On Mon, 2 Jun 2008 19:10:22 -0700, "Superman Hughes TrollKiller of
s*** 24bit & squarewheel" <BillHughes@[EMAIL PROTECTED]
> wrote:
>
>"Terry Dactille ©~®" <pterry@[EMAIL PROTECTED]
> wrote in message
>news:kcnru3h0glgaf7mjo2v4vb6usvt9mqjc29@[EMAIL PROTECTED]
>> On Sat, 5 Apr 2008 01:47:51 -0800, "Superman Hughes Troll and s***
>> bag" <BillHughes@[EMAIL PROTECTED]
> wrote:
>>
>>
>> Neurobiology of Impulsive-Aggressive Personality-Disordered Patients
>> Larry J. Siever, M.D.
>>
>> Dr. Siever is professor of psychiatry and director of the Outpatient
>> Psychiatry Division at Mount Sinai School of Medicine in New York. He
>> also directs the Mood and Personality Disorders Program in Mount
>> Sinai, a federally funded research program that investigates the
>> neurobiology of the schizophrenic spectrum personality disorders. Dr.
>> Siever serves as executive director of Mental Illness Research,
>> Education and Clinical Center at the Bronx VA Medical Center.
>>
>>
>> While the causes of the aggression and violence that we encounter
>> daily on our TV screens and newspapers are complex and multifactorial,
>> many of our patients suffer from a more explicit difficulty in
>> containing their aggressive impulses, particularly when frustrated or
>> provoked. This results in interpersonal conflict, disruptive
>> relation****ps, familial abuse and occupational failure. It is
>> precisely this type of impulsive aggression that appears to have
>> im****tant neurobiological as well as psychosocial underpinnings. These
>> patients with a "short fuse" have a limited capacity to suppress or
>> delay the impulse to aggression when frustrated or provoked.
>>
>> From an evolutionary perspective, aggression is a response to a
>> potential threat or provocation across a variety of species and seems
>> to be an inborn response tendency. Human beings in particular have
>> evolved higher-order cortical centers that serve to suppress the
>> emergence of more primitive forms of aggression when these are deemed
>> inappropriate. To understand the neurobiological basis of aggression,
>> an understanding of both the cortical inhibitory mechanisms and the
>> more primitive limbic systems involved in the generation and
>> modulation of aggression is required.
>>
>> Thus, the prefrontal cortices, particularly the orbital prefrontal
>> cortex and the ventral medial prefrontal cortex, play a key role in
>> inhibiting limbic regions involved in the generation of the
>> aggression. The anterior cingulate cortex may be involved in
>> evaluating affectively charged stimuli, just as the amygdala responds
>> to threat and provocative stimuli. These subcortical regions may then
>> serve to signal other critical nodes, such as the hypothalamus, that
>> modulate the body's hormonal internal milieu and cortical regions
>> initiating motor action.
>>
>> Personality Disorders
>> Impulsive aggression is a hallmark of several of the Axis II dramatic
>> clusters or Cluster B diagnoses. The prototype of a personality
>> disorder marked by impulsive aggression is borderline personality
>> disorder (BPD), where impulsive aggression is coupled with a highly
>> reactive and unstable affect modulation. Thus, patients with BPD will
>> respond to disappointment and frustrations with intense emotions like
>> rage, fear of abandonment and dysphoria. These affects then serve to
>> trigger the generation of an impulsive, often aggressive, response to
>> the provocation.
>>
>> For example, a woman with BPD learns through a phone call of a mutual
>> acquaintance that her boyfriend has slept with her best friend. She
>> rips the phone cord from the wall, throws the phone against the wall,
>> and then smashes a bottle and proceeds to cut herself with it, drawing
>> blood. These actions exemplify aggression--both other-directed and
>> self-directed acts--in response to a provocative event that touched on
>> deeply experienced vulnerabilities around feelings of low self-esteem,
>> envy and fears of abandonment.
>>
>> Patients with narcissistic personality disorder may also act
>> aggressively in an impulsive manner when feeling humiliated or
>> "narcissistically injured." Finally, patients with antisocial
>> personality disorder may act aggressively with little apparent remorse
>> about their aggressive and antisocial behaviors, which may result in
>> criminal activities.
>>
>> While the propensity to impulsive aggression interacts with an
>> exquisite affective sensitivity and lability in BPD, it can be
>> associated with the shallow affect of histrionic personality disorder
>> and psychopathic traits in antisocial personality disorder. Thus, the
>> more affectively labile individual with BPD may be more likely to seek
>> treatment, while individuals with antisocial personality disorder may
>> more likely be seen in forensic settings due to their illegal
>> behaviors.
>>
>> The S*****onin System
>> The s*****onin system has been the most extensively studied
>> neuromodulator system in relation to impulsive aggression. Studies of
>> the s*****onin metabolite 5-hydroxyindoleacetic acid (5-HIAA) suggested
>> that people with major depressive disorder may demonstrate reduced
>> concentrations of cerebrospinal fluid (CSF) 5-HIAA. A more careful
>> study of this phenomena suggested a bimodal distribution in depressed
>> patients, with violent suicidal acts associated with low CSF 5-HIAA
>> and nonviolent attempts, such as overdoses, associated with a more
>> "normal" mode of CSF 5-HIAA (Asberg et al., 1976). Subsequent studies
>> demonstrated that low CSF 5-HIAA also occurred in criminal offenders
>> and armed-forces personnel with a history of violence (Cocarro and
>> Siever, 2002). Studies with s*****onergic agonists such as
>> d,l-fenfluramine, which causes the release of s*****onin, blockade of
>> reuptake and direct agonism of 5-HT2 receptors, resulted in blunted
>> hormone responses in personality-disordered patients with impulsive
>> aggression. In a study of male patients with clearly defined major
>> affective disorder and/or personality disorder, patients with BPD
>> evidenced blunted prolactin responses to fenfluramine, compared to
>> responses of controls and another personality-disorder comparison
>> group. The degree of impulsive aggression was inversely correlated
>> with the prolactin response to fenfluramine (Coccaro et al., 1989).
>> This measure provides a putative index of s*****onergic responsiveness
>> in the hypothalamus that might not reflect a more generalized
>> s*****onergic deficit. This result was replicated in a study of
>> patients with impulsive-aggressive personality disorders using the
>> agent d-fenfluramine (Coccaro et al., 1996a; Coccaro et al., 1996b) as
>> well as in studies using the direct 5HT2C agonist
>> metachlorophenylpiperazine (m-CPP) (Coccaro et al., 1997).
>>
>> The s*****onin system modulates activity of inhibitory areas in the
>> prefrontal cortex and related areas such as the anterior cingulate
>> cortex. Some of these areas have been do***ented to be im****tant in
>> the modulation of aggression. For example, the well-known story of
>> Phineas Gage--dependable and hard-working railroad construction worker
>> who became irascible and aggressive following an injury--is consistent
>> with the role of the orbital frontal cortex and ventral medial frontal
>> cortex in inhibiting the emergence of aggression and modulating social
>> judgment.
>>
>> A variety of case studies of patients with damaged orbital frontal
>> cortex or frontal tem****al dimensions with frontal and tem****al
>> hypoperfusion suggests that a damaged orbital frontal cortex can
>> result in irritability and angry outbursts (New et al., 1998b).
>> Furthermore, postnatal lesions of the prefrontal cortex, particularly
>> in orbital regions, early in development may result in antisocial and
>> aggressive behavior in adulthood (Bechara et al., 2001). A propensity
>> to violent behavior has also been found in patients with tem****al lobe
>> tumors or lesions. Electrical stimulation of the amygdala has been
>> associated with rage attacks, and a reduced ability to recognize a
>> threat may be associated with bilateral amygdala lesions. These
>> considerations suggest that impairment or reduction in prefrontal
>> cortical inhibition of subcortex capacity or exaggerated
>> responsiveness in excitatory circuits of subcortical areas such as the
>> amygdala may be associated with aggression. Reduced prefrontal gray
>> matter has been associated with autonomic deficits and aggression in
>> patients with antisocial personality disorder (Raine et al., 2000).
>> Decreased blood flow or glucose metabolism has been re****ted in the
>> tem****al and frontal cortex of violent offenders and psychiatric
>> patients.
>>
>> Given that s*****onin can modulate prefrontal cortical activity,
>> reduced s*****onergic activity might be expected to result in reduced
>> brain activity in critical cortical inhibitory regions such as the
>> orbital frontal, ventral medial and anterior cingulate cortex.
>> Impulsive-aggressive patients with personality disorders demonstrate
>> blunted responses of orbital frontal, ventral medial and cingulate
>> cortex of the glucose metabolic increases induced by acute
>> pharmacologic administration of fenfluramine (Siever et al., 1999).
>> This is a more direct test of s*****onergic modulation of inhibitory
>> regions of interest in the cortex than neuroendocrine responses.
>> Reduced glucose metabolism was founded in the medial and orbital
>> frontal cortex, the left-middle and superior tem****al left gyrus, the
>> left parietal lobe, and the left caudate in a later study of BPD
>> marked by impulsive aggression (Soloff et al., 2000). The 5-HT2
>> agonist m-CPP induces metabolic increases in the orbital frontal and
>> other prefrontal cortical regions, as well as other cortical and
>> limbic regions. In personality-disordered patients marked by impulsive
>> aggression, the metabolic responses to m-CPP were reduced in the
>> orbital frontal and anterior cingulate cortices (New et al., 2002).
>> Both the fenfluramine and m-CPP studies also suggested that
>> correlations between prefrontal and amygdala activity found in normal
>> controls were absent in the impulsive-aggressive patients, raising the
>> possibility that a disconnection between inhibitory centers and limbic
>> centers involved in the generation of aggression may be responsible
>> for the disinhibition of aggression. This dysjunction may be related
>> to underactivation of s*****onin activity modulating the prefrontal
>> cortex and/or overactivation of the limbic cortex.
>>
>> S*****onin's effects on the prefrontal cortex may be mediated largely
>> by 5-HT2A receptors, which enhance prefrontal activity through
>> innervation of inhibitory interneurons. Thus, while responsiveness to
>> m-CPP is reduced, suggesting reduced 5-HT2 responsiveness, it is also
>> possible to directly examine the number of 5-HT2 binding sites.
>> Platelet and postmortem studies suggest that the number of 5-HT2A
>> receptors, which are the predominant neuronal 5-HT2 receptors in the
>> cortex, are actually increased in platelets and postmortem brains of
>> people who have attempted suicide (Mann et al., 1992; Pandey et al.,
>> 1990).
>>
>> A recent preliminary study of 5-HT2 receptor binding in
>> impulsive-aggressive personality-disordered patients in our laboratory
>> suggested actual increases in 5-HT2 receptor binding, even in patients
>> who previously demonstrated reduced responses to m-CPP (Siever et al.,
>> 2002). These results raise the possibility of a defect in transduction
>> distal to the receptor and possibly compensatory upregulation of the
>> 5-HT2 receptor. While the pathophysiology of this receptor system
>> needs to be more fully characterized, it is clearly implicated in the
>> external and directed aggression observed in personality-disordered
>> patients as well as the self-directed violence seen in suicide
>> attempters.
>>
>> Catecholamines
>> While the evidence is not as compelling for the role of catecholamines
>> in aggression as for s*****onin, a number of animal and clinical
>> studies suggest that increased reactivity of the noradrenergic and
>> dopaminergic system may facilitate aggressive behavior in humans.
>> Reduced presynaptic concentrations of catecholamines, such as
>> norepinephrine, coupled with supersensitive postsynaptic receptors,
>> may be responsible for exaggerated irritability in response to stress.
>> A re****t has suggested that there is a positive correlation between
>> the growth hormone response to clonidine (Catapres) and irritability
>> in personality-disordered and healthy volunteer subjects (Coccaro and
>> Siever, 2002).
>>
>> Peptides
>> Vasopressin plays an im****tant role in modulating memory and behavior.
>> A positive correlation between CSF vasopressin and life history of
>> aggression has been re****ted in personality-disordered subjects, which
>> is consistent with animal studies that show a vasopressin antagonist
>> reduced aggression (Coccaro et al., 1998). Opiate-binding protein has
>> been associated with aggression in healthy male volunteers and
>> metenkephalin levels have been associated with self-injurious behavior
>> (Coccaro and Siever, 2002).
>>
>> Steroids such as testosterone have been correlated with aggression in
>> normal human subjects, as well as in psychiatric and criminal
>> populations. Reduced cholesterol has been associated with aggressive
>> behavior and suicide attempts. Primates randomized to low-cholesterol
>> diets have also displayed increases in aggressive behavior. Therefore,
>> it appears likely that aggression is moderated by a variety of
>> neuromodulators, including monoamines, neuropeptides and
>> neurosteriods.
>>
>> Genetics
>> Twin and adoption in family studies sup****t heritability of
>> aggression. Heritability estimates vary from 44% to 72% in adults
>> (Bergeman and Seroczynski, 1998). While it is clear that there is no
>> gene or gene coding for aggression, it is possible that polymorphisms
>> in genes that regulate the activity of neuromodulators such as
>> s*****onin or genes for structural components of critical brain regions
>> regulating aggression may contribute to individual differences in the
>> susceptibility to aggressive behavior.
>>
>> For example, a mutation of the monoamine oxidase-A gene was linked to
>> impulsive violence in an extended family pedigree, and its genetic
>> alteration was associated with altered catecholamine metabolism. While
>> this is an unusual genetic variant, relatively common polymorphisms
>> exist in relation to s*****onin-related genes such as tryptophan
>> hydroxylase (TPH), 5-HT1B receptor, 5-HT2A receptor and 5-HT1A
>> receptor. An allele for TPH polymorphism has been associated with
>> suicide attempts in violent offenders and with impulsive aggression in
>> personality-disordered patients in some but not all studies (New et
>> al., 1998a; Nielsen et al., 1998). More recent pilot studies suggest a
>> relation****p between alleles of the 5-HT1B receptor, which modulates
>> pre-synaptic release of s*****onin, as well as the 5-HT2A receptor, in
>> relation to impulsive aggression and personality-disordered patients
>> (New et al., 2002).
>>
>> Treatment Implications
>> An increased understanding of the neurobiology of aggression has
>> enabled the development of agents that may be ultimately successful in
>> reducing a tendency to respond to frustration with irritable
>> aggression. A number of uncontrolled studies and, more recently,
>> double-blind, placebo-controlled trials have suggested that selective
>> s*****onin reuptake inhibitors may reduce irritability and aggression
>> consistent with the hypothesis of reduced s*****onergic activity in
>> aggression (Coccaro and Kavoussi, 1997). Mood stabilizers that dampen
>> limbic irritability may also be im****tant in reducing the
>> susceptibility to react to provocation or threatening stimuli by
>> overactivation of limbic system structures such as the amygdala.
>> Carbamazepine (Tegretol), diphenylhydantoin (Dilantin) and divalproex
>> sodium (Depakote) have all yielded promising results, not only in open
>> trials but in more recent placebo-controlled trials of patients with
>> personality disorders or other psychiatric disorders with aggressive
>> behavior (Coccaro and Siever, 2002).
>>
>> Excessive dopaminergic activity might suggest that neuroleptic
>> medications might be of help, and, indeed, atypical neuroleptics have
>> been successful in reducing aggression and other symptoms of BPD,
>> including a recent double-blind study of olanzapine (Zyprexa)
>> (Zanarini and Frankenburg, 2001). Anti-adrenergic agents such as
>> b-blockers have also been shown to reduce aggression in populations
>> with brain injuries and dementia, presumably by dampening excessive
>> noradrenergic activity (Ratey et al., 1992). Finally, there have been
>> some re****ts of the use of the antiandrogens to more specifically
>> reduce ***ually related aggression (Coccaro and Siever, 2002).
>>
>> An increased understanding of the neurobiology of impulsive aggression
>> may ultimately help us to understand psychosocial treatments that are
>> grounded in theoretical frameworks that include this diathesis as part
>> of their formulation. Thus, the emotional dysregulation often
>> resulting in impulsive, self-destructive behaviors becomes a target of
>> the cognitive-behavioral technique, dialectical behavioral therapy,
>> and the diathesis to aggressive behavior is part of psychoanalytic
>> formulations of BPD (Kernberg, 1992). Cognitive-behavioral therapies
>> strive to validate and understand the intense affects experienced by
>> people with these personality disorders but provide alternative ways
>> of channeling the impulses generated by these intense feelings away
>> from self-injurious or aggressive behaviors toward more
>> interpersonally effective coping strategies. Psychoanalytic therapies
>> use exploration of unconscious conflict in here-and-now distortions of
>> the transference to help ****ft deeply ingrained assumptions and
>> strategies.
>>
>> Often, medications used to reduce the diathesis to impulsive
>> aggression may help facilitate the intrapsychic ****fts that are the
>> goals of these therapies. They are more useful in disorders such as
>> BPD, where affects are intensely experienced and yearning for
>> attachment is great. Impulsive aggression is found in antisocial
>> personality disorder and is often accompanied by a psychopathy or
>> emotional "agnosia" that makes it less amenable to psychiatric
>> treatment, but responses have been observed in therapeutic communities
>> or highly cohesive self-help groups. Thus, the promise that an
>> increased understanding of the neurobiology of aggression holds for
>> therapeutic and possibly future preventive treatment still remains to
>> be realized, but current research is providing a promising foundation.
>>
>> --
>>
>>
>> "A winner makes commitment. A loser makes promises."
>>
>> "The path of least resistance is the path of the loser."
>
>
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>
I was required to take the officer's test, while in Advanced
Individual Training, which means I have a 59 IQ, and you didn't!
God Bless America, Bill O|||||||O
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