Loading ...
Sorry, an error occurred while loading the content.

Re: [psychiatry-research] Schizophrenia - cause and effect

Expand Messages
  • John M Price PhD
    On Wed, 31 Jan 2001, Mike Miller wrote: [snip] ... The pursuit eye-movement disorder is likely the best genetic marker in this regard. I also have spoken with
    Message 1 of 5 , Jan 31, 2001
      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
      this regard.

      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,
      > 22-53.
      > 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
      this paper.

      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
      thinking scientifically.

      John M. Price, PhD jmprice@...
      Life: Chemistry, but with feeling! | PGP Key on request or FTP!
      Comoderator: sci.psychology.psychotherapy.moderated Atheist# 683
    • Ian Pitchford
      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
      Message 2 of 5 , Feb 1, 2001
        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,
        71(6), 396-401.

        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,
        23(1), 65-72.

        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,
        37(3), 142-5.

        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
        <<<>>> <<<>>> <<<>>> <<<>>> <<<>>> <<<>>>
      • Jim Goodwin
        Tony: Post Traumatic Stress Disorder (PTSD) is the name/diagnosis the American Psychiatric Association has given to the physical effects upon the CNS that
        Message 3 of 5 , Feb 2, 2001

          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.
          Clinical Psychologist
        Your message has been successfully submitted and would be delivered to recipients shortly.