies: Hippocampus & Trauma �Decrease volume (size) of the hippocampus ◦ This is a robust finding �Vietnam vets: 8 to 26% reduction depending on the study � 7% reduction in women with history of childhood sexual abuse � 16% reduction in hippocampal volume in women with BPD (often associated with a history of abuse) ◦ Seen in other psychiatric disorders such as schizophrenia ◦ Has been shown to occur in animal models involving experimental stressors

Chicken or the Egg?

The Chicken or the Egg? (Gilbertson, et. al. 2002)

Chicken or Egg? (cont. ) �Apfel, et. al. (2011) ◦ Gilbertson study did not contain true longitudinal data ◦ This of course would be nearly impossible to do in this type research ◦ Apfel study looked at hippocampal volume in 244 male Gulf War Veterans �Study included those with current PTSD and those where the symptoms of PTSD were remitted

Chicken or Egg? (cont. ) �In addition to measuring symptoms of PTSD (using the Clinician Administered PTSD Scale (CAPS) assessment tool: ◦ Measured presence or absence of depression ◦ Measured lifetime drinking history ◦ History of other (non-combat related) stressors �Used structural MRI techniques to measure hippocampal volume

Chicken or Egg? (cont. ) �Started with four groups of subjects ◦ Subjects with no traumatic exposure ◦ Subjects with exposure but no PTSD ◦ Subjects with a previous diagnosis of PTSD but have recovered ◦ Subjects with chronic PTSD (lifetime and current) �The first two groups had identical hippocampal volume and were combined into one group for the further analysis

Chicken or Egg? (cont. ) �Results ◦ Subjects with current/lifetime PTSD �Subjects with current/lifetime PTSD had smaller hippocampi by 5. 1% than those who had never developed PTSD � 6. 5% smaller hippocampi than those who had recovered from PTSD ◦ Note: there was no difference in hippocampal size between those who never had PTSD and those who had recovered from PTSD ◦ Hmmm…

Chicken or Egg? (cont. ) �The significant differences remained even after accounting for the following factors: ◦ Early life trauma ◦ Current and lifetime alcohol use ◦ Depression and treatment with antidepressants � Thus, a smaller hippocampus cannot be a vulnerability factor (e. g. a genetically driven cause) of PTSD; if this were the case, the group that recovered should have a hippocampal size that is smaller than those who never developed PTSD. This finding does NOT mean that hippocampal size is NOT related to the symptoms of PTSD

Chicken or Egg? (cont. ) �The results raise the possibility that hippocampal volume is state-dependent and might vary over time e. g. the hippocampus may itself recover from the effects of PTSD; support for this interpretation? ◦ Duration & severity of PTSD symptoms are negatively correlated with hippocampal volume ◦ Hippocampal volume can increase as a result of long-term Paxil treatment ◦ Hippocampal volume might change as a result of exercise, other medications and abstinence from alcohol �E. G. Neurogenesis and/or neuroplasticity

Slightly Different Interpretation of the Data �People who recover from PTSD or who recover more readily may not have experienced a smaller hippocampal volume �However, those who have the smaller (perhaps genetically driven) hippocampi are ◦ More prone (higher risk) to develop PTSD which may be more treatment resistant ◦ Thus a smaller hippocampus would be detrimental to recovery �Bottom line: does this study show a causal effect of a smaller hippocampus on the development of PTSD?

Symptoms Associated with Hippocampal Damage? (Reexperiencing) �Dissociation and/or intrusive thoughts �Illusions and/or hallucinations �Behavioral disinhibition: causes the definition of incoming stimuli towards fight/flight responses �Along with amygdaloid activation, hippocampal damage may prevent proper evaluation & categorization of experiences/stimuli ◦ May lead to reacting to new or neutral stimuli as threatening ◦ This would lead to either aggressive behavior or possibly to withdrawal

DEVELOPMENTAL ISSUES: HYPERAROUSAL & TRAUMA

Some Developmental Issues: Hyperarousal & Trauma �Two primary systems associated with hyperarousal (stress response systems) ◦ Hypothalamic pituitary axis (HPA) ◦ The Sympathetic Nervous System

Hypothalamic Pituitary Axis System Sympathetic Nervous

Maltreatment in Children �Ciccheti and Rogosh (2001): ◦ Children who had multiple stressors (physically and sexually abused) showed substantially elevated AM cortisol levels ◦ Children with only one type of stressor (physical abuse) showed a trend toward lower AM cortisol levels ◦ Thus, maltreatment is associated with higher activity in the hypothalamic pituitary axis; and the number & type of stressors matters

Children: Following Acute Stressors � Pervanidou, et. al. (2007): studied (60) children exposed to motor vehicle accidents (MVAs) ◦ After 1 month post accident � 30% had PTSD and exhibited elevated plasma NE levels than those without PTSD and controls �Salivary cortisol levels were also higher ◦ At 6 months, 15 of the 30 continued to meet PTSD criteria �NE levels remained higher (even higher at 6 months than 1 month) �However, cortisol levels were now back to baseline ◦ Relationship between environment & brain chemistry

Enhancing Brain Activity

Positive Effects on the Brain �Enhance brain derived neurotrophic factors (BDNFs) �Hippocampal Neurogenesis �Monitoring nutrition �Non-pharmaceutical interventions ◦ Eye Movement Desensitization & Reprocessing (EMDR) ◦ Cognitive Behavioral Therapy ◦ Spirituality ◦ Breathing, biofeedback, neurofeedback ◦ Meditation/Mindfulness �Cognitive Remediation

Influences on Neuronal Development �Biochemical influences ◦ Nerve Growth Factor (NGF): a protein that controls the development and survival of certain neuron/axons; also called a neurotrophin (means “nerve nourishment”) �Prevents apoptosis (programmed mechanism of cell death) �Positive life’s experiences cause increased neurotrophin secretion which increase branching of incoming axons �Evidence that PTSD disrupts brain derived neurotrophic factors in hippocampus (L&M)

Mindfulness: “Being awake to life as it is unfolding” �Study the effects of mindfulness on genetic expression (activity) ◦ Experimental group: experienced meditators who engaged in mindfulness ◦ Control group: engaged in quiet nonmeditative activities

Mindfulness �Results: ◦ Changes in genetic & molecular activity in the experimental group only ◦ Genes affected were those involved in anti -inflammatory regulation and those involved with response to analgesic drugs

Neurogenesis �Creation of new nerve cells (neurons) in the brain does not happen easily �Three areas: Olfactory epithelium, Subventricular zone & Hippocampus �What is associated with smaller hippocampal volume? ◦ Alcoholism ◦ Repeated traumatic exposure ◦ Depression

Hippocampal Neurogenesis �Selective serotonergic reuptake inhibitors: ◦ Prozac, Paxil, Zoloft, Celexa, Lexapro, Lovox) ◦ Have been associated with neurogenesis in some parts of the hippocampus ◦ Two have been approved for PTSD �Zoloft �Paxil

Hippocampal Neurogenesis �Exercise: ◦ Relationship between exercise and neurogenesis established in rodents for some time ◦ Columbia University: in human beings, exercise appears to create new hippocampal neurons in the dentate gyrus, which is a part of the hippocampus

Nutrition �The brain thrives on proteins, oxygen and glucose; however, neurons cannot generate these materials and rely on glial (supportive) cells in the brain �Vitamins are important for brain function (especially B vitamins) �Anxiety can be decreased by decreasing: ◦ Alcohol ◦ Caffeine ◦ Raw sugars

What Facilitates Neural Plasticity? �Fostering includes: a positive environment which ◦ Safety and security where person has clear expectations of the environment itself and those around him/her ◦ Opportunity for exploring and interacting with the environment ◦ Learning opportunities ◦ Appropriate amounts of sensory stimulation ◦ Interpersonal connections (vagal nerve research to be covered later)

Schizophrenia, Cognition, Cognitive Remediation and Recovery

Schizophrenia �Positive symptoms �Negative Symptoms �Functional Disabilities �Cognitive deficits ◦ Psychopharmacology has not been very successful in reducing cognitive deficits ◦ But what is cognition?

What is Cognition? �Cognition is defined as “all processes by which sensory input is transformed, reduced, elaborated, stored, recovered, and used. It is concerned with these processes even when they operate in the absence of relevant stimulation, as in images and hallucinations…” (from the Wikipedia Free Encyclopedia, 2005)

Some of the Domains of Cognition �Memory (working memory) �Attention �Perception �Knowledge representation �Reasoning �Creativity �Problem solving

So what causes cognitive deficits associated with schizophrenia?

Biological findings Laboratory of Neuro Imaging And Brain Mapping Division, UCLA School Of Medicine �From neuroimaging: ◦ Enlarged lateral ventricles ◦ Decreased hippocampal volume and other limbic structures

Biological Findings (cont. ) Laboratory of Neuro Imaging And Brain Mapping Division, UCLA School Of Medicine �Schizophrenia is related to excessive pruning of gray matter in higher brain regions

Amount of synaptic growthpruning 1 st Theory: Changes are evident early on but parallel to controls Controls Schizophrenia Age 5 10 15 20 Keshavan, et. al. J of Psychiatric Research (1994)

Amount of synaptic growthpruning 2 nd Theory: Changes in Synaptic structures more pronounced in adolescence Controls Schizophrenia Age 5 10 15 20 Keshavan, et. al. J of Psychiatric Research (1994)

Cognitive Remediation Therapies

Cognitive Remediation and Recovery �Cognitive remediation therapy (CRT), also called cognitive enhancement therapy (CET), is a cognitive rehabilitation therapy developed to improve neurocognitive abilities such as attention, working memory, cognitive flexibility and planning, and executive functioning which leads to improved social functioning.

Examples of Some CET techniques �The Stroop Test: Selection Attention �N Back Test: Working Memory �Wisconsin Card Sort: Reasoning and Conceptual Flexibility “Test me, test me, why don’t you arrest me. ” Random Grateful Dead Quote

The Stroop Test: Selective Attention �Measures accuracy, reaction time and neural functioning

The Stroop Test: Selective Attention �The anterior cingulate cortex is involved in whether the response is correct or not (e. g. response evaluation). This Photo by Unknown Author is licensed under CC BY-SA

N Back Test: Working Memory

N Back Test: Working Memory �Activates and involves various parts of the cortex This Photo by Unknown Author is licensed u

Wisconsin Card Sort Test: Reasoning & Conceptual Flexibility

Wisconsin Card Sort Test: Reasoning & Conceptual Flexibility �Requires activation of various regions of the prefrontal cortex

Wisconsin Card Sort Test: Reasoning & Conceptual Flexibility �Brain ◦ ◦ regions involved in : Strategic planning Organized searching Modulating impulsive responding Directing behavior toward achieving a goal

Bottom Line �Cognitive symptoms must be addressed in a number of diagnoses ◦ Mental illness (and addiction) is not a life sentence ◦ The brain can change for the good or the bad; it depends on our genes, our environment and our will to heal �Recovery means helping the whole person through whatever means it takes

Polyvagal Theory, Vagal Nerve Stimulation (VNS) and Trauma & Depression

The Vagus Nerve Picture provided by Peter Jurek, MA, MS http: //www. peterjurek. com

Polyvagal Theory �How things work: ◦ Cortical Control of brainstem ◦ Brainstem regulation of the autonomic nervous system ◦ Autonomic nervous system �Sympathetic nervous system �Parasympathetic nervous �Mammals versus reptiles and vagal evolution (and the freezing response)

Polyvagal Theory: Dr. Stephen Porges � Taken from Bing Images

Polyvagal Theory �In what clinical conditions might you expect to see the freezing response? ◦ ◦ Traumatic exposure Depression Anxiety diagnoses Other?

Social Engagement System �Changes in cardiopulmonary function �Voice quality: prosody ◦ Intonation and tone ◦ Stress and rhythm ◦ Vocalizations in our pets (my lovely Noelle!) �Eye contact and movement �Facial and head muscles

Polyvagal Theory in Practice: what can we do? �Explain the roles the different systems play �Educate that what their nervous systems/bodies are doing is based on survival, trying to keep the person safe (minimize disappointment, shame or anger about these biological responses) �Discuss that interpersonal interactions can change nervous system function �Minimize “older” circuit activity (next slide)

Minimize Older Circuit Activity �Mindfulness ◦ Mindful of which environmental triggers lead to freezing response ◦ Become mindful of what happens in the body e. g. what physical effects occur before the freezing response ◦ Encourage small movements �Be aware of any changes in activity in the sympathetic nervous system (muscle tension, sweating, heart racing, racing thoughts, etc. )

Explaining to Clients �We are mammals not reptiles ◦ Mammals have newer vagal system ◦ Newer vagal system is part of social engagement system which may need to be strengthened ◦ But we have the older vagal system which, while important, may need to be weakened �The vagal nerve is not damaged by trauma, depression, etc. ; it has in essence been “reset”. Therapy can help restore the original “setting”

What is vagal nerve stimulation (VNS)? �Note: this is an FDA approved technique (2005) for refractory depression; also approved (1997) as adjunctive therapy for partial-onset epilepsy �A pulse generator is surgically implanted in the left chest area under the clavicle �The leads from the generator are “wrapped” around the left vagus nerve branch; the right branch is avoided since it controls some aspects of cardiac function �Intermittent pulses are delivered to the nerve

How does VNS work? �Exact anti-depressant mechanism unknown ◦ Stimulation does affect blood flow in various regions of the brain ◦ As a result, neurotransmitter activity increases, including 5 -HT and NE which would have an anti-depressant affect �Side-effects: alteration of voice quality & loudness (during pulses only), hoarseness, throat pain, dyspnea (shortness of breath) & paresthesia �Enhance social engagement system? ? ?

Other uses for VNS? �Various anxiety disorders �Alzheimer’s disease �Migraines �Fibromyalgia

�“A fine glass vase goes from treasure to trash, the moment it is broken. Fortunately, something else happens to you and me. Pick up your pieces. Then, help me gather mine. ” ― Vera Nazarian, The Perpetual Calendar of Inspiration