| 1 | Schizophr. Res. 2000 Apr 42: 83-90 |
|---|---|
| PMID | 10742646 |
| Title | Increased morbid risk for schizophrenia in families of in-patients with bipolar illness. |
| Abstract | It has been reported that relatives of probands with severe, psychotic forms of bipolar illness have increased rates of schizophrenia but not the relatives of individuals with milder, non-psychotic forms of disorder. In this study, we examined the prevalence of psychiatric disorders in the first degree relatives of a sample of 103 inpatients with bipolar disorder and in a matched control sample of 84 healthy individuals. Relatives of cases and controls were interviewed using the FH-RDC to determine familial morbid risk for schizophrenia and bipolar disorder. Age- and sex-adjusted morbidity risks were calculated in both samples according to the method of Strömgren. The morbid risks for both bipolar disorder (4.9%) and schizophrenia (2.8%) were higher in relatives of patients than in relatives of controls (0.3% and 0.6% respectively). The relative risks were 14.2 [95% confidence interval (CI)=3.1-64.2] for bipolar disorder and 4.9 (95% CI=1.3-18.8) for schizophrenia. Relatives of women with early onset of bipolar illness had the highest morbid risks for both bipolar illness and schizophrenia. The presence of more than one patient with bipolar disorder in a family increased the risk for schizophrenia nearly fourfold (RR=3.5, 95% CI=1.2-10.2). There was no additional effect of presence of psychotic features. Our results suggest that the transmission of psychosis is not disorder-specific. Bipolar illness characterised by a high familial loading is associated with increased risk of schizophrenia in the relatives. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypal |
| 2 | Psychiatry Res 2001 Nov 108: 29-38 |
| PMID | 11677065 |
| Title | Similar effect of family history of psychosis on Sylvian fissure size and auditory P200 amplitude in schizophrenic and bipolar subjects. |
| Abstract | Several cerebral studies point to the non-specificity of structural and functional changes described in schizophrenia and bipolar disorders. Furthermore, the origin of these changes is still unclear. The present study investigated the effect of a family history (FH) of psychotic disorders in first-degree relatives on computed tomographic (CT) measures (ventricular, cerebral and Sylvian fissure size) and auditory event-related potentials (amplitudes and latencies of peak components in oddball paradigms) in 30 schizophrenic patients and 24 bipolar type I patients. We found a significant correlation between FH and the size of the right Sylvian fissure, and between FH and auditory P200 amplitude. More specifically, the schizophrenic and bipolar patients with negative FH (n=36) had larger right Sylvian fissures and smaller P200 amplitude than patients with positive FH (n=18). These findings were independent of the specific diagnosis, gender, and age of subjects. Our results suggest some underlying process common to schizophrenia and bipolar I disorder, and they provide support for the continuum view of the nosologic structure of psychotic illness. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypal |
| 3 | Psychiatry Res 2001 Nov 108: 29-38 |
| PMID | 11677065 |
| Title | Similar effect of family history of psychosis on Sylvian fissure size and auditory P200 amplitude in schizophrenic and bipolar subjects. |
| Abstract | Several cerebral studies point to the non-specificity of structural and functional changes described in schizophrenia and bipolar disorders. Furthermore, the origin of these changes is still unclear. The present study investigated the effect of a family history (FH) of psychotic disorders in first-degree relatives on computed tomographic (CT) measures (ventricular, cerebral and Sylvian fissure size) and auditory event-related potentials (amplitudes and latencies of peak components in oddball paradigms) in 30 schizophrenic patients and 24 bipolar type I patients. We found a significant correlation between FH and the size of the right Sylvian fissure, and between FH and auditory P200 amplitude. More specifically, the schizophrenic and bipolar patients with negative FH (n=36) had larger right Sylvian fissures and smaller P200 amplitude than patients with positive FH (n=18). These findings were independent of the specific diagnosis, gender, and age of subjects. Our results suggest some underlying process common to schizophrenia and bipolar I disorder, and they provide support for the continuum view of the nosologic structure of psychotic illness. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypal |
| 4 | Eur Neuropsychopharmacol 2004 Oct 14: 373-9 |
| PMID | 15336298 |
| Title | Prepulse inhibition in fawn-hooded rats: increased sensitivity to 5-HT1A receptor stimulation. |
| Abstract | Prepulse inhibition of startle is a model of sensorimotor gating, which is disrupted in alcoholism, as well as mental illnesses such as schizophrenia. The fawn-hooded (FH) rat strain has been used as an animal model of alcoholism. FH rats showed significantly lower startle amplitude than Wistar-Kyoto (WKY) rats and Sprague-Dawley (SD) rats. Increasing doses of the 5-HT(1A) receptor agonist 8-OH-DPAT caused disruption of PPI, with the effect being significantly greater in FH rats compared to WKY rats. In all strains, treatment with 0.5 mg/kg of 8-OH-DPAT significantly reduced PPI. In contrast, 0.1 mg/kg of 8-OH-DPAT caused disruption only in the FH strain. Treatment with amphetamine, apomorphine and MK-801 also significantly reduced PPI, however, there was no difference between the strains. This study shows increased sensitivity of FH rats to the disruption of PPI caused by 5-HT(1A) receptor stimulation, suggesting a link between 5-HT(1A) receptors, sensorimotor gating and aspects of the FH rat phenotype. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypal |
| 5 | Am. J. Med. Genet. B Neuropsychiatr. Genet. 2004 May 127B: 35-41 |
| PMID | 15108177 |
| Title | Multiple dimensions of familial psychopathology affect risk of mood disorder in children of bipolar parents. |
| Abstract | The aim of our study was to determine whether familial loading of unipolar disorder, bipolar disorder, and substance use disorder are associated with DSM-IV mood disorders in adolescents at risk for bipolar disorder. One hundred and forty adolescents aged 12-21 years of 86 bipolar parents participated in the study. Lifetime DSM-IV diagnoses of the bipolar offspring were assessed with the Schedule for Affective Disorders and schizophrenia for School Age Children Kiddie-SADS-Present and Lifetime Version (SADS-PL). Parents were interviewed using the Family History Research Diagnostic Criteria (FH-RDC) which were used to calculate a continuous familial loading score (FL) for unipolar disorder, bipolar disorder, and for substance use disorder in first- and second-degree relatives of the adolescents. FL for unipolar disorder and substance use disorder were strong and independent predictors for lifetime mood disorders in the adolescents. The gender adjusted hazard ratios for mood disorders in the children were 1.5 (95% confidence interval (CI) = 1.2-2.0) for FL of unipolar disorder and 1.8 (95% CI = 1.3-2.4) for FL of substance use disorder. Expression of mood disorders in children of bipolar parents varies with the degree of additional FL of unipolar disorder and substance use disorder in the extended family. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypal |
| 6 | Schizophr. Res. 2004 Jun 68: 309-17 |
| PMID | 15099612 |
| Title | Validity of the family history method for diagnosing schizophrenia, schizophrenia-related psychoses, and schizophrenia-spectrum personality disorders in first-degree relatives of schizophrenia probands. |
| Abstract | This study examined the validity of the family history method for diagnosing schizophrenia, schizophrenia-related psychoses, and schizophrenia-spectrum personality disorders in first-degree relatives of schizophrenia probands. This is the first large-scale study that examined the validity of the family history method for diagnosing DSM-III-R personality disorders. The best estimate DSM-III-R diagnoses of 264 first-degree relatives of 117 adult-onset schizophrenia probands based on direct structured diagnostic interviews, family history interview, and medical records were compared to Family History Research Diagnostic Criteria (FH-RDC) diagnoses based on the NIMH Relative Psychiatric History Interview and to family history Structured Clinical Interview for DSM-III-R: Personality Disorders (SCID-II) diagnoses based on the SCID-II adapted to a third person format. Diagnoses of relatives were made blind to proband diagnostic status. The median sensitivity for schizophrenia and the related psychoses was 29% (range 0-50%), the median specificity 99% (range 98-100%), and the median positive predictive value (PPV) 67% (range 20-80%). The median sensitivity for the personality diagnoses was 25% (range 14-71%), the median specificity 100% (range 99-100%), and the median PPV 100% (range 67-100%). The family history method has low sensitivity but has excellent specificity and PPV for schizophrenia, schizophrenia-related psychoses, and schizophrenia-spectrum personality disorders. The kappa coefficient for the family history method was moderately good for the psychoses (0.598) and for paranoid and schizotypal personality disorder (0.576). Using the family history method, the validity of making schizophrenia-related personality disorder diagnoses was comparable to that of making psychotic disorder diagnoses. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypal |
| 7 | Schizophr. Res. 2004 Jun 68: 309-17 |
| PMID | 15099612 |
| Title | Validity of the family history method for diagnosing schizophrenia, schizophrenia-related psychoses, and schizophrenia-spectrum personality disorders in first-degree relatives of schizophrenia probands. |
| Abstract | This study examined the validity of the family history method for diagnosing schizophrenia, schizophrenia-related psychoses, and schizophrenia-spectrum personality disorders in first-degree relatives of schizophrenia probands. This is the first large-scale study that examined the validity of the family history method for diagnosing DSM-III-R personality disorders. The best estimate DSM-III-R diagnoses of 264 first-degree relatives of 117 adult-onset schizophrenia probands based on direct structured diagnostic interviews, family history interview, and medical records were compared to Family History Research Diagnostic Criteria (FH-RDC) diagnoses based on the NIMH Relative Psychiatric History Interview and to family history Structured Clinical Interview for DSM-III-R: Personality Disorders (SCID-II) diagnoses based on the SCID-II adapted to a third person format. Diagnoses of relatives were made blind to proband diagnostic status. The median sensitivity for schizophrenia and the related psychoses was 29% (range 0-50%), the median specificity 99% (range 98-100%), and the median positive predictive value (PPV) 67% (range 20-80%). The median sensitivity for the personality diagnoses was 25% (range 14-71%), the median specificity 100% (range 99-100%), and the median PPV 100% (range 67-100%). The family history method has low sensitivity but has excellent specificity and PPV for schizophrenia, schizophrenia-related psychoses, and schizophrenia-spectrum personality disorders. The kappa coefficient for the family history method was moderately good for the psychoses (0.598) and for paranoid and schizotypal personality disorder (0.576). Using the family history method, the validity of making schizophrenia-related personality disorder diagnoses was comparable to that of making psychotic disorder diagnoses. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypal |
| 8 | Mol. Psychiatry 2007 Mar 12: 273-82 |
| PMID | 17179997 |
| Title | Interleukin 3 and schizophrenia: the impact of sex and family history. |
| Abstract | Chromosome 5q21-33 has been implicated in harboring risk genes for schizophrenia. In this paper, we report evidence that multiple single nucleotide polymorphisms in and around interleukin 3 (IL3) are associated with the disease in the Irish Study of High-Density schizophrenia Families (ISHDSF), the Irish Case-Control Study of schizophrenia (ICCSS) and the Irish Trio Study of schizophrenia (ITRIO). The associations are sex-specific and depend on the family history (FH) of schizophrenia. In all three samples, rs31400 shows female-specific and FH-dependent associations (P=0.0062, 0.0647 and 0.0284 for the ISHDSF, ICCSS and ITRIO, respectively). Several markers have similar associations in one or two of the three samples. In haplotype analyses, identical risk and protective haplotypes are identified in the ISHDSF and ITRIO samples in several multimarker combinations. For ICCSS, the same haplotypes are implicated; however, the risk haplotypes observed in the family samples become protective. Several significant markers, rs440970, rs31400 and rs2069803, are located in and around known estrogen response elements, promoter and enhancer of the IL3 gene. They may explain the sex-specific associations and be functional for the expression of IL3 gene. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypal |
| 9 | Mol. Psychiatry 2008 Oct 13: 930-8 |
| PMID | 17667962 |
| Title | Association study of CSF2RB with schizophrenia in Irish family and case - control samples. |
| Abstract | Colony stimulating factor 2 receptor, beta (CSF2RB) is the shared subunit of receptors for interleukin 3 (IL3), colony stimulating factor 2 (CSF2) and IL5, and is responsible for the initiation of signal transduction triggered by ligand binding. In our previous study, we showed the evidence that the IL3 gene is associated with schizophrenia and the associations observed are sex-specific and dependent on family history (FH). In this article, we studied 10 single-nucleotide polymorphisms in the CSF2RB gene in the Irish Study of High-Density schizophrenia Families (ISHDSF) and the Irish Case - Control Study of schizophrenia (ICCSS), and tested allele and haplotype associations with schizophrenia. Using the pedigree disequilibrium test, we found that two markers (rs11705394 and rs7285064) reached nominal significance. In sex-stratified analyses, for both the markers the association signals were mainly derived from male subjects. In the ICCSS sample, we found that several markers (rs2072707, rs2284031 and rs909486) showed sex-specific and FH-dependent associations with schizophrenia. In multimarker haplotype analyses, both ISHDSF and ICCSS samples showed globally significant associations in multiple linkage disequilibrium (LD) blocks sharing minimal LD. Since CSF2RB is essential for IL3 signaling, the findings that both IL3 and CSF2RB showed sex-specific and FH-dependent associations suggest that the IL3 pathway is involved in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypal |
| 10 | Schizophr. Res. 2008 Sep 104: 279-86 |
| PMID | 18562177 |
| Title | Investigating if psychosis-like symptoms (PLIKS) are associated with family history of schizophrenia or paternal age in the ALSPAC birth cohort. |
| Abstract | Psychosis-like symptoms (PLIKS) occur in about 15% of the population, but it is unclear to what extent PLIKS share aetiological mechanisms in common with those for schizophrenia. We examined whether the presence of PLIKS was associated with a family history of schizophrenia (FH-SCZ), or with advancing paternal age, using data from 6356 children in the ALSPAC birth cohort who participated in a semi-structured PLIKS interview at 12 years of age. We found no evidence of association between FH-SCZ and suspected or definite PLIKS (adjusted OR=0.94, 95%CI 0.44, 2.00; p=0.880). There was weak evidence that advancing paternal age was associated with increased PLIKS (adjusted OR per 10-year age increase=1.23, 95%CI 0.99, 1.55; p=0.058). Although not a priori hypotheses, family history of depression (adjusted OR=1.28, 95%CI 1.04, 1.57; p=0.018), and younger maternal age (adjusted OR per 10-year age increase=0.62, 95% CI 0.47, 0.82; p<0.001) both showed stronger evidence of association with suspected or definite PLIKS. Overall our findings provide little evidence that these established risk factors for schizophrenia show a similar relationship with PLIKS, suggesting that the presence of PLIKS is unlikely to be a strong marker of early expression of the pathology underlying schizophrenia. Whether future studies of PLIKS will increase our understanding of mechanisms underlying the development of schizophrenia, or prove useful in prediction of this disorder, remains to be seen. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypal |
| 11 | Int J Methods Psychiatr Res 2009 Jun 18: 96-109 |
| PMID | 19507167 |
| Title | Parent-child agreement and prevalence estimates of diagnoses in childhood: direct interview versus family history method. |
| Abstract | Diagnostic information on children is typically elicited from both children and their parents. The aims of the present paper were to: (1) compare prevalence estimates according to maternal reports, paternal reports and direct interviews of children [major depressive disorder (MDD), anxiety and attention-deficit and disruptive behavioural disorders]; (2) assess mother-child, father-child and inter-parental agreement for these disorders; (3) determine the association between several child, parent and familial characteristics and the degree of diagnostic agreement or the likelihood of parental reporting; (4) determine the predictive validity of diagnostic information provided by parents and children. Analyses were based on 235 mother-offspring, 189 father-offspring and 128 mother-father pairs. Diagnostic assessment included the Kiddie-schedule for Affective Disorders and schizophrenia (K-SADS) (offspring) and the Diagnostic Interview for Genetic Studies (DIGS) (parents and offspring at follow-up) interviews. Parental reports were collected using the Family History - Research Diagnostic Criteria (FH-RDC). Analyses revealed: (1) prevalence estimates for internalizing disorders were generally lower according to parental information than according to the K-SADS; (2) mother-child and father-child agreement was poor and within similar ranges; (3) parents with a history of MDD or attention deficit hyperactivity disorder (ADHD) reported these disorders in their children more frequently; (4) in a sub-sample followed-up into adulthood, diagnoses of MDD, separation anxiety and conduct disorder at baseline concurred with the corresponding lifetime diagnosis at age 19 according to the child rather than according to the parents. In conclusion, our findings support large discrepancies of diagnostic information provided by parents and children with generally lower reporting of internalizing disorders by parents, and differential reporting of depression and ADHD by parental disease status. Follow-up data also supports the validity of information provided by adolescent offspring. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypal |
| 12 | Schizophr. Res. 2010 May 118: 98-105 |
| PMID | 20083391 |
| Title | A reappraisal of the association between Dysbindin (DTNBP1) and schizophrenia in a large combined case-control and family-based sample of German ancestry. |
| Abstract | Dysbindin (DTNBP1) is a widely studied candidate gene for schizophrenia (SCZ); however, inconsistent results across studies triggered skepticism towards the validity of the findings. In this HapMap-based study, we reappraised the association between Dysbindin and SCZ in a large sample of German ethnicity. Six hundred thirty-four cases with DSM-IV SCZ, 776 controls, and 180 parent-offspring trios were genotyped for 38 Dysbindin SNPs. We also studied two phenotypically-defined subsamples: 147 patients with a positive family history of SCZ (FH-SCZ+) and SCZ patients characterized for cognitive performance with Trail-Making Tests A and B (TMT-A: n=219; TMT-B: n=247). Given previous evidence of gene-gene interactions in SCZ involving the COMT gene, we also assessed epistatic interactions between Dysbindin markers and 14 SNPs in COMT. No association was detected between Dysbindin markers and SCZ, or in the FH-SCZ+ subgroup. Only one marker (rs1047631, previously reported to be part of a risk haplotype), showed a nominally significant association with performance on TMT-A and TMT-B; these findings did not remain significant after correction for multiple comparisons. Similarly, no pair-wise epistatic interactions between Dysbindin and COMT markers remained significant after correction for 504 pair-wise comparisons. Our results, based on one of the largest samples of European Caucasians and using narrowly-defined criteria for SCZ, do not support the etiological involvement of Dysbindin markers in SCZ. Larger samples may be needed in order to unravel Dysbindin's possible role in the genetic basis of proposed intermediate phenotypes of SCZ or to detect epistatic interactions. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypal |
| 13 | Schizophr. Res. 2010 Jul 120: 121-30 |
| PMID | 20303240 |
| Title | The impact of a family history of psychosis on age-at-onset and positive and negative symptoms of schizophrenia: a meta-analysis. |
| Abstract | The results of research on the relation of family history (FH) of psychosis with clinical presentation in schizophrenia have been mixed. To date, there have been no comprehensive reviews that have examined this body of research. The current review quantitatively evaluates research on the relation of FH with two aspects of schizophrenia, age-at-onset and symptom presentation. Studies investigating the influence of a FH on age-at-onset (N=15 studies), age-at-onset and sex (N=12 studies), and/or positive (N=11 studies) and negative symptoms (N=12 studies) in patients with schizophrenia were included in the meta-analyses. Results showed that FH has a small but significant impact on age-at-onset as well as negative symptoms. Of most interest was the finding that sex differences in age-at-onset are not observed in samples with a FH. Furthermore, there was a significant interaction between FH and sex with respect to negative symptoms. The findings of the current review are discussed in light of the diathesis-stress model. Theoretical assumptions and empirical research are reviewed to support the notion that FH influences susceptibility and presentation through similar mechanisms. Implications of the current findings, limitations of the review, and directions for future research are highlighted. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypal |
| 14 | Am. J. Med. Genet. B Neuropsychiatr. Genet. 2012 Jul 159B: 567-79 |
| PMID | 22592928 |
| Title | Paternal age effect on age of onset in bipolar I disorder is mediated by sex and family history. |
| Abstract | This study investigated for the first time in the psychiatric literature the effect of parental age on age-of-onset (AO) in bipolar I disorder (BPI) in relation to proband sex and family history (FH) for major psychoses in a sample of 564 BPI probands. All probands, 72.68% of their first-degree and 12.13% of their second-degree relatives were directly interviewed. The FH-method was used for all unavailable relatives. The diagnoses were made according to DSM-IV(TR) . The impact of parental age on proband early/late AO was evaluated through logistic regression with the cut-off for early AO determined through commingling analysis. We found evidence for a significant influence of increasing paternal age, and especially age ? 35 years, on AO of BPI disorder in the total sample (OR = 0.54, CI: 0.35-0.80), in the female subsample (OR = 0.44, CI: 0.25-0.78), in the sporadic subsample (OR = 0.64, CI: 0.38-0.95), and in the subsample with FH of recurrent unipolar major depression (Mdd-RUP) (OR = 0.55, CI: 0.34-0.87). No significant effect of paternal age on disease AO was found in patients with FH of bipolar (BP), schizoaffective disorders (SA), or schizophrenia (SCZ), nor in males. Mean age was significantly higher in fathers of sporadic cases and of cases with FH of Mdd-RUP than in fathers of cases with FH of BP/SA/SCZ (P = 0.011). Maternal age had no significant effect either in the total sample or in subsamples defined by proband sex or FH. In conclusion, in our sample increasing paternal age lowered the onset of BPI selectively, the effect being related to the female sex and FH-type. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypal |
| 15 | Psychiatry Res 2012 May 197: 23-8 |
| PMID | 22503358 |
| Title | Family history of psychosis negatively impacts age at onset, negative symptoms, and duration of untreated illness and psychosis in first-episode psychosis patients. |
| Abstract | Family history (FH) of psychosis has been a focus of investigations attempting to explain the heterogeneity in schizophrenia. Previous studies have demonstrated that FH is associated with earlier age at onset, severity of positive and negative symptoms, and the duration of untreated illness (DUI). The current study examined the impact of FH on the clinical presentation and help-seeking behaviors of a well-characterized, first-episode sample. The present study utilized the Symptom Onset in schizophrenia (SOS) Inventory, the Positive and Negative Syndrome Scale (PANSS), and structured interviews on FH to examine these relationships in a large (n=152) sample of predominantly African American patients. Results showed that patients with a first-degree FH of psychosis had a younger age at onset of both the prodrome and psychosis, but did not differ in duration of prodromal period. Furthermore, FH and sex interacted to influence severity of negative, but not positive symptoms. Finally, FH interacted with sex to influence both the DUI and DUP in that only males with FH had longer DUI and DUP. The findings have implications for understanding the impact of specific family-related mechanisms on both clinical and help-seeking factors, as well as for informing future family-based intervention efforts. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypal |
| 16 | Indian J Psychol Med 2012 Oct 34: 355-9 |
| PMID | 23723544 |
| Title | Family history correlates of digit ratio abnormalities in schizophrenia. |
| Abstract | The differences in digit ratio are proposed to arise due to differential effects of sex steroids on the growth of finger bones. In this study, we sought to examine the sex differences and the influence of family history of psychosis on digit ratio in patients with schizophrenia compared to matched healthy controls (HCs). Digit ratio (2D: 4D) was examined for a large sample of schizophrenia patients (n=200) and HC (n=177) to evaluate the potential effects of family history. The right hand 2D: 4D digit ratio was lesser in schizophrenia patients compared to HC (0.97±0.05 vs 0.98±0.04, t=2.2, P=0.02). There was a significant difference in the right hand 2D: 4D digit ratio of female patients with schizophrenia when compared to female HCs (0.96±0.05 vs 0.98±0.03, t=2.1, P=0.03) while males showed no such difference on either hands. On the contrary, family history?positive males showed a significantly greater digit ratio for the left hand (FH present (0.99±0.04) vs HC (0.97±0.04), t=2.15, P=0.03), while there was no difference between family history?positive females and HC. Overall, in patients, reversal of expected "directionality" in digit ratio was observed in our study with greater left 2D: 4D in male patients having a family history of schizophrenia being a novel finding. Reversal of sexual dimorphism has been linked to the pathogenesis of schizophrenia. It is possible that such reversal might have a putative genetic basis, perhaps only in men with schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypal |
| 17 | ISRN Psychiatry 2013 -1 2013: 620361 |
| PMID | 23738220 |
| Title | Chronic phencyclidine increases synapsin-1 and synaptic adaptation proteins in the medial prefrontal cortex. |
| Abstract | Phencyclidine (PCP) mimics many aspects of schizophrenia, yet the underlying mechanism of neurochemical adaptation for PCP is unknown. We therefore used proteomics to study changes in the medial prefrontal cortex in animals with PCP-induced behavioural deficits. Male Wistar rats were injected with saline or 5?mg/kg phencyclidine for 5 days followed by two days of washout. Spontaneous alternation behaviour was tested in a Y-maze and then proteins were extracted from the medial prefrontal cortex. 2D-DIGE analysis followed by spot picking and protein identification with mass spectrometry then provided a list of differentially expressed proteins. Treatment with 5?mg/kg phencyclidine decreased the percentage of correct alternations in the Y-maze compared to saline-treated controls. Proteomics analysis of the medial prefrontal cortex found upregulation of 6 proteins (synapsin-1, Dpysl3, Aco2, Fscn1, Tuba1c, and Mapk1) and downregulation of 11 (Bin1, Dpysl2, Sugt1, ApoE, Psme1, ERp29, Pgam1, Uchl1, Ndufv2, Pcmt1, and Vdac1). A trend to upregulation was observed for Gnb4 and Capza2, while downregulation trends were noted for alpha-enolase and FH. Many of the hits in this study concur with recent postmortem data from schizophrenic patients and this further validates the use of phencyclidine in preclinical translational research. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypal |
| 18 | ISRN Psychiatry 2013 -1 2013: 620361 |
| PMID | 23738220 |
| Title | Chronic phencyclidine increases synapsin-1 and synaptic adaptation proteins in the medial prefrontal cortex. |
| Abstract | Phencyclidine (PCP) mimics many aspects of schizophrenia, yet the underlying mechanism of neurochemical adaptation for PCP is unknown. We therefore used proteomics to study changes in the medial prefrontal cortex in animals with PCP-induced behavioural deficits. Male Wistar rats were injected with saline or 5?mg/kg phencyclidine for 5 days followed by two days of washout. Spontaneous alternation behaviour was tested in a Y-maze and then proteins were extracted from the medial prefrontal cortex. 2D-DIGE analysis followed by spot picking and protein identification with mass spectrometry then provided a list of differentially expressed proteins. Treatment with 5?mg/kg phencyclidine decreased the percentage of correct alternations in the Y-maze compared to saline-treated controls. Proteomics analysis of the medial prefrontal cortex found upregulation of 6 proteins (synapsin-1, Dpysl3, Aco2, Fscn1, Tuba1c, and Mapk1) and downregulation of 11 (Bin1, Dpysl2, Sugt1, ApoE, Psme1, ERp29, Pgam1, Uchl1, Ndufv2, Pcmt1, and Vdac1). A trend to upregulation was observed for Gnb4 and Capza2, while downregulation trends were noted for alpha-enolase and FH. Many of the hits in this study concur with recent postmortem data from schizophrenic patients and this further validates the use of phencyclidine in preclinical translational research. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypal |
| 19 | Psychol Med 2013 Jan 43: 119-31 |
| PMID | 22575089 |
| Title | Neuropsychological performance and family history in children at age 7 who develop adult schizophrenia or bipolar psychosis in the New England Family Studies. |
| Abstract | Persons developing schizophrenia (SCZ) manifest various pre-morbid neuropsychological deficits, studied most often by measures of IQ. Far less is known about pre-morbid neuropsychological functioning in individuals who later develop bipolar psychoses (BP). We evaluated the specificity and impact of family history (FH) of psychosis on pre-morbid neuropsychological functioning. We conducted a nested case-control study investigating the associations of neuropsychological data collected systematically at age 7 years for 99 adults with psychotic diagnoses (including 45 SCZ and 35 BP) and 101 controls, drawn from the New England cohort of the Collaborative Perinatal Project (CPP). A mixed-model approach evaluated full-scale IQ, four neuropsychological factors derived from principal components analysis (PCA), and the profile of 10 intelligence and achievement tests, controlling for maternal education, race and intra-familial correlation. We used a deviant responder approach (<10th percentile) to calculate rates of impairment. There was a significant linear trend, with the SCZ group performing worst. The profile of childhood deficits for persons with SCZ did not differ significantly from BP. Neuropsychological impairment was identified in 42.2% of SCZ, 22.9% of BP and 7% of controls. The presence of psychosis in first-degree relatives (FH+) significantly increased the severity of childhood impairment for SCZ but not for BP. Pre-morbid neuropsychological deficits are found in a substantial proportion of children who later develop SCZ, especially in the SCZ FH+ subgroup, but less so in BP, suggesting especially impaired neurodevelopment underlying cognition in pre-SCZ children. Future work should assess genetic and environmental factors that explain this FH effect. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypal |
| 20 | Mol Genet Genomic Med 2014 Jul 2: 326-31 |
| PMID | 25077175 |
| Title | Telomere length, family history, and paternal age in schizophrenia. |
| Abstract | Leukocyte telomere length (LTL) is longer in association with advanced paternal age, but this association has not been examined along with family history (FH) in schizophrenia. LTL was measured by PCR and compared across cases and controls as part of a study to examine the characteristics of paternal age related schizophrenia. The 53 schizophrenia cases had similar mean LTL as 20 controls, although cases were significantly older than controls and overwhelmingly smoked cigarettes. Multivariate analyses showed that a FH of schizophrenia was associated with longer LTL in both male and female cases. Later paternal age was also related to longer LTL in male cases, but with shorter LTL in female cases. Male cases with older fathers and a FH had the longest LTL. The genetic architecture associated with a familial risk for schizophrenia may include pathways that lengthen LTL. Paternal aging conferred an additional increase in LTL lengthening in male cases, but reduced LTL in female cases. The gender difference in LTL for paternal aging is consistent with the severe illness features reported for female cases with older fathers and could implicate epigenetic alterations in the paternal X chromosomal region with advanced paternal age in association with the risk for schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypal |
| 21 | Brain Imaging Behav 2015 Mar 9: 128-40 |
| PMID | 25744101 |
| Title | ERBB4 polymorphism and family history of psychiatric disorders on age-related cortical changes in healthy children. |
| Abstract | Genetic variations in ERBB4 were associated with increased susceptibility for schizophrenia (SCZ) and bipolar disorders (BPD). Structural imaging studies showed cortical abnormalities in adolescents and adults with SCZ or BPD. However, less is known about subclinical cortical changes or the influence of ERBB4 on cortical development. 971 healthy children (ages 3-20 years old; 462 girls and 509 boys) were genotyped for the ERBB4-rs7598440 variants, had structural MRI, and cognitive evaluation (NIH Toolbox ®). We investigated the effects of ERBB4 variants and family history of SCZ and/or BPD (FH) on cortical measures and cognitive performances across ages 3-20 years using a general additive model. Variations in ERBB4 and FH impact differentially the age-related cortical changes in regions often affected by SCZ and BPD. The ERBB4-TT-risk genotype children with no FH had subtle cortical changes across the age span, primarily located in the left temporal lobe and superior parietal cortex. In contrast, the TT-risk genotype children with FH had more pronounced age-related changes, mainly in the frontal lobes compared to the non-risk genotype children. Interactive effects of age, FH and ERBB4 variations were also found on episodic memory and working memory, which are often impaired in SCZ and BPD. Healthy children carrying the risk-genotype in ERBB4 and/or with FH had cortical measures resembling those reported in SCZ or BPD. These subclinical cortical variations may provide early indicators for increased risk of psychiatric disorders and improve our understanding of the effect of the NRG1-ERBB4 pathway on brain development. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypal |