by
Stephanie Deighton;
Lisa Buchy;
Kristin S. Cadenhead;
Tyrone D. Cannon;
Barbara A. Cornblatt;
Thomas H. McGlashan;
Diana O. Perkins;
Larry J. Seidman;
Ming T. Tsuang;
Elaine Walker;
Scott W. Woods;
Carrie E. Bearden;
Daniel Mathalon;
Jean Addington
Background
Recent research suggests that a traumatic brain injury (TBI) can significantly increase the risk of later development of psychosis. However, it is unknown whether people at clinical high risk (CHR) of psychosis have experienced TBI at higher rates, compared to otherwise healthy individuals. This study evaluated the prevalence of mild TBI, whether it was related to past trauma and the relationship of mild TBI to later transition to psychosis.
Methods
Seven-hundred forty-seven CHR and 278 healthy controls (HC) were assessed on past history of mild TBI, age at first and last injury, severity of worst injury and number of injuries using the Traumatic Brain Injury Interview. Attenuated psychotic symptoms were assessed with the Scale of Psychosis-risk Symptoms. IQ was estimated using the Wechsler Abbreviated Scale of Intelligence and past trauma and bullying were recorded using the Childhood Trauma and Abuse Scale.
Results
CHR participants experienced a mild TBI more often than the HC group. CHR participants who had experienced a mild TBI reported greater total trauma and bullying scores than those who had not, and those who experienced a mild TBI and later made the transition to psychosis were significantly younger at the age at first and most recent injury than those who did not.
Conclusion
A history of mild TBI is more frequently observed in CHR individuals than in HC. Inclusion or study of CHR youth with more severe TBI may provide additional insights on the relationship between TBI and later transition to psychosis in CHR individuals.
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.
by
Scott W. Woods;
Barbara C. Walsh;
Jean Addington;
Kristin S. Cadenhead;
Tyrone D. Cannon;
Barbara A. Cornblatt;
Robert Heinssen;
Diana O. Perkins;
Larry J. Seidman;
Sarah I. Tarbox;
Ming T. Tsuang;
Elaine Walker;
Thomas H. McGlashan
Background: Longitudinal studies of the clinical high risk (CHR) syndrome for psychosis have emphasized the conversion vs non-conversion distinction and thus far have not focused intensively on classification among non-converters. The present study proposes a system for classifying CHR outcomes over time when using the Structured Interview for Psychosis-risk Syndromes and evaluates its validity. Method: The system for classifying CHR outcomes is referred to as "current status specifiers," with "current" meaning over the month prior to the present evaluation and "specifiers" indicating a set of labels and descriptions of the statuses. Specifiers for four current statuses are described: progression, persistence, partial remission, and full remission. Data from the North American Prodromal Longitudinal Study were employed to test convergent, discriminant, and predictive validity of the current status distinctions. Results: Validity analyses partly supported current status distinctions. Social and role functioning were more impaired in progressive and persistent than in remitted patients, suggesting a degree of convergent validity. Agreement between CHR current statuses and current statuses for a different diagnostic construct (DSM-IV Major Depression) was poor, suggesting discriminant validity. The proportion converting to psychosis within a year was significantly higher in cases meeting progression criteria than in those meeting persistence criteria and tended to be higher than in those meeting full remission criteria, consistent with a degree of predictive validity. Discussion: CHR syndrome current status specifiers could offer a potentially valid and useful description of current clinical status among non-converters. Study in additional samples is needed.
Objective: Individuals with both physical and mental health problems may have elevated levels of emergency department (ED) service utilization either for index conditions or for associated comorbidities. This study examines the use of ED services by Medicaid beneficiaries with comorbid diabetes and schizophrenia, a dyad with particularly high levels of clinical complexity.
Methods: Retrospective cohort analysis of claims data for Medicaid beneficiaries with both schizophrenia and diabetes from fourteen Southern states was compared with patients with diabetes only, schizophrenia only, and patients with any diagnosis other than schizophrenia and diabetes. Key outcome variables for individuals with comorbid schizophrenia and diabetes were ED visits for diabetes, mental health-related conditions, and other causes.
Results: Medicaid patients with comorbid diabetes and schizophrenia had an average number of 7.5 ED visits per year, compared to the sample Medicaid population with neither diabetes nor schizophrenia (1.9 ED visits per year), diabetes only (4.7 ED visits per year), and schizophrenia only (5.3 ED visits per year). Greater numbers of comorbidities (over and above diabetes and schizophrenia) were associated with substantial increases in diabetes-related, mental health-related and all-cause ED visits. Most ED visits in all patients, but especially in patients with more comorbidities, were for causes other than diabetes or mental health-related conditions.
Conclusion: Most ED utilization by individuals with diabetes and schizophrenia is for increasing numbers of comorbidities rather than the index conditions. Improving care in this population will require management of both index conditions as well as comorbid ones.
by
Scott W. Woods;
Jean Addington;
Carrie E. Bearden;
Kristin S. Cadenhead;
Tyrone D. Cannon;
Barbara A. Cornblatt;
Daniel H. Mathalon;
Diana O. Perkins;
Larry J. Seidman;
Ming T. Tsuang;
Elaine Walker;
Thomas H. McGlashan
Background: Antipsychotic medication use rates have generally been rising among youth with psychiatric disorders, but little is known about use rates of antipsychotics or other psychotropic medications in patients at high risk for psychosis.
Method: Baseline psychotropic medication use rates were compared in two research cohorts of patients at high risk for psychosis that enrolled between 1998-2005 (n. = 391) and 2008-2011 (n. = 346). Treatment durations and antipsychotic doses were described for cohort 2.
Results: Median age was 17. years in cohort 1 and 18. years in cohort 2. The rate of prescription of any psychotropic at baseline was roughly 40% for each cohort. Antipsychotic prescription rates were 24% among sites that permitted baseline antipsychotic use in cohort 1 and 18% in the cohort 2; the decline did not quite reach statistical significance (p. = 0.064). In cohort 2 the mean. ±. SD baseline chlorpromazine-equivalent dose was 121. ±. 108. mg/d, and lifetime duration of antipsychotic treatment was 3.8. ±. 5.9. months.
Discussion: Although the rate of antipsychotic prescription among high-risk youth may have fallen slightly, the nearly one-in-five rate in the second cohort still constitutes a significant exposure. Mitigating factors were that doses and durations of treatment were low. As for other nonpsychotic conditions, it is incumbent on our field to develop alternative treatments for high-risk patients and to generate additional evidence for or against the efficacy of antipsychotics to help define their appropriate role if alternative treatments fail.
Cigarette smokers with schizophrenia exhibit more severe cognitive dysfunction during smoking abstinence than control smokers, and cognitive deficits are associated with higher rates of smoking cessation failure (Dolan et al., 2004; Wing et al., 2012). The pro-cognitive effects of nicotine may result from enhanced dopamine (DA) release in the prefrontal cortex (PFC). Catechol-O-methyltransferase (COMT) is the primary enzyme responsible for DA metabolism in cortical brain regions. Allelic variation at a single nucleotide polymorphism (SNP) in the COMT gene at position 158 in the membrane-bound form (rs4680 or Val158met) strongly influences the level of COMT activity.
Objectives: Several studies suggest that adolescent marijuana use predicts earlier age at onset of schizophrenia, which is a crucial prognostic indicator. Yet, many investigations have not adequately established a clear temporal relationship between the use and onset. Methods: We enrolled 247 first-episode psychosis patients from six psychiatric units and collected data on lifetime marijuana/alcohol/tobacco use, and ages at onset of prodrome and psychosis in 210 of these patients. Cox regression (survival analysis) was employed to quantify hazard ratios (HRs) for effects of diverse premorbid use variables on psychosis onset. Results: Escalation of premorbid use in the 5 years prior to onset was highly predictive of an increased risk for onset (e.g., increasing from no use to daily use, HR = 3.6, p < 0.0005). Through the analysis of time-specific measures, we determined that daily use approximately doubled the rate of onset (HR = 2.2, p < 0.0005), even after controlling for simultaneous alcohol/tobacco use. Building on previous studies, we were able to determine that cumulative marijuana exposure was associated with an increased rate of onset of psychosis (= 0.007), independent of gender and family history, and this is possibly the reason for age at initiation of marijuana use also being associated with rate of onset in this cohort. Conclusions: These data provide evidence of a clear temporal relationship between escalations in use in the five years pre-onset and an increased rate of onset, demonstrate that the strength of the association is similar pre- and post-onset of prodromal symptoms, and determine that early adult use may be just as important as adolescent use in these associations.
by
Danijela Piskulic;
Lu Liu;
Kristin S. Cadenhead;
Tyrone D. Cannon;
Barbara A. Cornblatt;
Thomas H. McGlashan;
Diana O. Perkins;
Larry J. Seidman;
Ming T. Tsuang;
Elaine Walker;
Scott W. Woods;
Carrie E. Bearden;
Daniel H. Mathalon;
Jean Addington
Deficits in social cognition are well established in schizophrenia and have been observed prior to the illness onset. Compared to healthy controls (HCs), individuals at clinical high risk of psychosis (CHR) are said to show deficits in social cognition similar to those observed in patients experiencing a first episode of psychosis. These deficits have been observed in several domains of social cognition, such as theory of mind (ToM), emotion perception and social perception. In the current study, the stability of three domains of social cognition (ToM, social perception and facial emotion perception) was assessed over time along and their association with both clinical symptoms and the later development of psychosis. Six hundred and seventy-five CHR individuals and 264 HC participants completed four tests of social cognition at baseline. Of those, 160 CHR and 155 HC participants completed assessments at all three time points (baseline, 1 year and 2 years) as part of their participation in the North American Prodrome Longitudinal Study. The CHR group performed poorer on all tests of social cognition across all time points compared to HCs. Social cognition was not associated with attenuated positive symptoms at any time point in the study. CHR individuals who developed a psychotic disorder during the course of the study did not differ in social cognition compared to those who did not develop psychosis. This longitudinal study demonstrated mild to moderate, but persistent ToM and social perception impairments in those at CHR for psychosis compared to HCs.
by
Yoonho Chung;
Kristen M. Haut;
George He;
Theo G.M. van Erp;
Sarah McEwen;
Jean Addington;
Carrie E. Bearden;
Kristin Cadenhead;
Barbara Cornblatt;
Daniel H. Mathalon;
Thomas McGlashan;
Diana Perkins;
Larry J. Seidman;
Ming Tsuang;
Elaine Walker;
Scott W. Woods;
Tyrone D. Cannon
In a recent prospective longitudinal neuroimaging study, clinical high-risk (CHR) individuals who later developed full-blown psychosis showed an accelerated rate of gray matter thinning in superior and medial prefrontal cortex (PFC) and expansion of the ventricular system after applying a stringent correction for multiple comparisons. Although cortical and subcortical volume loss and enlarged ventricles are well characterized structural brain abnormalities among patients with schizophrenia, no prior study has evaluated whether these progressive changes of neuroanatomical indicators are linked in time prior to onset of psychosis. Therefore, we investigated the relationship between the changes in cortical gray matter thickness and ventricular volume using the longitudinal neuroimaging data from the North American Prodrome Longitudinal Study at the whole-brain level. The results showed that ventricular expansion is linked in time to progressive reduction of gray matter, rather than to structural changes in proximal subcortical regions, in a broadly distributed set of cortical regions among CHR youth, including superior, medial, lateral, and inferior PFC, superior temporal gyrus, and parietal cortices. In contrast, healthy controls did not show the same pattern of associations. The main findings were further replicated using a third assessment wave of MRI scans in a subset of study participants who were followed for an additional year. These findings suggest that the gray matter regions exhibiting aberrant rates of thinning in relation to psychosis risk are not limited to the PFC regions that survived the statistical threshold in our primary study, but also extend to other cortical regions previously implicated in schizophrenia.
Adolescents with 22q11.2 Deletion Syndrome (22q11.2DS) and Schizotypal Personality Disorder (SPD) are at increased risk for the development of psychosis based, respectively, on genetic or behavioral factors. Thus both groups would be expected to manifest heightened rates of the prodromal signs that typically precede psychosis. Although there are now standardized procedures for assessing prodromal symptoms, there has been little research on the manifestation of these symptoms in 22q11.2DS patients, and no studies of differences in prodromal symptom patterns between genetically and behaviorally defined at-risk groups.
In this study, demographically-matched groups of 23 SPD, 23 22q11.2DS, and 23 control participants were administered the Structured Interview for Prodromal Syndromes (SIPS). Both risk groups showed elevated positive, negative, disorganized, and general prodromal symptoms, as well as elevations on 10 of the same individual symptom items, relative to the control group. Approximately 60% of individuals in the 22q11.2DS group and 70% of individuals in the SPD group met symptom criteria for a prodromal psychosis syndrome. The 22q11.2DS group scored significantly higher than the SPD group on the “decreased ideational richness” item and showed a trend toward greater motor abnormalities.
The results suggest that these two high-risk groups are similar in prodromal symptom presentation, possibly as a result of overlapping causal mechanisms, and that standardized measures of prodromal syndromes like the SIPS can be used to identify 22q11.2DS patients at greatest risk for conversion to psychosis.