16: Neurological and Psychiatric Disorders

16: Neurological and Psychiatric Disorders
Cognitive Neuroscience David Eagleman Jonathan Downar

Chapter Outline Alzheimer’s Disease: Burning Out with Age?
Frontotemporal Dementia: Like a Cancer of the Soul Huntington’s Disease: A Genetic Rarity, in Two Senses Tourette Syndrome: A Case of Involuntary Volition?

Chapter Outline Obsessive-Compulsive Disorder: Neurological or Psychiatric? Schizophrenia: A Dementia of the Young Bipolar Disorder Depression: A Global Burden

Alzheimer’s Disease: Burning Out with Age?
Dementias are neurologic disorders characterized by slow deterioration of higher cognitive functions. Such functions include language, memory, judgement, and emotion. Alzheimer’s disease or Alzheimer’s dementia is thought to affect about 24 million people world-wide.

Figure Subtypes of dementia. Alzheimer’s disease is the most common form of dementia worldwide.

The major deficit of Alzheimer’s is the loss of episodic memory. Executive functions decline throughout Alzheimer’s disease. Biological markers of Alzheimer’s disease include amyloid-beta plaques and neurofibrillary tau tangles.

Figure 16.4 The plaques and tangles associated with Alzheimer’s disease. (a) A microscopic view of both the plaques and the tangles in the brain of a patient with Alzheimer’s disease. (b) Plaques and tangles spread over the brain as the disease worsens.

Figure 16.5 The formation of beta- amyloid plaques and tau tangles in Alzheimer’s disease. (a) Beta-amyloid plaques form from extracellular accumulations of beta-amyloid peptides, which are generated during the normal metabolic activity of neurons. (b) Hyperphosphorylation of the tau proteins leads them to detach from microtubules and clump into neurofibrillary tangles.

Most cases of Alzheimer’s disease occur in individuals over age 60. The epsilon 4 variant of the apolipoprotein E (ApoE4) gene seems to increase the risk of developing the disease. Genetic forms of Alzheimer’s disease account for only a small percentage of cases.

Figure 16.7 Comparison of maps of functional connectivity and amyloid plaque deposits in patients with Alzheimer’s Disease. (a) A map showing areas of the brain that serve as the busiest “hubs” of brain activity. (b) The density of beta-amyloid plaques in patients with Alzheimer’s disease. note the overlap in brain regions apparent when comparing these two maps.

Treatment of Alzheimer’s disease There are currently no cures for Alzheimer’s disease. No medications significantly slow down or reverse the progression of the disease. Acetylcholinesterase inhibitors and NMDA glutamate receptor antagonists sometimes slow the progression of the disease.

A potential treatment uses the immune system to remove plaques, but this has not resulted in any clinical improvement. Social, mental, and physical activity can decrease the risk and severity of Alzheimer’s disease.

Frontotemporal Dementia: Like a Cancer of the Soul
This dementia results from progressive atrophy of the brain. This is most common in the inferior frontal lobes and anterior temporal lobe. The age of onset is typically about 40 – 50 years of age. Personality and social behaviors change significantly.

Figure 16.8 In patients with frontotemporal dementia, the frontal lobes and temporal pole degenerate, leaving smaller gyri and larger sulci.

Behavioral variant frontotemporal dementia (bvFTD) is most common. This is characterized by progressive semantic dementia, personality changes and loss of empathy. Frontotemporal dementia is sometimes associated with an increase in creativity.

Figure 16.9 Patients with semantic dementia lose the ability to recall the concepts of things, not just their names. Here, a patient with semantic dementia was asked to draw a swan from memory. The patient drew the swan as an animal with four legs, rather than the two legs of a bird.

Huntington’s Disease: A Genetic Rarity, in Two Senses
Patients perform restless involuntary movements of the face, trunk, and limbs. It commonly also includes psychiatric symptoms such as depression, apathy, anxiety, delusions, and hallucinations. The biological cause is degeneration of the anterior caudate nucleus of the striatum.

Figure Brain degeneration in Huntington’s disease. The atrophy is especially pronounced in the anterior caudate nucleus, as can be seen in these two coronal slices through the brain.

Figure A simplified view of the corticostriatal loop that is important for motor control and is affected in Huntington’s disease. In healthy control subjects, the excitatory direct pathway and the inhibitory indirect pathway are balanced, allowing for control of voluntary movement. In Huntington’s disease, the medium spiny neurons of the indirect pathway degenerate, leaving the excitatory direct pathway as the main driver of behavior.

Huntington’s disease is caused by the mutation of an autosomal dominant gene. This mutation encodes the inclusion of a trinucleotide repeat of the sequence CAG in the final protein. Most people have fewer than 28 CAG repeats, and this results in no issues. Individuals with more than 35 repeats are at an increased risk of developing the disease.

Risk factors for Huntington’s disease include both genetic and environmental factors. Treatment for Huntington’s disease involves dopamine receptor antagonists. These relieve some of the motor and psychiatric symptoms.

Figure Gene–environment interactions play a role in many diseases. Most disorders are not caused by a single gene. Instead, many different genes may interact with one another, with some combinations having protective and others having harmful effects. These effects also interact with environmental factors, which may also be protective or harmful in different combinations. This complex interaction of genetic and environmental effects determines the presence and severity of many diseases.

Tourette Syndrome: A Case of Involuntary Volition?
In Tourette syndrome, the individual repeats purposeless movements of the face, head, shoulders, or hands. There are also verbal tics, which are purposeless noises like throat-clearing and snorting or meaningless phrases.

Tourette syndrome is typically a disorder of childhood. Studies suggest there is a genetic basis to Tourette syndrome, but no gene has been isolated.

Pediatric Autoimmune Neuropsychiatric Disorder Associated with group A Streptococcal infection (PANDAS) This is characterized by the tics of Tourette syndrome or the intrusive thoughts and behaviors of obsessive compulsive disorder. Sometimes occurs in patients shortly after they have had a throat infection caused by the bacteria Group A streptococcus.

Patients have a decrease in gray matter in the caudate nucleus and lateral motor and premotor cortex. Gray matter is thinner in medial motor areas.

Figure Neuroanatomical abnormalities in Tourette syndrome. (a) Areas of shared cortical thinning in siblings who both have Tourette Syndrome. The affected areas include the anterior cingulate cortex and dorsomedial prefrontal cortex, as well as the lateral premotor cortex. (b) Areas activated during motor tics of the fingers. note the activation in the anterior cingulate cortex, within the area affected by the disorder.

Therapy for Tourette syndrome includes education and acceptance. Neurolepic medications are prescribed for the most severe cases, where the tics interfere significantly with daily life.

Obsessive-Compulsive Disorder: Neurological of Psychiatric?
“Neurological” disorders and “psychiatric” disorders are grouped based on the nature of the condition. Conditions with an observable brain abnormality were considered neurological.

A more modern criteria based on the symptoms. Psychiatric conditions impact emotion, motivation, social behaviors, personality, or reality testing. Neurological conditions impact strength, movement, sensory perception, memory, attention, or level of consciousness.

Figure Some brain disorders are traditionally considered neurological, while others are traditionally considered psychiatric. The distinction is somewhat arbitrary, since both categories of disorders involve abnormal functioning of the neural pathways of the brain. This survey of scientific articles published in the peer reviewed journals Neurology and American Journal of Psychiatry from 1990 to 2011 shows whether the conditions named were more commonly considered neurological or psychiatric.

Obsessive-compulsive disorder is a psychiatric disorder that affects about 2 – 3% of the population. Symptoms include obsessions (intrusive, disturbing thoughts) and compulsions (stereotyped, ritualized behaviors).

Obsessions include contamination, fear of committing inappropriate acts, symmetry and number, and hoarding. The most common age of onset for symptoms of obsessive-compulsive disorder is either about age 11 or 23.

Figure Two corticostriatal loops are consistently identified as important in studies of patients with OCD. One of the loops goes from the anterior caudate nucleus to the dorsomedial prefrontal cortex and nearby anterior cingulate cortex. The other loop goes from the ventral striatum to the lateral orbitofrontal cortex. These loop circuits tend to show excessive activity in OCD compared to healthy controls.

There is increased activity in the circuits connecting the basal ganglia to the orbitofrontal, anterior cingulate, and dorsomedial prefrontal cortex. The pattern of activity differs depending on the types of obsession.

Figure Symptom-specific brain abnormalities in OCD. Patients diagnosed with different types of OCD viewed images designed to provoke their specific symptoms, such as compulsive hand-washing, mistake-checking, or hoarding. The patients displayed different patterns of brain activity, depending on which type of symptoms they had.

Cognitive behavioral therapy addresses cognitive distortions and decreases anxiety. Medications than increase serotonin reduce the obsessions, compulsions, and anxiety. Neuroleptics are sometime prescribed for severe cases.

Schizophrenia: A Dementia of the Young
Schizophrenia is characterized by loss of contact with reality. The age of onset is typically around early adulthood. Schizophrenia affects about 1% of the world’s population.

Positive symptoms include hallucinations and delusions. Delusions include paranoid delusions, delusions of reference, delusions of passivity, and somatic delusions. Negative symptoms include poverty of speech, apathy, social withdrawal, and loss of emotion.

Antipsychotic medications treat the positive symptoms, but do not treat the negative symptoms. Such medications often cause unwanted side effects. Second-generation antipsychotic medications are no better at treating the negative symptoms.

There is a genetic basis to schizophrenia, but no specific genes have been identified. Environmental factors during fetal development or early life seem important in the incidence of schizophrenia.

Figure A family pedigree of the DISC1 gene. This pedigree shows five generations of a family known to carry the DISC1 mutation. Individuals with the mutation are marked with a dot, and individuals with a known diagnosis are indicated by a color code. note that the same genetic mutation leads to different types of mental illness in different individuals, and that not everyone who carries the mutation has an illness; this illustrates the importance of gene–gene and gene–environment interactions.

Neurodevelopmental factors Abnormal pruning of neurons Smaller cell bodies of neurons Decreased functioning of inhibitory GABA interneurons in the cortex

Figure Compared with healthy control subjects, individuals with schizophrenia show a decrease in gray matter over time. The abnormal loss of gray matter usually begins in adolescence, well before the symptoms of psychosis become prominent in early adulthood.

Figure The hypothesis of abnormal neuron migration in schizophrenia. If neurons fail to migrate to the correct layers of the cortex during development, they may not connect or communicate properly. In some studies of the layers of cortex in individuals with schizophrenia, the gABAergic interneurons fail to migrate to the correct location. This disrupts the circuitry of the cortex at a microscopic level.

Dopamine hypothesis There is too much dopamine signaling or the dopamine receptors are oversensitive. The first-generation antipsychotic drugs were dopamine D2 receptor antagonists. Drugs that increase dopamine, such as amphetamines and cocaine, can mimic the positive symptoms of schizophrenia.

Figure Antipsychotic medications are D2 receptor antagonists. (a) All known antipsychotic medications act by blocking the D2 dopamine receptor. The medication must block about 65–80% of the receptors in the ventral striatum in order to achieve its desired effect. (b) The effective dose of antipsychotic medications correlates closely with how tightly they bind to D2 receptors. Medications with higher affinity for D2 receptors are effective at lower daily doses.

Glutamate hypothesis Schizophrenia is caused by too little glutamate neurotransmission. NMDA receptor antagonists, like ketamine, can mimic both the positive and negative symptoms of schizophrenia. Many of the genes associated with schizophrenia affect NMDA glutamate receptors.

Figure The loops connecting the prefrontal cortex to the striatum and thalamus use a variety of neurotransmitters, including dopamine, glutamate, and GABA. The interaction of dopamine and glutamate in these loops means that the glutamate and dopamine hypotheses of schizophrenia are not mutually exclusive—both neurotransmitters likely play a role in the illness, as does GABA.

Bipolar Disorder Normal mood alternates with periods of depression and mania. This affects 1% of the population and a milder form may affect as much as 4-5% of the population. The age of onset is about 20 years of age. There is a genetic basis to the condition, but no specific genes have been identified.

Bipolar Disorder Figure Individuals with bipolar disorder cycle from a depressed state to a manic state and back again. These cycles can vary in length, with a single phase of the cycle lasting from days to months, depending on the individual.

Bipolar Disorder Individuals with bipolar disorder show thinner gray matter in the Bilateral ventrolateral frontal cortex Bilateral anterior insula Dorsomedial prefrontal cortex Subgenual cingulate cortex Some of these regions are also affected in unipolar depression.

Bipolar Disorder Figure Brain regions with gray matter loss in bipolar disorder. Compared to healthy controls, patients with bipolar disorder have a reduction in gray matter in certain areas, including the anterior insula, ventrolateral prefrontal cortex, and ventromedial prefrontal cortex. (lines at lower right indicate the positions of these axial slices within the brain.

Bipolar Disorder Common treatments include
Mood-stabilizing drugs, such as lithium Anti-dpileptic drugs

Bipolar Disorder Figure Mood stabilizers for bipolar disorder. Several different classes of medications are used as mood stabilizers in bipolar disorder. These include the element lithium, antipsychotic medications (of which haloperidol or risperidone are two examples among dozens available), and certain antiepilepsy medications such as valproic acid, carbamazepine, and lamotrigine.

Depression: A Global Burden
Impact of Depression Causes of Depression Neurochemical Effects of Depression on Brain Functional Effect of Depression on the Brain Treatment of Depression

Impact of Depression Depression is characterized by a low mood that makes it difficult to carry out the functions necessary for daily life. Individuals with depression do not take pleasure in typical activities, lack motivation and energy, and have altered sleep patterns and appetite.

Impact of Depression Figure Depression is one of the leading causes of years of life lost to disability, worldwide. Darker colors indicate countries with a higher burden of years lost to disability from depression.

Impact of Depression The worldwide incidence of depression is 5% at any one time. In the United States, the incidence is 5% for men and 10% for women. Lifetime incidence is roughly double the one-time incidence rates. The cost of depression is estimated to be about $80 billion per year in the U.S.

Impact of Depression Figure Depression over the adult lifespan. Hospitalizations for major depression peak at ages from the late 30s to early 50s, and again in late life. The rates of illness and hospitalization are nearly twice as high in women as in men.

Causes of Depression Mood disorders run in families, suggesting a genetic basis. Depression may be an evolutionary adaptation to suffering a trauma or defeat Depression causes the individual to stay away from opponents and predators while waiting for better times.

Causes of Depression Figure Interacting effects of genetic background and environmental events in depression. In one influential study (Caspi et al., 2003), having two copies of the short form of the 5HTTlPR serotonin transporter gene, as well as a more stressful life, significantly increased the individual’s chance of developing depression.

Neurochemical Effects of Depression on Brain
Monoamine hypothesis of depression There is a shortage of the monoamine neurotransmitters. By inhibiting the enzyme monoamine oxidase, which breaks down these transmitters, mood will be improved.

Serotonin hypothesis More specific than the monoamine hypothesis. There is, specifically, a shortage of serotonin. Selective serotonin reuptake inhibitors specifically affect serotonin levels.

Other biological theories There are abnormalities with glutamate neurotransmission. There are low levels of the neuronal growth factor brain-derived neurotrophic factor (BDNF).

Figure Selective serotonin reuptake inhibitors (SSRIs) work by blocking the reuptake of serotonin into the presynaptic terminal, thus increasing the concentration of serotonin in the synaptic cleft.

Functional Effect of Depression on the Brain
Networks of brain areas are under- and over-activated in individuals with depression. The subgenual cingulate cortex is consistently hyperactive. This hyperactivity returns to normal following successful treatment of depression. The dorsolateral and dorsomedial prefrontal cortex tend to be less active.

Figure The subgenual cingulate cortex plays a key role in regulating the amygdala and other core limbic structures, and it is overactive in major depression. It is part of a larger network of cortical and subcortical regions involved in emotion regulation. In patients who recover from depression, the activity of the subgenual cingulate cortex returns to normal—a consistent finding across many different types of treatment for depression, including medications, therapy, and brain stimulation.

The pattern of hyper- and hypo-active brain regions differs across individuals. Current research is examining the interactions between different brain regions.

Treatment of Depression
Three major treatments are used for individuals with depression Psychotherapy Pharmacotherapy Somatic therapy

In psychotherapy, the patient interacts with a clinician to work through the causes of their depression. Cognitive therapy is about as effective as pharmacotherapy The effects seem to persist for a longer time than the medication does.

Figure Response to antidepressant medication versus cognitive behavioral therapy in depression. After 16 weeks of treatment, the percent of subjects responding to treatment is similar for both antidepressant medication and for cognitive behavioral therapy.

Anti-depressant medications include Monoamine oxidase inhibitors (MAOIs) Tricyclic antidepressants (TCAs) Selective serotonin reuptake inhibitors (SSRIs) All of these are about equally effective. Different medications are more or less effective for different individuals.

Figure Successfully alleviating the symptoms of depression is associated with a decrease in activity in the subgenual cingulate cortex. This proved to be true not just for patients treated with an SSRI medication, but even for patients who improved while taking a placebo.

Somatic therapies are more invasive. These include Repetitive transcranial magnetic stimulation Electroconvulsive therapy Deep brain stimulation

16: Neurological and Psychiatric Disorders

Similar presentations

Presentation on theme: "16: Neurological and Psychiatric Disorders"— Presentation transcript:

Similar presentations

About project

Feedback

Log in

Auth with social network:

16: Neurological and Psychiatric Disorders

Similar presentations

Presentation on theme: "16: Neurological and Psychiatric Disorders"— Presentation transcript:

Similar presentations

About project

Feedback