1Biol. Psychiatry 2004 Oct 56: 476-82
PMID15450782
TitleA high prevalence of organ-specific autoimmunity in patients with bipolar disorder.
AbstractIn a previous study, we reported an increased prevalence of thyroperoxidase antibodies (TPOA) in patients with bipolar disorder. Here we report the prevalence of other organ-specific autoantibodies: H/K adenosine triphosphatase (ATPA), glutamic acid decarboxylase-65 (GAD65A), and GAD-67 (GAD67A).
ATPA, GAD65A, and GAD67A were determined (via a commercially available enzyme linked immunosorbent assay for ATPA, and a standardized radio immunoassays for GAD65A and GAD67A)in the sera of 239 patients with DSM-IV bipolar disorder, in 74 patients with DSM-IV schizophrenia, and in 220 healthy control subjects.
The positivity prevalences for ATPA and GAD65A (but not GAD67A) were elevated in bipolar patients compared with those in healthy control subjects (11.7 vs. 6.1% and 11.3 vs. 2.6% respectively; p <.05). schizophrenia patients did not show such statistically higher prevalence. The elevated prevalence of ATPA and GAD65A in bipolar disorder was associated with neither rapid cycling nor the use of lithium. Interestingly, the presence of GAD65A (and not that of TPOA and ATPA) tended to be associated with the activity of bipolar disorder. The level of TPOA was negatively correlated with the serum level of sIL-2R, a measure of T cell activation.
Bipolar disorder is associated with organ-specific autoimmunity to the antigens TPO, H/K ATPase, and GAD65.
SCZ Keywordsschizophrenia, schizophrenic
2Psychiatry Res 2006 Jun 142: 151-6
PMID16631931
TitleInfluence of antipsychotic medication on pain perception in schizophrenia.
AbstractA number of clinical observations indicate that pain processing might be disturbed in psychotic disorders such as schizophrenia. Only a few studies have investigated pain perception in schizophrenia. The main objective of this study was the investigation of thresholds of warmth perception (WP), thermal pain onset (TPO) and thermal pain tolerance (TPT) in acute schizophrenic patients and the influence of antipsychotic medication on the patients' responses. We investigated 23 schizophrenic subjects who had been not received antipsychotic treatment for 8 weeks, and we then reassessed them 3 days later after the introduction of neuroleptics. Acute symptoms of schizophrenia were measured using the Scales for the Assessment of Positive and Negative Symptoms. Thresholds were determined by a contact thermode on both volar wrists. schizophrenic patients showed significantly increased thresholds of WP and TPO relative to healthy controls. Antipsychotics did not alter pain thresholds. We found no correlation between pain perception and psychometric scales. Our findings demonstrate altered warmth and heat pain perception in acute schizophrenia. We believe that our findings can be attributed to information-processing abnormalities of the disorder and that they are not specific to pain processing, per se, since both WP and TPO were significantly different. Future studies should evaluate attentional deficits in schizophrenia in relation to pain perception.
SCZ Keywordsschizophrenia, schizophrenic
3Psychiatry Res 2006 Jun 142: 151-6
PMID16631931
TitleInfluence of antipsychotic medication on pain perception in schizophrenia.
AbstractA number of clinical observations indicate that pain processing might be disturbed in psychotic disorders such as schizophrenia. Only a few studies have investigated pain perception in schizophrenia. The main objective of this study was the investigation of thresholds of warmth perception (WP), thermal pain onset (TPO) and thermal pain tolerance (TPT) in acute schizophrenic patients and the influence of antipsychotic medication on the patients' responses. We investigated 23 schizophrenic subjects who had been not received antipsychotic treatment for 8 weeks, and we then reassessed them 3 days later after the introduction of neuroleptics. Acute symptoms of schizophrenia were measured using the Scales for the Assessment of Positive and Negative Symptoms. Thresholds were determined by a contact thermode on both volar wrists. schizophrenic patients showed significantly increased thresholds of WP and TPO relative to healthy controls. Antipsychotics did not alter pain thresholds. We found no correlation between pain perception and psychometric scales. Our findings demonstrate altered warmth and heat pain perception in acute schizophrenia. We believe that our findings can be attributed to information-processing abnormalities of the disorder and that they are not specific to pain processing, per se, since both WP and TPO were significantly different. Future studies should evaluate attentional deficits in schizophrenia in relation to pain perception.
SCZ Keywordsschizophrenia, schizophrenic
4Indian J. Med. Res. 2013 Dec 138: 888-93
PMID24521631
TitleThyroid dysfunction in major psychiatric disorders in a hospital based sample.
AbstractAbnormalities in thyroid hormonal status is common in major psychiatric disorders. Although the relevance of thyroid dysfunction to bipolar disorder is well-recognized, yet the association between thyroid dysfunction and schizophrenia-spectrum disorders is under-emphasized. The aim of this study was to examine and compare the rates of abnormal thyroid hormonal status in patients with schizophrenia-spectrum disorders and mood disorders in an inpatient tertiary care general hospital psychiatry unit.
This was a retrospective hospital-based study on 468 inpatient samples. Data on serum thyroid stimulating hormone (TSH), T3 (triiodothyroxine), T4 (L-thyroxine), free unbound fractions of T3 and T4 (FT3 and FT4) were obtained from records of 343 patients, 18 patients were anti-TPO (anti thyroid peroxidase antibody) positive. The rates of abnormal thyroid hormonal status were compared using the chi square test.
Abnormal thyroid hormonal status in general, and presence of hypothyroidism and hyperthyroidism, in particular were seen in 29.3, 25.17 and 4.08 per cent patients with schizophrenia spectrum disorders, respectively. These were comparable to the rates in patients with mood disorders (23.24, 21.62 and 1.62%, respectively). Eleven of the 18 patients with antiTPO positivity had a schizophrenia-spectrum disorder. There were no gender differences.
Thyroid dysfunction was present in patients with schizophrenia-spectrum disorder as well as mood disorders. Autoimmune thyroid disease was more commonly seen in patients with schizophrenia-spectrum disorders compared to mood disorders. The findings reiterate the relevance of screening patients with schizophrenia-spectrum disorders for abnormal thyroid hormonal status.
SCZ Keywordsschizophrenia, schizophrenic
5J Neural Transm (Vienna) 2015 Sep 122: 1289-301
PMID25626716
TitleGenomic structural variants are linked with intellectual disability.
AbstractMutations in more than 500 genes have been associated with intellectual disability (ID) and related disorders of cognitive function, such as autism and schizophrenia. Here we aimed to unravel the molecular epidemiology of non-specific ID in a genetic isolate using a combination of population and molecular genetic approaches. A large multigenerational pedigree was ascertained within a Dagestan Genetic Heritage research program in a genetic isolate of indigenous ethnics. Clinical characteristics of the affected members were based on combining diagnoses from regional psychiatric hospitals with our own clinical assessment, using a Russian translation of the structured psychiatric interviews, the Diagnostic Interview for Genetic Studies and the Family Interview for Genetic Studies, based on DSM-IV criteria. Weber/CHLC 9.0 STRs set was used for multipoint parametric linkage analyses (Simwalk2.91). Next, we checked CNVs and LOH (based on Affymetrix SNP 5.0 data) in the linked with ID genomic regions with the aim to identify candidate genes associated with mutations in linked regions. The number of statistically significant (p ? 0.05) suggestive linkage peaks with 1.3 < LOD < 3.0 we detected in a total of 10 genomic regions: 1q41, 2p25.3-p24.2, 3p13-p12.1, 4q13.3, 10p11, 11q23, 12q24.22-q24.31, 17q24.2-q25.1, 21q22.13 and 22q12.3-q13.1. Three significant linkage signals with LOD >3 were obtained at 2p25.3-p24.2 under the dominant model, with a peak at 21 cM flanked by loci D2S2976 and D2S2952; at 12q24.22-q24.31 under the recessive model, with a peak at -120 cM flanked by marker D12S2070 and D12S395 and at 22q12.3 under the dominant model, with a peak at 32 cM flanked by marker D22S683 and D22S445. After a set of genes had been designated as possible candidates in these specific chromosomal regions,we conducted an exploratory search for LOH and CNV based on microarray data to detect structural genomic variants within five ID-linked regions with LOD scores between 2.0 and 3.9. In these selected regions we obtained 173 ROH segments and 98 CN segments. Further analysis of region 2p25.3-p24.2 revealed deletions within genes encoding MYTL, SNTG2 and TPO among five of 21 affected cases at 2p25.3-p24.2. In the ID-linked region at 12q24.22-12q24.31 19 out of 21 ID cases carried segmental CNV and 20 of 21 them displayed ROH segments with mean size lengths for ID cases 2512 kb (500-6,472 kb) and for healthy control 682 kb (531-986 kb), including the genes MED13L, HRK, FBXW8, TESC, CDK2AP1 and SBNO1. Seven of 21 affected pedigree members displayed segmental deletions at 22q12.3 that includes the gene LARGE. Eight affected pedigree members carried ROH segments and 6 CN segments at 10p11.23-p11.21 containing the genes ZEB1, c10orf68 and EPC1. Our linkage and structural genomic variation analyses in a remote highland genetic isolate with aggregation of ID demonstrated that even highly isolated single kindred ID has oligo/polygenic pathogenesis. The results obtained implicate 10 genomic regions linked with ID that contain some of previously reported candidate genes, including HRK, FBXW8, TESC, CDK2AP1 and SBNO1 at 12q24 that were shown in recent studies as associated with brain measures derived from MRI scans.
SCZ Keywordsschizophrenia, schizophrenic
6Schizophr. Res. 2015 Aug 166: 37-42
PMID25982813
TitleFree thyroxine levels are associated with cognitive abilities in subjects with early psychosis.
AbstractSubjects with a psychotic disorder show mild to moderate cognitive impairment, which is an important determinant of functional outcome. The underlying biological process of cognitive impairment in psychosis is unclear. We aimed to explore whether hypothalamic-pituitary-thyroid axis hormones or thyroid autoimmunity modulate cognitive functioning in subjects with early psychosis.
We studied 70 patients with a psychotic disorder (<3years of illness) and a control group of 37 healthy subjects (HS). Plasma levels of thyroid-stimulating hormone (TSH), free thyroxine (FT4) and thyroid-peroxidase (TPO-Abs) and thyroglobulin antibodies (TG-Abs) were determined. Cognitive assessment was performed with the MATRICS Cognitive Consensus Cognitive Battery. We also explored the relationship between thyroid variables and cognition in three subgroups of psychotic patients: psychosis not otherwise specified, affective psychosis (bipolar disorder or schizoaffective disorder) and non-affective psychosis (schizophrenia or schizophreniphorm disorder).
In patients with early psychosis, higher FT4 levels (but not TSH or thyroid antibodies) were associated with better cognitive performance in attention/vigilance and overall cognition. The relationship between FT4 levels and the attention/vigilance domain remained significant in a multivariate analysis after adjusting for education level, age, gender, substance use, and benzodiazepine and antipsychotic treatments. We did not find a significant association between FT4 and cognitive performance in HS. In the exploratory analysis by psychotic subtypes, subjects with affective psychosis had increased FT4 levels and better cognitive profile than those with non-affective psychosis.
Our study suggests that FT4 levels are associated with cognitive abilities (attention/vigilance and overall cognition) in individuals with early psychosis.
SCZ Keywordsschizophrenia, schizophrenic
7Hum Brain Mapp 2015 Jan 36: 213-25
PMID25209949
TitleIllness denial in schizophrenia spectrum disorders: a function of left hemisphere dominance.
AbstractImpaired illness awareness or anosognosia is a common, but poorly understood feature of schizophrenia that contributes to medication nonadherence and poor treatment outcomes. Here we present a functional imaging study to measure brain activity at the moment of illness denial. To accomplish this, participants with schizophrenia (n?=?18) with varying degrees of illness awareness were confronted with their illness beliefs while undergoing functional MRI. To link structure with function, we explored the relationships among impaired illness awareness and brain activity during the illness denial task with cortical thickness. Impaired illness awareness was associated with increased brain activity in the left temporoparieto-occipital junction (TPO) and left medial prefrontal cortex (mPFC) at the moment of illness denial. Brain activity in the left mPFC appeared to be a function of participants' degree of self-reflectiveness, while the activity in the left TPO was associated with cortical thinning in this region and more specific to illness denial. Participants with impaired illness awareness had slower response times to illness related stimuli than those with good illness awareness. Increased left hemisphere brain activity in association with illness denial is consistent with the literature in other neuropsychiatric conditions attributing anosognosia or impaired illness awareness to left hemisphere dominance. The TPO and mPFC may represent putative targets for noninvasive treatment interventions, such as transcranial magnetic or direct current stimulation.
SCZ Keywordsschizophrenia, schizophrenic
8Eur Arch Psychiatry Clin Neurosci 2015 Feb 265: 67-72
PMID25193677
TitleAssociation between autoimmune thyroiditis and depressive disorder in psychiatric outpatients.
AbstractThyroid diseases are often associated with psychiatric disorders. The prevalence of autoimmune thyroiditis in the general population is estimated to be at about 5-14 %. A clinical study was conducted to evaluate the association between autoimmune thyroiditis and depression in psychiatric outpatients. Fifty-two patients with depression and nineteen patients with schizophrenia (serving as control group), attending a psychiatric outpatient unit, were included. In addition to the measurement of thyroid-stimulating hormone (TSH), free triiodothyronine, free thyroxine, antithyroid peroxidase (anti-TPO) antibodies, and anti-thyroglobulin antibodies, ultrasound examination of the thyroid gland was performed. The proportion of pathologically increased anti-TPO levels in patients with depression was high. Furthermore, the distribution of pathologically increased anti-TPO levels was significantly (? (2) = 5.5; p = 0.019) different between patients with depression (32.7 %) and patients with schizophrenia (5.3 %). In a gender- and age-adjusted logistic regression, the odds ratio of uni- or bipolar patients with depression for an autoimmune thyroiditis was ten times higher (95 % CI = 1.2-85.3) when compared with schizophrenia patients. TSH basal level did not differ between patients with depression and patients with schizophrenia. Our study demonstrates a strong association between anti-TPO levels, which are considered to be of diagnostic value for autoimmune thyroiditis (in combination with a hypoechoic thyroid in ultrasonography) with uni- or bipolar depression. It should be noted that the routinely measured TSH level is not sufficient in itself to diagnose this relevant autoimmune comorbidity.
SCZ Keywordsschizophrenia, schizophrenic