The pathophysiology of schizophrenia may be influenced by interaction of genetic, neurodevelopmental, environmental and/or psychological factors, which make it difficult to elucidate the etiology of the disorders through clinical phenomenology. Therefore, it needs to find out endophenotypes specific to schizophrenia before onset of clinical expressions. Recently, many researchers have been concerned about subjects at high risk for schizophrenia genetically or clinically using neuroimaging techniques. In this review, we summarized neuroimaging findings performed on subjects at high risk for schizophrenia. In genetic high risk subjects, fronto-temporal abnormalities were observed, while clinical high risk subjects showed frontal abnormalities, suggestive of susceptibility markers to schizophrenia.
Endophenotypes ; Neuroimaging ; Schizophrenia

OBJECTIVES: This study was conducted to investigate the possibility of neurological soft signs as an endophenotype for schizophrenia by examining neurological soft signs in patients, their unaffected siblings and normal comparison subjects. METHODS: The study sample consisted of 32 patients, 25 of their unaffected siblings and 30 normal comparison subjects. Neurological soft signs were evaluated using the Cambridge Neurological Inventory Part 2. soft sign assessment. RESULTS: The patients were significantly more impaired than normal comparison subjects (p = 0.047) on primitive reflex. The patients were significantly more impaired than siblings (p = 0.004) and normal comparison subjects (p = 0.021) on motor coordination. The siblings performed better on sensory integration than the patients (p = 0.020) and normal comparison subjects (p = 0.036). CONCLUSIONS: This study suggests that neurological soft signs might be a potential biomarker for schizophrenia, but might not be an endophenotype for schizophrenia.
Endophenotypes ; Humans ; Reflex ; Schizophrenia* ; Siblings*

OBJECTIVES : Theory of mind (ToM) is the ability to conceptualize other people's mental states in order to explain their behavior. This study compared the ToM ability of schizophrenia patients, their first-degree biological relatives, and healthy controls. METHODS : ToM animation test was administered to schizophrenia patients (N=28), their healthy first-degree relatives (N=26), and healthy controls (N=28). The Korean version of schizotypal personality questionnaire (SPQ) was used to assess the schizotypal personality trait of all three groups. RESULTS : Schizophrenia patients and their first-degree relatives showed decreased accuracy on ToM animation test compared to healthy controls [F(2,78)=29.75, p<.001]. Additionally, first-degree relatives performed worse than the control group and better than schizophrenia patients. First-degree relatives had similar SPQ scores compared to healthy controls but showed decreased ToM accuracy compared to healthy controls. CONCLUSION : ToM deficits in schizophrenia patients are apparent. The ToM deficit in first-degree relatives of schizophrenia patients raises the possibility that ToM deficit may be a endophenotype for schizophrenia pathology.
Endophenotypes ; Humans ; Surveys and Questionnaires ; Schizophrenia ; Theory of Mind

There is growing interest in the genetic analysis of schizophrenia using endophenotypes rather than clinical diagnosis or symptom dimensions. Endophenotypes could be alternative phenotypes for the clinical phenotypes. With their intermedicate and quantitative characteristics, endophenotypes could be functionally important links in the pathways between the genetic variation and clinical expression of the disorder. In this regard, the neurophysiological and neurocognitive endophenotypes used in the genetic analysis of schizophrenia have been reviewed.
Diagnosis ; Endophenotypes* ; Genetic Variation ; Genetics* ; Phenotype ; Schizophrenia*

OBJECTIVES: Neurological soft signs have been regarded as endophenotypes associated with the genetic basis of schizophrenia. This study was to investigate the intra-familial correlations of the neurological soft signs according to their genetic loading. METHODS: Schizophrenic patients(N=14) were included, who had one parent with a family history of schizophrenia and the other without it. Genetic loading was determined by the patient's family history of schizophrenia using the Family Interview for Genetic Studies(FIGS). These parents were subdivided into two groups. The first group was designated as'presumed carriers'(N=9) of genetic loading, who had one or more schizophreic first- or second-degree relatives. The second group was designated as'presumed non-carriers'(N=11) of genetic loading, who had no schizophrenic first- or second-degree relatives. Normal controls(N=12) consisted of people without schizophrenic relatives. NSS were evaluated using the Neurological Evaluation Scale-Korean Version (NES-K), and the intra-familial correlations of NSS were tested using the Intra-Class Coefficients(ICC) method. RESULTS: The scores of Motor Coordination subdimension of NES-K were significantly correlated between the patients and their presumed carriers(ICC=.804, p=.016), but not significantly correlated between the patients and their presumed noncarriers. In other subdimensions of NES-K, no significant correlation were found between the patients and their parents regardless of the genetic loading. But, there were no statistically significant differences in the scores of Motor Coordination subdimension of NES-K between the patients and controls. CONCLUSION: This study did not prove that the neurological soft signs might be an endophenotype of schizophrenia that cosegregate with the genetic loading. The future study using more subjects than this would be needed.
Endophenotypes ; Genetic Load ; Humans ; Parents ; Schizophrenia

One of the most widely recognized neurophysiologic endophenotypes for schizophrenia is deficient gating or inhibition of the P50 component of the auditory event-related potential(ERP). A deficit in P50 sensory gating refers to a dysfunction in the mechanism responsible for modulating the brain's sensitivity of filtering out irrelevant or background stimuli, perhaps as a result of dysfunction in inhibitory neural circuits. In this paper, we review the neuronal and genetic aspects as well as medication effects on P50 in schizophrenia.
Endophenotypes ; Evoked Potentials ; Neurons ; Schizophrenia* ; Sensory Gating

Although the Contingent Negative Variation (CNV) paradigm has been useful in schizophrenia, limited research involving such paradigm in subjects with Bipolar Disorder (BD) has produced contradictory findings. To the best of our knowledge, no study has investigated CNV in Paediatric Bipolar Disorder (PBD) subjects. Thirty remitted PBD patients and thirty matched healthy control group subjects participated in the study. No significant between group main effect could be found for either CNV latency or amplitude. We propose that CNV is unlikely to be a true endophenotype of BD. However, absence of CNV finding during euthymic phase in BD may help us in advancing our understanding of BD and such finding may, in fact, have some specificity with regard to differentiating BD from schizophrenia.
Bipolar Disorder ; Contingent Negative Variation ; Endophenotypes ; Humans ; Schizophrenia ; Sensitivity and Specificity

The etiologies of alcohol dependence may be divided into three factors:biological, psychological, and social factors. Among these, many of the current articles deal with the genetic factors, due to rapid developments in methodology and so on. Because of these reasons, it is thought that it would be worthful to review the articles related to the genetic etiologies and other neurobiological etiologies of alcohol dependence at this point. Because alcohol dependence is a complicated and heterogenous disease, it is not likely to be associated with a single gene polymorphism. And as it is still early times in identifying its genetic etiology, I think it is not easy to make conclusion in this field now. However, I believe that many recent studies using endophenotype and haplotype will give us more promising results. The fact that unlike other substances, alcohol dose not act on only one or two neurotransmitter receptors makes neurobiological research to be not easy one. It is interesting that some of the articles reported in this fields recently dose not confined to brain reward system but extended to CRF or molecular biology.
Alcoholism* ; Brain ; Endophenotypes ; Haplotypes ; Molecular Biology ; Receptors, Neurotransmitter ; Reward

OBJECTIVES: This study intended to identify the deficits of cognitive control among patients with bipolar I disorder and their first-degree relatives, and identify the possibility of cognitive control as an endophenotype of bipolar disorder. METHODS: The study included three groups: euthymic states patients with bipolar I disorder (n = 55), unaffected first-degree relatives of probands with bipolar I disorder (n = 30), and a healthy control group (n = 51), that was matched on age, sex, and years of education. The AX version of the continuous performance test (CPT) was used to examine cognitive control. Error rate, correct response times of each subsets (AX, BX, AY, BY), and d' as an indication of accuracy sensitivity index were calculated. Psychopathology, intelligence, and psychomotor speed were also assessed. RESULTS: Patients with bipolar I disorder showed significantly worse error rates in the AX (p = 0.01) and BX (p = 0.02) subsets and d' (p = 0.05) than the others. They also showed more delayed correct response times than the healthy control group and first-degree relatives in all subsets (p < 0.01). But first-degree relatives showed neither high error rates nor delayed correct response times than healthy control group. CONCLUSIONS: These findings suggest that cognitive control is impaired in bipolar I disorder but less likely to be an endophynotype of bipolar I disorder.
Bipolar Disorder ; Education ; Endophenotypes ; Humans ; Intelligence ; Psychopathology ; Reaction Time

OBJECTIVES: Diminished suppression of the P50 response, a consistent finding in schizophrenia, has also been reported in patients with bipolar disorder. It is a promising endophenotype for schizophrenia, but its relationship to genetic liability in mood disorder is controversial. The present study investigated event-related brain potential (ERP) indices of auditory processing and sensory gating in mood disorder and subgroups of patients with bipolar disorder with or without a history of psychosis using the P50 dual-click procedure. METHODS: The P50 auditory evoked potential response to paired stimuli was measured in 77 subjects with mood disorder (58 with bipolar disorder and 19 with major depressive disorder) and 28 healthy controls. P50 parameters were compared between groups. RESULTS: P50 suppression in patients with mood disorder did not differ from that in the healthy subjects. Except for S1 latency, there were no significant differences in P50 parameters between the diagnosis groups. In patients with bipolar disorder, a history of psychosis made no difference to P50 parameters. CONCLUSION: P50 was not significantly impaired in patients with mood disorder. There has been much debate on the meaning of P50, and more studies including longitudinal within-subjects studies are warranted to clarify the meaning and mechanisms of P50.
Bipolar Disorder ; Brain ; Endophenotypes ; Evoked Potentials, Auditory ; Humans ; Mood Disorders ; Psychotic Disorders ; Schizophrenia ; Sensory Gating