Scott Yale

The deficit syndrome in the DSM-IV Field Trial: I. Alcohol and other drug abuse

Drug abuse is common in schizophrenia. Previous studies suggested patients with the deficit syndrome have a lower risk of drug abuse than do patients without deficit features. We distinguished deficit and nondeficit groups in the DSM-IV Field Trial dataset, and compared the two groups relative to current and lifetime (worst ever) severity of alcohol, cannabis, and other drugs of abuse. Deficit syndrome patients had a lower severity of current use of alcohol and other drugs, but the two groups did not differ significantly relative to cannabis use. Deficit patients also had less severe lifetime use of all three classes of drugs. These findings could not be attributed to differences between the deficit and nondeficit groups in demographics, severity of psychotic symptoms, chronicity of illness, or the quality of information available for the two groups. Deficit categorization and drug abuse were independently associated with poor level of function. Negative symptoms broadly defined were weaker predictors of drug abuse than was the deficit/nondeficit categorization. These findings further support the validity of the deficit syndrome of schizophrenia. Within schizophrenia, groups with relatively high or low risk for substance abuse can be identified.

Anxiety and substance use comorbidity among inpatients with schizophrenia

OBJECTIVE To determine the association between lifetime anxiety symptoms and anxiety disorders and substance use disorders among patients with schizophrenia. METHOD Participants were 184 inpatients with schizophrenia at the Schizophrenia Research Unit (SRU) at the New York State Psychiatric Institute (NYSPI). Multivariate logistic regression analyses were used to determine the relationship between specific anxiety symptoms and anxiety disorders and substance use disorders among inpatients with schizophrenia. RESULTS Anxiety symptoms and anxiety disorders were prevalent among 31.5% of the sample. Panic attacks were associated with a significantly increased odds (OR=7.4 (1.2, 47.1)) of comorbid alcohol or substance use disorders (lifetime). This association was specific to panic attacks and persisted after adjusting for differences in sociodemographic characteristics and comorbid anxiety symptoms and anxiety disorders. CONCLUSIONS These findings are consistent with and extend previous data by providing evidence of an association between panic attacks and increased likelihood of substance use disorders among inpatients with schizophrenia. Future studies that determine the nature of this relationship, the sequence of symptom onsets, and examine whether treatment of anxiety can influence the onset or outcome associated with substance use are needed.

Odor Identification, Eye Tracking and Deficit Syndrome Schizophrenia

BACKGROUND Deficit syndrome (DS) schizophrenia patients have smooth pursuit eye movement (SPEM) dysfunction. We examined if they also had smell identification deficits, since social affiliation is related to olfaction in other mammals. METHODS Sixty-seven patients had DS assessments: 31 patients had SPEM and 50 had Smell Identification Test (SIT) assessments, and 14 patients had both measurements. RESULTS DS patients had worse SPEM and SIT performance than the non-DS patients. Areas under the receiver-operator characteristic (ROC) curves for SIT and SPEM were both fairly accurate in identifying the DS. The odds ratio (OR) for the DS for impaired versus normal SPEM was 6.21 (95% confidence interval [CI]: 1.21, 32.25) and for microsmia versus normosmia was 10.4 (95% CI: 1.23, 88.18). Further analyses showed that the association of SIT with both SPEM and the DS could account for the SPEM-DS association. CONCLUSIONS We found a strong association between the DS and SIT scores suggesting that the neural substrates of olfaction may be related to social affiliation in humans, as they are in other mammals. These data further support the notion that the DS defines a homogeneous subgroup of schizophrenia patients and further suggest that dysfunction in the neural circuitry of olfaction may contribute to its pathophysiology.

The deficit syndrome in the DSM-IV Field Trial. Part II. Depressive episodes and persecutory beliefs.

Patients with the deficit syndrome are remarkable for their decrease in interest in social relationships, suggesting they have an abnormality in those brain regions controlling social behavior and social cognition. To further assess social behavior and social cognition in this group of patients, we examined the relationships among three aspects of the psychopathology: suspiciousness; major depressive episodes; and the deficit syndrome. These features of psychopathology were examined in two clinical samples: stable outpatients from a research clinic (the MPRC sample), and patients in the DSM-IV Field Trial. In both samples, patients with history of a depressive episode had more severe suspiciousness than those without such a history; other psychotic symptoms were not associated with depressive episodes. In the MPRC sample, patients with the deficit syndrome exhibited less severe suspiciousness than nondeficit patients; in the Field Trial sample, this same comparison had a nonsignificant trend in the same direction. In the Field Trial sample, patients with the deficit syndrome also had less severe delusions with a predominantly social content than did nondeficit patients. These findings suggest suspiciousness is a risk factor for major depression in schizophrenia, and that the decreased interests in social relationships exhibited by deficit syndrome patients is reflected in the content of their delusions.

Olfactory identification and WAIS-R performance in deficit and nondeficit schizophrenia

INTRODUCTION An expanding database supports the notion that the deficit syndrome (DS) is a discrete condition within schizophrenia and recent data argues that Smell Identification Deficits (SID) may have a primary relationship with its pathophysiology. If so, then the relationship of University of Pennsylvania Smell Identification Test (UPSIT) scores with other neurocognitive measures in DS patients may point to the neural substrate of the deficit syndrome. METHOD We examined the relationship of UPSIT scores and Wechsler Adult Intelligence Scale-Revised (WAIS-R) performance in 46 DSM-IV schizophrenia patients. The Schedule for the Deficit Syndrome (SDS) interview was used to subgroup the sample into 13 DS and 33 nondeficit syndrome (NDS) patients. RESULTS DS and NDS groups had similar mean ages, age of onset, and GAF scores, but DS patients had fewer years of education. DS and NDS patients also did not differ in full scale, verbal or performance IQ or in any WAIS-R subtest. However, UPSIT scores were significantly worse in the DS patients, most of whom met criteria for a clinically meaningful olfactory impairment. In DS patients, UPSIT scores were significantly correlated with Performance IQ, Block Design, and Object Assembly, all of which are associated with complex visual-motor organizational function thought to be mediated by parietal circuitry. UPSIT scores in NDS patients were significantly related with Vocabulary, Similarities, and Digit Symbol subtests, which are indicative of verbal functioning. CONCLUSION These preliminary data support previous findings suggesting that in addition to frontal neuropsychological abnormalities, DS patients may have greater performance impairments on tasks associated with parietal functioning. Our findings furthermore suggest that the parietal circuitry may be a conspicuous substrate for impaired odor identification ability in these patients. The lesser abnormalities in UPSIT ability in NDS patients may be attributed to verbal ability. These data are preliminary and further investigations with larger samples are needed to support our findings.

Delusions in individuals with schizophrenia : Factor structure, clinical correlates, and putative neurobiology

Background: Delusions are a central feature of schizophrenia, yet our understanding of their neurobiology is limited. Attempt to link dimensions of psychopathology to putative neurobiological mechanisms depends on careful delineation of symptoms. Previous factor analytic studies of delusions in schizophrenia were limited by several methodological problems, including the use of patients medicated with antipsychotics, inclusion of nondelusion symptoms in the analyses, and/or inclusion of patients with psychotic disorders other than schizophrenia. These problems may have possibly biased the resulting factor structure and contributed to the inconclusive findings regarding the neurobiology of positive symptoms. Our goal is to examine the factor structure of delusions in antipsychotic-free individuals with diagnoses of schizophrenia/schizoaffective disorder. Sampling and Methods: We assessed 83 antipsychotic-free individuals with DSM-IV diagnoses of schizophrenia/schizoaffective disorder. A principal component analysis was conducted on the delusions symptoms of the SAPS. Results: The principal component analysis resulted in three distinct and interpretable factors explaining 58.3% of the variance. The Delusions of Influence factor was comprised by delusions of being controlled, thought withdrawal, thought broadcasting, thought insertion, and mind reading. The Self-Significance Delusions factor was comprised by delusions of grandeur, reference, religious, and delusions of guilt/sin. The Delusions of Persecution factor was comprised solely by persecutory delusions. The three factors displayed distinct associations with hallucinations, bizarre behavior, attention, positive formal thought disorder, and avolition/apathy. Conclusions: The results indicate that delusions are best described by three distinct subtypes. The authors propose a novel model linking the three delusion subtypes, attributions to self/other, and putative neurobiological mechanisms. Implications for future research are discussed, as well as links to cognitive-behavioral conceptualizations of delusions.

Psychobiological heterogeneity of familial and sporadic schizophrenia

BACKGROUND Although schizophrenia is presumed to be heterogeneous, there has been limited success distinguishing familial from sporadic cases. We used psychobiological measures to examine heterogeneity, as they may be closer to neurobiology than symptoms. Smooth pursuit eye movement quality (SPEM) and dichotic listening (DL) tests to tones and words were used to assess hemispheric laterality asymmetry. METHODS Forty-six research unit patients participated in assessments of family history (FH) and physiological measures. FH was categorized by three exclusive groups: FH-1 patients had a chronic schizophrenia-related psychosis in a first-degree relative, FH-2 had it in second-degree relative, and FH-3 had no family member with a reoccurrence. RESULTS Analysis of variance showed a significant group difference for SPEM and DL tones. SPEM was significantly worse in all three schizophrenia groups than for the normal comparison subjects. Among the schizophrenia groups, the nonfamilial group (FH-3) had the worst SPEM quality, FH-2 had intermediate quality, and FH-1 had the best quality. Conversely, only the nonfamilials (FH-3) had normal right hemispheric lateralization for tones, whereas familials did not, and FH-2 again had intermediate values. The lateralization quotient for DL words did not significantly differ among the groups. CONCLUSIONS SPEM was affected most in sporadic, not familial schizophrenia, whereas dichotic listening was most affected in familial schizophrenia. This double dissociation supports the utility of the familial/sporadic distinction and suggests that etiological factors in different forms of schizophrenia may impact principally on distinct neurobiological substrates, despite similar patient phenomenology.

Low heart rate variability is not caused by typical neuroleptics in schizophrenia patients.

Both elevated cardiovascular mortality and low cardio-vagal (parasympathetic) heart rate variability (HRV)--a risk factor for postmyocardial infarction--are reported in schizophrenia (SZ). Since a number of medications have strong effects of cardiac conductivity, we thought it important to examine if typical neuroleptic medications might also affect HRV. We examined cardiac vagal activity during both neuroleptic treatment and a drug-free condition in seven SZ patients who were participating in a pilot double-blind, crossover study of placebo and haloperidol treatment. Twenty-four-hour Holter electrocardiograms were analyzed for high frequency HRV, quantitated as the percent of successive normal interbeat intervals greater than 50 milliseconds (PNN50), which is a good index of parasympathetic cardiac modulation. The patients showed unchanged PNN50 (8.4+/-9.5 versus 8.3+/-10.5; t=.22, df=6, P=.5) between the haloperidol treatment and drug-free conditions. Despite the elapsed time, change in medication, and altered clinical state, the PNN50s were highly correlated (Spearman r=.98, P=.000). SAPS positive symptom scores declined with treatment from 12.8+/-6.5 to 8.5+/-3.5; paired t=3.26: df=6; P=.01. PNN50s were significantly associated with positive (r=-.86, df=6, P=.012) and negative symptom scores (r=-.87, df=6, P=.01). We found low cardiovagal modulation in medication-free SZ patients that was associated with core SZ symptoms and was unchanged by haloperidol and benztropine treatment. The reduced HRV in SZ patients at baseline may render them at greater cardiovascular risk than healthy subjects when treated with medications having strong cardiovascular effects.

Could Stress Cause Psychosis in Individuals Vulnerable to Schizophrenia

It has long been considered that psychosocial stress plays a role in the expression of symptoms in schizophrenia (SZ), as it interacts with latent neural vulnerability that stems from genetic liability and early environmental insult. Advances in the understanding of the neurobiology of the stress cascade in both animal and human studies lead to a plausible model by which this interaction may occur: through neurotoxic effects on the hippocampus that may involve synaptic remodeling. Of late, the neurodevelopmental model of SZ etiology has been favored. But an elaboration of this schema that credits the impact of postnatal events and considers a role for neurodegenerative changes may be more plausible, given the evidence for gene-environment interaction in SZ expression and progressive structural changes observed with magnetic resonance imaging. Furthermore, new insights into nongliotic neurotoxic effects such as apoptosis, failure of neurogenesis, and changes in circuitry lead to an expansion of the time frame in which environmental effects may mediate expression of SZ symptoms.

Odor identification impairments in schizophrenia: relationship with demographic measures, clinical variables, and diagnostic subtypes.

Smell identification deficits are consistently found in schizophrenia (SZ), but little is known about the nature and characterization of this deficit or its relationship to the phenomenology of the illness. This study aims to further delineate smell identification errors in SZ by examining the relationship of patient demographic differences with smell-identification performance. Our results showed that a patients gender and education were related to odor-identification scores, with better performance seen in female patients and in those with greater educational attainment. However, there was no effect related to age, ethnicity, or socioeconomic status on odor identification. A smell identification deficit was also unrelated to clinical characteristics of the patients, including age at first hospitalization, number of psychiatric hospitalizations, and duration of illness. Odor identification also did not differ by SZ subtype, nor between SZ and schizoaffective disorder patients. These findings emphasize that odor identification deficits in SZ are unrelated to clinical illness features, cannot be explained by other confounds related to olfaction in the general population, and may be core features related to the SZ disease process.