Is there an association between advanced paternal age and endophenotype deficit levels in schizophrenia?

The children of older fathers have increased risks of developing schizophrenia spectrum disorders, and among those who develop these disorders, those with older fathers present with more severe clinical symptoms. However, the influence of advanced paternal age on other important domains related to schizophrenia, such as quantitative endophenotype deficit levels, remains unknown. This study investigated the associations between paternal age and level of endophenotypic impairment in a well-characterized family-based sample from the Consortium on the Genetics of Schizophrenia (COGS). All families included at least one affected subject and one unaffected sibling. Subjects met criteria for schizophrenia (probands; n = 293) or were unaffected first-degree siblings of those probands (n = 382). Paternal age at the time of subjects' birth was documented. Subjects completed a comprehensive clinical assessment and a battery of tests that measured 16 endophenotypes. After controlling for covariates, potential paternal age-endophenotype associations were analyzed using one model that included probands alone and a second model that included both probands and unaffected siblings. Endophenotype deficits in the Identical Pairs version of the 4-digit Continuous Performance Test and in the Penn Computerized Neurocognitive Battery verbal memory test showed significant associations with paternal age. However, after correcting for multiple comparisons, no endophenotype was significantly associated with paternal age. These findings suggest that factors other than advanced paternal age at birth may account for endophenotypic deficit levels in schizophrenia.

Prodromal and autistic symptoms in schizotypal personality disorder and 22q11.2 deletion syndrome.

Despite clear diagnostic distinctions, schizophrenia and autism share symptoms on several dimensions. Recent research has suggested the two disorders overlap in etiology, particularly with respect to inherited and noninherited genetic factors. Studying the relationship between psychotic-like and autistic-like symptoms in risk groups such as 22q11 deletion syndrome (22q11DS) and schizotypal personality disorder (SPD) has the potential to shed light on such etiologic factors; thus, the current study examined prodromal symptoms and autistic features in samples of 22q11DS and SPD subjects using standardized diagnostic measures, including the Structured Interview for Prodromal Symptoms (SIPS) and the Autism Diagnostic Inventory-Revised (ADI-R). Results showed that SPD subjects manifested significantly more severe childhood and current social as well as stereotypic autistic features, as well as more severe positive prodromal symptoms. The two groups did not differ on negative, disorganized, or general prodromal symptoms, but were distinguishable based on correlations between prodromal and autistic features; the relationships between childhood autistic features and current prodromal symptoms were stronger for the SPD group. The results suggest that childhood autistic features are less continuous with subsequent prodromal signs in 22q11DS patients relative to those with SPD, and the findings highlight the importance of studying the overlap in diagnostic phenomenology in groups at risk for developing psychosis and/or autism.

Family history of psychosis negatively impacts age at onset, negative symptoms, and duration of untreated illness and psychosis in first-episode psychosis patients.

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.

Does a parent-report measure of behavioral problems enhance prediction of conversion to psychosis in clinical high-risk adolescents?

Recent research on risk for psychosis has focused on youth who manifest subclinical signs that are often associated with the prodrome to psychosis. Standardized measures of prodromal symptoms have been shown to significantly enhance prediction of risk for conversion to an Axis I psychotic disorder. In the present study, a widely used parent-report measure of behavioral problems, the Child Behavior Checklist (CBCL) was administered to examine the clinical and diagnostic utility of the measure as an adjunctive screening instrument in the identification of at-risk youth. The CBCL, the Structured Interview for Prodromal Syndromes (SIPS), and other diagnostic measures were administered at baseline and at one year follow-up assessments to adolescents (n=41) at clinical high-risk for the development of a psychotic disorder. Analyses were conducted to compare the 14 at-risk adolescents who subsequently converted to psychosis to the 27 who did not. Conversion to psychosis was defined as conversion to an Axis I psychotic disorder or affective disorder with psychotic features. Consistent with expectations, at one year follow-up, compared to the Non-Converted participants, the Converted participants manifested significantly higher scores on the prodromal symptom scales of the SIPS. There were, however, no differences in CBCL social and behavioral ratings as a function of conversion status. It is concluded that the CBCL does not show promise as an alternative or adjunctive predictor of conversion to psychosis in at-risk adolescents.

Patient-level predictors and clinical correlates of duration of untreated psychosis among hospitalized first-episode patients.

OBJECTIVE: Duration of untreated psychosis (DUP) has been associated with poor early course outcomes of nonaffective psychotic disorders; however, less is known about predictors of DUP. This study examined patient-level predictors of DUP and clinical correlates of both DUP and duration of untreated illness (DUI), both of which have been implicated as prognostic indicators. METHOD: Participants included 109 first-episode patients hospitalized in 3 public-sector inpatient psychiatric units serving an urban, socially disadvantaged, predominantly African American community. DUP, DUI, and a number of clinical and psychosocial variables were measured using standardized methods. Patients were diagnosed with schizophrenia and related psychotic disorders according to the Structured Clinical Interview for DSM-IV Axis I Disorders. RESULTS: The median DUP and DUI were 22.3 and 129.9 weeks, respectively. Survival analyses revealed that, at any given time point, patients not living with family members were, on average, about 1.5 times as likely to be hospitalized as those living with family when controlling for mode of onset of psychosis. Patients not living in poverty were, on average, about 1.6 times as likely to be hospitalized as those living in poverty when controlling for mode. A greater burden of negative symptoms was associated with longer DUP (r = 0.23, P = .02), and poorer insight was associated with longer DUI (r = -0.24, P = .01). Longer DUP and DUI were associated with diverse adverse clinical characteristics, such as greater impairment in global functioning, poorer social functioning, and more psychosocial problems. CONCLUSIONS: There is a need for early intervention efforts to be directed to families (and their loved ones who live with them with emerging psychotic disorders or frank untreated psychotic syndromes), particularly families facing major socioeconomic challenges.

Cluster A Personality Disorders: Schizotypal, Schizoid and Paranoid Personality Disorders in Childhood and Adolescence.

Cluster A personality disorders (PD), including schizotypal personality disorder (SPD), paranoid personality disorder (PPD), and schizoid PD, are marked by odd and eccentric behaviors, and are grouped together because of common patterns in symptomatology as well as shared genetic and environmental risk factors. The DSM-IV-TR describes personality disorders as representing stable and enduring patterns of maladaptive traits, and much of what is understood about Cluster A personality disorders in particular stems from research with adult populations. Less in known about these disorders in children and adolescents, and controversy remains regarding diagnosis of personality disorders in general in youth. The current paper reviews the available research on Cluster A personality disorders in childhood and adolescence; specifically, we discuss differentiating between the three disorders and distinguishing them from other syndromes, measuring Cluster A disorders in youth, and the nature and course of these disorders throughout childhood and adolescence. We also present recent longitudinal data from a sample of adolescents diagnosed with Cluster A personality disorders from our research laboratory, and suggest directions for future research in this important but understudied area.

Longitudinal changes in cortisol secretion and conversion to psychosis in at-risk youth.

Elevations in hypothalamic-pituitary-adrenal (HPA) axis activity have been implicated in the origins and exacerbation of mental disorders. Several lines of investigation suggest HPA activity, indexed by increased cortisol, is elevated in patients with schizophrenia and other psychotic disorders. This study examined the relation of cortisol levels and longitudinal changes with psychotic outcomes in at-risk adolescents. Participants were 56 adolescents who met risk criteria for psychosis, namely, schizotypal personality disorder (n = 5), prodromal symptom criteria based on the Structured Interview for Prodromal Symptoms (n = 17), or both (n = 34). Of these, 14 subsequently met DSM-IV criteria for an Axis I psychotic disorder (schizophrenia, schizoaffective disorder, or mood disorder with psychotic features). Participants were assessed at baseline and then followed longitudinally. Salivary cortisol was sampled multiple times at initial assessment, interim follow-up, and 1-year follow-up. Area under the curve (AUC) was computed from the repeated cortisol measures. The findings indicate that at-risk subjects who subsequently developed psychosis showed significantly higher cortisol at the first follow-up, a trend at the 1-year follow-up, and a significantly larger AUC when compared to those who did not convert. A similar pattern of group differences emerged from analyses excluding those who may have converted prior to the 1-year follow-up. These findings converge with previous reports on HPA activity in psychosis, as well as theoretical assumptions concerning the effects of cortisol elevations on brain systems involved in psychotic symptoms. Future research with larger samples is needed to confirm and extend these results.

The impact of a family history of psychosis on age-at-onset and positive and negative symptoms of schizophrenia: a meta-analysis.

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.

Association of pre-onset cannabis, alcohol, and tobacco use with age at onset of prodrome and age at onset of psychosis in first-episode patients.

OBJECTIVE: Several reports suggest that cannabis use is associated with an earlier age at onset of psychosis, although not all studies have operationalized cannabis use as occurring prior to onset of symptoms. This study addressed whether pre-onset cannabis use, alcohol use, and tobacco use are associated with an earlier age at onset of prodromal and psychotic symptoms. Effects of the progression of frequency of use were examined through time-dependent covariates in survival analyses. METHOD: First-episode patients (N=109) hospitalized in three public-sector inpatient psychiatric units underwent in-depth cross-sectional retrospective assessments. Prior substance use and ages at onset of prodromal and psychotic symptoms were determined by standardized methods, and analyses were conducted using Cox regression modeling. RESULTS: Whereas classifying participants according to maximum frequency of use prior to onset (none, ever, weekly, or daily) revealed no significant effects of cannabis or tobacco use on risk of onset, analysis of change in frequency of use prior to onset indicated that progression to daily cannabis and tobacco use was associated with an increased risk of onset of psychotic symptoms. Similar or even stronger effects were observed when onset of illness or prodromal symptoms was the outcome. A gender-by-daily-cannabis-use interaction was observed; progression to daily use resulted in a much larger increased relative risk of onset of psychosis in females than in males. CONCLUSIONS: Pre-onset cannabis use may hasten the onset of psychotic as well as prodromal symptoms. Age at onset is a key prognostic factor in schizophrenia, and discovering modifiable predictors of age at onset is crucial.

The psychosis continuum and categorical versus dimensional diagnostic approaches.

This overview briefly presents recent thinking on the dimensional approach to understanding psychotic experiences. First, evidence is provided for a continuum of psychosis ranging from self-reported infrequent psychotic symptoms in the general population, to schizotypal traits, to schizotypal personality disorder, and finally to full-blown psychosis resulting in a diagnosable primary psychotic disorder. Variation within each of these types of psychotic experience is discussed. Then, a comparison is presented between categorical and dimensional approaches to the diagnosis of psychosis by highlighting four advantages of each approach. In doing so, it is emphasized that the categorical approach is beneficial primarily in terms of reliability, whereas the dimensional approach would enhance validity.

Schizotypy and nicotine, alcohol, and cannabis use in a non-psychiatric sample.

Schizotypy is a multidimensional personality construct that is characterized by perceptual abnormalities, social withdrawal, mild suspiciousness, and odd thinking patterns. This study examined the relationship between four dimensions of self-reported schizotypy and substance use involving nicotine, alcohol, and cannabis, in undergraduate students. Results showed that higher levels of disorganized schizotypy, or odd thinking and behavior, were associated with greater indices of use of all three substances. Furthermore, higher cognitive-perceptual schizotypy was selectively associated with cannabis use. Results confirm findings of recent research that has discovered associations among schizotypy and substance use, highlighting links between behavioral traits and use of nicotine, alcohol, and cannabis. This study is one of the first to examine a wide range of schizotypy domains, and to show selective effects of the disorganized domain of schizotypy.

Childhood and current autistic features in adolescents with schizotypal personality disorder.

The diagnostic boundaries between autistic- and schizophrenia-spectrum disorders have varied over the years, and some overlap in diagnostic criteria persists. The present study examined childhood and current signs of autistic disorder (AD) in adolescents with schizotypal personality disorder (SPD) or other personality disorders, as well as healthy controls. A structured interview was administered to rate participants' current symptoms. Participants' guardians were interviewed with the Autism Diagnostic Inventory-Revised (ADI-R), a clinical assessment of childhood and current autistic signs. Compared to both the other personality-disordered and healthy groups, adolescents with SPD were rated as having significantly more impairment on childhood and current social functioning, and having more unusual interests and behaviors. For the entire sample, impaired childhood social functioning and unusual interests and behaviors were associated with higher negative symptom scores. Current impairments in social functioning, unusual interests and behaviors, and communication were also linked with greater negative symptoms. However, neither childhood nor current autistic features significantly predicted later conversion to an Axis I psychotic disorder over the course of three years of follow-up. The findings indicate that past and current autistic signs are more common in adolescents with SPD, but neither current nor childhood autistic features are linked with conversion to psychosis.

Knowledge about schizophrenia and social distance toward individuals with schizophrenia: a survey among predominantly low-income, urban, African American community members.

This study surveyed 111 urban African American community members regarding their level of familiarity with mental illness, knowledge about schizophrenia, and social distance toward individuals with schizophrenia. The participants were predominantly Protestant, with relatively low educational attainment and low income. Knowledge and social distance scores were not significantly correlated. Independently significant predictors of knowledge about schizophrenia, which accounted for 49% of the variance in scores, included level of educational attainment, gender, having a friend with a history of psychiatric treatment, and having known someone with schizophrenia. Independent predictors of social distance scores included family history of psychiatric treatment and family history of schizophrenia, which accounted for 14% of variance in scores. Further research involving specific racial, ethnic, cultural, and socioeconomic groups is needed to better understand the complex associations underlying knowledge about schizophrenia and stigma.

Causes of schizophrenia reported by urban African American lay community members.

Although mental health professionals' "etiologic beliefs" concerning schizophrenia have evolved in accordance with diathesis-stress and neurodevelopmental models, little is known about etiologic attributions in nonclinical general population samples in the United States. Yet, course and outcome for people with the illness may be indirectly influenced by beliefs about causes in the larger community. Because of very limited research in this area, especially among African Americans in particular, this descriptive study investigated the causes of schizophrenia reported by 127 urban African Americans from the general population. The aim of this study was to assess the most commonly reported causes of schizophrenia, as well as the frequency of endorsing items from a list of 30 factors, some of which are congruent with current psychiatric conceptualizations of schizophrenia, whereas others are not. Results of this report complement previously reported findings from the same setting involving family members of patients with schizophrenia [Esterberg ML, Compton MT. Causes of schizophrenia reported by family members of urban African American hospitalized patients with schizophrenia. Compr Psychiatry 2006;47:221-226]. The 5 most commonly reported causes were disturbance of brain biochemistry (49.6%), drug/alcohol abuse (42.5%), hereditary factors (40.9%), brain injury (40.2%), and avoidance of problems in life (37.8%). The mean number of likely or very likely causes endorsed by participants was 7.5 +/- 5.7. Some 47.9% reported one or more esoteric factors as a cause. Of the 6 esoteric factors, possession by evil spirits (28.3%), radiation (20.2%), and punishment by God (19.7%) were most common. Esoteric causes were more commonly chosen by male participants, those with 12 years of education or less, and participants who reported never having known someone with schizophrenia. Future research should seek to better understand how esoteric beliefs about causation affect attitudes toward people with mental illnesses and acceptance of mental health treatment by those individuals. Beliefs about debunked personality, societal, family, and esoteric causes in this nonclinical sample indicate the need for improved psychoeducation of the community at large.

Nicotine consumption and schizotypy in first-degree relatives of individuals with schizophrenia and non-psychiatric controls.

Individuals with schizophrenia have very high rates of cigarette smoking, and much has been discovered about the influence of nicotine on brain functioning in schizophrenia. However, less is understood about the relationship between nicotine consumption and milder phenotypes related to schizophrenia, specifically schizotypy. This study examined the relationship between nicotine consumption and schizotypy in two unmedicated samples that included first-degree relatives and non-psychiatric controls. Forty-two first-degree relatives and 50 control participants were administered a self-report questionnaire on schizotypal features as well as a self-report questionnaire on smoking behavior. A positive relationship was found between smoking status and level of schizotypy, and higher levels of schizotypy significantly predicted the odds of being a smoker after controlling for gender and group status. Interestingly, group status was a significant moderator in the relationship between level of schizotypy and smoking status, such that the relationship between these two variables was only significant in the first-degree relatives. This is the first study to investigate the relationship between these variables in a sample of first-degree relatives of individuals with schizophrenia. Those individuals with more schizotypal features are presumably at greater risk for schizophrenia-spectrum disorders and thus may be more likely to smoke cigarettes given the known biochemical effects of nicotine on overt positive and negative symptoms of schizophrenia. Although relatives did not differ from controls in their level of self-reported schizotypy, the significant relationship between smoking status and schizotypy in the former group is likely explained by their genetic vulnerability to schizophrenia-spectrum disorders.

Movement abnormalities and the progression of prodromal symptomatology in adolescents at risk for psychotic disorders.

The link between movement abnormalities and psychotic disorders is presumed to reflect common neural mechanisms that influence both motor functions and vulnerability to psychosis. The prodromal period leading to psychotic disorders represents both a viable point for intervention and a developmental period that, if studied, could shed light on etiology; however, no published studies have examined the temporal progression of this link. A group with high levels of prodromal symptomatology (i.e., adolescents with schizotypal personality disorder [SPD]; n = 42) and both psychiatric controls (with other personality disorders or conduct disorder [OD]; n = 30) and nonpsychiatric controls ([NC]; n = 49) were recruited. Videotapes of structured psychiatric interviews were coded for movement abnormalities by raters blind to participants' diagnostic status, and follow-up assessments were conducted 1 year later. Controlling for psychotropic medications, the authors found that adolescents with SPD exhibited significantly more motor abnormalities in the face and upper body than did OD and NC controls. At baseline, movement abnormalities were positively correlated with the severity of positive, negative, and total prodromal symptoms. Within the SPD group, baseline movement abnormalities predicted symptom severity 1 year later. Movement abnormalities represent an early risk indicator that may be predictive of later symptom severity and potentially of psychosis onset.

Neurological soft signs and minor physical anomalies in patients with schizophrenia and related disorders, their first-degree biological relatives, and non-psychiatric controls.

BACKGROUND: Subtle neurological impairments and inconsequential minor anomalies of the face and limbs are manifestations of neurodevelopmental and ontogenic abnormalities that are consistently found at higher rates in individuals with schizophrenia compared to healthy controls. Limited research has been conducted on these traits among biological relatives of patients with schizophrenia. This study hypothesized that the mean NSS score and the mean MPA score would be greater in patients than controls and that first-degree relatives would have intermediate scores. Furthermore, it was hypothesized that NSS scores and MPA scores would not be correlated. This study also explored correlations between patients' NSS and MPA scores and their relatives' respective scores and sought to replicate the finding that NSS are associated with negative and disorganized symptoms of schizophrenia, whereas MPAs are not. METHODS: Patients with schizophrenia and related psychotic disorders (n=73), first-degree relatives (n=44), and non-psychiatric controls (n=54) were assessed. Measures included the Neurological Evaluation Scale, a structured examination for MPAs, and the Positive and Negative Syndrome Scale in patients. Analyses accounted for clustering within families. RESULTS: Both NSS and MPAs were greater in patients than controls, and first-degree relatives had intermediate scores. Furthermore, NSS and MPA scores were independent in all three groups. Correlations were found between patients' and their relatives' scores on one NES subscale (sensory integration) and total MPA score and several MPA regions (eyes, ears, and hands). This study replicated previous findings that in patients with schizophrenia, NSS are associated with negative, disorganized, and other domains of symptoms. Associations between MPAs and symptoms were sparse and inconsistent. CONCLUSION: These findings suggest that NSS and MPAs represent two quite distinct markers of risk for schizophrenia that may stem from genetic factors, as well as from environmental/developmental influences. Future research on multivariable risk prediction models may benefit from the use of somewhat independent risk markers or endophenotypes.

Associations between schizotypal features and indicators of neurological and morphological abnormalities.

OBJECTIVE: Limited research suggests that subtle neurological and morphological abnormalities that have been documented in patients with schizophrenia also may be associated with schizotypal traits in non-psychiatric samples. Based on the notion that neurological soft signs (NSS) may mark a genetic diathesis, this study hypothesized that NSS scores would be related to the level of schizotypy in relatives of schizophrenia patients and in controls. Additionally, associations between MPA scores and schizotypy were explored in these two groups. METHOD: Twenty-six first-degree relatives of schizophrenia patients and 38 controls with no personal or family history of psychosis were assessed for schizotypy using the Structured Clinical Interview for DSM-IV Axis II Disorders schizotypal personality disorder module, as well as the self-administered Schizotypal Personality Questionnaire. The Neurological Evaluation Scale and a structured examination for MPAs also were administered. RESULTS: Mean schizotypy scores did not differ between relatives and controls. Both NSS and MPAs were associated with the level of interviewer-assessed schizotypal features in controls but not in relatives of patients with schizophrenia. NSS and MPAs were not associated with self-reported schizotypy in either group. CONCLUSIONS: These findings demonstrate that both NSS and MPAs are associated with interview-based schizotypal traits, at least in non-psychiatric participants. Future research should seek to replicate these results in other samples of relatives and controls.

Assessing knowledge of schizophrenia: development and psychometric properties of a brief, multiple-choice knowledge test for use across various samples.

Psychosocial research on schizophrenia would benefit from reliable and valid measures of knowledge about schizophrenia. Although a variety of instruments have been developed to assess the effects of specific family psychoeducational programs, little research has been conducted on the psychometric properties of scales measuring knowledge about schizophrenia. This study assessed reliability and validity of a brief, easily administered, multiple-choice knowledge test completed by 441 participants from several samples: 144 lay community members, 77 family members of inpatients with schizophrenia, 170 police officers involved in a training program on mental illnesses, and 50 mental health professionals. After item analysis, good internal consistency reliability and construct validity were demonstrated for an 18-item version of this test. The findings demonstrate that knowledge about schizophrenia - a construct with potentially broad applicability in psychosocially oriented schizophrenia research - can be assessed with brief, self-administered, multiple-choice knowledge tests.

Brief reports: crisis intervention team training: changes in knowledge, attitudes, and stigma related to schizophrenia.

OBJECTIVE: Crisis intervention team (CIT) training provides police officers with knowledge and skills to improve their responses to individuals with mental illnesses. This study determined changes in knowledge, attitudes, and social distance related to schizophrenia among police officers after CIT training. METHODS: A survey was administered to 159 officers immediately before and after a 40-hour CIT training program in Georgia. Pre- and posttest data were gathered from surveys taken between December 2004 and July 2005. RESULTS: After the training, officers reported improved attitudes regarding aggressiveness among individuals with schizophrenia, became more supportive of treatment programs for schizophrenia, evidenced greater knowledge about schizophrenia, and reported less social distance toward individuals with schizophrenia. CONCLUSIONS: This study supports the hypothesis that an educational program for law enforcement officers may reduce stigmatizing attitudes toward persons with schizophrenia.