Effects of interaction of NOS1AP gene polymorphisms and childhood abuse on paranoid personality disorder features among male violent offenders in China.

BACKGROUND: Paranoid Personality Disorder (PPD) results from a complex synergy between genetic and environmental factors. Childhood abuse is one of risk factors. Nitric Oxide Synthase 1 Adaptor Protein (NOS1AP) is a candidate gene of schizophrenia, which has similar pathophysiology to PPD. This study investigated the role of NOS1AP gene polymorphisms and a history of childhood abuse in predicting PPD features among male violent offenders in the Chinese Han population. METHOD: Four NOS1AP Single Nucleotide Polymorphisms (SNPs), rs4145621, rs3751284, rs348624 and rs6680461 were genotyped in a sample of 423 male prisoners. Participant evaluations included demographic information, measures of childhood abuse (Child Trauma Questionnaire, CTQ), and PPD features (Personality Diagnostic Questionnaire-4, PDQ-4). Participants were divided into a PPD group and non-PPD group assessed by PDQ-4. RESULTS: Regression analysis revealed that emotional abuse, NOS1AP SNPs rs348624 and rs4145621 predicted PPD features (P < 0.05) among prison samples. Significant interactions between childhood abuse history and NOS1AP SNPs rs3751284 and rs6680461 were also observed. Individuals carrying the C allele of rs3751284 were susceptible to PPD features when exposed to higher levels of emotional neglect (P < 0.05); Individuals with the G allele of rs6680461 were susceptible to PPD features when exposed to higher levels of emotional, physical and sexual abuse (P < 0.01). CONCLUSIONS: These results suggest that the interaction between childhood abuse and NOS1AP gene polymorphisms may have an influence on PPD features, at least in male violent offenders.

Schizotypal traits, neurocognition, and paternal age in unaffected first degree relatives of patients with familial or sporadic schizophrenia.

Studies comparing cognitive processes between familial and sporadic schizophrenia have yielded inconsistent findings. In this study we examined differences in neurocognition and schizotypal traits in unaffected relatives of schizophrenia-spectrum patients with either the familial (multiplex) or the sporadic (simplex) subtype of the disorder, taking paternal age at birth into consideration. Simplex (n = 65; SR), multiplex (n = 35; MR) relatives and controls (n = 114) were compared on several cognitive functions and schizotypal traits; between-group differences were evaluated with and without including paternal age in the analyses. SR and MR had higher negative and paranoid traits compared with controls, but paternal age abolished the differences between the SR and control groups. When taking into account schizotypal traits and participants' age, controls outperformed MR in strategy formation and set-shifting and SR in psychomotor speed, set-shifting and executive working memory. After including paternal age in the analyses, controls outperformed MR in strategy formation, working memory and executive working memory and both groups in psychomotor speed and set-shifting. These findings suggest that multiplex relatives present with a "riskier" personality and cognitive profile when considering the effects of paternal age. Nevertheless, simplex relatives are impaired in fundamental cognitive processes, thus highlighting the detrimental effects of paternal age on neurocognition.

Gene expression study of mitochondrial complex I in schizophrenia and paranoid personality disorder.

OBJECTIVES: The aetiology and molecular mechanisms of schizophrenia (SCZ) and paranoid personality disorder (PPD) are not yet clarified. The present study aimed to assess the role of mitochondrial complex I and cell bioenergetic pathways in the aetiology and characteristics of SCZ and PPD. METHODS: mRNA levels of all genomic and mitochondrial genes which encode mitochondrial complex I subunits (44 genes) were assessed in blood in 634 SCZ, 340 PPD patients and 528 non-psychiatric subjects using quantitative real-time PCR, and associated comprehensive psychiatric, neurological and biochemical assessments. RESULTS: Significant expression changes of 18 genes in SCZ patients and 11 genes in PPD patients were detected in mitochondrial complex I. Most of these genes were novel candidate genes for SCZ and PPD. Several correlations between mRNA levels and severity of symptoms, drug response, deficits in attention, working memory, executive functions and brain activities were found. CONCLUSIONS: Deregulations of both core and supernumerary subunits of complex I are involved in the aetiology of SCZ and PPD. These deregulations have effects on brain activity as well as disorder characteristics.

[The concept of schizoidia in psychiatry : From schizoidia to schizotypy and cluster A personality disorders]. / Das Schizoidie-Konzept in der Psychiatrie : Von der Schizoidie über die Schizotypie zu den Cluster­A­Persönlichkeitsstörungen.

From a perspective of conceptual evolution schizoidia was initially considered to describe features both of the premorbid personality of schizophrenic patients and of the personalities of non-psychotic family members (Bleuler, Kahlbaum, Kraepelin). On a psychopatholocial level a close link to the complex basic symptom of autism was stressed. From the very beginnings of modern psychiatry schizoidia was discussed within a conceptual frame of schizophrenia spectrum disorders (Kretschmer, Hoch, Polatin). Approaches to operationalize these conceptual works laid the basis for the cluster A personalities in DSM-III. Due to the prominent concept of schizotypy (Kety, Rado, Meehl) three split up diagnostic categories of schizotypal, schizoid and paranoid personality disorders resulted. Cluster A personality disorders are frequent in community-based epidemiological studies. Health-care seeking behaviour due to primary personality-related problems, however, seems to be less paramount compared to cluster B and C personality disorders. Many family- and twin-based genetic studies convincingly stress a close link between schizotypal personality disorder and schizophrenia. This link is less pronounced for paranoid personality disorder, and even vanishingly low for schizoid personality disorder. From a perspective of schizophrenia spectrum disorders a vast amount of data from molecular genetic, neurobiological, neuropsychological and psychosocial research has impressingly confirmed this link for schizotypal personality disorder. Major research deficits, however, have to be noticed for paranoid and schizoid personality disorder.

The relationship between anxiety disorders and dimensional representations of DSM-IV personality disorders: A co-twin control study.

BACKGROUND: There is substantial comorbidity between personality disorders (PDs) and anxiety disorders (ADs). Sharing of familial risk factors possibly explains the co-occurrence, but direct causal relationships between the disorders may also exist. METHODS: 2801 persons from 1391 twin pairs from the Norwegian Institute of Public Health Twin Panel were assessed for all DSM-IV PDs and ADs. Bivariate Poisson-regression analyses were performed to assess whether PDs predicted ADs at three different levels: All PDs combined, PDs combined within DSM-IV-clusters and each individual PD separately. Next, bivariate co-twin control analyses were executed within monozygotic (MZ) and dizygotic (DZ) twin pairs. A similar analytic strategy was employed in multivariate models including PDs as independent variables. RESULTS: PDs predicted ADs at all levels of analysis in bivariate regression models. Bivariate co-twin control analyses demonstrated an increased risk of ADs in all PDs combined, all PD-clusters and in schizotypal, paranoid, borderline, antisocial, avoidant and dependent PD. In the multivariate regression model, all PD-clusters and schizotypal, borderline, avoidant and obsessive-compulsive PD predicted ADs. Only borderline and avoidant PD predicted ADs in the multivariate co-twin control analysis. LIMITATIONS: Over-adjustment may explain the results from the multivariate analyses. The cross-sectional study design hampers causal inference. CONCLUSIONS: Comorbidity between ADs and PDs can be largely accounted for by shared familial risk factors. However, the results are also consistent with a direct causal relationship partly explaining the co-occurrence. Our results indicate specific environmental factors for comorbidity of ADs and borderline and avoidant PDs that are not shared with other PDs.

A longitudinal twin study of cluster A personality disorders.

BACKGROUND: While cluster A personality disorders (PDs) have been shown to be moderately heritable, we know little about the temporal stability of these genetic risk factors. METHOD: Paranoid PD (PPD) and schizotypal PD (STPD) were assessed using the Structured Interview for DSM-IV Personality in 2793 young adult twins from the Norwegian Institute of Public Health Twin Panel at wave 1 and 2282 twins on average 10 years later at wave 2. Using the program Mx, we fitted a longitudinal latent factor model using the number of endorsed criteria for PPD and STPD. RESULTS: The stability over time of the criteria counts for PPD and STPD, estimated as polychoric correlations, were +0.34 and +0.40, respectively. The best-fit longitudinal model included only additive genetic and individual-specific environmental factors with parameter estimates constrained to equality across the two waves. The cross-wave genetic and individual-specific environmental correlations for a latent cluster A factor were estimated to equal +1.00 and +0.13, respectively. The cross-time correlations for genetic and environmental effects specific to the individual PDs were estimated at +1.00 and +0.16-0.20, respectively. We found that 68% and 71% of the temporal stability of PPD and STPD derived, respectively, from the effect of genetic factors. CONCLUSION: Shared genetic risk factors for two of the cluster A PDs are highly stable in adults over a 10-year period while environmental risk factors are relatively transient. Over two-thirds of the long-term stability of the common cluster A PD liability can be attributed to genetic influences.

A descriptive case-register study of delusional disorder.

OBJECTIVE: A few empirically based studies' data on delusional disorder (DD) exist. We aim to describe sociodemographic and clinical correlates of DD and to identify clinical profiles associated to DD and its subtypes. METHODS: This is a case-register study based on all those subjects attending community mental health services within a geographically well-defined area. Four hundred and sixty-seven patients had been diagnosed as DD cases at psychiatric services serving a catchment area of some 607,494 inhabitants living in South Barcelona (Spain) during a three-year period (2001-2003). A thorough systematic review of computerised medical records was used to establish DSM-IV diagnosis, rendering a valid sample of 370 patients who fulfilled DSM-IV criteria for DD. Independent variables gathered include sociodemographic data, family and personal psychiatric history, and comorbid diagnoses on all DSM-IV axes (including GAF). We used descriptive and univariate statistical methods to explore sample frequencies and correlates across DD types. RESULTS: The mean age of the patients was 55 years and the sample had a mean GAF score of 51 suggesting a poor functionality; 56.5% of the patients were female. The most frequent DD types were persecutory (48%), jealous (11%), mixed (11%) and somatic (5%), whilst 23% qualified for the NOS type. Most frequent symptoms identified were self-reference (40%), irritability (30%), depressive mood (20%) and aggressiveness (15%). Hallucinations were present in 16% of the patients (6% tactile; 4% olfactory). Nearly 9% had a family history of schizophrenia (higher among those with the jealous subtype) and 42% had a comorbid axis II diagnosis (mostly paranoid personality disorder). Depression was significantly more frequent among the persecutory and jealous types. Finally, global functioning was significantly better among jealous and mixed types and worse amongst erotomanic and grandiose cases (p=0.008). CONCLUSIONS: In the absence of other similar empirical data, this modest study provides unique empirical evidence of some clinical and risk correlates of DD and its subtypes.

Dimensional representations of DSM-IV cluster A personality disorders in a population-based sample of Norwegian twins: a multivariate study.

BACKGROUND: The 'odd' or 'Cluster A' personality disorders (PDs) - paranoid, schizoid and schizotypal PDs - were created in DSM-III with little empirical foundation. We have examined the relationship between the genetic and environmental risk factors for dimensional representations of these three personality disorders. METHOD: These personality disorders were assessed using the Structured Interview for DSM-IV Personality (SIDP-IV) in 1386 young adult twin pairs from the Norwegian Institute of Public Health Twin Panel. Using Mx, a single-factor independent pathway twin model was fitted to the number of endorsed criteria for the three disorders. RESULTS: The best-fit model included genetic and unique environmental common factors and genetic and unique environmental effects specific to each personality disorder. Total heritability was modest for these personality disorders and ranged from 21% to 28%. Loadings on the common genetic and unique environmental factors were substantially higher for schizotypal than for paranoid or schizoid PD. The proportion of genetic liability shared with all Cluster A disorders was estimated at 100, 43 and 26% respectively for schizotypal, paranoid and schizoid PDs. CONCLUSION: In support of the validity of the Cluster A construct, dimensional representations of schizotypal, paranoid and schizoid PD are all modestly heritable and share a portion of their genetic and environmental risk factors. No evidence was found for shared environmental or sex effects for these PDs. Schizotypal PD most closely reflects the genetic and environmental liability common to all three Cluster A disorders. These results should be interpreted in the context of the limited power of this sample.

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 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.

Genetic boundaries of the schizophrenia spectrum: evidence from the Finnish Adoptive Family Study of Schizophrenia.

OBJECTIVE: Identification of the genetically related disorders in the putative schizophrenia spectrum is an unresolved problem. Data from the Finnish Adoptive Family Study of Schizophrenia, which was designed to disentangle genetic and environmental factors influencing risk for schizophrenia, were used to examine clinical phenotypes of schizophrenia spectrum disorders in adopted-away offspring of mothers with schizophrenia spectrum disorders. METHOD: Subjects were 190 adoptees at broadly defined genetic high risk who had biological mothers with schizophrenia spectrum disorders, including a subgroup of 137 adoptees at narrowly defined high risk whose mothers had DSM-III-R schizophrenia. These high-risk groups, followed to a median age of 44 years, were compared diagnostically with 192 low-risk adoptees whose biological mothers had either a non-schizophrenia-spectrum diagnosis or no lifetime psychiatric diagnosis. RESULTS: In adoptees whose mothers had schizophrenia, the mean lifetime, age-corrected morbid risk for narrowly defined schizophrenia was 5.34% (SE=1.97%), compared to 1.74% (SE=1.00%) for low-risk adoptees, a marginally nonsignificant difference. In adoptees whose mothers had schizophrenia spectrum disorders, the mean age-corrected morbid risk for a schizophrenia spectrum disorder was 22.46% (SE=3.56%), compared with 4.36% (SE=1.51%) for low-risk adoptees, a significant difference. Within the comprehensive array of schizophrenia spectrum disorders, schizotypal personality disorder was found significantly more often in high-risk than in low-risk adoptees. The frequency of the group of nonschizophrenic nonaffective psychoses collectively differentiated high-risk and low-risk adoptees, but the frequencies of the separate disorders within this category did not. The two groups were not differentiated by the prevalence of paranoid personality disorder and of affective disorders with psychotic features. CONCLUSIONS: In adopted-away offspring of mothers with schizophrenia spectrum disorders, the genetic liability for schizophrenia-related illness (with the rearing contributions of the biological mothers disentangled) is broadly dispersed. Genetically oriented studies of schizophrenia-related disorders and studies of genotype-environment interaction should consider not only narrowly defined, typical schizophrenia but also schizotypal and schizoid personality disorders and nonschizophrenic nonaffective psychoses.

[Microdeletion 22q11.2. A too rarely diagnosed genetic change in psychiatric illnesses]. / Mikrodeletion 22q11.2. Eine zu selten diagnostizierte genetische Veränderung bei psychiatrischen Erkrankungen.

Microdeletion 22q11.2 with an estimated incidence of 1:4000 is known to cause the DiGeorge syndrome (DGS) or the velocardiofacial syndrome (VCFS), both usually being diagnosed in the newborn period or childhood. Recent studies have shown that children suffering from VCFS frequently develop psychiatric disorders in late adolescence or adulthood. Here we report the case of a 30-year-old man presenting with slight facial dysmorphisms, hypoparathyreoidism, minor cardiac anomalies, and slight cognitive impairments who had developed a severe personality disorder which eventually led to the diagnosis of microdeletion 22q11.2 with maternal inheritance. Psychiatric patients should be thoroughly examined for typical signs associated with this chromosomal anomaly. Genetic diagnosis is necessary because of the 50% probability of inheritance with possibly severe congenital anomalies. In view of a prevalence of 2% in an unselected group of patients with schizophrenic psychosis, microdeletion 22q11.2 is likely to be underdiagnosed.

Premorbid psychiatric risk factors for postictal psychosis.

Postictal psychosis (PIP) is a common and clinically significant sequela of inpatient epilepsy monitoring. A series of 622 patients with complex partial epilepsy undergoing video-EEG evaluations as candidates for epilepsy surgery were evaluated, by structured psychiatric interview, for individual and family psychiatric histories, depression, anxiety, and features of personality disorders. No patient had psychotic symptoms at baseline. Twenty-nine developed a PIP episode during monitoring. The a priori hypotheses were that patients with PIP would have higher baseline schizotypal and paranoid personality ratings and a greater prevalence of histories of psychiatric treatment and family history of psychotic illness. However, only a higher prevalence of mood disorder among first- and second-degree relatives distinguished the patients who developed PIP on logistic regression analyses (odds ratio=3.49, P=0.001). Possible mechanisms linking vulnerability toward mood disorders and the development of psychotic symptoms in epilepsy are discussed.

Schizophrenia and schizophrenia-spectrum personality disorders in the first-degree relatives of children with schizophrenia: the UCLA family study.

BACKGROUND: This study tested the hypothesis that childhood-onset schizophrenia (COS) is a variant of adult-onset schizophrenia (AOS) by determining if first-degree relatives of COS probands have an increased risk for schizophrenia and schizotypal and paranoid personality disorders. METHODS: Relatives of COS probands (n = 148) were compared with relatives of attention-deficit/hyperactivity disorder (ADHD) (n = 368) and community control (n = 206) probands. Age-appropriate structured diagnostic interviews were used to assign DSM-III-R diagnoses to probands and their relatives. Family psychiatric history was elicited from multiple informants. Diagnoses of relatives were made blind to information about probands' diagnoses. Final consensus diagnoses, which integrated family history, direct interview information, and medical records, are reported in this article. RESULTS: There was an increased lifetime morbid risk for schizophrenia (4.95% +/- 2.16%) and schizotypal personality disorder (4.20% +/- 2.06%) in the parents of COS probands compared with parents of ADHD (0.45% +/- 0.45%, 0.91% +/- 0.63%) and community control (0%) probands. The parents of COS probands diagnosed as having schizophrenia had an early age of first onset of schizophrenia. Risk for avoidant personality disorder (9.41% +/- 3.17%) was increased in the parents of COS probands compared with parents of community controls (1.67% +/- 1.17%). CONCLUSIONS: The psychiatric disorders that do and do not aggregate in the parents of COS probands are remarkably similar to the disorders that do and do not aggregate in the parents of adults with schizophrenia in modern family studies. These findings provide compelling support for the hypothesis of etiological continuity between COS and AOS.

Diagnostic accuracy and linkage analysis: how useful are schizophrenia spectrum phenotypes?

OBJECTIVE: Numerous studies suggest that the nonschizophrenic relatives of schizophrenic patients exhibit psychiatric and other features that discriminate them from normal comparison subjects. These features have been put forth as "spectrum" phenotypes that may be variant manifestations of the schizophrenia genotype. However, most of these studies do not address a key measurement question: does the diagnostic accuracy of these spectrum classifications warrant their use in genetic linkage studies of schizophrenia? METHOD: The authors reviewed 30 studies of putative indicators of the schizophrenic genotype: schizotypal personality disorder, eye tracking dysfunction, attentional impairment, auditory evoked potentials, neurological signs, neuropsychological impairment, and allusive thinking. RESULTS: Although each of 42 measures of these indicators discriminated the relatives of schizophrenic patients from the normal comparison subjects, a diagnostic accuracy analysis suggested that only six of these would improve the informativeness of genetic linkage data. CONCLUSIONS: Many proposed spectrum phenotypes for schizophrenia may not be useful for linkage analysis because of high false positive rates (poor specificity). Future work aimed at describing and developing phenotypes for linkage analysis should assess the diagnostic accuracy of proposed measures.

Evaluating the spectrum concept of schizophrenia in the Roscommon Family Study.

OBJECTIVE: The authors sought to evaluate whether the pattern of schizophrenia and related disorders in probands and their relatives can be explained by a single underlying continuum of liability to the "schizophrenia spectrum." METHOD: In the epidemiologically based Roscommon Family Study, the authors separately examined--in siblings, parents, and relatives of index and comparison probands--the familial aggregation and coaggregation of five hierarchically defined disorders: schizophrenia, schizoaffective disorder, schizotypal/paranoid personality disorder, other nonaffective psychoses, and psychotic affective illness. A multiple threshold model was fitted to these contingency tables by maximum likelihood. RESULTS: The multiple threshold model that constrained resemblance to be the same in siblings and parents fit the data well and estimated the correlation in liability to schizophrenia spectrum disorders between probands and first-degree relatives at 0.36. Parents, however, required higher levels of liability to manifest schizophrenia spectrum disorders than siblings. While schizophrenia and psychotic affective illness could be clearly assigned to the two extremes of the schizophrenia spectrum, the proper ordering of schizoaffective disorder, schizotypal/paranoid personality disorder, and other nonaffective psychoses could not be unambiguously determined. CONCLUSIONS: These results are consistent with the existence of a schizophrenia spectrum in which these five disorders are manifestations, of varying severity, of the same underlying vulnerability. This vulnerability is strongly transmitted within families.

Independent diagnoses of adoptees and relatives as defined by DSM-III in the provincial and national samples of the Danish Adoption Study of Schizophrenia.

BACKGROUND: This report describes the independent application of DSM-III criteria to the adoptees and relatives in the Provincial sample of the Danish Adoption Study of Schizophrenia of Kety and colleagues. We report these results and combine them with those reported previously for the Copenhagen sample to form the National sample. METHODS: Personal interviews and institutional record summaries of adoptees and biological and adoptive relatives were "blindly" diagnosed using DSM-III criteria. "Schizophrenia spectrum" was a priori defined as schizophrenia; schizoaffective disorder, mainly schizophrenic subtype; and schizotypal and paranoid personality disorders. RESULTS AND CONCLUSION: In the Provincial sample, the prevalence of "spectrum" disorders was significantly greater in biological relatives of schizophrenia spectrum vs control adoptees. The results were also consistent with the genetic transmission of individual diagnoses within the spectrum. When combined into the National sample, the results provided strong evidence for (1) the genetic transmission of DSM-III schizophrenia; (2) a genetic relationship between DSM-III schizophrenia, mainly schizophrenic schizoaffective disorder, and schizotypal personality disorder; and (3) the absence of a significant genetic relationship between the schizophrenia spectrum and either psychotic nonspectrum disorders, major depression, or anxiety disorders. We found no evidence for the familial environment transmission of schizophrenia spectrum disorders. These results are consistent with the findings reported by Kety and coworkers from their diagnostic review.

Delusions in schizophrenia spectrum disorders: diagnostic issues.

Family studies of schizophrenia frequently include relatives of schizophrenia probands with diagnoses falling within the schizophrenia spectrum. As part of an ongoing genetic linkage study of schizophrenia, the authors examined case material from 50 relatives (of schizophrenia probands) who received a DSM-III-R diagnosis of a nonaffective psychotic disorder or schizotypal or paranoid personality disorder. Eleven exhibited episodic or chronic delusions that resulted in diagnostic dilemmas, often arising from issues pertaining to the classification of delusional phenomena. Four of these cases are presented here. Unusual beliefs were often difficult to classify as odd beliefs versus full delusions, brief/transient versus persistent delusions, bizarre versus non-bizarre delusions. It is suggested that these might be considered continuous rather than dichotomous dimensions. Several possible implications for genetic studies of schizophrenia are discussed.

Schizotypal and paranoid personality disorder in the relatives of patients with schizophrenia and affective disorders: a review.

This review considers the possible familial relationship of schizotypal and paranoid personality disorders (SPD, PPD) to schizophrenia (SCZ) and affective disorders (AD). There have been few controlled studies on familial risk of SPD and PPD based on direct semi-structured interviews of relatives, blind to proband diagnosis. Three of six studies reported increased familial risk of SPD for SCZ probands, but with considerable variability in estimates of this risk. None of four studies reported a significant relationship between AD and familial SPD. There is substantial but less consistent evidence for a familial relationship between PPD and SCZ: three of six studies supported such a relationship, but one large study reported increased familial risk of PPD for AD and not for SCZ probands. There is also some evidence that negative symptoms are most characteristic of SPD in relatives of SCZ probands. Also discussed are issues concerning the adequacy of current criteria for defining schizophrenia spectrum pathology, and of diagnostic methods in this area.

Psychiatric illnesses in families of subjects with schizophrenia-spectrum personality disorders: high morbidity risks for unspecified functional psychoses and schizophrenia.

OBJECTIVE: The authors determined morbidity risks for psychiatric illnesses in the families of probands with schizophrenia-spectrum personality disorders. METHOD: Subjects were recruited from the community through newspaper advertisements. Subjects were identified as having schizophrenia-spectrum personality disorders (N = 30) if they met at least three, four, or three DSM-III-R criteria for schizoid (N = 14), schizotypal (N = 20), and/or paranoid (N = 15) personality disorder, respectively. The comparison subjects had no psychiatric diagnoses (N = 8) or had other personality disorders (N = 12); none of the subjects in either group had any DSM-III-R axis I diagnosis. Trained interviewers collected family history information about the relatives of the two groups; the interviewers were blind to the probands' diagnoses. RESULTS: The risks for schizophrenia, other functional psychoses, and schizophrenia-spectrum personality disorders were significantly higher in the relatives of subjects with schizophrenia-spectrum personality disorders than in the families of the comparison subjects. CONCLUSIONS: The high rate of schizophrenia in the families of probands with schizophrenia-spectrum personality disorders is consistent with the previous findings of higher than normal rates of these personality disorders in the biological relatives of schizophrenic patients. The significance of the high rate of unspecified functional psychoses is unclear. Use of the family study method, by which valid differential diagnosis of psychoses is possible, is indicated. The results from the current study do not rule out the possibility that the schizophrenia-spectrum personality disorders are related to psychoses in general rather than specifically to schizophrenia.

Schizophrenia and affective disorder: are they genetically linked?

The relationship between schizophrenic 'spectrum' disorders and affective illness was studied in the nuclear families of 90 chronic schizophrenic probands. An increased risk of schizophrenia and related disorders was demonstrated among the first-degree relatives of probands with a family history of major affective disorders. Conversely, relatives of probands with a family history of schizophrenic 'spectrum' disorders were at a greater risk of affective illness (major depression) than relatives of probands with no family history. These results lend support to the notion that a subset of affective disorders is associated with the liability to schizophrenia.