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.

Emotion antecedents in schizophrenia.

Emotion antecedents are defined as external or internal events that cause emotions in individuals. Their study brings us insight into individuals' emotion processing. Emotion antecedents have rarely been studied in schizophrenia. Thirty individuals with schizophrenia and 30 non-patient comparison subjects, matched by gender and age, related events when they felt extremely angry, disgusted, fearful, happy, sad and surprised. Each antecedent was summarized in a written sentence and 20 judges matched the antecedent with the correct emotion. The antecedents of individuals with schizophrenia were less frequently matched with their emotion than the antecedents of non-patient comparison subjects for all emotions. Moreover, error pattern analyses revealed distinct deficits for the emotion "fear". In the schizophrenia group, fear antecedents were more frequently judged as non-emotional, and non-fear antecedents were more often judged as fear antecedents when compared to the control group. A deficit in fear processing correlated with the Suspiciousness item on the Brief Psychiatric Rating Scale. Our results indicate differences in emotion processing in schizophrenia. Error pattern results are consistent with impairment in the appraisal of fear. Lower accuracy rates with schizophrenia subjects' antecedents may reflect lower emotion awareness for all emotions in schizophrenia. This study furthers the understanding of deficits in basic emotion processing in schizophrenia.

Loss aversion in schizophrenia.

BACKGROUND: Loss aversion in decision-making refers to a higher sensitivity to losses than to gains. Loss aversion is conceived as an affective interference in cognitive processes such as judgment and decision-making. Loss aversion in non-risky choices has not been studied in schizophrenia. METHOD: Forty-two individuals with schizophrenia and 42 non-patient control subjects, matched by gender and age, were randomized to two different scenarios (a buying scenario and a selling scenario). Subjects were asked to evaluate the price of a decorated mug. Schizophrenia subjects were re-tested four weeks later with the other scenario. RESULTS: Contrary to non-patient controls, schizophrenia subjects did not show loss aversion. In the schizophrenia group, absence of loss aversion was correlated with age, duration of illness, number of months in State hospitals, and poorer performance in the Wisconsin Card Sorting Test, but not with current psychopathology and two domains of emotional experience. CONCLUSIONS: Absence of loss aversion in schizophrenia represents a deficit in the processing of emotional information during decision-making. It can be interpreted as a lack of integration between the emotional and the cognitive systems, or to a more diffuse and de-differentiated impact of emotional information on decision-making. Future studies should bring more clarity to this question.

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 scale's sensitivity during clinical trials should be performed.

Suicidality in opioid-dependent subjects.

We determined suicide attempt characteristics in 160 opioid-dependent subjects. Three aspects of suicide vulnerability were also examined: familial aggregation of suicidal behaviors, degree of aggression/impulsivity, and smoking. Forty-eight percent of subjects had a personal history of suicide attempt. A personal history of suicide attempt was associated with an early onset of heroin use, but not with gender differences. A family history of suicide was a progressive risk factor for suicide attempt. Subjects with a personal history of suicide attempt had a higher degree of aggression/impulsivity and smoked more cigarettes. In conclusion, opioid-dependent subjects who attempt suicide show familial aggregation and clinical expressions of suicidal liability similar to those described in other psychiatric groups.

A review of emotion deficits in schizophrenia.

Emotion deficits in schizophrenia have been described since the time of Kraepelin. However, no comprehensive review of clinical emotion studies has ever been conducted. In this work, studies that used diagnostic criteria and were published in English were selected from an extensive PubMed search. Fifty-five studies on emotion expression repeatedly showed that individuals with schizophrenia (IWSs) display fewer overt expressions than nonpatient comparison subjects (NCSs) in verbal, facial, and acoustic channels. No clear differences were found between IWSs and depressed subjects. Sixty-nine studies examined emotion experience in schizophrenia. IWSs report higher anhedonia, and they tend to show more negative emotions in real-life event studies. In evocative studies, they report a similar degree of pleasantness and a similar or higher degree of unpleasantness. From 110 studies, it can be concluded that emotion recognition is impaired in schizophrenia in all channels. These deficits in social perception are correlated with neurocognitive deficits and some social skills. IWSs show dysfunction in the three domains of emotion expression, emotion experience, and emotion recognition, and these dysfunctions appear to be independent of each other across domains. These deficits in basic emotion processing may be linked to psychopathology and functional outcomes.

Loneliness in schizophrenia and its possible correlates. An exploratory study.

Social attachment is a biological and affective need. When this need is not met, people experience loneliness. Loneliness is associated with impaired social cognition, and is a risk factor for broad based morbidity across the adult lifespan even after controlling for multiple factors. However, little is known about loneliness in schizophrenia. Eighty-seven non-depressed individuals with schizophrenia or schizoaffective disorder (including 51 inpatients) and 58 control subjects completed the revised UCLA Loneliness scale. Social cognition was assessed with a self-report questionnaire and a performance-based task. Social trait perception was assessed with a facial task. Comorbid medical diagnoses were available for all inpatients. Patients reported greater loneliness levels than controls, while in- and out-patients did not significantly differ. In patients, loneliness was associated with self-report measures of social cognition. Patients' loneliness scores predicted a diagnosis of drug abuse/dependence, number of drugs used, hypertension and abnormal hemoglobin A1c levels. Patients experienced higher levels of loneliness than controls, independently of their objective social isolation. Loneliness did not rely on the same psychological processes in patients than in controls. Loneliness in schizophrenia is a symptom that deserves more scrutiny, particularly as it relates to the high prevalence of metabolic syndrome in this population.

What can the study of first impressions tell us about attitudinal ambivalence and paranoia in schizophrenia?

Although social cognition deficits have been associated with schizophrenia, social trait judgments - or first impressions - have rarely been studied. These first impressions, formed immediately after looking at a person's face, have significant social consequences. Eighty-one individuals with schizophrenia or schizoaffective disorder and 62 control subjects rated 30 neutral faces on 10 positive or negative traits: attractive, mean, trustworthy, intelligent, dominant, fun, sociable, aggressive, emotionally stable and weird. Compared to controls, patients gave higher ratings for positive traits as well as for negative traits. Patients also demonstrated more ambivalence in their ratings. Patients who were exhibiting paranoid symptoms assigned higher intensity ratings for positive social traits than non-paranoid patients. Social trait ratings were negatively correlated with everyday problem solving skills in patients. Although patients appeared to form impressions of others in a manner similar to controls, they tended to assign higher scores for both positive and negative traits. This may help explain the social deficits observed in schizophrenia: first impressions of higher degree are harder to correct, and ambivalent attitudes may impair the motivation to interact with others. Consistent with research on paranoia and self-esteem, actively-paranoid patients' positive social traits judgments were of higher intensity than non-paranoid patients'.

Facial expressiveness in patients with schizophrenia compared to depressed patients and nonpatient comparison subjects.

OBJECTIVE: Blunted affect is a major symptom in schizophrenia, and affective deficits clinically encompass deficits in expressiveness. Emotion research and ethological studies have shown that patients with schizophrenia are impaired in various modalities of expressiveness (posed and spontaneous emotion expressions, coverbal gestures, and smiles). Similar deficits have been described in depression, but comparative studies have brought mixed results. Our aim was to study and compare facial expressive behaviors related to affective deficits in patients with schizophrenia, depressed patients, and nonpatient comparison subjects. METHOD: Fifty-eight nondepressed inpatients with schizophrenia, 25 nonpsychotic inpatients with unipolar depression, and 25 nonpatient comparison subjects were asked to reproduce facial emotional expressions. Then the subjects were asked to speak about a specific emotion for 2 minutes. Each time, six cross-cultural emotions were tested. Facial emotional expressions were rated with the Facial Action Coding System. The number of facial coverbal gestures (facial expressions that are tied to speech) and the number of words were calculated. RESULTS: In relation to nonpatient comparison subjects, both patient groups were impaired for all expressive variables. Few differences were found between schizophrenia and depression: depressed subjects had less spontaneous expressions of other-than-happiness emotions, but overall, they appeared more expressive. Fifteen patients with schizophrenia were tested without and with typical or atypical antipsychotic medications: no differences could be found in study performance. CONCLUSIONS: The patients with schizophrenia and the patients with depression presented similar deficits in various expressive modalities: posed and spontaneous emotional expression, smiling, coverbal gestures, and verbal output.

Suicide attempts and family history of suicide in three psychiatric populations.

The influence of a family history of suicide on suicide attempt rate and characteristics in depression, schizophrenia, and opioid dependence was examined. One hundred sixty inpatients with unipolar depression, 160 inpatients with schizophrenia, and 160 opioid-dependent patients were interviewed. Overall, a family history of suicide was associated with a higher risk for suicide attempt, with high-lethality method, with repeated attempts, and with number of attempts, while the interaction between family history and diagnostic group was not significant. Thus, a positive family history of suicide was a risk factor for several suicide attempt characteristics independent of psychiatric diagnosis.

Implicit emotion perception in schizophrenia.

Explicit but not implicit facial emotion perception has been shown to be impaired in schizophrenia. In this study, we used newly developed technology in social neuroscience to examine implicit emotion processing. It has been shown that when people look at faces, they automatically infer social traits, and these trait judgments rely heavily on facial features and subtle emotion expressions even with neutral faces. Eighty-one individuals with schizophrenia or schizoaffective disorder and 62 control subjects completed a computer task with 30 well-characterized neutral faces. They rated each face on 10 trait judgments: attractive, mean, trustworthy, intelligent, dominant, fun, sociable, aggressive, emotionally stable and weird. The degree to which trait ratings were predicted by objectively-measured subtle emotion expressions served as a measure of implicit emotion processing. Explicit emotion recognition was also examined. Trait ratings were significantly predicted by subtle facial emotional expressions in controls and patients. However, impairment in the implicit emotion perception of fear, happiness, anger and surprise was found in patients. Moreover, these deficits were associated with poorer everyday problem-solving skills and were relatively independent of explicit emotion recognition. Implicit emotion processing is impaired in patients with schizophrenia or schizoaffective disorder. Deficits in implicit and explicit emotion perception independently contribute to the patients' poor daily life skills. More research is needed to fully understand the role of implicit and explicit processes in the functional deficits of patients, in order to develop targeted and useful remediation interventions.

A dimensional impulsive-aggressive phenotype is associated with the A218C polymorphism of the tryptophan hydroxylase gene: a pilot study in well-characterized impulsive inpatients.

Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the biosynthesis of serotonin, and association and linkage studies of its variants in suicidal and impulsive-aggressive behavior have brought conflicting results. This pilot study was designed to investigate whether TPH A218C genotypes could be associated with impulsive behavioral tendencies (IBTs) in consecutively admitted nonpsychotic nonorganic inpatients. Patients (20 females and 34 males; age, 38.8 +/- 11.8) did not differ from healthy nonimpulsive controls (16 females and 11 males; age, 35.2 +/- 10.2) regarding TPH genotypes, but in the patients, the number of IBT was related to the presence of the 218C allele. It was concluded that impulsive-aggressive behavior may be associated with the TPH genotype in well-characterized impulsive patients and that the present results stress the importance of considering impulsiveness-aggressiveness in studies investigating the relationship between suicidal behavior and TPH genotypes.

Serotonergic function and suicidal behavior in schizophrenia.

Recent studies suggest that altered serotonergic (5-HT) function, as assessed by lower prolactin (PRL) response to fenfluramine (FEN), a specific 5-HT releaser and uptake inhibitor, is associated with suicidal behavior in either depressed and personality disordered patients. The purpose of this study was to investigate, in schizophrenic patients, the relationship between suicidal behavior and PRL response to D-fenfluramine (D-FEN). A D-FEN test was performed in 18 healthy controls and 33 drug-free DSM-IV schizophrenic patients (12 with a history of suicide attempts, 21 without it). Schizophrenic patients with a history of suicide attempts showed a lower PRL response to D-FEN (Delta PRL) compared to schizophrenic patients without such history (P<0.04) and also compared to healthy controls (P<0.0003). Delta PRL did not differentiate schizophrenic patients without suicide attempts and controls. These findings could not be explained by PRL basal hormonal levels, age, sex, menstrual status, demographic or clinical characteristics. These results suggest that PRL response to D-FEN is a marker of suicidal tendencies also in schizophrenia, supporting the hypothesis that a dysfunction in serotonergic function is associated with suicidal behavior regardless of the psychiatric diagnosis.

Optimizing dosing in atypical neuroleptic monotherapy.

ATYPICAL NEUROLEPTICS HAVE BECOME THE FIRST LINE OF TREATMENT FOR PSYCHOTIC DISORDERS, BUT SOME QUESTIONS REMAIN: what are their optimal dosages and is more medication more efficacious? For clozapine, it is recommended to aim for a plasma level above 350 ng/mL for nonresponders and partial responders. It should be specified that this plasma level should be obtained exactly 12 h after the last dose. For risperidone, optimal daily doses range between 4 and 8 mg, and there is no indication that a higher dose would bring additional improvement. For olanzapine, a quite different situation is encountered. There is a good indication that daily doses of 30 and 40 mg can increase clinical response. It appears that plasma levels above 23 ng/mL may predict response. For quetiapine, reports on the utility of dosages greater than 800 mg/day are anecdotal at this point, and more studies should be conducted. For ziprasidone, dosages above 40 mg/day should be used, but daily doses above 200 mg have not yet been systematically investigated.

Immediate affective motivation is not impaired in schizophrenia.

BACKGROUND: Among the various cognitive and affective evaluations that contribute to decisions about whether to engage in a future activity, three affective evaluations are particularly relevant: 1) interest in the activity itself, 2) the pleasure anticipated from the activity and 3) the excitement experienced while looking forward to the activity. In addition to these pre-activity evaluations, affective evaluations that are done after the activity is completed impact people's motivation to repeat the same activity. Although extant research suggests that these affective processes may be impaired in schizophrenia, it is not clear whether these impairments are mostly secondary to cognitive deficits. METHOD: In three independent studies utilizing simple laboratory tasks with minimal cognitive demands, patients with schizophrenia or schizoaffective disorder and healthy control subjects evaluated their pleasure, interest, and excitement immediately before and after completing the tasks. RESULTS: Patients' anticipated pleasure and posttest evaluations of pleasure and interest were significantly greater than controls'. No group differences were found for excitement. In patients, there were significant negative correlations between anticipated pleasure, pretest excitement and depression scores, and between pretest interest and negative symptoms. CONCLUSIONS: In these experiments, immediate affective evaluations reported by participants with schizophrenia or schizoaffective disorder were greater or similar to controls'. This finding is consistent with recent affective research showing that experiences of pleasure are intact in schizophrenia. These results emphasize the need to disentangle affective from cognitive processes in order to better understand the complex impairments present in schizophrenia spectrum disorders.

Negative symptoms, past and present: a historical perspective and moving to DSM-5.

The diagnosis of schizophrenia includes "positive" and "negative" symptoms. These titles were developed to respectively reflect if the symptoms are additions to normal experiences, such as delusions and hallucinations, or if they refer to the absence or the loss of normal emotional function or behavior. This paper describes the history of the negative symptom concept, from its origins up to the considerations for the DSM-5, including the steps that produced the current conceptualizations. The DSM-5 only includes deficits in emotional expression and avolition as negative symptoms, which can be assessed from interview information. Factor analyses show they encompass most other negative symptom items. In addition to using these negative symptoms in a categorical manner to make a diagnosis, the DSM-5 has quantitative severity ratings of the negative symptoms, along with ratings of delusions, cognitive symptoms, motor symptoms, disorganization, depression and mania. With this approach, the different symptom domains, including negative symptoms, can be measured and tracked over time. Another change in the DSM-5 is the dropping of the schizophrenia subtypes that have been included in earlier volumes, as they were not useful in treatment decisions or prognosis. An intended outcome of these changes in DSM-5 is for clinicians to directly treat the individual psychopathological domains of the disorder for optimizing individual outcomes. Finally, this paper includes descriptions of the negative symptom items from over a dozen different scales.

Inpatients with schizophrenia report impaired situational motivation but intact global and social motivation.

It is well established that individuals with schizophrenia are less active and engaged than healthy control subjects, and motivation deficits are considered a core symptom of the disease. However, it remains unclear if schizophrenia individuals perceive themselves as less motivated than others, and there is a scarcity in research examining the relationship between perceived motivation, psychopathology and personality traits. Eighty-six inpatients with schizophrenia and 45 non-patient control participants completed the Motivation and Energy Inventory, which consists of Global Motivation, Social Motivation and Situational Motivation (the motivation individuals experience when they are engaging in an activity). Participants also completed personality questionnaires and an affective evocative task. Compared to controls, schizophrenia participants reported lower situational motivation, and comparable global and social motivation. Situational motivation was negatively predicted by negative temperament, affective ambivalence and depression level. Our results are consistent with the idea that schizophrenia individuals are not impaired in their motivational disposition but lack energy during the implementation of their goals. This may reflect impairment in the prediction, maintenance and/or modulation of required effort and energy during goal-directed actions, and is predicted by some affective processes. Improving situational motivation may be an effective therapeutic approach in people with schizophrenia.

Familiarity preference in schizophrenia is associated with ambivalent attitudes towards others.

OBJECTIVE: Preferences or attitudes towards others are often shaped through implicit memory processes, and they serve a critical function in our social lives. Preferences driven by implicit familiarity (mere exposure effect) are particularly important when making judgments about others and forming attitudes of liking and social interaction. In schizophrenia, little is known about the effect of familiarity preference on judgments and attitudes toward others. METHODS: Subjects included 79 patients with a diagnosis of schizophrenia or schizoaffective disorder and 61 non-patient control subjects. Familiarity preference and trait judgments about others were assessed using a computer task in which neutral faces were rated on positive and negative character traits. "Attractiveness" was rated twice at the beginning and at the end, to measure familiarity preference. Clinical ratings were also obtained. RESULTS: Patients and controls both demonstrated a positive familiarity preference effect. However, the groups differed on the predictive value of familiarity preference for trait judgments. In both groups, the presence of a familiarity preference effect predicted greater positive trait judgments. In patients only, the presence of a familiarity preference effect also predicted, although the correlation was less significant, greater negative trait judgments. CONCLUSION: The findings are consistent with a preserved familiarity preference effect in individuals with schizophrenia and that the effect is primarily associated with changes in positive attitudes. However, in individuals with schizophrenia this effect is also linked with inferences about negative traits, resulting in ambivalence towards others. This finding may contribute to the impaired social functioning of people with schizophrenia.

Behavioral validation of avolition in schizophrenia.

BACKGROUND: Since Kraepelin, avolition, a core symptom of schizophrenia, has been defined as a decrease in spontaneous, self-initiated and purposeful behaviors observed in daily life activities. However, the concurrent validity of commonly-used avolition measures has not been studied, and direct observation may offer a more objective way to measure avolition. METHOD: A direct observation measure of spontaneous and self-initiated behaviors that can be observed in an inpatient setting was defined with the use of time sampling method. This direct observation measure was used with fifty inpatients with schizophrenia. Additionally, patients were asked to rate their current interest in and their level of engagement in 10 active behaviors during the preceding 7 days. Clinicians rated the patients' engagement in the same activities for the preceding 7 days as well. RESULTS: The direct observation measure showed very good psychometric properties. Three clinical negative symptom scales showed moderate to high correlation with the direct measure. Concerning the retrospective ratings, patients' self-assessments were poorly correlated with clinicians' ratings, but showed high correlation with their subjective interests. CONCLUSIONS: Clinical rating scales of negative symptoms show moderate to good concurrent validity as measures of avolition in schizophrenia. However, patients' self-reports do not appear to provide valid indices of avolition. Our results favor clinical negative symptoms scales that use observers' reports only, over patients' self-reports. The direct observation of patients' behavior offers a precise and objective measure of avolition that may be useful in drug challenges and clinical trials.

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.