Adhesio interthalamica alterations in schizophrenia spectrum disorders: A systematic review and meta-analysis

Magnetic resonance imaging (MRI) studies have reported a variety of brain abnormalities in association with schizophrenia. These include a higher prevalence of an absent adhesio interthalamica (AI; also known massa intermedia), a gray matter junction that is present between the two thalami in approximately 80% of healthy subjects. In this meta-analytic review, we describe and discuss the main AI MRI findings in schizophrenia spectrum disorders (SSDs) to date. The MEDLINE and ISI Web of Knowledge^SM databases were searched up to December 2010, for studies that used MRI to assess AI in patients with SSD and controls. From fourteen potential reports, eleven were eligible to be part of the current review. These studies included 822 patients with SSD and 718 healthy volunteers. There was a large degree of variability in the MRI methods they employed. Patients with SSD had a higher prevalence of absent AI than healthy volunteers (odds ratio = 1.98; 95% confidence interval 1.33-2.94; p = 0.0008). This association was evident in both male and female SSD subjects, and there was no evidence that the prevalence was related to age or duration of illness. The significance of the absence of an AI for SSD may be clarified by studies in large, longitudinal community-based samples using standardized methods.     

Adhesio interthalamica in individuals at high-risk for developing psychosis and patients with psychotic disorders

Abnormal neurodevelopment in midline structures such as the adhesio interthalamica (AI) has been reported in psychotic disorders, but it is unknown whether individuals at risk for the disorder share the AI findings observed in patients with florid psychosis. Magnetic resonance imaging of 162 patients with first-episode psychosis (FEP), 89 patients with chronic schizophrenia, 135 individuals at ultra high-risk (UHR) of psychosis (of whom 39 later developed psychosis), and 87 healthy controls were used to investigate the length and prevalence of the AI. The relation of the AI length to lateral ventricular enlargement was also explored. The patients with FEP and chronic schizophrenia as well as UHR individuals had a shorter AI than the controls, but there was no difference in the AI findings between the UHR individuals who did and did not subsequently develop psychosis. There was a negative correlation between the AI length and lateral ventricular volume in all the diagnostic groups. The absence of the AI was more common in the chronic schizophrenia patients when compared with all other groups. These results support the notion that the AI absence or shorter length could be a neurodevelopmental marker related to vulnerability to psychopathology, but also suggest that schizophrenia patients may manifest progressive brain changes related to ongoing atrophy of the AI after the onset.     

Magnetic resonance imaging of the thalamus and adhesio interthalamica in twins with schizophrenia

CONTEXT: Abnormalities of the thalamus are thought to be central to the pathophysiology of schizophrenia. These abnormalities include altered structure and shape of the thalamus itself and possibly changes to the adhesio interthalamica (or massa intermedia), the gray matter bridge connecting the 2 thalamic lobes. However, it is not clear to what extent these abnormalities are determined by the genetic liability for schizophrenia. OBJECTIVE: To investigate thalamic volume and the presence of the adhesio interthalamica in monozygotic (MZ) twins concordant or discordant for schizophrenia. DESIGN: Study of MZ twins. SETTING: Patients were drawn from inpatient and outpatient clinics. Twin controls were recruited from a volunteer twin register and through media advertisements. PARTICIPANTS: A total of 123 twins participated: 19 MZ twin pairs concordant for schizophrenia, 15 MZ schizophrenic twins and 16 MZ nonschizophrenic twins drawn from 17 pairs discordant for schizophrenia, and 27 MZ twin pairs without schizophrenia. Groups were matched for age, sex, handedness, level of education, parental socioeconomic status, and ethnicity. MAIN OUTCOME MEASURES: The volume of the thalamus (including right and left hemispheres) was measured (in cubic centimeters) and the presence of the adhesio interthalamica was ascertained from structural magnetic resonance images. RESULTS: Concordant twin pairs displayed significantly reduced thalamic volume compared with control twins, even when covarying for effects of whole-brain volume, age, and sex. There was a significant linear decrease in thalamic volume (control greater than discordant nonschizophrenic greater than discordant schizophrenic greater than concordant). In all groups, right thalamus was larger than left thalamus. There was no difference across groups in the frequency of the adhesio interthalamica. CONCLUSIONS: Volumetric thalamic abnormalities in schizophrenia occur in twin pairs concordant for schizophrenia. These abnormalities may mark the substantial genetic contribution to the illness seen in concordant twin pairs, whereas the adhesio interthalamica is unlikely to be affected in schizophrenia.     

A magnetic resonance imaging study of the adhesio interthalamica in schizophrenia

Several recent studies have found a relationship between midline cerebral malformations (cavum septi pellucidum, absence of the adhesio interthalamica) and schizophrenia. In this study, we investigated whether the adhesio interthalamica is more often absent in patients with schizophrenia than healthy cases and whether the absence of the adhesio interthalamica may be related to the volume of the third ventricle. Twenty-six patients (11 male, 15 female) in the schizophrenia group and twenty-nine (11 male, 18 female) cases in the control group were examined by MRI. The adhesio interthalamica was found to be absent more often among patients with schizophrenia compared with control subjects and patients without adhesio interthalamica did not have significantly larger third ventricle volumes. The absence of the adhesio interthalamica may be important in explaining the association between the abnormalities of brain midline structures and schizophrenia.     

Prevalence and length of the adhesio interthalamica in schizophrenia spectrum disorders

We used magnetic resonance imaging to investigate the prevalence and length of the adhesio interthalamica (AI) in 72 schizophrenia patients, 47 schizotypal disorder patients, and 81 healthy controls. The AI was more often absent and shorter in both disorders than in controls, possibly reflecting common neurodevelopmental abnormalities in the schizophrenia spectrum.     

Association between absence of the adhesio interthalamica and amygdala volume in schizophrenia

Abnormal neurodevelopment in midline structures such as the adhesio interthalamica (AI) has been reported in schizophrenia, but not consistently replicated. We investigated the prevalence and anterior-posterior length of the AI in 62 schizophrenia patients (32 males, 30 females) and 63 healthy controls (35 males, 28 females) using magnetic resonance imaging. We also explored the relation between the AI and volumetric measurements for the third ventricle, medial temporal structures (amygdala, hippocampus, and parahippocampal gyrus), superior temporal sub-regions, and frontal lobe regions (prefrontal area and anterior cingulate gyrus). The AI was absent in 24.2% (15/62) of the schizophrenia patients and in 9.5% (6/63) of the controls, showing a significant group difference. For the length of the AI, schizophrenia patients had a shorter AI than controls, and males had a shorter AI than females. The subjects without an AI had a significantly larger third ventricle and smaller parahippocampal gyrus than the subjects with an AI for both groups. We found a significant diagnosis-by-AI interaction for the amygdala. The schizophrenia patients without an AI had a smaller bilateral amygdala than those with an AI, whereas the AI was not associated with the volume of the amygdala in the control subjects. These findings suggest that the absence of AI in schizophrenia could be a marker of developmental abnormalities in the neural network including the thalamus and connected amygdaloid regions, which may play an important role in the pathogenesis of schizophrenia.     

Elevated homocysteine levels in young male patients with schizophrenia

OBJECTIVE: Elevated plasma homocysteine has been found to be a risk factor for Alzheimer's disease as well as cerebral vascular disease, suggesting that some risk factors can accelerate or increase the severity of several CNS disease processes. The authors measured plasma homocysteine levels in patients with chronic schizophrenia in their catchment area. METHOD: A one-way analysis of covariance with age and sex as covariates was performed on the total plasma homocysteine levels of 193 patients with schizophrenia compared with 762 subjects without the diagnosis of schizophrenia who were evaluated in a screening program for employee health. RESULTS: The effect of schizophrenia was marked: the mean homocysteine level was 16.3 micro M (SD=11.8) in patients with schizophrenia compared with 10.6 micro M (SD=3.6) in healthy comparison subjects. The difference between groups was almost entirely attributable to the homocysteine levels of young male patients with schizophrenia. CONCLUSIONS: Elevated levels of homocysteine in young male patients with schizophrenia could be related to the pathophysiology of aspects of this illness.     

Various bilateral olfactory deficits in male patients with schizophrenia

Olfactory identification deficits in schizophrenia patients are well documented. Less is known about the functioning of other olfactory domains and the possibility of lateralized dysfunctions. Thirty male schizophrenia patients and 30 male healthy controls underwent unirhinal assessment of various olfactory domains: detection threshold (dimethyl disulfide, phenyl ethanol), quality discrimination, and odor ratings (familiarity, pleasantness, edibility, intensity) of pure chemicals (Munich Olfaction Test), as well as familiarity and edibility judgments and identification of everyday odors. Aside from impaired identification, patients showed impaired familiarity and edibility judgments of everyday odors. With regard to odor ratings of pure chemicals, group differences were observed only in pleasantness ratings, with higher ratings in patients. Furthermore, patients had reduced sensitivity with dimethyl disulfide and reduced quality discrimination compared with controls. Further analyses showed that identification deficits were not attributable to reduced sensitivity but may be associated with impairments in quality discrimination. Olfactory dysfunctions were found across both nostrils. Results suggest specific dysfunctions in olfactory processing in schizophrenia patients, including early stages of the odor identification process.     

Anterior hippocampal volume reduction in male patients with schizophrenia

Quantitative high resolution magnetic resonance imaging (MRI) was utilized to measure anterior, posterior, and total hippocampal volumes in 27 male patients with chronic schizophrenia and 24 male controls. To optimize measurement techniques, hippocampal volumes were: (1) acquired with 1.4-mm slices; (2) excluded with the amygdala; (3) normalized for position; and (4) corrected for total intracranial volume (ICV). The results of a linear mixed effects regression analysis, which made it possible to analyze total anterior and total posterior hippocampal volumes separately, indicated that the anterior hippocampus was significantly smaller in the schizophrenic group relative to the control group. There were no significant group differences with respect to posterior hippocampal volumes, and no significant correlations between hippocampal volumes and illness duration. A significant lateralized asymmetry was also noted in both groups with the right hippocampal volume being larger than the left. These preliminary findings support a significant anterior hippocampal volume reduction in men with schizophrenia as well as a similar hippocampal volume asymmetry in both male controls and schizophrenics.     

Cavum septum pellucidum and adhesio interthalamica in schizophrenia: an MRI study

Several studies have independently suggested that patients with schizophrenia are more likely to have an enlarged cavum septum pellucidum (CSP) and an absent adhesio interthalamica (AI), respectively. However, neither finding has been consistently replicated and it is unclear whether there is an association between these two midline brain abnormalities. Thus, we compared the prevalence of absent AI and the prevalence, size and volume of CSP in 38 patients with schizophrenia and 38 healthy controls using magnetic resonance imaging (MRI). There were no between group differences in the presence or volume of CSP; however, an enlarged CSP was commoner among patients than controls. There was also a positive correlation between CSP ratings and volumes. No differences in the presence or absence of the AI were found between patients and controls; however, an absent AI was commoner in male patients with schizophrenia than females. There was absolutely no overlap between the presence of a large CSP and an absence of AI. In conclusion, our findings are in line with several case series and other MRI investigations that have shown a higher incidence of putatively developmental brain abnormalities in patients with schizophrenia, particularly in males, and support the neurodevelopmental model of this disorder.     

Smoking and tardive dyskinesia in male patients with chronic schizophrenia

Interactions between smoking and movement disorders include the contrasting associations of more cigarette smoking with reductions in Parkinson's disease and increases in tardive dyskinesia (TD) symptoms. Here we examine the relationship between smoking and TD in a large sample of inpatients with schizophrenia. We used cross-sectional naturalistic methods to analyze the prevalence and severity of neuroleptic-induced TD in relation to cigarette smoking among 764 male chronic and medicated inpatients meeting DSM-IV criteria for schizophrenia. We administered a detailed questionnaire including general information, medical and psychological conditions, and smoking behaviors. We evaluated TD severity using the abnormal involuntary movement scale (AIMS) and psychopathology using the Positive and Negative Syndrome Scale (PANSS). The main statistical analyses used cross-tabulations for the prevalence of TD by smoking and multivariate regression analyses for continuous measures (AIMS and PANSS). We found that the prevalence of TD did not significantly differ between smokers (41% = 237/578) and non-smokers (37% = 69/186). Secondary outcomes showed a significant association between the AIMS total score and age, duration of illness and hospitalization times. Thus, smoking was not associated with TD in male Chinese schizophrenics, but consistent with previous reports, older patients with a longer duration of illness and more hospitalizations showed greater severity of TD.     

Reduced concentrations of thalamic N-acetylaspartate in male patients with schizophrenia

OBJECTIVE: The authors measured N-acetylaspartate (a putative neuronal marker) in the right and left thalamus of 17 male patients with schizophrenia using in vivo proton magnetic resonance spectroscopic imaging ((1)H MRSI). METHOD: (1)H MRSI was performed on 17 medicated male patients with schizophrenia and 10 male comparison subjects. Concentrations of N-acetylaspartate, creatine, and choline were determined in the thalamic regions bilaterally. RESULTS: The patients with schizophrenia demonstrated significantly lower concentrations of N-acetylaspartate than the comparison subjects in both the right and left thalamic regions. Right thalamic N-acetylaspartate and left thalamic N-acetylaspartate were significantly correlated in the patients but not in the comparison subjects. There was no association between N-acetylaspartate and duration of illness or medication dose. No group differences or lateralized asymmetries in choline or creatine were noted. CONCLUSIONS: The finding of reduced concentrations of N-acetylaspartate bilaterally suggests neuronal dysfunction and/or loss in both the right and left thalamic regions in male patients with schizophrenia.     

Correlates of rapid neuroleptic response in male patients with schizophrenia

Correlates of neuroleptic response latency were assessed in 16 male schizophrenic inpatients during 4 weeks of fixed dose (20 mg/day) haloperidol treatment. Rapid responders showed a mean 40% reduction in Brief Psychiatric Rating Scale (BPRS) positive symptom scores by day 10 of treatment. Rapid responders had significantly lower plasma homovanillic acid (pHVA) concentrations compared to non-rapid responders during week 4 of haloperidol treatment. However, rapid versus non-rapid responders did not differ with respect to demographics, baseline positive or negative BPRS symptom scores, performance on tests of neuropsychological function, or mean plasma haloperidol concentrations.     

非典型抗精神病药对男性精神分裂症患者性功能影响的初步分析

目的 探讨喹硫平、利培酮、奥氮平及氯氮平对男性精神分裂症患者性功能影响的差异.方法 将门诊就诊的男性精神分裂症患者145例,分为喹硫平组 30 例、利培酮组 47 例、奥氮平组 31 例及氯氮平组 37 例.检测各组患者血清泌乳素水平.使用简明男性性功能量表、阳性与阴性综合征量表(PANSS)评估性功能及精神症状,用副反应量表(TESS)评估药物治疗的不良反应.共观察8周.结果 治疗第 8 周末,利培酮组的性功能量表总分及因子分均较治疗前降低,奥氮平组的性唤起因子及性功能因子得分有所下降,氯氮平组的性满意度因子及性功能因子得分有所下降.喹硫平组得分无明显变化.利培酮组和奥氮平组治疗第 8 周末的血清泌乳素水平高于基线水平[利培酮组:(12±5)ng/ml,(20±6)ng/ml,t=13.92,P＜0.01;奥氮平组:(13±6)ng/ml,(18±5)ng/ml,t=8.27,P＜0.01],喹硫平组和氯氮平组无明显变化.影响男性精神分裂症患者性功能的因素有泌乳素、年龄及TESS分.结论 常见非典型抗精神病药物对男性精神分裂症患者的性功能影响有所不同.     

Diurnal cortisol patterns of young male patients with schizophrenia

Aims: It has been suggested that schizophrenic patients are more vulnerable to stress than healthy persons, and that stressors can trigger a psychotic episode or worsen symptoms. The biological system often studied in relation to stress is the hypothalamic–pituitary–adrenal (HPA) axis, which controls the release of cortisol. We investigated whether the diurnal basal activity of the HPA axis differed between young male patients with schizophrenia and healthy controls. Methods: Twenty‐seven male patients (mean age 22 ± 5 years) and 38 healthy male control subjects (mean age 22 ± 3 years) were included in the present study. Saliva was sampled at five time points during the day: directly after awakening, 30 min thereafter, and at 12.00 hours, 16.00 hours and 22.00 hours. Results: The cortisol concentration decreased significantly more during the day in the patient group thanin the control group. Patients also showed a significantly decreased area under the curve with respect to the increase, again indicating that the cortisol concentrations decreased more during the day in patients than in controls. Both the morning increase and the area under the curve with respect to the increase were significantly negatively correlated with negative symptom severity. Conclusions: Patients with schizophrenia showed a different daytime sensitivity of the HPA axis. Our findings further suggest that an increase in negative symptom severity is related to a decreased HPA axis sensitivity.     

Magnetic resonance imaging of the thalamus in male patients with schizophrenia

Thalamic abnormalities have been hypothesized to explain much of the psychopathology in schizophrenia, however, quantitative magnetic resonance imaging (MRI) studies have yielded discrepant results as to whether there are thalamic volume alterations. The current study utilized high resolution MRI and an axial voluming protocol to determine if there was a significant reduction in the volume of the thalamus in patients with schizophrenia. Quantitative analysis was performed on magnetic resonance images of the brain in 41 male medicated schizophrenic patients and 39 male normal control subjects similar in age, education and handedness. There were no group differences in thalamic volumes between controls and patients with schizophrenia, even after adjusting for intracranial volume, total brain tissue volume, and gray matter volume. There were also no significant correlations between thalamic volume and either current neuroleptic dose or illness duration. However, there was a significant right greater than left thalamic volume asymmetry in schizophrenics and controls, and the degree of thalamic volume asymmetry was similar in both groups. The failure to detect any significant difference in thalamic volumes may be due to the heterogeneity of the schizophrenic population and as yet undetermined chronic effects of neuroleptic medication on the thalamus. However, another reasonable explanation for the study findings is that quantitative MRI voluming of the entire thalamus may not be sensitive enough to detect more subtle regional neuropathology within the thalamus.     

抗精神病药对男性精神分裂症患者垂体-性腺轴的影响

目的：研究氯丙嗪、利培酮、奎硫平及奥氮平对男性精神分裂症患者垂体．性腺轴的影响。方法：88例首发男性精神分裂症患者随机分为氯丙嗪组、利培酮组、奎硫平组及奥氮平组，检测治疗前、治疗4周及8周血清促卵泡素（FSH）、黄体生成素（LH）、催乳素（PRL）、睾酮（T）的水平变化。结果：氯丙嗪组治疗8周后，血清PRL水平显著高于治疗前。利培酮组在治疗4周及8周后PRL水平均显著高于治疗前，治疗8周后T及LH水平显著低于治疗前。奎硫平组在治疗4周及8周后血清PRL、LH、T水平与治疗前比较差异均无显著性。奥氮平组治疗4周后PRL水平显著高于治疗前，治疗8周后即与治疗前差异无显著性。结论：奎硫平对垂体．性腺轴激素水平无明显影响。     

Hippocampal dysfunction during free word association in male patients with schizophrenia

In schizophrenia, speech production deficits in patients with positive formal thought disorder (FTD e.g. loosening of associations and derailment) have been attributed to impairments in the semantic network. The brain area implicated in the retrieval of associated (i.e. relational) concepts is the hippocampus, a key region in the psychopathology of schizophrenia. However, its role in schizophrenic speech production and FTD in particular is yet little understood.

To investigate the neural correlates of associative verbal retrieval, twelve patients with schizophrenia with varying degrees of FTD and twelve matched healthy control subjects underwent a free verbal association (FVA), a semantic (SVF) and a phonological verbal fluency (PVF) task while brain activity was measured with fMRI. The tasks varied in the relational binding operations needed for linking the stimulus to the respective response.

Compared to control subjects, patients revealed attenuated left hippocampal activity during both semantic word generation tasks (FVA, SVF). Contrasting verbal fluency with FVA, a failure in recruiting the anterior cingulate gyrus emerged in the patient group. A negative correlation was found between right middle temporal activity and the severity of FTD during FVA.

The hippocampus seems to play a major role in word generation. In schizophrenia, attenuated hippocampal activity during semantic tasks strengthens the hypothesis of impaired relational memory processes, affecting thought and language.     

C-reactive protein serum level in drug-free male Egyptian patients with schizophrenia

Despite the growing research interest in the role of immunological markers in schizophrenia, few studies, with conflicting results, have focused on the association between high sensitivity C-reactive protein (hs-CRP) levels and clinical characteristics in schizophrenia. In this cross-sectional case-control study, a sample of 200 antipsychotic-free male Egyptian schizophrenia patients was assessed by the Positive and Negative Syndrome Scale (PANSS) and compared with 200 healthy controls as regards serum hs-CRP level using an immunoturbidimetric method. CRP level for patients (geometric mean = 3.3 mg/L) was significantly (P = 0.000) higher than that for controls (geometric mean = 1.4 mg/L). PANSS scores and patients' data, which significantly correlated with serum hs-CRP level, were entered into a stepwise multiple regression analysis. Results of this analysis showed that PANSS negative symptom score was second only to the waist circumference, with which they explained 54.7 % of the variation in serum hs-CRP. Comparable results were obtained when patients, controls and the relevant confounders were included in one multivariate analysis. We concluded that in Egyptian men, waist circumference and schizophrenia diagnosis are strong predictors of raised CRP level independent of a number of potentially confounding variables. In antipsychotic-free patients, CRP level is higher than in healthy controls and is positively correlated with the severity of the psychopathology as measured by PANSS. This relationship is especially notable in negative, but not positive symptoms.     

抗精神病药对男性精神分裂症患者垂体-性腺轴的影响

目的:研究氯丙嗪、利培酮、奎硫平及奥氮平对男性精神分裂症患者垂体性腺轴的影响。方法:88例首发男性精神分裂症患者随机分为氯丙嗪组、利培酮组、奎硫平组及奥氮平组,检测治疗前、治疗4周及8周血清促卵泡素(FSH)、黄体生成素(LH)、催乳素(PRL)、睾酮(T)的水平变化。结果:氯丙嗪组治疗8周后,血清PRL水平显著高于治疗前。利培酮组在治疗4周及8周后PRL水平均显著高于治疗前,治疗8周后T及LH水平显著低于治疗前。奎硫平组在治疗4周及8周后血清PRL、LH、T水平与治疗前比较差异均无显著性。奥氮平组治疗4周后PRL水平显著高于治疗前,治疗8周后即与治疗前差异无显著性。结论:奎硫平对垂体性腺轴激素水平无明显影响。