Michelle L. Esterberg

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.

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.

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.

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.

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.

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.

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.

Associations between olfactory identification and verbal memory in patients with schizophrenia, first-degree relatives, and non-psychiatric controls

OBJECTIVE Olfactory identification deficits and verbal memory impairments may represent trait markers for schizophrenia. The aims of this study were to: (1) assess olfactory identification in patients, first-degree relatives, and non-psychiatric controls, (2) determine differences in verbal memory functioning in these three groups, and (3) study correlations between olfactory identification and three specific verbal memory domains. METHOD A total of 106 participants-41 patients with schizophrenia or related disorders, 27 relatives, and 38 controls-were assessed with the University of Pennsylvania Smell Identification Test (UPSIT) and the Wechsler Memory Scale-Third Edition. Linear mixed models, accounting for clustering within families and relevant covariates, were used to compare scores across groups and to examine associations between olfactory identification ability and the three verbal memory domains. RESULTS A group effect was apparent for all four measures, and relatives scored midway between patients and controls on all three memory domains. UPSIT scores were significantly correlated with all three forms of verbal memory. Age, verbal working memory, and auditory recognition delayed memory were independently predictive of UPSIT scores. CONCLUSIONS Impairments in olfactory identification and verbal memory appear to represent two correlated risk markers for schizophrenia, and frontal-temporal deficits likely account for both impairments.

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.