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O. Sydow,
P. Hansson,
D. Young,
B. Meyerson,
E-O. Backlund,
T. Ebendal,
L.O. Farnebo, R. Freedman,
B. Hamberger,
B. Hoffer,
Å. Seiger,
I. Strömberq,
L. Olson
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ABSTRACT: Parkinson's disease has been the object of several therapeutic strategies based upon replacement of the degenerating dopaminergic neurons. Adrenal medullary transplants were tried initially, because of the biochemical relationship between chromaffin cells of the medulla and dopaminergic neurons of the substantia nigra. Compared to transplant of fetal neurons, autologous grafts of adrenal medullary tissue has the advantage of using a readily available source of tissue without the problems of immunosuppression. However, these cells have not proven to be as effective as fetal neurons, probably because they do not fully differentiate into neurons. In animal models, brief treatment with nerve growth factor can facilitate such differentiation. This study is a clinical evaluation of the efficacy of adrenal medullary cell transplantation, combined with nerve growth factor infusion.Two patients were selected who were moderately to severely affected (Hoehn–Yahr stage 2 in on-phase and stage 4 in off-phase). After adrenalectomy, small pieces of medulla were prepared and implanted stereotactically into the dorsal putamen on one side of the brain. A catheter filled with mouse beta-nerve growth factor (NGF) was placed close to the grafts. Infusion of NGF was continued for one month.Despite a progressively deteriorating course prior to surgery, both patients showed improvement on the rating scales postoperatively. There was also significant improvement in timed motor tests. Motor readiness evoked potentials showed increased voltage over the operated hemisphere.The study points to methods and feasibility of supplying nerve growth factor intraparenchymally to the human brain. Possible implications with respect to other growth factors, particularly Glial cell-line Derived Neurotrophic factor (GDNF) are discussed.
European Journal of Neurology 01/2011; 2(5):445 - 454. · 3.69 Impact Factor
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ABSTRACT: Antipsychotic effects of clonidine were evaluated in one schizo-affective and seven schizophrenic patients, using a double-blind, cross-over design to compare placebo, clonidine, and standard neuroleptic drugs. Mean improvement on clonidine and neuroleptics was equal, and improvement scores on the two treatments were closely correlated for individual patients. Clonidine was selected because it blocks noradrenergic but not dopaminergic neurotransmission. Patients were selected because of co-existing psychosis and tardive dyskinesia, a movement disorder thought to be caused by the antidopaminergic properties of the neuroleptics. For all patients, dyskinesia improved when neuroleptics were discontinued during clonidine and placebo periods of the study. The data provide preliminary evidence that clonidine may be an effective alternative to neuroleptics, particularly for patients for whom the dopaminergic blocking action of the neuroleptics is undesirable. The study also prompts re-evaluation of theories of a unique role for dopamine in schizophrenia.
Acta Psychiatrica Scandinavica 08/2007; 65(1):35 - 45. · 4.22 Impact Factor
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ABSTRACT: Studies of neurobiological disorders in the brain, including schizophrenia, rely on the use of postmortem brain tissues, in which an understanding of the effects of various pre- and postmortem variables on gene expression is critical. In several different brain regions, pH has been shown to have a large effect on postmortem brain gene expression patterns. One region that has not yet been evaluated in such studies is the hippocampus, a region often implicated in schizophrenia research. In the present study, we show that postmortem brain pH is similar across different brain regions. Brain pH accounted for greater variation in hippocampal gene expression profiles than any other parameter evaluated, including gender and schizophrenia. The predictive value of brain pH in an independent sample set was also greater than the disease, demonstrating that pH represents one of the most important control parameters in human postmortem gene expression studies in schizophrenia.
Brain Research 09/2006; 1106(1):1-11. · 2.73 Impact Factor
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ABSTRACT: Evidence of genetic linkage for schizophrenia at chromosome 15q14 has been reported in nine independent studies, but the molecular variants responsible for transmission of genetic risk are unknown. National Institute of Mental Health Schizophrenia Genetics Initiative families were genotyped for single nucleotide polymorphisms (SNPs) and dinucleotide repeat markers in the 15q14 linkage region and analyzed based on the presence of particular alleles of the dinucleotide repeat marker D15S165 in the 15q14 region. Two alleles showed both familial transmission disequilibrium and population-wide association with schizophrenia. The two groups identified by these two D15S165 alleles differ in age of onset, number of hospitalizations and intensity of nicotine abuse, as well as in predominant ethnicity. Variations in the frequency of SNPs in CHRNA7, the alpha-7-nicotinic acetylcholine receptor subunit gene at 15q14, were found in each group. Further sequencing in these two groups may yield more definitive identification of the molecular pathology.
Genes Brain and Behavior 02/2006; 5 Suppl 1:14-22. · 3.48 Impact Factor
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ABSTRACT: Nicotine is known to induce the release of multiple neurotransmitters, including glutamate and dopamine, through activation of nicotinic receptors. Gene expression in the N-methyl-d-aspartate postsynaptic density (NMDA-PSD), as well as other functional groups, was compared in postmortem hippocampus of schizophrenic and nonmentally ill smokers and nonsmokers utilizing a microarray and quantitative RT-PCR approach. The expression of 277 genes was significantly changed between all smokers and nonsmokers. Specific gene groups, most notably genes expressed in the NMDA-PSD, were prevalent among these transcripts. Analysis of the interaction between smoking and schizophrenia identified several genes in the NMDA-PSD that were differentially affected by smoking in patients. The present findings suggest that smoking may differentially modulate glutamatergic function in schizophrenic patients and control subjects. The biological mechanisms underlying chronic tobacco use are likely to differ substantially between these two groups.
Molecular Brain Research 11/2005; 139(2):317-32. · 2.00 Impact Factor
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ABSTRACT: Schizophrenia patients have insufficient inhibitory processing of identical paired auditory stimuli. This deficient "auditory gating" is thought to have physiological relevance, and its severity correlates with certain measures of both positive and negative symptoms. Schizophrenia patients also represent the heaviest smoking population subgroup. Because smoking temporarily normalizes their auditory gating deficit, this may represent a form of self-medication. Although this deficit is unresponsive to treatment with typical antipsychotic drugs, it does respond to the atypical antipsychotic clozapine. The normalization of this deficit by smoking may account for some of the intense drive to smoke that is experienced by schizophrenia patients. However, the normalizing effect of nicotine is transient and is not observed with repeated administration. Auditory gating is modulated by the alpha7 nicotinic receptor subtype, a rapidly desensitizing low-affinity nicotinic receptor. Agents that selectively activate the alpha7 receptor represent a novel class of therapeutic agents for use in the treatment of schizophrenia. Whether selective alpha7 agonists will have beneficial effects on symptoms other than the auditory gating deficit has not yet been established. The first developed alpha7-selective agonist, 3-2,4-dimethoxybenzylidene anabaseine (DMXB-A), normalizes auditory gating in three distinct animal models of the deficit. DMXB-A is a prototype for this potential new drug class, but proof-of-concept for this type of pharmacotherapy will not be available until the completion of planned clinical trials assessing DMXB-A's effects in schizophrenia patients. Additional avenues to the potential normalization of auditory gating deficits are also discussed, focusing on the novel efficacy of clozapine and the potential utility of allosteric modulators of nicotinic receptors.
Current Drug Targets - CNS & Neurological Disorders 05/2002; 1(2):149-62.
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American Journal of Medical Genetics 01/2002; 105(8):655-7.
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S Leonard,
L E Adler,
K Benhammou,
R Berger,
C R Breese,
C Drebing,
J Gault,
M J Lee,
J Logel,
A Olincy,
R G Ross,
K Stevens,
B Sullivan,
R Vianzon,
D E Virnich,
M Waldo,
K Walton, R Freedman
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ABSTRACT: Patients with mental illness have a higher incidence of smoking than the general population and are the major consumers of tobacco products. This population includes subjects with schizophrenia, manic depression, depression, posttraumatic stress disorder (PTSD), attention-deficit disorder (ADD), and several other less common diseases. Smoking cessation treatment in this group of patients is difficult, often leading to profound depression. Several recent findings suggest that increased smoking in the mentally ill may have an underlying biological etiology. The mental illness schizophrenia has been most thoroughly studied in this regard. Nicotine administration normalizes several sensory-processing deficits seen in this disease. Animal models of sensory deficits have been used to identify specific nicotinic receptor subunits that are involved in these brain pathways, indicating that the alpha 7 nicotinic receptor subunit may play a role. Genetic linkage in schizophrenic families also supports a role for the alpha 7 subunit with linkage at the alpha 7 locus on chromosome 15. Bipolar disorder has some phenotypes in common with schizophrenia and also exhibits genetic linkage to the alpha 7 locus, suggesting that these two disorders may share a gene defect. The alpha 7 receptor is decreased in expression in schizophrenia. [(3)H]-Nicotine binding studies in postmortem brain indicate that high-affinity nicotinic receptors may also be affected in schizophrenia.
Pharmacology Biochemistry and Behavior 01/2002; 70(4):561-70. · 2.53 Impact Factor
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ABSTRACT: C3H and DBA/2 mice differ in their hippocampal inhibitory function, as measured by the inhibitory gating of pyramidal neuron response to repeated auditory stimulation. This functional difference appears to be related to differences in expression of the alpha7 nicotinic cholinergic receptor, which may be generally expressed by interneurons. This study examines the relationship between genetic variation in alpha7 receptor subunit expression and GABAergic interneuron distribution in various regions and layers of the hippocampus in the two mouse strains. Subpopulations of hippocampal interneurons in both mouse strains were found to bind [(125)I]alpha-bungarotoxin. However, the distribution of the [(125)I]alpha-bungarotoxin-positive hippocampal interneurons was significantly different between C3H and DBA/2 mice. In region CA1, and to a lesser extent in region CA3, DBA/2 mice had increased numbers of [(125)I]alpha-bungarotoxin-positive neurons in stratum lacunosum-moleculare and decreased numbers in stratum oriens. Similar differences in GABAergic neuron distribution were observed in region CA1 in the two strains. C3H/DBA/2 F1 animals were backcrossed to the C3H parental strain for six generations, with selection for either the DBA/2 or C3H allelic variant of the alpha7 receptor gene. The distribution of [(125)I]alpha-bungarotoxin labeling closely resembled the DBA/2 parental phenotype in animals retaining the DBA/2 allele of the alpha7 gene. These data suggest that the alpha7 receptor gene locus may influence the anatomical organization of at least a subset of hippocampal interneurons by an as yet unidentified mechanism. This difference in interneuron anatomy may also contribute to functional differences in inhibitory sensory gating between the two strains.
Brain Research 01/2002; 922(2):180-90. · 2.73 Impact Factor
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ABSTRACT: Schizophrenia is assumed to have complex inheritance because of its high prevalence and sporadic familial transmission. Findings of linkage on different chromosomes in various studies corroborate this assumption. It is not known whether these findings represent heterogeneous inheritance, in which various ethnic groups inherit illness through different major gene effects, or multigenic inheritance, in which affected individuals inherit several common genetic abnormalities. This study therefore examined inheritance of schizophrenia at different genetic loci in a nationally collected European American and African American sample. Seventy-seven families were previously genotyped at 458 markers for the NIMH Schizophrenia Genetics Initiative. Initial genetic analysis tested a dominant model, with schizophrenia and schizoaffective disorder, depressed type, as the affected phenotype. The families showed one genome-wide significant linkage (Z = 3.97) at chromosome 15q14, which maps within 1 cM of a previous linkage at the alpha 7-nicotinic receptor gene. Chromosome 10p13 showed suggestive linkage (Z = 2.40). Six others (6q21, 9q32, 13q32, 15q24, 17p12, 20q13) were positive, with few differences between the two ethnic groups. The probability of each family transmitting schizophrenia through two genes is greater than expected from the combination of the independent segregation of each gene. Two trait-locus linkage analysis supports a model in which genetic alleles associated with schizophrenia are relatively common in the general population and affected individuals inherit risk for illness through at least two different loci.
American Journal of Medical Genetics 01/2002; 105(8):794-800.
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ABSTRACT: Abnormal sensory inhibition is observed in the majority of schizophrenic patients. DBA/2 mice spontaneously exhibit a similar deficit in sensory inhibition and thus provide a model for drug development targeted to this physiologic abnormality. The impaired sensory inhibition is characterized by diminished response of the hippocampal evoked potential to the second of closely paired auditory stimuli (500-m/sec interstimulus interval). Subnormal levels of hippocampal alpha7 nicotinic cholinergic receptors are associated with the deficient sensory inhibition in both DBA/2 mice and people with schizophrenia.
Our study examined the inhibition of the P20-N40 auditory evoked potential in DBA/2 mice after intragastric administration of DMXB-A (3-2,4-dimethoxybenzylidine anabaseine), an alpha7 nicotinic receptor partial agonist. After presentation of auditory stimuli, electroencephalographic responses were recorded and measured to monitor the effects of the DMXB-A, alone and in combination with selective nicotinic antagonists.
Gastric administration of DMXB-A (10 mg/kg) improved sensory inhibition in DBA/2 mice. This improvement was blocked by alpha-bungarotoxin, but not mecamylamine, indicating that DMXB-A exerts its effects through the alpha7 nicotinic receptor.
Intragastrically administered DMXB-A improves deficient sensory inhibition in DBA/2 mice through stimulation of alpha7 nicotinic receptors. These studies agree with results from previous studies with subcutaneously administered DMXB-A.
Biological Psychiatry 11/2001; 50(7):493-500. · 8.28 Impact Factor
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ABSTRACT: Auditory sensory gating is an electrophysiological assay that has been employed in clinical and basic research to clarify the neurobiological basis of perceptual and attentional impairments associated with schizophrenia and other diseases. In addition to genetically-linked characteristics, this measure also exhibits potentially confounding sensitivity to behavioral state, most notably acute stress. The goal of the present study is to determine if auditory sensory gating of evoked potential component P50 ('P1') could be measured during rapid eye movement (REM) sleep, as an alternative to the waking state.
The suppression of vertex-recorded auditory evoked potential components, P30, P50 and N100, was measured as a function of stimulus redundancy using the paired-click paradigm during all-night sleep in 10 control subjects. Average evoked responses were computed separately for 30 min periods of waking, REM sleep, and non-REM (stage 2) sleep.
Evoked response component P50 exhibited suppression to the paired-click stimulus during REM sleep, not significantly different than waking. Suppression of wave N100 was significantly poorer during both sleep stages than waking. Component P30 was not suppressed in response to repetitive stimuli under any state of vigilance.
In addition to waking, response suppression of evoked potential component P50 can be measured during REM sleep, thus allowing the separation of trait- and state-dependent effects in future investigations of auditory sensory gating.
Clinical Neurophysiology 08/2001; 112(7):1154-65. · 3.41 Impact Factor
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ABSTRACT: Cocaine addiction, as with other stimulant abuse, produces psychotic symptoms. Although often moderate to mild in severity, these symptoms are, nevertheless, associated with poorer over-all outcome. Recent studies suggest diminished nicotinic cholinergic neurotransmission as a mechanism of a physiological deficit found in schizophrenia, failure of auditory sensory inhibition. Diminished inhibitory sensory gating also occurs in cocaine addicts, probably because of their increased catecholaminergic neurotransmission, which blocks the inhibition. In the present study, 11 cocaine addicts in the first week of detoxification were recorded electrophysiologically, after which the effects of 6 mg of nicotine gum, were assessed in a double-blind placebo-controlled crossover design. The test was repeated 10 days later. Treatment with nicotine, but not placebo, briefly reversed the inhibitory abnormality on both test days. Although nicotine itself may not be a desirable therapeutic agent, because desensitization of nicotinic receptors limits the time course of its effect, the study identifies a previously unexploited therapeutic target for new drug development for the neuropsychiatric sequelae of cocaine addiction.
Neuropsychopharmacology 07/2001; 24(6):671-9. · 7.99 Impact Factor
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ABSTRACT: This paper is a review of a recent findings on the pathology of hippocampal interneurons in schizophrenia, with specific emphasis on a protein expressed by these cells, the alpha7-nicotinic acetylcholine receptor subunit. Convergent information indicates that interneurons in the hippocampus and other forebrain structures are decreased in number and function in subjects with schizophrenia. Among the neurochemical markers that are decreased in the hippocampus are synapsin I, cholecystokinin, somatostatin, glutamic acid decarboxylase, and nitric oxide synthase. GABA uptake sites and the GABA synthetic enzyme glutamic acid decarboxylase are also diminished. Included among these findings is decreased binding of alpha-bungarotoxin, which binds to low-affinity nicotinic acetylcholine receptors, such as the alpha7-nicotinic receptor. Co-labeling experiments in rodents indicate that these markers are expressed on overlapping populations of hippocampal interneurons. Thus, the finding of decreased neurochemical function of hippocampal interneurons is a widely replicated finding, with different groups reporting markedly similar findings using independent post mortem samples and different neurochemical strategies. Decreased alpha-bungarotoxin binding or decreased alpha7-nicotinic receptor immunoreactivity has also been found in the frontal cortex and in the nucleus reticularis thalami of schizophrenic subjects. The alpha7-nicotinic receptor subunit gene on chromosome 15q14 is a site of heritability for schizophrenia and bipolar affective disorder, and in, particular, for a deficit in inhibitory neuronal function associated with these illnesses. Thus, the post mortem data are further supported by psychophysiologic and genetic investigations that indicate a deficit in inhibitory interneuronal function, involving the alpha7-nicotinic receptor. The alpha7-receptor is a ligand-gated ion channel that admits calcium ions into cells, and it has been proposed to have various developmental roles. Its malfunction may be part of the developmental pathogenesis of schizophrenia.
Journal of Chemical Neuroanatomy 01/2001; 20(3-4):299-306. · 2.43 Impact Factor
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R Freedman,
S Leonard,
J M Gault,
J Hopkins,
C R Cloninger,
C A Kaufmann,
M T Tsuang,
S V Farone,
D Malaspina,
D M Svrakic,
A Sanders,
P Gejman
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ABSTRACT: The transmission/disequilibrium test was used for fine mapping of the linkage of schizophrenia to the chromosome 15q13-14 region, the site of a candidate gene, the alpha7 nicotinic acetylcholine receptor subunit gene (CHRNA7), in parent-child triads from the NIMH Schizophrenia Genetics Initiative families. This candidate gene was identified from neurobiological studies of deficits in schizophrenics of the inhibitory gating of the P50 auditory evoked potential. The neurobiological deficit was also used as a phenotype for subsequent linkage analysis. In the present study, significant genotype-wise disequilibrium (P < 0.007) was found at D15S165, a polymorphic simple sequence marker physically located within 1 megabase of both CHRNA7 and a partially duplicated, expressed sequence that includes exons 5-10 of CHRNA7. Replication of this result was found in an additional set of families. The results support this region as a chromosomal location involved in the genetic transmission of schizophrenia.
American Journal of Medical Genetics 01/2001; 105(1):20-2.
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S Buervenich,
A Carmine,
M Arvidsson,
F Xiang,
Z Zhang,
O Sydow,
E G Jönsson,
G C Sedvall,
S Leonard,
R G Ross, R Freedman,
K V Chowdari,
V L Nimgaonkar,
T Perlmann,
M Anvret,
L Olson
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ABSTRACT: Transgenic mice lacking the nuclear orphan transcription factor Nur-related receptor 1 (Nurr1) fail to develop mesencephalic dopamine neurons. There is a highly homologous NURR1 gene in humans (formerly known as NOT) which therefore constitutes a good candidate gene for neurologic and psychiatric disorders with an involvement of the dopamine neuron system, such as Parkinson's disease, schizophrenia, and manic-depression. By direct sequencing of genomic DNA, we found two different missense mutations in the third exon of NURR1 in two schizophrenic patients and another missense mutation in the same exon in an individual with manic-depressive disorder. All three mutations caused a similar reduction of in vitro transcriptional activity of NURR1 dimers of about 30-40%. Neither of these amino acid changes, nor any sequence changes whatsoever, were found in patients with Parkinson's disease or control DNA material of normal populations. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:808-813, 2000.
American Journal of Medical Genetics 01/2001; 96(6):808-13.
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ABSTRACT: The hippocampus rapidly inhibits its response to repetitive auditory stimulation, an example of an auditory sensory gating mechanism involved in human psychopathology. The neuronal basis of this inhibitory gating mechanism has been investigated in rats. Activation of the alpha 7 nicotinic receptor is required. alpha 7 nicotinic receptor activation also releases nitric oxide in the hippocampus and blockade of nitric oxide synthase reduces inhibitory gating of auditory response. There has not been a direct demonstration that blockade of nitric oxide synthase specifically prevents alpha 7 nicotinic receptor activation of the inhibition of auditory response. Therefore, the goal of the present study was to determine whether this functional effect of alpha 7 receptor activation requires release of nitric oxide. Lesions of the fimbria-fornix disrupt auditory gating by preventing cholinergic stimulation of the hippocampus. Following recovery from this surgery, rats were administered 3-(2,4-dimethoxybenzylidene) anabaseine (DMXB-A; 10 mg/kg, sc), an agonist at the alpha 7 receptor. DMXB-A restored auditory gating in the fimbria-fornix-lesioned rats, indicating that activation of the alpha 7 nicotinic receptor alone is sufficient to restore auditory gating following lesions of the fimbria-fornix. However, intracerebroventricular infusion of N(omega)-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase, blocked the DMXB-A-mediated restoration of auditory gating; infusion of the inactive D-enantiomer did not. Restoration of auditory gating by DMXB-A in the fimbria-fornix-lesioned rats was blocked by intracerebroventricular infusion of alpha-bungarotoxin, but not by mecamylamine or dihydro-beta-erythroidine. Together, these data support the hypothesis that nitric oxide mediates alpha 7 nicotinic receptor activation of gating of auditory response in rat hippocampus.
Brain Research 10/2000; 877(2):235-44. · 2.73 Impact Factor
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ABSTRACT: Attention-deficit/hyperactivity disorder (ADHD) and schizophrenia are both conceptualized as disorders of attention. Failure to inhibit the P50 auditory event-evoked response, extensively studied in schizophrenia, could also occur in ADHD patients, if these two illnesses have common underlying neurobiological substrates.
This study examined the inhibition of the P50 auditory event-evoked potential in 16 unmedicated adults with ADHD, 16 schizophrenic outpatients, and 16 normal control subjects. Auditory stimuli were presented in a paired stimulus, conditioning-testing paradigm.
The amplitude of initial or conditioning P50 response did not differ between the three groups; however, significant effects of psychiatric diagnosis on the amplitude of the test response and the ratio of the test to the conditioning response amplitudes were observed. Schizophrenic patients' P50 ratios and test amplitudes were higher than both the ADHD and normal groups.
Adults with ADHD do not have the inhibitory deficit seen in patients with schizophrenia, suggesting that the mechanism of attentional disturbance in the two illnesses may be fundamentally different.
Biological Psychiatry 07/2000; 47(11):969-77. · 8.28 Impact Factor
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S Leonard,
C Breese,
C Adams,
K Benhammou,
J Gault,
K Stevens,
M Lee,
L Adler,
A Olincy,
R Ross, R Freedman
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ABSTRACT: Biological and genetic evidence suggests a role for the neuronal nicotinic receptors in the neuropathophysiology of schizophrenia. Nicotine normalizes an auditory evoked potential deficit seen in subjects who suffer from the disease. Nicotinic receptors with both high and low affinity for nicotine are decreased in postmortem brain of schizophrenics compared to control subjects. The chromosomal locus of the human alpha-7 gene (15q14) is linked to the gating deficit with a lod of 5.3, and antagonists of the alpha-7 receptor (alpha-bungarotoxin and methyllycaconitine) induce a loss of gating in rodents. We have cloned the human alpha-7 gene and found it to be partially duplicated proximal to the full-length gene. The duplication is expressed in both the brain and in peripheral blood cells of normal subjects, but is missing in some schizophrenic subjects. The results of these studies suggest the presence of abnormal expression and function of the neuronal nicotinic receptor gene family in schizophrenia.
European Journal of Pharmacology 04/2000; 393(1-3):237-42. · 2.52 Impact Factor
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ABSTRACT: Schizophrenia is a complex illness with multiple pathophysiologic factors that contribute to its psychopathology. One strategy to identify these factors is to observe them in isolation from each other, by characterizing their expression in the relatives of schizophrenic probands. By Mendel's second law, each genetic factor should be independently distributed in a sibship, so that each can be observed by itself, uncomplicated by the general problems of the illness. Such independently distributed phenotypes are obviously useful for genetic analyses; however, they can also be considered together, to model how various brain dysfunctions may combine to produce psychoses. In addition to a sensory gating deficit linked to the alpha 7-nicotinic acetylcholine receptor locus, schizophrenics and their families have a number of other deficits, including decreased hippocampal volume on magnetic resonance images and increased plasma levels of the dopamine metabolite homovanillic acid. Although such research is far from complete, a heuristic model combining a sensory gating deficit, decreased hippocampal neuron capacity, and increased dopaminergic neurotransmission is consonant with current understanding of the neuropsychology of schizophrenia.
Biological Psychiatry 03/2000; 47(3):231-9. · 8.28 Impact Factor
