1. biological foundations of behavior

8/13/2019 1. Biological Foundations of Behavior

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Biological Foundations of Behavior

Behavioral Genetics

- There is a genetic component in the development of psychiatric disorders (e.g., schizophrenia,anxiety and mood disorders), as there is in many other psychological attributes , including

personality and intelligence.- Some traits are determined by the influence of a single gene (e. g., Huntington disease,

phenylketonuria), while most emerge from the interactions of many or hundreds of genes (i.e.,

they are polygenic).

- Behavior is likely the expression of thousands of genes, although single gene-mutations caninfluence certain behaviors in consistent ways.

- Also, specific chromosomes have been linked to disorders with behavioral symptoms.- Although complex, the associations between genotype, environment and phenotype are

amenable to systematic scientific inquiry.

- Note that for a given person/patient, what is genetic is not necessarily immutable.- Family risk studies

o There are a number of techniques used in behavior genetics.o Family risk studies compare how often a behavioral disorder or trait occurs in the

relatives of the affected individual (known as the probrand), with how often it occurs in

the general population.

- Twin Studieso Adoption studies, using monozygotic twins anddizygotic twins, reared in the same or

different homes, are used to distinguish the influence of genetic versus environmental

factors in the occurrence of traits and psychiatric disorders.

o If concordant, the disorder occurs in both twins.o If there is a genetic component in its development,a trait or disorder will have a higher

concordance rate in monozygotic twins than in dizygotic twins.- Chromosomal Disorders with Behavioral Manifestations


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- CNSo The human nervous systemconsists of the central nervous system (CNS) and the

peripheral nervous system (PNS). The CNS consists of the brain and spinal cord.

o Four lobes of the cerebral cortex - the frontal, temporal, parietal, and occipital - can beidentified on the lateral surface of the cerebral hemispheres (cerebrum) of the brain.

o The cerebrum also contains the limbic system, which contains medial parts of thefrontal, temporal, and parietal lobes and include the hippocampus, amygdala, fornix,

septum, parts of the thalamus, cingulate gyrus and related structures).

o The cerebral hemispheres are connected by the corpus callosum, anterior commissure,hippocampal commisure, and habenular commissure

o Lateralization of function


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The cerebral hemispheres (cont). Although the functions of the cerebral cortex are generally

represented on both the right and left hemispheres, they may not be

equally so.

The hemispheres of the brain have functions that are lateralized. hemispheric specialization

Right, or nondominant, hemisphereis associated primarily withperception; it is also associated with spatial relations, body image, and

musical and artistic ability. It is activated for intuition-type problem

solving. Stroke damage here is more likely to lead to apathy and

indifference.

Left, or dominant, hemisphereis associated with language functioninalmost all right-handed people (97%) and most left-handed people (60-

70%). Calculation-type problem solving predominates here.

It is larger than the right hemisphere and processes information faster.Stroke damage to the left hand side is more likely to lead to depression.

There are also sex differences in cerebral lateralization. Women have a larger corpus callosum and anterior commissure, and

thus appear to have greater interhemispheric communication than

men.

Men may have greater development of the right hemispheres, andtend to score highly in spatial tasks.

- Brain Lesionso Brain lesions caused by accident disease, surgery, or other insult are associated with

particular neuropsychiatric effects (to follow).

o Frontal Lobes (1). Frontal cortex:


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Important functions for the frontal lobes include speech (Brocas area,involved in the expressive aspect of speech), regulation of personality

and emotional expression, abstract thought, memory, executive

function, the capacity to initiate and stop tasks, and concentration.

Very important also is the regulation of motor function (primary motorcortex and associates are located there).

Lesionso may cause mood changes (depression with dominant lesions,

elevation of mood with nondominant lesions).

Lesions to dorsal prefrontal cortexo result in apathy, decreased drive or initiative, poor grooming,

decreased ability to think abstractly, and inability to speak

fluently (Broca aphasia [dominant lesions]).

Lesions to orbitofrontal cortexo may result in difficulty with judgment, withdrawal, fearfulness,

explosive mood, loss of inhibitions, emotional and personality

changes, and violent outbursts.

o Temporal Lobes (2). Temporal cortex:

Functions include language, memory and emotion. Lesions stem from stroke, tumor, and trauma. CNS-based herpes virus

infections often influence the temporal cortex. They result in impaired

memory, psychomotor seizures, and changes in aggressive behavior.

Lesions of the rostral (anterior) left temporal lobeo causes deficits in recall or learning of proper names.

Lesions of the dominanttemporal lobeo result in euphoria, auditory hallucinations, delusions, thought

disorders, and inability to understand language/poor verbal

comprehension (Wernicke aphasia).

Lesions of nondominant lobeo results in dysphoria, iritability, and decreased visual and musical

ability.

o Parietal Lobes (3). Parietal cortex

Involved in the intellectual processing of sensory info. On the left side (dominant): verbal processing. On the right (nondominant): visual-spatial processing Lesions of the dominant lobe (parietal cortex) Gerstmann syndrome

o may occur, whose symptoms include agraphia (inability towrite), acalculia (inability to perform calculations), finger

agnosia (patient is unable to recognize the fingers on his own,

or someone elses hands), and right-left disorientation.

Lesions of the nondominantlobe (parietal cortex)


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o Denial of illness (anosognosia, the patient either denies havingan illness , or is not aware of it, e.g., in left hemiparesis, may

deny the presence of a paralyzed limb)

o Neglect of the opposite side (sensory neglect; e. g., failure torespond to half of the visual field and possibly also ignore tactile

and auditory stimuli, resulting in not washing or dressingopposite side of body)

o Construction apraxia: the inability to copy drawings or tomanipulate objects to form patterns or designs, involves

impaired processing of visual-spatial information (e. g., cannot

copy a simple line drawing or clock face correctly)

o Occipital Lobes (4) Occipital cortex

The occipital lobeis the visual processing center that contains most ofthe visual cortex in mammals.

It is involved in the recall of objects, scenes, and distances; PET scansshow activity in this area during recall of visual images.

Destruction of the occipital cortex results in cortical blindness Anton Syndrome

o Due to bilateral occlusion of posterior cerebral arteries. Corticalblindness occurs, along with failure to acknowledge the

blindness. The latter may be due to the interruption of fibers

involved in self-assessment.

o Limbic Syndrome The limbic system functions in motivation, memory, emotions ( mediation

between cortex and lower centers), conditioned responses, violent and

sociosexual behaviors.


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Associated dysfunctions include apathy, aggression, vegetative-endocrinedisturbances, memory problems and the learning of new material.

o Hypothalamus The hypothalamus is responsible for the regulation of a number of physiologic

responses. It has been implicated in involuntary internal responses that

accompany emotional strategy and behaviors. These include :

o Increased heart and respirationo Regulation of endocrine balanceo Control of eating (hunger/thirst centers)o Elevation of blood pressure and diversion of blood to skeletal

muscles when angry

o Regulation of body temperatureso Regulation of sleep-wake cycle

Hypothalamus dysfunction Destruction of ventromedial hypothalamus results in hyperphagia and

obesity, while destruction of lateral hypothalamus results in anorexia

and starvation.

o Thalamus The thalamus is critical to pain perception. Dysfunction leads to impaired

memory and arousal.

o Reticular activating system (RAS) Involved in arousal, and wakefulness.

o Hippocampus The Hippocampus is critical for memory and new learning Table. Lesions and Memory (table reproduced from Kaplan Medical, USMLE

Step 1 Lecture Notes, Behavioral Sciences)

o Amygdala

Plays a critical role in emotional memory and rudimentary learning Kluver-Bucy syndrome

Results from removal of the amygdala. Causes taming, of theindividual, with no fear of natural enemies, sexual hyperactivity and

hyperorality, and a high rage threshold. Has been described as a Make

love, not warcondition.

Korsakoff syndrome


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Korsakoff syndrome is characterized by amnesia resulting from chronicthiamine (vitamin B1) deficiency. Associated with alcoholism, it may

result in neuronal damage in the thalamus.

Once neuronal damage occurs in the thalamus it is no longer treatablewith thiamine.

o Basal ganglia The basal ganglia function in the initiation and control of movement, and have

been implicated in depression and dementia.

Dysfunctions include disorders of movement such as Parkinson disease[substantia nigra], Huntington chorea/disease [caudate and putamen], and

Tourette syndrome [ caudate]. Others include Wilson disease, and Fahr disease.

Fahr Disease Fahr disease is a rare hereditary disorder that involves the calcification

of the basal ganglia. Onset occurs approximately at 30-years-old.

Dementia appears at approximately 50-years of age. The symptoms are

said to resemble the negative symptoms of schizophrenia.

o Pons The pons is important for REM sleep. Serves as start of NE pathway. Anomalies

have been linked to autism

o Cerebellum The cerebellumplays an important role in motor control. The cerebellum does not initiate movement, but it contributes to coordination,

precision, and accurate timing; it is key for balance.

It receives input from sensory systems and from other parts of the brain andspinal cord, and integrates these inputs to fine tune motor activity.[

Because of this fine-tuning function in the regulation of movement, damage tothe cerebellum does not cause paralysis, but instead produces disorders in finemovement, equilibrium, posture, and motor learning.

It may also be involved in some cognitive functions, such as attention andlanguage, and in the regulation of fear and pleasure responses.

Its movement-related functions are the most firmly established.Peripheral nervous system (PNS)

- The PNS consists of the somatic and autonomic nervous systems.- It contains all sensory, motor, and autonomic fibers outside of the CNS, including the spinal

nerves, cranial nerves, and peripheral ganglia. The PNS carries sensory information to the CNS

and motor information away from the CNS

- ANSo The autonomic nervous system, which consists of the sympatheticand

parasympathetic divisions, innervates the internal organs

o The autonomic nervous system coordinates emotions with visceral responsessuch asheart rate, blood pressure, and peptic acid secretion.

o Visceral responses occurring as a result of psychological stress are involved in thedevelopment and exacerbation of some physical illnesses


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Neurotransmissions: Syanpses, NTs

- Synapses and neurotransmitterso Information in the nervous system is transferred across the synaptic cleft ( the space

between the axon terminal of the presynaptic neuron and the dendrite of the

postsynaptic neuron) using chemical messengers called neurotransmitters.

When the presynaptic neuron is stimulated, a neurotransmitter is released. Ittravels across the synaptic cleft, and acts on receptors on the postsynaptic

neuron. Neurotransmitters are excitatory if they increase the likelihood that a

neuron will fireand inhibitory if they decrease the likelihood of that neuron

firing.

- Neurotansmissiono Presynaptic and postsynaptic receptors are proteins in the membrane of the neuron

that can recognize specific neurotransmitters

When stimulated by neurotransmitters, postsynaptic receptors may alter themetabolism of neurons by the use of second messenger. These messengers

include cyclic adenosine monophosphate(cAMP), lipids(e.g., diacylglycerol),Ca2+, and nitric oxide.

Changes in the number or affinity of receptors for specific neurotransmitterscan regulate the responsiveness of neurons(neuronal plasticity).

o The three major classes of neurotransmitters are (1). Biogenic amines (monoamines, best-known and earliest to be discovered,

present in small percentage of neurons),

(2). Amino acids (present in more than 70% of neurons) (3). Peptides(hundreds of different types but intermediate in terms of

abundance in neurons)

o Regulation The concentration of neurotransmitters in the synaptic cleftis closely related

to mood and behavior/psychiatric outcome.

A number of mechanisms affect this concentration. Following release by the presynaptic neuron, neurotransmitters are

removed from the synaptic cleft . The mechanisms include (1) reuptake

by presynaptic neuron, and (2) break-down by enzymes such as

monoamine oxidase (MAO)

- Psychiatric Conditions relating to neurotransmissiono Availability of specific neurotransmitters is associated with common psychiatric

conditions.

o Normalization of neurotransmitter availability by pharmacological agents is associatedwith symptom improvement in some of these disorders.


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(table is very important)

- Biogenic Amineso The biogenic amines, or monamines,include catecholamines, indolamines,

ethylamines, and quaternary amines.

o Metabolitesof the monoaminesare often measured in research and in psychiatricdiagnosis. This is because they are more easily measured in body fluids than the

monoamines/biogenic amines themselves.

o The monoamine theory of mood disorder hypothesizes that lowered monoamineactivity results in depression. Elevated levels result in mania.


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this one is also super important

o Dopamine Dopamine, a catecholamine, is involved in the pathophysiology of

schizophrenia and other psychotic disorders, Parkinson disease, mooddisorders. It is also involved in the conditioned fear response, and the

reward circuits for drugs of abuse.

In terms of synthesis, the amino acid tyrosineis converted to the precursor fordopamine by the enzyme tyrosine hydroxylase

At least 5 dopamine receptor subtypes (D1-D5) have been identified. Themajor site of action is D2 receptors for traditional antipsychotic

drugs/agents.

D1 and D4 (as well as D2 ) are sites for the newer atypical antipsychoticagents.

Dopaminergic tracts include the nigrostriatal, the tuberoindibular, and themesolimbic-mesocortical tracts.

Nucleus accumbens (NAc) dopamine pathway is the reward circuit wherepositive reinforcement occurs; the addiction pathway.

The nigrostriatal tractis involved in the regulation of muscle tone andmovement.

This tract degenerates in Parkinson disease


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Treatment with antipsychotic drugs, which block postsynapticdopamine receptors receiving input from the nigrostriatal tract, can

result in Parkinson-like symptoms (e.g., tremors, muscular rigidity,

bradykinesis).

Dopamine acts on the tuberoinfundibular tract, inhibiting the secretion ofprolactin from the anterior pituitary.

The blockade of dopamine receptors by antipsychotic drugs preventsthe inhibition of prolactin release. This results in elevated prolactin

levels.

The elevation of prolactin results in symptoms such as breastenlargement, galactorrhea, and sexual dysfunction.

The mesolimbic-mesocortical tract is associated with psychotic disorders. This tract may have a role in the expression of emotionssince it

projects into the limbic system and prefrontal cortex.

HYPERACTIVITY of the MESOLIMBIC tract has been thought to beassociated with the positive symptoms of schizophrenia.

HYPOACTIVITYof the MESOCORTICAL tract has been thought to beassociated with the negative symptoms of schizophrenia.

Amphetamines cause dopamine and NE release, blocking their uptake andleading to psychotic symptoms.

Tourette syndrome is associated with a hyperactive dopamine system.Thus, antipsychotics such as haloperidol may be used in treatmentwhen the symptoms are severe.

o Norepinephrine Norepinephrine, also a catecholamine, plays a role in mood, anxiety, arousal,

learning and memory.

Is transmitter of the sympathetic nerves of the autonomic nervous system ,mediating emergency response (e.g., tachycardia, bronchodilation, blood

pressure elevation)


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Implicated in previously mentioned monoamine hypothesis of depression. Synthesis

Like dopaminergic neurons, noradrenergic neurons synthesizedopamine.

However, dopamine beta-hydroxylase,present in noradrenergicneurons, converts this dopamine to norephinephrine.

Most noradrenergic neurons (approximately 10,000 per hemisphere in thebrain) are located in the locus ceruleus (in the upper pons).

o Serotonin Serotonin, an indolamine, plays a role in mood, sleep, sexuality, and impulse

control, among other psychological things.

Elevation of serotonin is associated with improved mood and sleep. On the other hand, it is associated with decreased sexual function (particularly

delayed orgasm).

Very high levels of serotonin are associated with psychotic symptoms. Changesin serotonin activity occur with the actions of hallucinogens/psychodelic drugs.

Serotonin has inhibitory influences on behavior. Decreased serotonin isassociated with poor impulse control.

Decreased serotonin is also related to depression. 5-HT is thus involved intherapeutic action of antidepressant treatments (e.g., 5-HT reuptake

inhibitors).

Drugs such as heterocyclic antidepressants (HCAs), and monoamine oxidaseinhibitors (MAOIs) ultimately increase the presence of serotonin and

norepinephrine in the synaptic cleft.

HCAs block reuptake of serotonin and norepinephrine, and SSRIs such asfluoxetine (Prozac) selectively block reuptake of serotonin by the presynaptic

neuron. MAOIs prevent the degradation of serotonin and norepinephrine by the enzyme

monoamine oxidase (MAO).

In terms of synthesis, the amino acid tryptophan is converted to serotonin (alsoknown as 5-hydroxy-tryptamine [5-HT]) by the enzyme tryptophan hydroxylase

as well as by an amino acid decarboxylase.

Most serotonergic cell bodies in the brain are contained in the dorsalraphe nucleus.

o Histamine Histamine is an ethylamine, and is affected by psychoactive drugs. Blockade of histamine receptors with drugs such as antipsychotics and tricyclic

antidepressants carries the common side effects of these drugs such as

sedation, and increased appetite leading to weight gain.

o Acetylcholine Acetylcholine (Ach), a quaternary amine, is the transmitter used by nerve-

skeletal (voluntary) muscle junctions.

Also used in many of the autonomic (involuntary) nervous system synapses Associated also with penile erection in males.


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Degradation of cholinergic neurons is associated with Alzheimer disease, Downsyndrome, and movement and sleep disorder(e.g., decreased REM sleep)

Dementias in general are associated with low acetylcholine levels (in amygdala,hippocampus and temporal cortex)

Cholinergic neurons synthesize Ach from acetyl coenzyme A and choline usingcholine acetyltransferase.

The nucleus basalis of Meynert is a brain area involved in production ofAch.

Acetylcholinesterase (AchE) breaks Ach down into choline and acetate. Involves receptors of the muscarinic and nicotinic types. By blocking the action of AchE (acetylcholinesterase), drugs such as donepezil

(Aricept), rivastigmine (Exelon) and galantamine (Reminyl) may delay

progression of Alzheimer disease but cannot reverse pathological changes.

Blockade of muscarinic Ach receptors with drugs such as antipsychotics andtricyclic depressants results in the classic anticholinergic adverse effects seen

with use of these drugs, including dry mouth, blurred vision, urinary hesitancy,

and constipation.

Anticholinergic agents are commonly used to treat the Parkinson-like symptomscaused by antipsychotic agents.

- Amino acid NTso These neurotransmitters are involved in most synapses in the brain and include

glutamate, gamma-aminobutyric acid (GABA), and glycine.

o Glutamate/glutamic acid One of major proteinogenic amino acids which is also a neurotransmitter. Principle excitatory neurotransmitter in the brain, thus stimulating neurons to

fire. Is involved in the major neuronal pathway that connects the cerebral cortex

and the corpus striatum. Also the neurotransmitter in the granule cells, themost numerous cells in the cerebellum.

Major NT in the visual pathway. An excitatory neurotransmitter that may be toxic to neurons (excitotoxicity)

and thus contribute to the pathophysiology of disorders such as schizophrenia,

Alzheimer disease, and other neurodegenerative diseases.

Basis for the production of symptoms of PCP (phencyclidine, angel dust) use .It is an antagonist of NMDA glutamate receptors.

Memantine [e.g., Namenda], a blocker of the N-methyl-D-aspartate (NMDA)receptor,a type of glutamate receptor, has been approved to treat (moderate

to severe) Alzheimer disease.

Glutamine agonists have produced seizures in nonhuman animal studies.o GABA

GABA is gamma amino-butyric acid, another amino acid neurotransmitter. Occurs almost exclusively in the brain, where it is the predominant

neurotransmitter in terms of quantity.

GABA is the principle inhibitory neurotransmitter in the CNS, reducing thefiring of neurons. It is present in about 25 to 40% of all brain synapses.


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It is synthesized from glutamate by the enzyme glutamic acid decarboxylase,which needs vitamin B6 (pyridoxine) as a cofactor.

GABA is involved in anxiety and the action of anxiolytic agents such asbenzodiazepines (e.g., diazepam [Valium]) and barbiturates (e.g., secobarbital

[Seconal]).

Benzodiazepines and barbiturates increase the affinity of GABA for its GABAAbinding site, allowing more chloride to enter the neuron.

The chloride-laden neurons then become hyperpolarized and inhibited,decreasing neuronal firing and ultimately decreasing anxiety.

Anticonvulsants also potentiate the activity of GABA. GABA is involved in anxiety and the action of anxiolytic agents such as

benzodiazepines (e.g., diazepam [Valium]) and barbiturates (e.g., secobarbital

[Seconal]).

Benzodiazepines and barbiturates increase the affinity of GABA for its GABAAbinding site, allowing more chloride to enter the neuron.

The chloride-laden neurons then become hyperpolarized and inhibited,decreasing neuronal firing and ultimately decreasing anxiety.

Anticonvulsants also potentiate the activity of GABA.o GLYCINE

Glycine is also a proteinogenic amino acid that serves as an inhibitoryneurotransmitter. It works on its own and as a regulator of glutamate activity.

- Neuropeptides:o ENDOGENOUS OPIOIDS

Enkephalins, endorphins, dynorphins, and endomorphins are opioids producedby the brain itself that act on opiate receptors and decrease pain and anxiety

and play a role in addiction and mood.

Placebo effects may be mediated by the endogenous opioid system. Priortreatment with an opioid receptor blocker such as naloxone may blockplacebo effects.

o Substance P Substance P is an 11 amino acid peptide that is a major transmitter for sensory

neurons that carry pain sensations from the peripheral tissues (especially the

skin) to the spinal cord.

Substance P is also found in numerous brain regions. Opiates relieve pain partly by blocking the release of substance P. Substance P and CCK in Anxiety disorders. Substance P in physical and mental pain and aggression.

o Others OTHER NEUROPEPTIDES have been implicated in various conditions. Cholecystokinin [CCK] and neurotensin in schizophrenia. Somatostatin, substance P, vasopressin, oxytocin, corticotropin-releasing factor

[CRF] in mood disorders (e.g., depression).

Somatostatin, and substance P in Huntington Disease.


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Somatostatin in Alzheimer disease. Neuropeptide Y in obesity.

Personality

- An individuals characteristic pattern of thinking, feeling and acting- May be, both informally and scientifically, described in terms of traits (e.g., shyness,

introversion-extroversion, sensation-seeking, optimism, hostility) that are stable and enduring.

Ones personality is unique to the individual.

- Behaviour genetics analyses suggest that roughly half (ball park 30-60%), on average, of thevariance in human personality (it does vary with different personality traits) is due to genetic

factors.

- From the evolutionary perspective (a major explanatory paradigm), human personality has beendescribed as an individuals unique variation on the general evolutionary design for human

nature (McAdams and Pals, 2006); Note, though, that personality may be reliably measured in

other species on the basis of similar traits.

- Personality differences may be observed in neuroimaging analyses: e.g., frontal lobe regionsinvolved in behavioral inhibition are less active in extraverts (who are sociable and outgoing)

than introverts (who are less sociable and more inwardly-oriented).

- Neurotransmitter levels may vary with normal personality as with psychological disorders; e.g.,dopamine and dopamine-related activity tends to be higher in extraverts.

- Personality Changeo Personality change means that a patients fundamental way of interacting and behaving

have been affected.

o When a true personality change occurs, the clinician should always address thepossibility of brain injury.

o Almost every medical disorder can be associated with some type of personality change,however.

o Diseases that preferentially effect the frontal lobes or subcortical structures are morelikely to manifest with prominent personality change.

o Course of illness depends on the nature of the insult:o Changes due to medical conditions that are likely to yield to intervention (e.g.,

correction of hypothyroidism) are more amenable to improvement than those that are

static (e. g., brain injury due to head trauma), or progressive (e.g., Huntingtons disease)

in nature.

Summary

- There is a genetic component in the development of psychiatric disorders (e.g.,schizophrenia,anxiety and mood disorders), as there is in many other psychological attributes , including

personality and intelligence.

- Family risk and twin studies are among the techniques used in behavior genetics.- A number of chromosomal disorders have behavioral manifestations, as reviewed.- Major components of the brain and nervous system have been discussed in terms of localization

and function. There is some lateralization in terms of brain function.


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- Neurotransmission, and the roles of major behavioral neurotransmitters and neuropeptideshave been discussed.

- Personality has been defined, and the medical implications of personality change discussed.-

1. biological foundations of behavior

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