Introduction to Behavioral Neuroscience - PSYC 211 Lecture Notes PDF

Introduction to Behavioral Neuroscience PSYC 211 Lecture 23 of 24 – Autism, ADHD, Depression Textbook Chapter 16 Professor Jonathan Britt Questions? Concerns? Please write to [email protected]  NEURODEVELOPMENT DISORDERS People often...

Introduction to Behavioral Neuroscience PSYC 211 Lecture 23 of 24 – Autism, ADHD, Depression Textbook Chapter 16 Professor Jonathan Britt Questions? Concerns? Please write to [email protected]  NEURODEVELOPMENT DISORDERS People often make a distinction between mental illnesses and neurodevelopment disorders. Mental illnesses can occur at any age, and they can be temporary or episodic. In contrast, neurodevelopmental disorders are clearly evident in childhood or at birth, and they are lifelong disabilities. Neurodevelopment disorders include autism, intellectual disability, ADHD, and motor disorders such as Tourette’s syndrome.  SEX DIFFERENCES Some mental illnesses affect males and females at similar rates. For example, rates of schizophrenia and bipolar disorder are similar between the sexes. Some mental illnesses are more common in females. For example, Anxiety disorders, major depressive disorder, obsessive-compulsive disorder, and PTSD are nearly 2 times more common in females. Anorexia is 3 times more common in females. Bulimia is 10 times more common in females. Some neurodevelopment disorders are more common in males. For example… Autism is 4 times more common males. ADHD is 4 times more common males. Intellectual disability is 2 times more common in males. Tourette’s syndrome is 3 times more common in males.  SEX DIFFERENCES One theory about these sex differences is that they aren’t real. Maybe we underdiagnose anxiety and depressive disorders in males. Maybe we underdiagnose neurodevelopment disorders in females. People certainly have perceptual biases in what they consider to be normal and abnormal behaviour in men and women. Maybe males and females exhibit similar symptoms, but our perceptual biases create the illusion of a sex difference. Or perhaps there are real differences in symptom presentations, but these only reflect differences in how men and women are socialized in our society. Maybe males and female have the same underlying symptomology, but they express it differently. Women are thought to be better at masking symptoms (camouflaging) in some cases. There is no doubt that our culture contributes to sex differences in diagnoses by affecting how symptoms are presented and how they are perceived.  AUTISM DIAGNOSES Large studies have evaluated the prevalence of harmful gene variations in people diagnosed autism and their close relatives. Male are 4 times as likely to receive a diagnosis of autism. On average, males who get the diagnosis have significantly fewer harmful gene variants than females who have the diagnosis. Autism is often seen in people who have rare gene copy number variations (CNVs), where a section of the genome is duplicated or missing. CNVs seem to cause autism at much higher rate in males than in females. Within families, females with CNVs present with much fewer and less severe symptoms than males do. Females seem to be protected in some way. Rare CNVs are inherited from mothers much more than they are from fathers, seemingly because males are more strongly affected by these gene variants. Why do harmful gene variants tend to produce autism, intellectual disability, and ADHD in males more often than females? It is unlikely that perceptual biases and socialization fully explain this difference, given that neurodevelopment disorders are often diagnosed at a very young age.  SEX CHROMOSOMES Mammals & Birds, butterflies, most insects some fish & reptiles XX – females ZZ - males the homogametic sex XY – males ZW - females the heterogametic sex Within species, the heterogametic sex tends to show slightly more variability at a very young age on all kinds of traits (from body morphology to cell physiology). In humans, males show more variability than females in birth weight brain morphology basal energy expenditure blood parameters quantitative and nonverbal reasoning visuospatial abilities verbal abilities Presumably, having one X chromosome creates developmental instability, whereas two XX chromosomes promotes developmental robustness.  MENTAL ILLNESS SEX DIFFERENCES Why are diagnoses of major depression and anxiety disorders more common in females than males? One explanation is the sex difference in social and cultural stressors. Women experience higher rates of abuse, poverty, discrimination, etc. Another explanation is the sex difference in hormone fluctuations. The incidence and severity of anxiety and depression fluctuate with changes in hormone signaling in females, particularly around puberty, childbirth, and menopause. Hormone signaling dramatically affects neural network dynamics, and the brains of females must constantly adapt to changes in hormone signaling. For example, many women experience “hot flashes” around menopause. Due to sudden changes in hormone signaling, the hypothalamus mistakenly believes body temperature is way too high, and it can take many years for the hypothalamus to adjust to menopause-related changes in hormones.  AUTISM Autistic spectrum disorder encompasses a wide range of developmental disorders with diverse underlying causes. It is associated with genetic and environmental factors that affect early brain development. It is characterized by troubles with social interaction and communication, and by restricted and repetitive behavior. The incidence of autism is around 2% of population. Parents usually notice signs during the first two or three years of their child's life. Social impairments are often the first symptoms to emerge. Some infants with autistic disorder do not seem to care whether they are held. Some arch their backs when picked up, as if they do not want to be held.  AUTISTIC DISORDER Many people with autism have abnormal or even nonexistent language. They may echo what is said to them or refer to themselves as others do – in the second or third person (e.g., you or he instead of I). A third of people with autism do not develop enough natural speech to meet their daily communication needs. People with autism generally have atypical interests and behaviors. They may show stereotyped movements, such as flapping their hand back and forth or rocking back and forth. They may exhibit compulsive or ritualistic behaviour.  AUTISTIC DISORDER Most people diagnosed with autism have clear cognitive impairments and reduced imaginative ability, but this is not always the case. Mild forms of autism (often called Asperger’s syndrome) mostly just involve deficient or absent social interactions and repetitive and stereotyped behaviors along with obsessional interest in narrow subjects. There is not always a pronounced delay in language development nor significant cognitive deficits. Many people diagnosed with autism have an additional (comorbid) psychiatric diagnosis such as intellectual disability, seizure disorder, ADHD, depression, and anxiety disorder. A third of people with autism have an intellectual disability. A third of people with autism have seizure disorder.  AUTISTIC DISORDER The heritability of autism is between 70% and 90%. 10% of cases have been linked to rare chromosomal abnormalities (deletions, duplications, and inversions of genetic material). Other cases are associated with multigene interactions involving common and uncommon gene variants. Some cases have been linked to maternal viral infections during pregnancy.  AUTISTIC DISORDER There are often abnormalities in brain development in autistic children, but there is not much consistency across people and across studies. At birth, there are rarely pronounced differences in the brains of kids who develop autism, yet brain growth often proceeds abnormally quickly, and total brain volume may be 10% larger than average by 2–3 years of age. By adulthood, most people with autism have a brain size within the normal range. The cellular and molecular bases of this early brain growth spurt are unknown, but there are many hypotheses: – Altered neuronal migration during early gestation – Abnormal formation of synapses and dendritic spines – Overconnectivity in key brain regions – Unbalanced excitatory–inhibitory neural networks  AUTISTIC DISORDER Some fMRI studies on people with autism have revealed abnormalities in brain activity (e.g., less activity in their fusiform face area when they look at photos of human faces).  AUTISM TREATMENT The main goals when treating children with autism are to lessen the impact of the associated deficits and family distress, and to increase quality of life and functional independence. Intensive, sustained special education programs and behavior therapy early in life can help children acquire self-care, communication, and life skills, and often improve functioning and decrease symptom severity and maladaptive behaviors. Medications generally do not address the core symptoms, but often help reduce the irritability, inattention, and repetitive behaviors. A variety of medications may be tried, including: – anticonvulsants (↑ GABA receptor activity) – antidepressants (↑ serotonin receptor activity) – antipsychotics (↓ dopamine receptor activity) – stimulants (↑ dopamine receptor activity)  ATTENTION-DEFICIT/HYPERACTIVITY DISORDER ADHD is a mental disorder characterized by problems paying attention, difficulty controlling (inhibiting) behavior in an age-appropriate manner, and hyperactivity. More than 5% of children in North America are now being treated for ADHD. The symptoms generally appear before the age of 12, are present for more than six months, and cause problems in school, home, or elsewhere. ADHD is usually first identified in the classroom, where children are expected to sit quietly and pay attention to a teacher or work steadily on project  ADHD SYMPTOMS In general, children with ADHD often … – show reckless and impetuous behavior – act without reflecting – let interfering activities intrude into ongoing tasks – have difficulty withholding a response Examples of symptoms of inattention: – “often has difficulty sustaining attention in work or play activities” – “is often easily distracted by extraneous stimuli” Diagnosis can be difficult because the symptoms are not well defined. Many children with ADHD have a good attention span for tasks they find interesting, and some hyperactivity, inattention, and impulsivity are within the range of normative behaviors. ADHD is often associated with learning disabilities, depression, anxiety, low self-esteem, aggression, and conduct disorder.  ATTENTION-DEFICIT/HYPERACTIVITY DISORDER The heritability of ADHD is 75% to 90%, but diagnosis rates vary widely across communities, ranging from 1% to 16% of children. Boys are diagnosed 3-4 times more often than girls. Drug and alcohol use as well as infections during pregnancy are associated with increased risk for the child, as is low birth weight. Certain cases are related to trauma. Management of ADHD typically involves counseling and medications, often stimulants that raise dopamine levels by blocking or reversing the dopamine reuptake transporter (e.g., Ritalin and Adderall). Antidepressants may also be helpful.  MAJOR AFFECTIVE DISORDERS MOOD DISORDERS Affect As a noun, affect refers to feelings or emotions. Just as the primary symptom of schizophrenia is disordered thoughts, affective disorders are characterized by disordered feelings. Mood Serious mood disorder (affective) disorder There are two principal types of mood disorders: bipolar disorder and major depressive disorder.  MOOD DISORDERS Bipolar disorder A serious mood disorder characterized by cyclical periods of mania and depression. It affects ~2% of the population. ~80% of the risk is attributed to genetics. Major A serious mood disorder that consists of unremitting depression or depressive periods of depression that do not alternate with periods of mania. disorder (MDD) Prevalence is approximately 7% in women and 3% in men. ~40% of the risk is attributed to genetics. Environmental factors include traumatic/abusive childhood experiences.  MOOD DISORDERS Affective disorders are prevalent and dangerous. People with mood disorders have a very high risk of self-harm and suicide They usually feel unworthy, hopeless, and have strong feelings of guilt  BIPOLAR DISORDER Mania Episodes of mania are characterized by a sense of euphoria that is not justified by the circumstances People with mania usually exhibit nonstop speech and motor activity Diagnosis of mania is partly a matter of degree; one would not call exuberance and a zest for life pathological  BIPOLAR DISORDER TREATMENT Lithium Chemical element Lithium is commonly prescribed for bipolar disorder It is most effective for treating the manic phase of bipolar disorder Once mania is eliminated, depression usually does not follow The therapeutic effect of lithium is very rapid. The mechanism of action is unknown. Some anticonvulsant drugs, particularly voltage-gated sodium channel blockers, are also prescribed as mood stabilizers. These drugs slightly reduce neural activity. Antipsychotics and antidepressants may also be prescribed, often in combination with a mood stabilizer.  MAJOR DEPRESSIVE DISORDER There are several established and experimental biological treatments for major depressive disorder (MDD), including… – Drugs that increase serotonin and/or norepinephrine signaling by inhibiting their enzymatic breakdown (e.g., monoamine oxidase inhibitors, MAOi) or by blocking their reuptake (e.g., tricyclics and serotonin specific reuptake inhibitors, SSRIs). – Electroconvulsive therapy (ECT) – Ketamine (NMDA glutamate receptor blocker) – Deep brain stimulation – Transcranial magnetic stimulation – Vagus nerve stimulation – Bright-light therapy (phototherapy) – Sleep deprivation  MAJOR DEPRESSIVE DISORDER Tricyclic Inhibits the reuptake of serotonin and norepinephrine antidepressant (but also affects other neurotransmitters). Serotonin specific A class of drugs that specifically inhibit the reuptake of serotonin reuptake inhibitor without affecting the reuptake of other neurotransmitters. (SSRI) The most common one is Prozac (fluoxetine). Similar drugs are Celexa, Paxil, Zoloft, etc… Serotonin and Antidepressant drug that specifically inhibits reuptake of norepinephrine norepinephrine and serotonin without affecting reuptake of other reuptake inhibitor neurotransmitters. (SNRI)  MONOAMINE HYPOTHESIS The monoamine hypothesis of depression was developed largely based on the success of tricyclic and SSRI treatments. The idea is that depression may relate to insufficient monoamine receptor activity (the monoamines are serotonin, norepinephrine, and dopamine). Because symptoms of depression are generally not relieved by dopamine receptor agonists (such as amphetamine and cocaine), researchers largely focused their efforts on the other two monoamines: norepinephrine and serotonin.  MONOAMINE HYPOTHESIS Serotonin is made from the amino acid tryptophan. Giving people a low-tryptophan diet and then a tryptophan-free amino acid “cocktail” tends to lower tryptophan levels and decreases serotonin (5-HT) synthesis. While this serotonin depletion procedure can spark a depressive episode in people susceptible to depression, there is clearly not a simple 1-to-1 connection between low serotonin and depression. SSRIs and SNRIs rapidly increase brain levels of 5-HT and norepinephrine, but symptom relief often follows several weeks of continuous use. It is unknown why monoaminergic drugs normalize mood.  ROLE OF THE FRONTAL CORTEX fMRI studies have been done on many depressed patients, before and after a variety of successful treatments. This data is noisy, and few correlations exist. One area of the anterior cingulate (subgenual ACC) was found to be less active after peoples’ depression lifted, but clinical trials targeting this region with deep brain stimulation were unsuccessful. Additional clinical trials are underway with deep brain stimulation (DBS), transcranial magnetic stimulation (TMS), and vagal nerve stimulation (VNS).  OTHER BIOLOGICAL TREATMENTS Electroconvulsive therapy (ECT) Used therapeutically to alleviate severe depression and bipolar disorder. Seizures are electrically induced by applying brief electrical shocks to the head In contrast to the delayed therapeutic effects seen with monoamine related treatments, the effects of other biological treatments (including ECT, lithium, DBS, VNS, and sleep deprivation) are more rapid. The seizures induced by ECT often reduce symptoms within days.  ROLE OF SLEEP IN DEPRESSION One of the most prominent symptoms of depression is disordered sleep. People with depression often have shallow, fragmented sleep. They also tend to awaken frequently, especially toward morning. In general, depressed people spend more time in stage 1 sleep and less time in deep, slow-wave sleep (stages 3 and 4). They also enter REM sleep soon after falling asleep, much earlier in the night than other people.  ROLE OF SLEEP IN DEPRESSION For many people, one of most effective antidepressant treatments is total sleep deprivation. Total sleep deprivation tends to have an immediate antidepressant effect (but it also leads to some degree of mania). When depression lifts after staying up overnight, it returns after a normal night's sleep. Perhaps a chemical builds up during waking hours that has some antidepressant effect, and it gets cleared away during sleep. REM sleep deprivation also works, although more slowly, over the course of several weeks (similar to SSRIs).