Ch 19- Neurobiology of Schizophrenia, Mood Disorders & Anxiety Disorders

Schizophrenia

• Schizophrenia is a disorder characterized by a break in reality with a splitting of the cognitive and emotional sides of personality.
• It affects 1% of the world's population.
• It is likely caused by multiple genes on different chromosomes, and is not a single-gene disorder.
• The disorder is related to genetic predisposition and prenatal/perinatal factors.
• Brain abnormalities in schizophrenia are thought to originate during prenatal cell proliferation and migration.

Neurochemical and Neuroanatomical Alterations

• Reduced glutamate receptor activity may contribute to schizophrenia.
• Reduced GABA biosynthesis enzyme (glutamic acid decarboxylase) activity may be related to impaired cognitive/emotional functions.
• Reduced dopaminergic neurotransmission in the mesocortical dopamine pathway may result in negative symptoms and cognitive changes.
• Excitatory neurotransmitter glutamate and its actions on NMDA receptors may be a factor
• Enlargement of the lateral and third ventricles, and widening of the frontocortical fissures and sulci are often observed in individuals with schizophrenia.
• Temporal lobe areas, such as the amygdala, hippocampus, and parahippocampal gyrus, show reduction in size.

Temporal Lobe Alterations

• Temporal lobe reductions may contribute to positive symptoms.
• Brain studies in adolescents with early onset schizophrenia show progressive loss of cortical gray matter in the temporal lobes, somatosensory, and motor cortices and dorsolateral cortex.
• The progressive loss in frontal lobe volume correlates with increased negative symptoms and reduced cognitive functioning.
• Functional alterations in the dorsolateral prefrontal cortex (reduced blood flow and metabolism) may impair goal-directed cognitive problem-solving.
• Reduced levels of reelin, an extracellular matrix protein involved in neuronal migration and synaptic function, are observed.

Mood Disorders

• Mood disorders are conditions characterized by emotional states, such as sadness or mania, that become chronic and uncontrollable.
• Alterations in the hypothalamic-pituitary-adrenal (HPA) system, serotonin, norepinephrine, and dopamine are related to symptoms of depression.
• Unipolar depression, also known as major depression, and bipolar disorder are two major classifications of mood disorders.
• Genetic, environmental, neurochemical, and neuroendocrine factors contribute to the pathogenesis and/or etiology of depression.
• Major depressive disorder is a mood disorder featuring a dysphoric mood and frequent insomnia, loss of appetite and body weight, reduced interest in pleasurable activities, and interpersonal relationship difficulties.

Depression and HPA System

• Chronic activation of the hypothalamic-pituitary-adrenal (HPA) system and elevated glucocorticoid secretion are observed in major depression.
• Antidepressant drugs that help normalize HPA hormone secretion often yield a good clinical response.
• Stress-related activation of the immune system increases the secretion of proinflammatory cytokines, which influences HPA hormone and monoamine metabolism and promotes chronic cortisol elevations.
• Reduced neurogenesis and decreased BDNF levels in the hippocampus have been implicated in stress-induced depression.

Bipolar Disorder

• Bipolar I disorder includes manic episodes and at least one major depressive episode.
• Bipolar II disorder features recurrent major depressive episodes with one or more hypomanic episodes.
• Elevated mood, irritable mood, inflated self-esteem are symptoms of manic episodes.

Generalized Anxiety Disorder (GAD)

• GAD is characterized by excessive and persistent worrying, lasting at least 6 months, along with at least three of six major symptoms.
• Underlying defects in norepinephrine and serotonin systems may play a role in GAD.
• Reduction in a2-adrenergic receptor binding and serotonin levels in the cerebrospinal fluid (CSF) are observed.
• Reduced platelet benzodiazepine binding in the left temporal hemisphere is also observed.

Panic Disorder

• Panic disorder is characterized by intense autonomic arousal and multiple disabling panic attacks, often involving symptoms like rapid heart rate, shortness of breath, and chest discomfort.
• The disorder features concerns about future panic attacks, and symptoms can last from minutes to an hour.
• Heightened sensitivity in the amygdala and neural circuit activation in the temporal lobe and brainstem are implicated in panic symptoms.
• Decreased GABA-benzodiazepine receptor binding in brain regions like the hippocampus, insula and prefrontal cortex may contribute to panic disorder.