Daniel Antonius

Avolition and expressive deficits capture negative symptom phenomenology: Implications for DSM-5 and schizophrenia research

The DSM-5 formulation presents an opportunity to refine the negative symptom assessments that are crucial for a schizophrenia diagnosis. This review traces the history of negative symptom constructs in neuropsychiatry from their earliest conceptualizations in the 19th century. It presents the relevant literature for distinguishing between different types of negative symptoms. Although a National Institute of Mental Health consensus initiative proposed that there are five separate negative symptom domains, our review of the individual items demonstrates no more than three negative symptom domains. Indeed, numerous factor analyses of separate negative symptom scales routinely identify only two domains: 1) expressive deficits, which include affective, linguistic and paralinguistic expressions, and 2) avolition for daily life and social activities. We propose that a focus on expressive deficits and avolition will be of optimum utility for diagnosis, treatment-considerations, and research purposes compared to other negative symptom constructs. We recommend that these two domains should be assessed as separate dimensions in the DSM-5 criteria.

In support of Bleuler: Objective evidence for increased affective ambivalence in schizophrenia based upon evocative testing

BACKGROUND Ambivalence and anhedonia have long been identified as schizophrenic symptoms. However, ambivalence has rarely been studied, and in most evocative studies, schizophrenia participants are not anhedonic. Affective neurosciences posit two evaluative systems (one for Positivity and one for Negativity), the coactivation of which produces ambivalence, and point to two asymmetries in affective processing: Positivity Offset (which measures our capacity to explore the environment) and Negativity Bias (a measure of reactivity to intense threat). These characteristics have not received much attention in schizophrenia research. METHODS Sixty-four individuals with schizophrenia and 32 non-patient control participants completed an evocative emotional task with pictures, sounds and words of various valences and intensities. Following each presentation, participants rated the level of pleasantness, unpleasantness, and arousal elicited by the stimulus. Finally, participants completed questionnaires on anhedonia, and practical life skills were assessed. RESULTS Schizophrenia participants showed higher levels of ambivalence, greater arousal, greater Positivity Offset, and non-significantly different hedonic capacities and Negativity Bias. Ambivalence to positive stimuli significantly correlated with duration of illness, current level of psychopathology, anhedonia questionnaires and practical life skills. Schizophrenia patients with negative symptoms did not differ from patients without negative symptoms on computer tasks. CONCLUSIONS Ambivalence is greater in schizophrenia, and can be understood as a de-differentiation of the activation of the two evaluative systems. Ambivalence to positive stimuli, which may reflect early-stage affective processing is associated with impairments in higher-level emotional processes and in everyday functioning. Future studies should clarify the status of anhedonia in schizophrenia.

White Matter Integrity and Lack of Insight in Schizophrenia and Schizoaffective Disorder

OBJECTIVE Poor insight into illness is commonly associated with schizophrenia and has implications for the clinical outcome of the disease. A better understanding of the neurobiology of these insight deficits may help the development of new treatments targeting insight. Despite the importance of this issue, the neural correlates of insight deficits in schizophrenia remain poorly understood. METHOD Thirty-six individuals diagnosed with schizophrenia or schizoaffective disorder underwent diffusion tensor imaging (DTI). The subjects were assessed on two dimensions of insight (symptom awareness and attribution of symptoms) using the Scale to Assess Unawareness of Mental Disorder (SUMD). Level of psychosis was assessed with the Positive and Negative Syndrome Scale (PANSS). RESULTS White matter abnormalities in the right superior frontal gyrus, left middle frontal gyrus, bilateral parahippocampal gyrus, adjacent to the right caudate head, right thalamus, left insula, left lentiform nucleus, left fusiform gyrus, bilateral posterior cingulate, left anterior cingulate, right cingulate gyrus, left lingual gyrus, and bilateral claustrum were associated with symptom unawareness. Misattribution of symptoms was related to deficits in the white matter adjacent to the right lentiform nucleus, left middle temporal gyrus, and the right precuneus. CONCLUSIONS Impaired insight in schizophrenia implicates a complex neural circuitry: white matter deficits in fronto-temporo brain regions are linked to symptom unawareness; compromised temporal and parietal white matter regions are involved in the misattribution of symptoms. These findings suggest the multidimensional construct of insight has multiple neural determinants.

Cortical thinning, functional connectivity, and mood-related impulsivity in schizophrenia: relationship to aggressive attitudes and behavior.

OBJECTIVE Aggression in schizophrenia is a major societal issue, leading to physical harm, stigmatization, patient distress, and higher health care costs. Impulsivity is associated with aggression in schizophrenia, but it is multidetermined. The subconstruct of urgency is likely to play an important role in this aggression, with positive urgency referring to rash action in the context of positive emotion, and negative urgency referring to rash action in the context of negative emotion. METHOD The authors examined urgency and its neural correlates in 33 patients with schizophrenia or schizoaffective disorder and 31 healthy comparison subjects. Urgency was measured using the Urgency, Premeditation, Perseverance, and Sensation-Seeking scale. Aggressive attitudes were measured using the Buss-Perry Aggression Questionnaire. RESULTS Positive urgency, negative urgency, and aggressive attitudes were significantly and selectively elevated in schizophrenia patients (Cohens d values, 1.21-1.50). Positive and negative urgency significantly correlated with the Aggression Questionnaire total score (r>0.48 in all cases) and each uniquely accounted for a significant portion of the variance in aggression over and above the effect of group. Urgency scores correlated with reduced cortical thickness in ventral prefrontal regions including the right frontal pole, the medial and lateral orbitofrontal gyrus and inferior frontal gyri, and the rostral anterior cingulate cortex. In patients, reduced resting-state functional connectivity in some of these regions was associated with higher urgency. CONCLUSIONS These findings highlight the key role of urgency in aggressive attitudes in people with schizophrenia and suggest neural substrates of these behaviors. The results also suggest behavioral and neural targets for interventions to remediate urgency and aggression.

Neuroimaging correlates of aggression in schizophrenia: an update.

Purpose of review Aggression in schizophrenia is associated with poor treatment outcomes, hospital admissions, and stigmatization of patients. As such it represents an important public health issue. This article reviews recent neuroimaging studies of aggression in schizophrenia, focusing on PET/single photon emission computed tomography and MRI methods. Recent findings The neuroimaging literature on aggression in schizophrenia is in a period of development. This is attributable in part to the heterogeneous nature and basis of that aggression. Radiological methods have consistently shown reduced activity in frontal and temporal regions. MRI brain volumetric studies have been less consistent, with some studies finding increased volumes of inferior frontal structures, and others finding reduced volumes in aggressive individuals with schizophrenia. Functional MRI studies have also had inconsistent results, with most finding reduced activity in inferior frontal and temporal regions, but some also finding increased activity in other regions. Some studies have made a distinction between types of aggression in schizophrenia in the context of antisocial traits, and this appears to be useful in understanding the neuroimaging literature. Summary Frontal and temporal abnormalities appear to be a consistent feature of aggression in schizophrenia, but their precise nature likely differs because of the heterogeneous nature of that behavior.

Low Vitamin D levels predict clinical features of schizophrenia

Vitamin D plays crucial roles in neuroprotection and neurodevelopment, and low levels are commonly associated with schizophrenia. We considered if the association was spurious or causal by examining the association of Vitamin D with Leukocyte Telomere Length (LTL), a marker of cellular aging. Vitamin D levels in 22 well-characterized schizophrenia cases were examined with respect to symptoms, cognition, and functioning. LTL was assessed using quantitative polymerase chain reaction (qPCR). The results showed that 91% (20) had deficient or insufficient Vitamin D levels, which were associated with excitement and grandiosity, social anhedonia, and poverty of speech. Sex-specific analyses showed strong associations of hypovitamintosis D to negative symptoms and decreased premorbid adjustment in males, and to lesser hallucinations and emotional withdrawal, but increased anti-social aggression in females. In females LTL was furthermore associated with Vitamin D levels. This study demonstrates a relationship of low vitamin D levels with increased cellular aging in females. It is also the first study to demonstrate potential sex-specific profiles among schizophrenia cases with hypovitaminosis.

Psychiatric Assessment of Aggressive Patients: A Violent Attack on a Resident

Aggressive patients often target psychiatrists and psychiatric residents, yet most clinicians are insufficiently trained in violence risk assessment and management. Consequently, many clinicians are reluctant to diagnose and treat aggressive and assaultive features in psychiatric patients and instead focus attention on other axis I mental disorders with proven pharmacological treatment in the hope that this approach will reduce the aggressive behavior. Unclear or nonexistent reporting policies or feelings of self-blame may impede clinicians from reporting assaults, thus limiting our knowledge of the impact of, and best response to, aggression in psychiatric patients. The authors pre-sent the case of a young adult inpatient with a long history of antisocial and assaultive behavior who struck and injured a psychiatric resident. With this case in mind, the authors discuss the diagnostic complexities related to violent patients, the importance of assessing violence risk when initially evaluating a patient, and the relevance of risk assessment for treatment considerations and future management. This report illustrates common deficiencies in the prevention of violence on inpatient psychiatric units and in the reporting and response to an assault, and has implications for residency and clinician training.

Olfactory processing, sex effects and heterogeneity in schizophrenia

INTRODUCTION Smell identification deficits are associated with negative symptoms in schizophrenia, particularly in males. Far less information is known about the relationship of odor detection sensitivity (acuity) and negative symptoms in schizophrenia, and currently there is a dearth in sex-stratified research specifically examining odor sensitivity and smell identification. METHODS Fifty-eight individuals with schizophrenia and 42 healthy comparison subjects were assessed on tests of odor sensitivity, smell identification and cognition. Negative symptoms were assessed with the Positive and Negative Syndrome Scale and the Schedule for the Deficit Syndrome. RESULTS In healthy males, increased odor detection sensitivity predicted better smell identification scores. In contrast, male schizophrenia patients showed a significant inverse relationship, in which increased odor sensitivity predicted lower smell identification scores. Odor sensitivity and smell identification were unrelated in both schizophrenia and healthy females. Olfactory processing was strongly linked to negative symptoms, but the relationships differed by sex. Emotional expression deficits were related to odor detection hypersensitivity in female patients, whereas smell identification deficits predicted these emotional deficits in male cases. CONCLUSION Sex differences in olfactory functioning were identified in healthy subjects and in schizophrenia patients. Smell identification was related to negative symptoms in males with schizophrenia, whereas odor detection sensitivity predicted these features in females. Sex differences should be considered in future analyses that employ odor stimuli for neuropsychiatric research.

A new rating scale for negative symptoms: The Motor-Affective-Social Scale

The commonly used rating scales for negative symptoms in schizophrenia have shown good reliability, but disagreement persists regarding both the content definition and the validity of several items. Instead, authors have recommended rating the specific behaviors that are defined as negative symptoms. To surmount these shortcomings, we developed a new rating scale for negative symptoms: the Motor-Affective-Social Scale (MASS). During a 5-minute structured interview, hand coverbal gestures, spontaneous smiles, voluntary smiling, and questions asked by the interviewer were counted and rated on 101 inpatients with a diagnosis of schizophrenia or schizoaffective disorder. Information on social behavior was obtained from nursing staff. The scale consisted of a total of eight items. The MASS showed high internal consistency (Cronbach alpha coefficient=0.81), inter-rater reliability, and test-retest reliability (intra-class correlation coefficient=0.81). Convergent validity analyses showed high correlations between MASS scores and scores on the Scale for the Assessment of Negative Symptom (SANS), and the negative symptoms subscale of the Positive and Negative Syndrome Scale (PANSS). The MASS showed excellent psychometric properties, practicality, and subject tolerability. Future research that includes the use of the MASS with other patient populations and that investigates the scales sensitivity during clinical trials should be performed.

A psychometric evaluation of the Personality Assessment Inventory - short form clinical scales in an inpatient psychiatric sample.

Few studies have assessed the psychometric properties of the Personality Assessment Inventory short-form (PAI-SF) clinical scales, and none have conducted these evaluations using participants from psychiatric inpatient units. The present study evaluated item-level tests of scaling assumptions of the PAI-SF using a large (N=503) clinical sample of participants who completed the PAI during their admission to a psychiatric inpatient unit. Internal consistency reliability was high across scales, and tests of item-scale convergence and discrimination generally confirmed hypothesized item groupings. Scale-level correlations supported unique variance being measured by each scale. Finally, agreement between the PAI short- and full-form scales was found to be high. The results are discussed with regards to scale interpretation.