Re: [psychiatry-research] Schizophrenia - cause and effect
On Wed, 31 Jan 2001, Mike Miller wrote:
> When a person with schizophrenia has an identical twin, that twin will
> develop schizophrenia about 50% of the time. That means that the disorder
> is not a purely genetic disorder because 50% of identical twins (who share
> *all* of their genes with a schizophrenic person) will not develop
> schizophrenia. On the other hand, they will often have schizophrenic-like
> symptoms even if they don't have the full disorder.
The pursuit eye-movement disorder is likely the best genetic marker in
I also have spoken with a number of people on this. When they have a case
in front of them, they would occasionally visit the home. Even if they
file said 'no family history' they would find eccentricities more often
than not. In one instance, they mother was destroying a nice built in
fireplace to retrieve a letter she thought had dropped behind it some 5
years earlier. Sounds like a family Hx to me!
> There are many questions about the effects of sexual abuse. I know of no
> evidence that schizophrenia may be precipitated by sexual abuse. Also,
> there are reasonable studies that conclude that sexual abuse of young
> people does not cause them to become mentally ill as adults. The
> following article was criticized heavily by a radio personality (Dr. Laura
> Schessinger, a physiologist), but it appears to be scientifically sound
> and it appeared in psychology's top journal.
> Rind, Bruce; Tromovitch, Philip; Bauserman, Robert. (1998). A
> meta-analytic examination of assumed properties of child sexual abuse
> using college samples. Psychological Bulletin. Vol 124(1), Jul 1998,
> Many lay persons and professionals believe that child sexual abuse (CSA)
> causes intense harm, regardless of gender, pervasively in the general
> population. The authors examined this belief by reviewing 59 studies based
> on college samples. Meta-analyses revealed that students with CSA were, on
> average, slightly less well adjusted than controls. However, this poorer
> adjustment could not be attributed to CSA because family environment (FE)
> was consistently confounded with CSA, FE explained considerably more
> adjustment variance than CSA, and CSA-adjustment relations generally
> became nonsignificant when studies controlled for FE. Self-reported
> reactions to and effects from CSA indicated that negative effects were
> neither pervasive nor typically intense, and than men reacted much less
> negatively than women. The college data were completely consistent with
> data from national samples. Basic beliefs about CSA in the general
> population were not supported.
In addition to this, look to the journal Sexuality & Culture, 2000
(Spring), v4n2. It has the rebuttal to the data free campaign against
One article, a nice review of the reviews, is available at their site:
Most of what people think about CSA is patently false, brought to us by
the psychodynamic psychotheapists well known for making things up, and not
John M. Price, PhD jmprice@...
Life: Chemistry, but with feeling! | PGP Key on request or FTP!
Comoderator: sci.psychology.psychotherapy.moderated Atheist# 683
- Tony Brindle wrote:
I am looking for advice. I have been assisting a young man who
experiences schizophrenia to pursue a claim for criminal injury after
he was sexually abused as a teenager. My friend is sure that the
schizophrenia he suffers from now was brought out and has been made
worse as a result of the abuse.
REPLY: Please don't take anything I say as being remotely authoritative, but I
think you need to distinguish between sexual abuse, or any other sort of abuse,
and the experience of that abuse, because psychological factors influence the
extent of the physiological stress response. There is no doubt that a prolonged
stress response is damaging and can disrupt cognition through the sympathetic
nervous system and the release of glucocorticoids, and maybe through an
increase in AChE inhibitors (see Sapolsky, R. M. (1998). Why zebras don't get
ulcers: An updated guide to stress, stress-related diseases, and coping. (2nd
ed.). New York, NY: W. H. Freeman and Company. CONTACT:
sapolsky@... and Sapolsky, R. M. (1998). The stress of Gulf War
syndrome. Nature, 393, 308-309 - Kaufer, D., Friedman, A., Sedman, S., & Soreq,
H. (1998). Acute stress facilitates long-lasting changes in cholinergic gene
expression. Nature, 393, 373-377. CONTACT Hermona Soreq soreq@...),
but the relationship between stress and schizophrenia, if any, remains obscure,
though work continues.
According to a recent review "neuroendocrine studies in patients with
schizophrenia have not not been able to demonstrate clear-cut abnormalities
that would allow the delineation of a neurobiological hypothesis with the same
stringency as in depression and anxiety. One reason for this is that the
schizophrenic phenotype is extremely variable, ranging from acute exacerbation
with disturbed content and formal organization of thought, hallucinations,
arousal, and inadequate affect, to a so-called "negative sympom pattern"
dominated by social withdrawal and loss of motivation, sometimes accompanied by
a flattened affect. Frequently symptoms of severe anxiety and depression
coexist, which further obscures neuroendocrine study results" (Holsboer, F.
(1999). Clinical neuroendocrinology. In D. S. Charney, E. J. Nestler, & B. S.
Bunney (Eds.), Neurobiology of mental illness . Oxford; New York, NY: Oxford
University Press. pp. 156-157)
However, a number of other studies on the relationship between stress hormones
and neurochemicals implicated in schizophrenia have been published since this
review, and the authors of these studies can probably give you expert guidance:
Lee, D., Huang, W., Wang, L., Copolov, D., & Lim, A. T. (2000). Glucocorticoid
modulation of dopamine mediated effects on hypothalamic atrial natriuretic
factor neurons. Molecular Psychiatry, 5(3), 332-6.
Dopamine (DA) plays an important role in cognition, neuroendocrine functions
and psychosis.1,2 Whilst stress adversely affects some of these functions, its
neurobiological basis remains unclear.3 In the rat hypothalamus, a concurrent
activation of D5and D2 receptors by dopamine produces a biphasic effect on the
function of atrial natriuretic factor (ANF) neurons.4 Whereas low doses (10-8
and 10-7 M) of DA suppress the release and pro-ANF mRNA expression, high doses
(10-6 and 10-5 M) of the amine produce an opposite effect through the
interaction of D5 and D2 receptors. We report here that the augmenting effect
of DA on the hypothalamic neurons is inhibited by a synthetic glucocorticoid,
dexamethasone (DM), in both time-dependent and dose-related manner with an EC50
of 0.1 nM. Furthermore, the inhibition is blocked by 100 nM of RU38486
(P<0.01), a glucocorticoid receptor antagonist, but not by an equivalent dose
of RU28318, a mineralocorticoid receptor antagonist. In contrast, DM failed to
modulate low doses (10(-8) to 10(-7) M) of DA-induced suppression of ir-ANF
release and pro-ANF mRNA expression that was mediated primarily through D2
receptors. We conclude that glucocorticoids markedly alter DA-induced biphasic
effects by down-regulating D5, but not D2, receptor-mediated neurobiological
events. Hence, in severe stress, high levels of circulating glucocorticoids may
render dopamine to act as a potent suppressor of neurons that possess both D5
and D2 receptors. The possibility that this novel mechanism of stress hormone
or glucocorticoids may, in part, undermine DA-mediated neurophysiology in
critical regions of the brain, which links to psychosis now needs to be
CONTACT: Dan Lee, Cell Biology Laboratory, Division of Molecular Schizophrenia,
Mental Health Research Institute of Victoria, Parkville, Australia 3052
Goldman, M. B., & Wood, G. J. (2000). Adrenocorticotropin inhibition by
restoration of normal evening cortisol levels: a measure of putative
hippocampus-mediated glucocorticoid feedback in humans. Neuroendocrinology,
Hippocampus-mediated glucocorticoid negative feedback is thought to be relevant
to the pathophysiology of neuropsychiatric disorders, but no reliable method of
measuring it in humans has been developed. Converging lines of evidence
indicate that basal hypothalamic-pituitary-adrenal axis activity during the
unstressed circadian trough is primarily regulated by this feedback process. To
assess whether negative feedback can be demonstrated under these circumstances,
we studied normal controls (n = 5) who were pretreated with metyrapone to lower
their basal evening cortisol levels. On two separate occasions, in double-blind
randomized order, subjects received an infusion of cortisol or of saline.
Restoration of normal evening plasma cortisol by the cortisol infusion produced
a drop in plasma adrenocorticotropin (ACTH) apparent in the last sample
obtained at +200 min (p < 0.05). The ACTH response in schizophrenic patients (n
= 4), whose mental illness may arise from hippocampal dysfunction, was
relatively blunted compared to that seen in normals (p < 0.02).
11-Desoxycortisol levels paralleled the ACTH responses across conditions and
subject groups. These preliminary data suggest that hippocampus-mediated
glucocorticoid feedback can be measured in normal subjects and may provide an
index of hippocampal dysfunction in neuropsychiatric patients.
CONTACT: M. B. Goldman, Psychiatric Institute, University of Illinois in
Affiliation with University of Chicago, Department of Psychiatry, University of
Chicago Pritzker School of Medicine, Chicago, IL, USA. m-goldman@...
Duval, F., Mokrani, M. C., Crocq, M. A., Bailey, P. E., Diep, T. S., Correa,
H., & Macher, J. P. (2000). Dopaminergic function and the cortisol response to
dexamethasone in psychotic depression. Progress in Neuro-Psychopharmacology and
Biological Psychiatry, 24(2), 207-25.
1. It has been hypothesized that psychotic symptoms in depression may be due to
increased dopamine activity secondary to hypothalamic-pituitary-adrenal (HPA)
axis overactivity. 2. To test this hypothesis, the authors examined the
cortisol response to dexamethasone suppression test (DST, 1 mg orally) and
multihormonal responses to apomorphine (APO, 0.75 mg s.c.)--a dopamine
agonist--in 150 drug-free hospitalized patients with DSM-IV major depressive
episode with psychotic features (MDEP, n=35), major depressive episode without
psychotic features (MDE, n=74), or schizophrenia paranoid type (SCZ, n=41), and
27 hospitalized healthy controls (HCs). 3. MDEPs showed increased activity of
the HPA system (i.e. higher post-DST cortisol levels) than HCs, SCZs and MDEs.
However, there were no differences in adrenocorticotropic hormone (ACTH),
cortisol, prolactin and growth hormone (GH) responses to APO between MDEPs and
MDEs and HCs. On the other hand, SCZs showed lower APO-induced ACTH stimulation
and a higher rate of blunted GH than HCs, MDEs and MDEPs, suggesting a
functional alteration of the hypothalamic dopamine receptors in SCZs. 4. In the
total sample and in each diagnostic group, DST suppressors and non-suppressors
showed no differences in hormonal responses to APO. 5. These results suggest a
lack of causal link between HPA axis hyperactivity and dopamine dysregulation.
In contrast to schizophrenia, psychotic symptoms in depression seem not to be
related to dopamine function dysregulation.
CONTACT: F. Duval, Centre Hospitalier, Rouffach, France.
Muck-Seler, D., Pivac, N., Jakovljevic, M., & Brzovic, Z. (1999). Platelet
serotonin, plasma cortisol, and dexamethasone suppression test in schizophrenic
patients. Biological Psychiatry, 45(11), 1433-9.
BACKGROUND: Serotonin (5-HT) regulates hypothalamic-pituitary-adrenal (HPA)
axis activity. Abnormal response to the dexamethasone suppression test (DST)
and altered platelet 5-HT concentration have been shown in some schizophrenic
patients. METHODS: Platelet 5-HT and plasma cortisol concentrations were
determined simultaneously in 86 male schizophrenic patients before and after
DST. Basal plasma cortisol and platelet 5-HT levels were also determined in 69
healthy male persons. RESULTS: Schizophrenic patients had higher plasma
cortisol and platelet 5-HT concentrations than healthy persons. An abnormal
escape from dexamethasone suppression was observed in 50% of patients. In these
patients predexamethasone cortisol and platelet 5-HT concentrations were higher
than in patients with normal DST. CONCLUSIONS: This study demonstrates that
schizophrenic patients have the HPA axis dysregulation that could be connected
with a disturbance in the 5-HT system.
CONTACT: D. Muck-Seler, Laboratory for Molecular Neuropharmacology, Ruder
Boskovic Institute, Zagreb, Croatia.
Newcomer, J. W., Craft, S., Askins, K., Hershey, T., Bardgett, M. E.,
Csernansky, J. G., Gagliardi, A. E., & Vogler, G. (1998). Glucocorticoid
interactions with memory function in schizophrenia. Psychoneuroendocrinology,
Glucocorticoid (GC) exposure can affect brain function, including potential
adverse effects on hippocampal physiology and on specific elements of cognitive
performance. In a prior study of healthy adult humans, decreased verbal memory
performance was detected during four days of double-blind, placebo-controlled
dexamethasone (DEX) treatment. Using an identical experimental design and
sample size (n = 19), the cognitive effect of DEX treatment was studied in 11
subjects with schizophrenia, compared with 8 receiving placebo. In contrast to
the effect in healthy adults, GC treatment with DEX at this dose (cumulative
3.5 mg) and duration did not decrease verbal memory performance or other
measures of cognitive function in the patients with schizophrenia. When data
from this experiment was compared with data from the previous study of healthy
adults, covarying differences in baseline memory performance, a significant
3-way interaction was detected between subject group, treatment condition, and
the repeated measurements of verbal memory performance across baseline,
treatment and washout (F[3,87] = 4.84, p = .0066), suggesting differential
cognitive effects of DEX in the patients versus the previously studied healthy
subjects. Baseline plasma cortisol concentrations (0800 h) prior to DEX
treatment were inversely correlated with baseline delayed (rs = -0.536, p =
.03) verbal recall performance, supporting a previous report. The current
results await replication using a larger sample size but provide preliminary
evidence for an altered behavioral response to acute GC exposure in
schizophrenic versus healthy subjects, and further evidence for a relationship
between chronic changes in circulating cortisol and the memory impairments
found in this disorder.
CONTACT: J. W. Newcomer, Department of Psychiatry, Washington University School
of Medicine, St. Louis, MO 63110, USA. newcomerj@...
Jakovljevic, M., Muck-Seler, D., Pivac, N., & Crncevic, Z. (1998). Platelet
5-HT and plasma cortisol concentrations after dexamethasone suppression test in
patients with different time course of schizophrenia. Neuropsychobiology,
Platelet 5-HT and plasma cortisol concentrations were determined in 59
schizophrenic patients with different time course of illness before and after
dexamethasone suppression test (DST). An abnormal DST (nonsuppression) was
observed in 51% of patients. In these patients basal cortisol and platelet 5-HT
concentrations were higher than in patients with normal DST. After DST, plasma
cortisol levels were higher in nonsuppressors with intermittent and
intermittent-chronic time course, whereas platelet 5-HT concentrations were
increased in nonsuppressors with intermittent-chronic time course. The results
suggest that schizophrenic patients have dysregulated
hypothalamic-pituitary-adrenal axis as shown by a high rate of DST
nonsuppression, and that nonsuppressors showed hypercortisolemia and
hyperserotonemia independent of the time course of schizophrenia. No
significant association between DST and time course of the illness was found.
CONTACT: University Psychiatric Clinic, Clinical Hospital Center, Croatian
Institute for Brain Research, Zagreb, Croatia.
<<<>>> <<<>>> <<<>>> <<<>>> <<<>>> <<<>>>
Ian Pitchford <Ian.Pitchford@...>
Editor, Evolutionary Psychology Online
Centre for Psychotherapeutic Studies
School of Health and Related Research
University of Sheffield, S10 2TA, UK
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Post Traumatic Stress Disorder (PTSD) is the
name/diagnosis the American Psychiatric Association
has given to the physical effects upon the CNS that
"traumatic" environmental factors can have on one. The
US federal government and many state governments in
the USA actually pay physical disability payments to
people physically/mentally disabled by this
environmentally induced illness.
Yes, many perceive environment plays a part in the
health of one's CNS.
Jim Goodwin, Psy.D.