OS 202 Neurobiology of Psychiatric Symptoms PDF

OS 202: HUMAN BODY AND MIND 1: INTEGRATION AND CONTROL SYSTEMS NEUROBIOLOGY OF PSYCHIATRIC SYMPTOMS UPCM 2029 | Dr. Joseph Anlacan | LU3 A.Y. 2024-2025 OUTLINE B.​ FR...

OS 202: HUMAN BODY AND MIND 1: INTEGRATION AND CONTROL SYSTEMS NEUROBIOLOGY OF PSYCHIATRIC SYMPTOMS UPCM 2029 | Dr. Joseph Anlacan | LU3 A.Y. 2024-2025 OUTLINE B.​ FRONTAL LOBE SYNDROME ​ Damage to the frontal lobe I.​ Introduction D.​ Etiology ​ Symptoms A.​ Emotion, Thought, E.​ Key Brain Regions ​Slowed thinking Behavior as Brain Involved in Thought, ​Poor judgment Functions Behavior, and ​Social withdrawal B.​ Neuroanatomy Emotions ​Apathy II.​ Thought F.​ Summary ​Disinhibition A.​ Frontal Lobe IV.​ Neurochemistry of ​ Symptoms are seen in the following B.​ Frontal Lobe Thought, Behavior, and ​Schizophrenia due to frontal lobe hypofunction Syndrome Emotions ​Traumatic brain injury III.​ Emotion A.​ Serotonin ​Frontotemporal dementia A.​ Amygdala and the B.​ Epinephrine and ​Alzheimer’s disease Fear Response norepinephrine ○​ Case of Phineas Gage B.​ Temporal Lobe: Role C.​ Dopamine ​ Classic case where the function of the frontal lobe was in Emotion V.​ Summary discovered C.​ Prefrontal Cortex: VI.​ References ​ A metal rod punctured the brain and destroyed the frontal Role in Emotion VII.​ Appendix lobes bilaterally ​ Gage survived and looked normal since people were able to talk Acronyms: to him PFC - Prefrontal Cortex ​ Gage survived but his personality changed due to frontal lobe DLPFC - Dorsolateral Prefrontal Cortex damage. PBN - Parabrachial Nucleus ​ He had slow thinking, personality changes for judgment, VMPFC - Ventromedial Prefrontal Cortex apathy, deterioration, and social withdrawal. OFC - Orbitofrontal Cortex ​ Executive, planning, motivation, and judgment were all CSF - Cerebrospinal Fluid affected due to the damage. MDMA - 3,4-methylenedioxymethamphetamine, also called “Molly” or “Ecstasy” III.​ EMOTION VTA - Ventral Tegmental Area ​ Higher emotions ○​ Controlled by the prefrontal cortex I.​ INTRODUCTION ○​ Includes affections, pride, guilt, pity, envy, resentment, joy, contentment A.​ EMOTION, THOUGHT, BEHAVIOUR AS BRAIN FUNCTIONS ​ Basic drives ​ “The mental apparatus... must have an anatomical counterpart in ○​ Controlled by the limbic system the structure of the body.... It is the task of anatomy to discover it.” ○​ Includes feeding, sex, reproduction, pleasure, fear, aggression – Sigmund Freud ​ The brain has structures for normal emotion, thought, behavior, and pathologic counterpart ​ Disturbances in thought, behavior, and emotion are common psychiatric symptoms B.​ NEUROANATOMY ​ The brain contains 1011 neurons ○​ 100,000,000,000! (one hundred billion) ○​ 100,000,000,000,000 (one hundred trillion) synaptic interconnections between neurons ​ Neurotransmitters are transmitted, then received by neuron receptors ​ Neurons form specific circuits and pathways for processing information and performing certain functions ​ Complexity of the human brain parallels the complexity of the human mind Figure 2. The limbic system. (Enlarged in appendix) II.​ THOUGHT A.​ AMYGDALA AND THE FEAR RESPONSE A.​ FRONTAL LOBE MOTOR RESPONSES OF FEAR ​ Conscious thoughts are dedicated to the frontal lobe ​ Frontal Lobe ​ Feelings of fear may be expressed through behaviors such as ○​ Prefrontal cortex (most anterior part of the frontal lobe) avoidance ​ Functions ​ Other motor responses are to fight or run away (flight) in order to ​Executive function survive threats from the environment ​Motivation ​Attention ​Sequencing of actions ○​ Predominantly, DLPFC (Dorsolateral Prefrontal Cortex) ​Focus ​Remembering instructions ​ Brain management system ​ Subdivision ​Dorsolateral prefrontal (thoughts and cognitions) ​Ventromedial prefrontal (emotions) ​Orbitoprefrontal ○​ Motor strip ○​ Supplementary motor area ○​ Broca’s area Figure 3. Motor responses of fear. PAG = Periaqueductal Gray Figure 1. Frontal lobe Trans 10 TG5: Cabatingan, Cabrera, Cadag, Cagayan, Camacho, Camama, Campo TH: Punongbayan 1 of 5  BREATHING OUTPUT ​ Corticostriothalamocortical loop ○​ Bottom-up circuit that drives compulsivity ​ Changes in respiration may occur during a fear response ○​ Loop with projections from the dorsal striatum to the thalamus, ○​ These changes are regulated by activation of the parabrachial from the thalamus to the orbitofrontal cortex (OFC), and from the nucleus (PBN) via the amygdala OFC back to the dorsal striatum ○​ Can be modulated “top-down” from the OFC ​ If top-down response inhibition system is inadequate or is overcome by activity from the dorsal striatum, compulsive behaviors may result. ○​ In patients with OCD, this loop becomes hyperactive E.​ KEY BRAIN REGIONS INVOLVED IN THOUGHT, BEHAVIOR, AND EMOTIONS Figure 4. Breathing output in fear response AUTONOMIC OUTPUT OF FEAR ​ These include increases in heart rate (HR) and blood pressure (BP) ​ Involves locus coeruleus Figure 7. Key brain regions involved in affect and mood disorders. (A) Orbital prefrontal cortex and VMPFC. (B). Dorsolateral PFC. (C) Hippocampus and amygdala. (D) Anterior cingulate complex ​ VMPFC: emotions ​ DLPFC: executive function ​ Amygdala, hippocampus: fear response ​ Orbital PFC: obsession ○​ In individuals with OCD, there is a heightened assessment of danger ​ Anterior cingulate complex: compulsion ○​ Works together with orbital PFC, creating a loop that explains why compulsion is also repetitive F.​ SUMMARY Figure 5. Autonomic output of fear ​ Thoughts, emotions, and subsequent behavior are subserved in various areas of the brain. B.​ TEMPORAL LOBE: ROLE IN EMOTION ​ Conscious thought, executive function such as planning, judgment, ​ Left temporal lobe motivation, are brain functions seated in the frontal lobe, ○​ Philosophical specifically the prefrontal cortex, and more predominantly in the ○​ Humorless DLPFC. ​ Bilateral temporal lobe ​ Emotions are regulated in the limbic system (basic drives), and the ○​ Hyposexuality prefrontal cortex (higher-level emotions), predominantly in the ○​ Emotional intensity VMPFC, as well as the interplay between these two brain regions. ​ Right temporal lobe ○​ Excessive emotionality IV.​ NEUROCHEMISTRY OF THOUGHT, BEHAVIOR, ○​ Sadness, elation AND EMOTIONS ​ Neurotransmitters C.​ PREFRONTAL CORTEX: ROLE IN EMOTION ○​ How neurons communicate at the molecular level ​ Ventromedial Prefrontal Cortex (VMPFC) ○​ Chemical neurotransmission ○​ LEFT ​ Major mechanism by which the brain regulates thought, ​ Activation lifts mood, causes laughter emotion, and behavior ​ Lesions may cause depression and uncontrollable crying ○​ Regulate neuronal pathways with specific functions ○​ RIGHT ○​ Target of most psychotropic and neurologic medications ​ Activation causes depression ​ Lesions may produce laughter, euphoria A.​ SEROTONIN ​ Clinical application ​ Monoamine neurotransmitter ○​ For example, if you want to treat depression, you may perform ​ Synthesized: repetitive transcranial magnetic stimulation, and activate the ○​ From tryptophan PFC, specifically the left VMPFC. ○​ By cell bodies clustered in the midline raphe nuclei of the brainstem D.​ ETIOLOGY ​ Regulates mood, appetite, sexual desire, and function (among others) ​ Technically not a “happy hormone,” it’s more of a “not depressed” hormone ​ Low serotonin levels in the cerebrospinal fluid (CSF) in those who have committed suicide ○​ Low levels of serotonin associated with symptoms of depression ○​ Depressed mood, guilt feelings, irritability, disgust, fear, and anxiety ​ Abnormal levels of serotonin can lead to disorder such as Obsessive Compulsive Disorder (disgust) and panic disorder (anxiety) Figure 6. Circuitry of compulsivity and motor response inhibition. OS 202 Neurobiology of Psychiatric Symptoms 2 of 5  From Batch 2028 Trans NEUROTRANSMITTER TARGETS ​ Sympatholytic Drugs ○​ Beta Blockers ​ They block the receptors for epinephrine. ○​ Alpha Agonists ​ They are centrally acting, and prevent the release of norepinephrine. ​ Psychotropic Drugs ○​ Drugs for ADHD ​ Ex: Norepinephrine Reuptake Inhibitors (NRI) and Serotonin Norepinephrine Reuptake Inhibitor (SNRI) ​ Regulated and Illicit Drugs ○​ Amphetamines C.​ DOPAMINE ​ Cell bodies are located in the VTA (ventral tegmental area) of midbrain, the hypothalamus, and the substantia nigra Figure 8. Serotonin production and release. ○​ The ones found in the VTA have important functions as ​ Antidepressants that target serotonin emboldened below ○​ Selective Serotonin Reuptake Inhibitors (SSRI) ​ Functions: ○​ Serotonin Norepinephrine Reuptake Inhibitors (SNRI) ○​ Regulation of motor activity ○​ Serotonin Norepinephrine Disinhibitors (SNDI) ​ For Parkinson’s ​ Conditions treated ○​ Reward and motivation ○​ Major Depressive Disorder (MDD) ○​ Salience attribution ○​ Obsessive-Compulsive Disorder (OCD) ○​ Generalized Anxiety Disorder (GAD) ○​ Panic Disorder ​ Illicit drugs that target serotonin ○​ MDMA (ecstasy) ​ Triggers a large release of serotonin ​ Taking it can lead to irreversible damage to neurons that release serotonin ​ Neurotoxic B.​ EPINEPHRINE AND NOREPINEPHRINE Figure 10. Dopaminergic pathway. REWARD AND MOTIVATION ​ Dopamine released during pleasurable activities ○​ Anything that we do that is pleasurable is associated with the release of dopamine (e.g., enjoying food, gambling) ​ Drive, motivation, pleasure-seeking ○​ This gives us the drive and motivation to repeat the things that we find pleasurable ​ ↓ Dopamine ○​ Leads to a lack of motivation ○​ Leads to anhedonia Figure 9. Norepinephrine pathway. ​ Patients with MDD (Major Depressive Disorder) ​ Epinephrine: Systemic hormone ​ No longer enjoy activities that they enjoy before ○​ It is normally released into the bloodstream. ○​ Seen in depression, anorexia, or poor appetite ○​ Can be found in both systemic circulation and CSF Reward Pathway involves Dopamine: Addiction ​ Norepinephrine: Found mostly in the brain ​ Many addicting substances directly increase dopamine (e.g., ○​ It is a locally acting hormone, with exceptions. methamphetamine, cocaine) ○​ Neurotransmitter communicating between two neurons ​ Some behaviors can be linked to dopamine release resulting in ​ Cell bodies located at the locus ceruleus of the brainstem behavioral addictions ​ Fight or flight hormones ○​ There are situations wherein the organism still seeks the ​ Causes of sympathetic activation pleasurable thing even if the results are bad. INCREASE IN EPINEPHRINE AND NOREPINEPHRINE ○​ This was experimented on rats: ​ Cause anxiety symptoms ​ This involves a lever that triggers the release of dopamine to ○​ Can be classified into: Central and Peripheral the rats. These rats keep on pulling the lever, even skipping ○​ Central symptoms their meals. ​ Due to excessive arousal from sympathetic activation: ○​ This is what happens with addiction → they are no longer logical ​Psychic anxiety ​Hyperarousal SALIENCE ATTRIBUTION ​Hypervigilance ​ Allows our attentional system to focus on relevant information and ​Panic attacks make proper connections ​Insomnia ​ Overactive dopamine system causes delusions and hallucinations ○​ Peripheral symptoms because of misattribution (seen in psychosis) ​ Due to activation of adrenergic receptors in systemic area: ○​ You put too much attention to a detail and misinterprets it (e.g., ​Palpitations thinking that someone you passed by is stalking you) → ​Sweating psychosis ​Cold extremities ○​ Hallucinations and Delusions ​Tremors and trembling ​ Hallucinations: internally-generated ​ Coffee ​Dr. J. Ancalan also emphasized that patients experiencing ○​ Another way to increase epinephrine and norepinephrine is this symptom can be convinced that these are not real drinking coffee ​ Delusions: hallucinations that you really believe in ○​ An adenosine antagonist ​ ↑ Dopamine (mesolimbic dopaminergic tract) ​ Adenosine is an inhibitor of epinephrine and norepinephrine ​ Causes: ​ As we drink coffee, epinephrine and norepinephrine are not ​Psychotic disorders (e.g., schizophrenia) inhibited, causing palpitations. ​Delirium (should be managed) ​Drug-induced psychosis (e.g., stimulants increase dopamine) OS 202 Neurobiology of Psychiatric Symptoms 3 of 5 From Batch 2028 Trans ​ Hypoactivity of dopamine neurons in mesocortical dopamine pathway CLASSIC DOPAMINE PATHWAYS AND KEY BRAIN REGIONS ○​ Mediates cognitive, negative, and affective symptoms of schizophrenia NEUROTRANSMITTERS ​ NT target of antipsychotic drugs ○​ Dopamine Receptor Antagonists (DRA), Serotonin Dopamine Antagonists (SDA) ​ NT target of illicit drugs ○​ MAP ○​ Cocaine V.​ SUMMARY Table 1. SUMMARY Category Details Psychiatric Disturbances in thought, emotion, and behavior Symptoms due to disruptions in normal brain function. Neuroanatomical Correlates: Prefrontal Cortex (anterior part of the frontal lobe) Figure 11. Classic dopamine pathway and key brain regions. Thoughts/ Predominantly Dorsolateral prefrontal cortex ​ Nigrostriatal dopamine pathway executive function (DLPFC) ○​ Controls motor function and movement ​ Mesolimbic dopamine pathway Predominantly Ventromedial prefrontal cortex Higher emotions ○​ Mediates positive symptoms of psychosis such as delusions (VMPFC) and hallucinations Neuroanatomical Correlates: Limbic System ​ Mesocortical dopamine pathway ○​ Hypoactivity Two key structures of the limbic system, the ○​ Negative symptoms, cognitive symptoms (dorsolateral Basic drives and amygdala and hippocampus, are part of the prefrontal cortex or DLPFC), affective symptoms (ventromedial emotions temporal lobe prefrontal cortex or VMPFC) ○​ Schizophrenia Neurotransmitter Influence Impact on brain circuits and pathways CLASSIC MESOLIMBIC DOPAMINE HYPOTHESIS OF POSITIVE SYMPTOMS OF SCHIZOPHRENIA Mood regulation, depression, anxiety, Serotonin obsessions, compulsions Norepinephrine Fear response, hypervigilance, anxiety, insomnia Pleasure, reward and motivation, salience Dopamine attribution, addiction, psychosis Note: These are not the only functions of the above neurotransmitters. The stated functions and symptoms are also not exclusive to one neurotransmitter and requires a complex interplay of different circuits and neurotransmitters VI.​ REFERENCES Anlacan, J. (2025). Neurobiology of Psychiatric Symptoms [Lecture] UPCM 2028 Trans (February 5, 2024). Neurobiology of Psychiatric Symptoms Figure 12. Mesolimbic dopamine hypothesis. ​ Hyperactivity of dopamine neurons ○​ Positive symptoms of psychosis ​ Delusions and hallucinations CLASSIC MESOCORTICAL DOPAMINE HYPOTHESIS OF COGNITIVE, NEGATIVE, AND AFFECTIVE SYMPTOMS OF SCHIZOPHRENIA Figure 13. Mesocortical dopamine hypothesis VII.​ APPENDIX OS 202 Neurobiology of Psychiatric Symptoms 4 of 5  Figure 2. The limbic system. OS 202 Neurobiology of Psychiatric Symptoms 5 of 5