Schizophrenia, Affective Disorders, Anxiety Disorders, & Obsessive Compulsive Disorder PDF

Schizophrenia, Affective Disorders, Anxiety Disorders, and Obsessive Compulsive Disorder Schizophrenia Affects approximately 1 percent of the world’s population. Means “split mind”. Atypical prenatal development. Three categories of the symptoms: P...

Schizophrenia, Affective Disorders, Anxiety Disorders, and Obsessive Compulsive Disorder Schizophrenia Affects approximately 1 percent of the world’s population. Means “split mind”. Atypical prenatal development. Three categories of the symptoms: Positive Negative Cognitive Positive Symptoms Excess of typical functioning. Symptoms include: Thought disorders: disorganized, irrational thinking. Delusions: a belief that is contradicting the reality. Hallucinations: perceptions of stimuli that are not actually present (75 percent of individuals). Negative Symptoms They present an absence or decrease in typical behaviors. Reduced emotional response, lack of speech, lack of initiative and persistence, anhedonia (inability to experience pleasure), and social withdrawal. Cognitive Symptoms Produced by abnormalities in the brain region that overlap with those involved in negative symptoms. Difficulty sustaining attention, low psychomotor speed, deficits in learning and memory, poor abstract thinking, and poor problem solving. Genetic Factors Heritability plays a role, but no “schizophrenia gene” has bee found. Evidence for linkage to susceptibility for schizophrenia has been reported. Mutations Gene known as DISC1 (disrupted in schizophrenia 1) Involved in regulation of embryonic and adult nurogenesis, neuronal migration druing embryonic development, function of the postsynaptic density in excitatory neurons, and function of mitochondria. Also appears to increase of other mental disorders, including bipolar disorder, major depressive disorder, and autism. Twin and Adoption Studies Heritable trait. Higher rate in monochorionic monozygotic twins (share the same placenta). Parental Age Children of older fathers are more likely to develop schizophrenia. Increased likelihood of mutations in chromosomes of cells that produce sperms. Epigenetics Control the expression of genes, and are influenced by an individual’s experiences. Rare mutations or epigenetic factors may predispose people to schizophrenia. Long strads of DNA that constitutes the chromosomes are wound around a series of proteins known as histones. Methyl groups (-CH3) attach to histone proteins, prevents these regions from being translated into messenger RNA. Methylation of histone proteins prevents the expression of particular genes Epigenetic changes are initiated by environmental events such as exposure to toxins, and some epigenetic changes can be transmitted of offspring. Environmental Factors Epidemiology is the study of the distribution and causes of diseases in populations. Schizophrenia is related to several environmental factors such as: seaso of birth, viral epidemics, vitamin D deficiency, population density, prenatal malnutrition, substance abuse, and complications fo pregnancy and birth. The Mesolimbic Dopamine Pathway: Positive Symptoms Effects of Dopamine Agonists and Antagonists  Chlorpromazine (antipsychotic drug) initially used to reduce shock and anxiety after suregery. Found to dramatically reduce the positive symptoms of schizophrenia. Other drugs to reduce positive symptoms: dopamine antagonists that block D2 and D3 dopamine receptors. Positive symptoms sare caused by hyperactivity of dopaminergic synapses in the mesolimbic pathway. Dopamine agonists such as cocaine, amphetamine, and L-DOPA, increase positive symptoms of schizophrenia. Consequences of Long-Term Drug Treatment of Schizophrenia Slowness in movement, lack of facial expression, and general weakness. Tardive dyskinea approximately in one-third of all patients who took these antipsychotic drugs. Involuntary movements of face and neck. PAtients are unable to stop moving. Supersensitivity: compensatory mechanism in which some type o receptors become more sensitive if theyr are inhibited for a period of time by a drug that blocks them. The Mesocortical Dopamine Pathway: Negative and Cognitive Symptoms Clozapine, atypical antipsychotic medications, joined with risperidone, olanzapine, ziprasidone, and aripiprazole. Hypofrontality Negative an cognitive symptoms are a result of brain abnormalities, especially in the prefrontal cortex, target of the mesocortical pathway. Negative symptoms are caused primarily by hypofrotality, decreased activity of the frontal lobes – in particular of the dorsolateral prefontral cortex (d1PFC). May also be responsible for hyperactivity in the mesolimbuc related to positive symptoms. Atypical Antipsychotics Antipsychotic drugs fail to reduce negative and cognitive symptoms: Decreased activation of dopamine receptors in the prefrontal cortex, and drugs that block dopamine receptors would make these symptoms worse. Unlike original antipsychotics, they increase dopaminergic activity in prefrontal cortex and reduce it in the mesolimbic system. Aripiprazole; acts as a partial agonist at dopamine receptors. A drug that has a very high affinity for a particular receptor but activates that receptor less than does the normal ligand. Aripiprazole serves as ana atagonist in the mesolimbic system, where too much dopamine is present.  Serves as an agonist in regions such as the prefrontal cortex, where too little dopamine is present. The Role of Glutamate Decreased glutamate activity, resulting in hypofrontality, may contribute to negative an cognitive symptoms in schizophrenia. Chronic, low oses of glutamate antagonist drugs, such as PCP (phencyclidine) and ketamine (“Special K”) produced negative and cognitive symptoms in healthy individuals. PCP is an Indirect and antagonist of glutamate NMDA receptors. These drugs alos decrease the level of dopamine utilization in this region. Hypoactivity of NMDA and dopamine receptors appear to play an important role in producing negative and cognitive symptoms: Suppressing these receptors causes hypofrontality, which appears to be the primary cause of these two categories of symptoms. Developmental Changes DISC1, a genetic contributor to schizophrenia. Two theories: Abnormalities in pyramidal neurons of the prefrontal cortex are primary cause of the process that leads to schizophrenia. Abnormalities in the striatal dopaminergic system are primary cause of process that leads to schizophrenia. Affective Disorders Characterized by disordered feelings. People may have feeling of extreme elation (mania) or despair (depression). Diagnosis of depression, approximately 3 percent in men and 7 percent in women. Two main types of affective disorders: Bipolar disorder: Impacts men and women in approximately equal numbers. Alternating periods of mania and depression. Can last a few days to several months. Severe and difficult to treat. Major depressive disorder (MDD): Depression without mania. May be continuous and unremitting, or, may come in episodes. Mania without periods of depression may occur, but it is rare. Genetic Factors: Heritable characteristic. 10 times more likely to develop these disorders than are people without diagnosed relatives.  Heritability studies suggest that genetic anomalies are at least partly responsible for affective disorders. Concordance rates: 69 percent in monozygotic twins, versus 13 percent in dizygotic twins. RORA gene, involved in control of circadian rhythms. Association with the occurrence of major depressive disorder. GRM8 and RORB. Biological Treatments Monoamine oxidase (MAO) inhibitors. Drugs that inhibit the reuptake of norepinephrine or serotonin or interfere with NMDA receptors. Electroconvulsive therapy. Transcranial magnetic stimulation. Deep brain deprivation. Vagus nerve stimulation. Bright-light therapy (phototherapy). Treated by lithium and some anticonvulsant or antipsychotic drugs. Pharmacological Treatment Antidepressants. Iproniazid, reduced symptoms of depression. Iproniazid inhibits the activity of MAO. Although these drugs were fisrt antidepressants, MAO inhibitors can be harmful side effects, so they must be used with caution. Tricyclic antidepressants: These drugs inhibit the reuptake of 5-HT and norepinephrine by terminal buttons. Both the MAO inhibitors and the tricyclic antidepressant drugs are monoaminergic agonists. Selective serotonin reuptake inhibitors (SSRIs). Example; fluoxetine (Prozac), citalopram (Celexa), and paroxetine (Paxil). Widely prescribed for their antidepressant properties and for their ability to reduce the symptoms of obseesive-compulsive disorder and social phobia. Serotonin and norepinephrine reuptake inhibitors (SNRIs): These include milnacipran, duloxetine, and venlafaxine. SSRIs and SNRIs have fewer nonspecific actions, and therefore fewer side effects, than the tricyclic antidepressants and MAO inhibitors. All antidepressant drugs increase the amount of monoamine neurotransmitters present in the synapse to bind to the postsynaptic and presynaptic receptors. There is a therapeutic lag and it requires several weeks of taking the drug for a person to experience antidepressant effects.  In response to several weeks of elevated levels of neurotransmitter (particularly 5-HT), presynaptic autoreceptors desesitize and become less sensitive to the neurotransmitter. Unfortunately, stimulating the postsynaptic receptors is also responsible for the side effects of these drugs. Ketamine Currently used antidepressant drugs inhibit the reuptake of serotonin, norepinephrine, or dopamine, and NMDA antagonist, ketamine, may alleviate the symptoms of treatment-resistant depression. Patients showed an improvement in their symptoms. It appears that ketamine is an effective but short-term treatment for severe depression. Lithium Drug used to treat bipolar disorder. Does not supress typical feeling of emotions; it leaves patients able to feel and express joy and sadness in response to events in their lives. Patients have received the drug continously for years without any apparent ill effects. Between 70 and 80 percent of pacients with bipolar disorder show a positive response to lithium within one to two weeks. Side effects: Hand tremors, weight gain, excessive urine production, and thirst. Toxid doses produce nausea, diarrhea, motor incoordination, confusion, and coma. Patient’s blood levels of lithium must be tested regularly to be certain that they do not receive an overdose. The drug stabilizes the population of certain classes of neurotransmitter receptors in the brain and prevents wide shifts in neural sensitivity. Lithium has an effect on the function of DISC1 in the postsynaptic density. Mutation of DISC1 increases the likelihood of bipolar disorder as weel as schizophrenia, and lithium appears to compensate for the adverse effects of this mutation. Electroconvulsive Therapy Involves a brief electrical shock used to induce a seizure that can reduce depressive symptoms. Was originally used for a variety of disorders, including schizophrenia, its used is now most typically limited to treatment of mania and depression. Prolonged and excessive use of ECT causes barin damage, resulting in long-lasting impairments in memory. Judicious use of ECT during the interim period before antidepressant drugs become effective has undoubtedly saved the lives of some suicidal patients. Decreases brain activity and raises the seizure thresholf of the brain, making it less likely for another seizure to occur. Vagus Nerve Stimulation Electrical stimulation of the vagus nerve is another intervention that shows some promise of reducing the symptoms of depression. The procedure was originally developed as a treatment to prevent seizures in patients with seizure disorders. Approximately 80 percent of the axons in the vagus are afferent, so electrical stimulation of the vagus nerve activates several regions of the brain stem. Helpful for patients with treatment-resistant depression. Transcranial Magnetic Stimulation The ability of TMS to provide some of the benefits of ECT without introducing the risk of cognitive impairments or memory loss. Deep Brain Stimulation DBS may alos be useful therapy for treatment-resistan depression. Electrodes just below the subgenual anterior cingulate cortex (subgenual ACC), a region of the medial prefrontal cortex. The subgenual ACC is located below the “knee” at the front of the corpus callosum. Deep brain stimulation has also been directed the nucleus accumbens. Because depression is characterized by sadness, apathy, and loss of pleasure, this region appeared to be a logical target for DBS. Role of the Frontal Cortex Decelopment od depression. Studies of depressed patients: hyperactivity of the subgenual ACC region, along with decreased activity in other regions of the frontal cortex, including: Dorsolateral PFC. Ventrolateral PFC. Ventromedial PFC. Orbitofrontal cortex. Antidepressant treatments reliably decrease the activity of the subgenual ACC and, usually, increase the activity of other regions of the frontal cortex. Subgenual ACC is reciprocally connected with several regions of the prefrontal cortex. It is also connected with the amygdala, hippocampus, and nucleus accumbens. The prefrontal cortex play an important role in inhibition of the amygdala, which is involved in the acquisition and expression of negative emotional responses such as fear. The Monoamine Hypothesis Depression is caused by a low level of activity of one or more monoaminergic synapses. Two monoamines:  Norepinephrine and Serotin. Dopamine hypothesis: Dopamine agonist can produce the symptoms of schizophrenia and dopamine anatgonist can reduce them. Monoamine hypothesis: monoamine antagonists can produce symptoms of depression and monoamine agonists can reduce them. Tryptophan depletion procedure: low-tryptophan diet, followed by an amino acid drink containing no tryptophan, cause blood leves of tryptopahn to be very low, reducing serotonin synthesis. Research focuses on role of norepinephrine and serotonin. Depletion of tryptophan in brain causes recurrence of depressive symptoms. 5-HT plays a role in mood, although exact nature is unknown. Role of the 5-HT Transporter Some studies found that stressful life events increase probability of depression for those with one or two copies of the short alleles for the 5-HTT promoter. However, role in depression is unclear and need further research. Role of Neurgenesis Can take place in the dentate gyrus – a region of the hippocampal formation in adult brain. Antidepressant treatment increases hippocampal neurogenesis in lab animals. Evidence that exercise induces neurogenesis in the human brain. Role of Circadian Rhythms Sleep disturbances are characteristic of affective disorders. Sleep deprivation can reduce depression in some people. Role of Zeitgebers Some people become depressed during winter season. Symptoms of this form of depression is calle seasonal affective disorder (SAD). Includes lethargy and sleep disturbances. Craving for carbohydrates and an accompanying weight gain. Appears to have a genetic basis. Allele of the gene responsible for teh production of melanopsin, the retinal photpigment that detects the presence of light and synchronizes circadian rhythms. SAD can be treated with phototherapy, exposing people to bright light for several hours a day. Light serves as a zeitgeber. Anxiety Disorders Characterized by unrealistic, unfounded fear and anxiety. Most common psychiatric disorders.  Contributing biological factors: Panic disorders. Agoraphobia. Generalized anxiety disorder. Social anxiety disorder. Symptoms Panic disorder includes episodic attacks of acute anxiety. Periods of intense and unremitting terror that range from a few seconds to a few hours. Women are approximately twice likely as men to experience panic disorder. Emerges in early adolescence. Include many physical symptoms, such as: Shortness of breath. Clammy sweat, irregularities in heartbeat. Dizziness. Faintness. Feelings of unreality. Anticipatory anxiety the fear that another pani attack will occur. Is a symptom fo another anxiety disorder: agoraphobia. Include intense fear or anxiety about leaving home, being in open spaces, or being in enclosed spaces or in lines or crowds. Generalized anxiety disorder are excessive anxiety and worry, difficulty in controlling these symptoms, and clinically significant signs of distress and disruption of their lives. Social anxiety disorder is persistent, excessive fear of being exposed to the scrutiny of other people that leads to avoid social situations that involve speaking or performing in public. Genetic and Environmental Factors Variation of gene that encodes production of the brain derived neurotrophic factor (BDNF) protein may play a role in anxiety disorders. BDNF regulates neuronal survival and differentiation during development, plays a role in long-term porentiation and memory, and is associated with anxiety and depression. Family and twin studies support a genetic component to anxiety disorders. Environmental Factors Also contribute to experience of anxiety disorders. Treatment Sometimes treated with benzodiazepines. Benzodiazepines are often used for emergency medical treatment of anxiety disorders because therapeutic effects of these drugs have a rapid onset.  Less appropiate for long-term treatment. They cause sedation, they include tolerance and withdrawal symptoms, and they have a potential for abuse. Serotonin also plays a role in anxiety disorders. Obsesive-Compulsive Disorder Persistent and involuntary thoughts, images, or urges that will not leave them – and compulsions – behaviors that they cannot keep from performing. Symptoms Include concern or disgust with bodily secretions, dirt, germs, and the like; fear that something terrible might happen. The need for symmetry, order, or exactness. Most compulsions fall into one of four categories: Counting, cheking, clenaing, and avoidance. Are seen in a variety of mental disorders, including schizophrenia. Individuals with obsessive-compulsive disorder recognize that their thoughts and behaviors are irrational. Trichotillomania (hair pulling disorder). Compulsice behaviors seen in OCD are forms od species-typical behaviors that released from normal control mechanisms by a brain dysfunction. Genetic and Environmental Factors Heredity plays a role; greater concordance rate in monozygotic twins than in dizygotic twins. Damage to or the dysfunction of the basal ganglia, cingulate gyrus, and prefrontal cortex. Can be caused by a group of A β-hemolytic streptococcal infection. Brain damage at birth, encephalitis, and head trauma. Treatment Serotonergic agonists such as clomipramine, fluoxetine, and fluvoxamine used for treating OCD. Clomipramine also used for three other compulsions. Researchers believe symptoms relieved by increasing the activity of serotonergic pathways with inhibitory role in behaviors. Other options Deep brain stimulation may also be effective.