Emotion processing and theory of mind in schizophrenia patients and their unaffected first-degree relatives

Previous studies have suggested that social cognition is affected in individuals with schizophrenia. The purpose of this study was to explore to what extent social cognition deficits are shared by unaffected first-degree relatives, and the nature of the relationship between performance in different paradigms of social cognition. 20 Schizophrenia patients (7 females, 31 ± 10 years), 20 healthy age- and gender-matched individuals, 20 unaffected first-degree relatives of the schizophrenia patients (11 females, 50 ± 20 years), and 20 healthy individuals matched for age and gender were recruited. Patients showed deficits in the detection of social Faux Pas (0.80 ± 0.17 vs. controls: 0.94 ± 0.09, p = 0.025) and the correct identification of Theory of Mind stories (0.71 ± 0.13 vs. controls: 0.82 ± 0.12, p = 0.038). Relatives performed poorly in the Faces Test (0.83 ± 0.14 vs. controls: 0.9 ± 0.08, p = 0.048), the Reading the Mind in the Eyes Test (0.59 ± 0.17 vs. controls: 0.71 ± 0.14, p = 0.046) and the detection of social Faux Pas (0.8 ± 0.2 vs. controls: 0.93 ± 0.09, p = 0.024). Abnormalities were independent of age, years of education, and general cognitive performance in patients and their relatives. Performance in an Emotion Processing task (Faces Test) was correlated with performance in theory of mind tests in healthy individuals and relatives of patients with schizophrenia only. These results suggest that schizophrenia patients and their unaffected first-degree relatives display similar but nonidentical patterns of social cognition processing.     

No evidence for impaired 'theory of mind' in unaffected first-degree relatives of schizophrenia patients

OBJECTIVE: The aim of this study was to investigate the possibility that 'theory of mind' (ToM) impairments are associated with schizophrenia liability. METHOD: Forty healthy control subjects and 79 first-degree biological relatives of schizophrenia patients (32 siblings and 47 parents) received the Eyes Test, during which subjects are asked to choose the word best describes the mental state of a person whose eyes are depicted on a photograph. RESULTS: The affected relatives (n = 14) performed worse on the Eyes Test compared with the controls (P = 0.0001), whereas the unaffected relatives (n = 65) showed intact performances (P = 0.4). The Eyes Test values did not correlate with age and IQ. There was no significant difference between male and female participants. CONCLUSION: ToM deficits, as measured by the Eyes Test, are not associated with schizophrenia liability.     

Subtle deficits of cognitive theory of mind in unaffected first-degree relatives of schizophrenia patients

Alterations of theory of mind (ToM) and empathy were implicated in the formation of psychotic experiences, and deficits in psychosocial functioning of schizophrenia patients. Inspired by concepts of neurocognitive endophenotypes, the existence of a distinct, potentially neurobiologically based social-cognitive vulnerability marker for schizophrenia is a matter of ongoing debate. The fact that previous research on social-cognitive deficits in individuals at risk yielded contradictory results may partly be due to an insufficient differentiation between qualitative aspects of ToM. Thirty-four unaffected first-degree relatives of schizophrenia patients (21 parents, 8 siblings, 5 children; f/m: 30/4; mean age: 48.1 ± 12.7 years) and 34 controls subjects (f/m: 25/9; mean age: 45.9 ± 10.9 years) completed the ‘Movie for the Assessment of Social Cognition’—a video-based ToM test—and an empathy questionnaire (Interpersonal Reactivity Index, IRI). Outcome parameters comprised (1) ‘cognitive’ versus ‘emotional’ ToM, (2) error counts representing ‘undermentalizing’ versus ‘overmentalizing’, (3) empathic abilities and (4) non-social neurocognition. MANCOVA showed impairments in cognitive but not emotional ToM in the relatives’ group, when age, gender and neurocognition were controlled for. Relatives showed elevated error counts for ‘undermentalizing’ but not for ‘overmentalizing’. No alterations were detected in self-rated dimensions of empathy. Of all measures of ToM and empathy, only the IRI subscale ‘fantasy’ was associated with measures of psychotic risk, i.e. a history of subclinical delusional ideation. The present study confirmed subtle deficits in cognitive, but not emotional ToM in first-degree relatives of schizophrenia patients, which were not explained by global cognitive deficits. Findings corroborate the assumption of distinct social-cognitive abilities as an intermediate phenotype for schizophrenia.     

精神分裂症患者未患病一级亲属的认知功能研究

目的 探讨精神分裂症未患病的一级亲属认知功能的特点。方法 对110例精神分裂症患者未患病一级亲属（亲属组）及50例正常对照（对照组）进行认知功能测验,包括持续注意力测试（CPT）、威斯康星卡片分类测试（WCST）、修订版韦氏记忆量表（WMS-RC）的逻辑记忆和词语流畅性测试。结果 精神分裂症患者一级亲属在WMS-RC逻辑记忆中的即刻逻辑记忆、延迟逻辑记忆,词语流畅性测试中的词语总数、词语正确数,CPT中的视觉漏报、视觉平均反映时间1和2、听觉漏报数、听觉平均反应时间1和2的成绩均差于对照组（P〈0.05）。结论 精神分裂症未患病的一级亲属存在一定程度的认知功能损害,提示认知损害可能是精神分裂症的内表型指标之一。     

Tract-specific white matter microstructural alterations in subjects with schizophrenia and unaffected first-degree relatives

Brain Imaging and Behavior - White matter tracts alterations have been reported in schizophrenia (SZ), but whether such abnormalities are associated with the effects of the disorder itself and/or...     

Cognitive deficits in unaffected first-degree relatives of schizophrenia patients: a meta-analytic review of putative endophenotypes

Cognitive deficits may index genetic liability for schizophrenia and are candidate endophenotypes for the illness. In order to compare the degree of sensitivity among cognitive tasks to group differences between healthy relatives and controls and the influence of moderator variables, this review reports mean effect sizes for 43 cognitive test scores from 58 studies of cognitive performance in the unaffected adult relatives of schizophrenia patients. Results indicate reliable relative-control differences, in the small to medium effect size range, over a diverse array of tasks, with the largest effect sizes seen in complex versions of continuous performance tasks, auditory verbal learning, design copy tests, and category fluency. Three study design features were found to have significant effects on overall effect size magnitude: groups unmatched on education, groups unmatched on age, and asymmetric psychiatric exclusion criteria. After excluding studies with the latter 2 design features, reliable performance differences were still observed over a smaller subset of cognitive test variables, with the largest effect sizes seen in Trails B (d = 0.50) and performance measures from both simple (d = 0.56) and complex (d = 0.60-0.66) versions of continuous performance tasks. Four of the 6 largest effect sizes reflect tasks with high executive control demands in common, such as working memory demands, set shifting, and inhibition of prepotent responses. Cognitive deficits, particularly those tapping such executive control functions, should continue to prove valuable as endophenotypes of interest in the search for specific genetic factors related to schizophrenia.     

Unirhinal olfactory function in schizophrenia patients and first-degree relatives

Previous studies report birhinal impairments in odor identification in patients with schizophrenia and their family members. The authors employed unirhinal odor identification and detection threshold sensitivity tests in schizophrenia patients, healthy first-degree family members, and healthy comparison subjects. Patients and family members showed deficits in odor identification performance in both nostrils. Odor detection thresholds differed only between patients and healthy comparison subjects. Comparable odor identification deficits in both patients and healthy family members suggest that odor identification measures may serve as a sensitive endophenotypic vulnerability marker and that unirhinal olfactory measures are as precise, if not more so, than birhinal performance measures.     

Olfactory physiological impairment in first-degree relatives of schizophrenia patients

BACKGROUND: Efforts to characterize genetic vulnerability to schizophrenia are increasingly focused on the identification of endophenotypes--neurobiological abnormalities that are evident in individuals at risk. Behavioral studies have demonstrated olfactory impairments in odor detection and identification in unaffected 1st-degree relatives of schizophrenia patients, suggesting that abnormalities in this simple sensory system may serve as candidate endophenotypes. It is unclear, however, whether these behavioral abnormalities reflect basic olfactory sensory processing deficits or nonspecific disruptions of attention and cognition. METHOD: Unirhinal chemosensory olfactory evoked potentials were acquired from 14 unaffected 1st-degree relatives of schizophrenia patients and 20 healthy individuals with equivalent age and gender distributions, using 3 different concentrations of hydrogen sulfide. Subjects were also assessed behaviorally for ability to detect and identify odors. RESULTS: Family members exhibited left nostril olfactory detection impairments and bilateral olfactory identification abnormalities. They had reduced evoked potential response amplitudes for the initial N1 component in the left nostril. The subsequent P2 evoked potential response was reduced bilaterally. The pattern and magnitude of family member deficits were comparable to those previously observed for schizophrenia patients. CONCLUSION: 1st-degree relatives of schizophrenia patients exhibit specific neurophysiological impairments in early olfactory sensory processing. The presence of these neurophysiological abnormalities in both schizophrenia patients and their unaffected 1st-degree relatives suggests that these represent genetically mediated vulnerability markers or endophenotypes of the illness.     

Neurological soft signs and neurocognitive deficits in remitted patients with schizophrenia,their first-degree unaffected relatives,and healthy controls

European Archives of Psychiatry and Clinical Neuroscience - Neurological soft signs (NSS) and neurocognitive deficits (ND) are highly prevalent in schizophrenia, and have been separately proposed...     

Gastric dysmotility in healthy first-degree relatives of patients with schizophrenia

Gastric dysmotility has been reported in patients suffering from major depression or schizophrenia. An increased sympathetic activity modulating the gastric pacemaker located in the antrum of the stomach has been suggested as the underlying pathology. Similar to patients suffering from schizophrenia, their first-degree relatives showed alterations in cardiac autonomic modulation. Here we aimed to investigate gastric myoelectrical activity in healthy relatives of patients suffering from paranoid schizophrenia.     

Cerebral phosphate metabolism in first-degree relatives of patients with schizophrenia

OBJECTIVE: Most phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS) studies have described measures of lower membrane anabolism or greater catabolism in the frontal lobes of patients with schizophrenia. The purpose of the present study was to evaluate whether these findings can also be detected in young subjects at genetic risk for schizophrenia. METHOD: Fourteen children and siblings of patients with schizophrenia (mean age=16.7 years) and 14 comparison subjects (mean age=16.9 years) were included in a (31)P-MRS study of the frontal lobe. RESULTS: The high-risk subjects had significantly lower mean ratios of phosphomonoesters to phosphodiesters (0.25 versus 0.31) and higher mean phosphodiester values (37.59% versus 34.87%) than comparison subjects. CONCLUSIONS: These findings suggest greater phospholipid breakdown even in young first-degree relatives of patients with schizophrenia. This suggestion is discussed with respect to the membrane phospholipid hypothesis of schizophrenia.     

Recognition memory for faces in schizophrenia patients and their first-degree relatives

It has consistently been shown that schizophrenia patients are impaired in recognition memory for faces. However, studies have not examined the specificity of this deficit relative to other cognitive functions nor the relationship between this deficit and particular schizophrenia symptoms. In addition, no studies have examined recognition memory for faces in unaffected biological relatives of schizophrenia patients who likely share some of the genetic diathesis for this disorder without presenting the potential confounds of mentally ill study samples. The Faces subtests from the Wechsler Memory Scale—Third Edition were used to evaluate recognition memory for faces in 39 schizophrenia patients, 33 of their first-degree relatives and 56 normal controls. Both schizophrenia patients and their relatives were impaired, relative to control participants, in recognition memory for faces after partialing out group differences in spatial attention or verbal memory. Further, recognition memory for faces was associated with positive symptoms in the schizophrenia group and schizotypal personality traits in the relative group. These findings may have important implications for reducing etiological heterogeneity among schizophrenia populations, identifying disorder susceptibility among their relatives and furthering understanding of disorder etiology.     

Facial emotion recognition in euthymic patients with bipolar disorder and their unaffected first-degree relatives

BackgroundFacial emotion recognition (FER) is an important task associated with social cognition because facial expression is a significant source of non-verbal information that guides interpersonal relationships. Increasing evidence suggests that bipolar disorder (BD) patients present deficits in FER and these deficits may be present in individuals at high genetic risk for BD. The aim of this study was to evaluate the occurrence of FER deficits in euthymic BD patients, their first-degree relatives, and healthy controls (HC) and to consider if these deficits might be regarded as an endophenotype candidate for BD.MethodsWe studied 23 patients with DSM-IV BD type I, 22 first-degree relatives of these patients, and 27 HC. We used the Penn Emotion Recognition Tests to evaluate tasks of FER, emotion discrimination, and emotional acuity. Patients were recruited from outpatient facilities at the Institute of Psychiatry of the University of Sao Paulo Medical School, or from the community through media advertisements, had to be euthymic, with age above 18 years old and a diagnosis of DSM-IV BD type I.ResultsEuthymic BD patients presented significantly fewer correct responses for fear, and significantly increased time to response to recognize happy faces when compared with HC, but not when compared with first-degree relatives. First-degree relatives did not significantly differ from HC on any of the emotion recognition tasks.ConclusionOur results suggest that deficits in FER are present in euthymic patients, but not in subjects at high genetic risk for BD. Thus, we have not found evidence to consider FER as an endophenotype candidate for BD.     

Attentional deficits in patients with schizophrenia and in their non-psychotic first-degree relatives

The aim of this study was to investigate whether non-psychotic relatives of schizophrenic probands have deficits in sustained attention as measured by the Continuous Performance Test, Identical Pairs version (CPT-IP) and whether such deficits are associated with negative schizotypal personality disorders. The study subjects were 23 schizophrenic probands, 45 of their first-degree relatives and 36 normal controls. For each subject, attention was assessed during five conditions (2 standard, 2 slow, 1 easy) of visual stimuli (numbers and shapes). Schizotypy status was determined with the physical anhedonia and social anhedonia scales of Chapman et al. (Chapman, L.J., Chapman, J.P., Raulin, M.L., 1976. Scales for physical and social anhedonia. Journal of Abnormal Psychology 42, 374-382). The CPT-IP sensitive index d' in the standard shape condition was significantly lower in schizophrenics and in their relatives than in controls. For all d' values, the percentage of impaired first-degree relatives was at an intermediate level between patients and control individuals. Furthermore, the schizophrenic probands made more random errors in the standard and in the slow number conditions than the other two groups. None of the schizotypy measures correlated with the CPT-IP deficits. These results suggest that spatial sustained attention deficit may be a vulnerability marker for schizophrenia; however, this deficit and the negative dimension of schizotypal personality disorders may be distinct traits.     

Neuromuscular and psychomotor abnormalities in patients with schizophrenia and their first-degree relatives

In previous studies of schizophrenic patients, neuromuscular (histopathological and electrophysiological) and psychomotor (finger tapping) abnormalities were found. The present study was designed to investigate relationships between these abnormalities and a family history of psychosis in 14 schizophrenic patients and 25 unaffected first-degree relatives compared to 14 healthy controls. Muscle biopsies were performed in either m. tibialis anterior or m. lateralis. Macro EMG recordings were made from m. tibialis anterior. A finger tapping test was used to investigate psychomotor performance. Neuromuscular abnormalities (muscle biopsies and/or macro EMG) and/or aberrant psychomotor performance (finger tapping test) were found in 13 (93%) patients, 14 (56%) first-degree relatives and in three (21%) controls. A statistically significant relationship for the psychomotor, but not neuromuscular changes to a family history of psychosis was found using a logistic regression method. The percentage of patients, relatives and healthy controls exhibiting were 36/40/7% in the muscle biopsy, 50/20/0% in the macro EMG, and 71/82/14% in the finger tapping investigations. A higher frequency of neuromuscular and psychomotor abnormalities was found in patients with schizophrenia and their first-degree relatives compared to healthy controls. The relationship between psychomotor findings and a family history of psychosis indicate that central aspects of motor aberrations are associated with a hereditary disposition of psychosis. The neuromuscular as well as psychomotor changes indicate that schizophrenia may be a systemic disease involving the central nervous system as well as peripheral organs. An altered cell membrane is suggested to be an underlying factor based on the type of neuromuscular findings.     

Striatal dysfunction in schizophrenia and unaffected relatives.

BACKGROUND: Schizophrenia has been frequently associated with impaired inhibitory control. Such control is known to involve the striatum. Here, we investigate whether impaired inhibitory control is associated with abnormal striatal activation in schizophrenia. First-degree relatives of patients were also tested to examine whether striatal abnormality is associated with schizophrenia, or with the risk for the illness. METHODS: Both functional MRI and behavioral data were acquired during a task designed to invoke inhibitory control in 21 patients, 15 unaffected siblings, and 36 matched controls. Subjects must refrain from responding to designated stop cues occurring within a series of motor cues. Subjects could anticipate the occurrence of stop cues as the likelihood of these cues increased in a linear fashion throughout the task. RESULTS: Control subjects showed striatal activation while responding to motor cues. This activation increased in a linear fashion when the likelihood of having to inhibit the response was increased. Both patients siblings did not show anticipation-related increase in either striatal activation. However, only patients showed behavioral impairments. CONCLUSIONS: Striatal abnormalities occur in schizophrenia patients and unaffected siblings. Thus striatal abnormalities may be related to an increased (genetic) risk to develop schizophrenia.     

Low olfactory bulb volume in first-degree relatives of patients with schizophrenia

OBJECTIVE: There is a substantial genetic contribution to schizophrenia but no way to readily identify individuals at risk. Biological abnormalities reflecting greater genetic vulnerability may be discovered by examining healthy family members of patients with schizophrenia. There is evidence that olfactory impairments are common in patients. The authors previously reported that patients have abnormal olfactory bulbs, assessed by magnetic resonance imaging (MRI). This study examined olfactory bulbs in patients' relatives to determine whether low bulb volume represents an endophenotypic marker of genetic vulnerability. METHOD: Olfactory psychophysical measures and MRI scans of olfactory bulbs were acquired from 19 healthy first-degree relatives, 20 healthy comparison subjects with similar age and gender distributions, and the 11 patient probands of these relatives. Olfactory bulb volumes were measured by using a reliable region-of-interest procedure. RESULTS: The patients had impaired ability to detect odors and had lower olfactory bulb volumes than the comparison subjects. Although the family members had normal olfactory ability, they exhibited low right bulb volume. The patients had smaller left, but not right, olfactory bulbs than their own healthy relatives. CONCLUSIONS: The findings in family members suggest that structural abnormalities of the olfactory system in schizophrenia may partly reflect preexisting genetic vulnerability to illness. Preliminary analyses suggest that right olfactory bulb volume may serve as an endophenotypic marker of genetic vulnerability, while left bulb volume may reflect overt disease among individuals who share genetic vulnerability. Bulb abnormalities in patients are consistent with reports of cellular abnormalities affecting peripheral olfactory receptor neurons.     

Impaired cognitive flexibility and motor inhibition in unaffected first-degree relatives of patients with obsessive-compulsive disorder

OBJECTIVE: Obsessive-compulsive disorder (OCD) is highly heritable. Attempts to delineate precise genetic contributions have met with limited success. There is an ongoing search for intermediate cognitive brain markers (endophenotypes) that may help clarify genetic contributions. The aim was to assess inhibitory control processes in unaffected first-degree relatives of OCD patients for the first time with objective tests. METHOD: The Intradimensional/Extradimensional Shift, Stop-Signal, and Cambridge Gamble tasks were administered to 20 unaffected first-degree relatives, 20 OCD patient probands with washing/checking symptoms, and 20 healthy matched comparison subjects without a family history of OCD. RESULTS: Unaffected first-degree relatives and OCD patient probands showed cognitive inflexibility (extradimensional set shifting) and motor impulsivity (stop-signal reaction times). Decision making (Cambridge Gamble task) was intact. CONCLUSIONS: Deficits in cognitive flexibility and motor inhibition may represent cognitive endophenotypes for OCD. Such measures will play a key role in understanding genotype/phenotype associations for OCD and related spectrum conditions.