Shortening of the hippocampal formation in first-episode schizophrenic patients

Abstract Shortening of hippocampal formation (HF) in chronic schizophrenic patients have been demonstrated in our previous study. The purpose of the present study is to test if shortening of the HF occurs in schizophrenic patients suffering their initial psychotic episode. We performed contiguous, 1 mm thick, magnetic resonance imaging scans in 20 first-episode schizophrenic patients, 21 chronic schizophrenic patients, and 25 healthy subjects. Both groups of schizophrenic patients demonstrated significant shortening of the HF compared with normal controls (first-episode schizophrenia, 5.3%; chronic schizophrenia, 8.0%). However, the HF length was not significantly different between the first-episode and chronic schizophrenic patients. No significant correlation was seen between the HF length and the duration of illness in chronic schizophrenic patients. These results suggest that the HF shortening observed in schizophrenic patients may be genetic and/or developmental in origin.     

Fornix integrity and hippocampal volume in male schizophrenic patients.

BACKGROUND: The hippocampus has been shown to be abnormal in schizophrenia. The fornix is one of the main fiber tracts connecting the hippocampus with other brain regions. Few studies have evaluated the fornix in schizophrenia, however. A focus on fornix abnormalities and their association with hippocampal abnormalities might figure importantly in our understanding of the pathophysiology of schizophrenia. METHODS: Line-scan diffusion tensor imaging (DTI) was used to evaluate diffusion in the fornix in 24 male patients with chronic schizophrenia and 31 male control subjects. Maps of fractional anisotropy (FA) and mean diffusivity (D(m)), which are indices sensitive to white-matter integrity, were generated to quantify diffusion within the fornix. We used high spatial resolution magnetic resonance imaging (MRI) to measure hippocampal volume. RESULTS: FA and cross-sectional area of the fornix were significantly reduced in patients compared with control subjects. D(m) was significantly increased, whereas hippocampal volume was bilaterally reduced in patients. Reduced hippocampal volume was correlated with increased mean D(m) and reduced cross-sectional area of the fornix for patients. Patients also showed a significant correlation between reduced scores on neuropsychologic measures of declarative-episodic memory and reduced hippocampal volumes. CONCLUSIONS: These findings demonstrate a disruption in fornix integrity in patients with schizophrenia.     

Risperidone failed to improve polydipsia-hyponatremia of the schizophrenic patients

The effect of risperidone on polydipsia-hyponatremia was evaluated in six hospitalized schizophrenic patients. The normalized diurnal weight gain (NDWG), urine-specific gravity (USG), urine and plasma osmolarity, and serum sodium were monitored during 9 months of risperidone treatment. The dose of risperidone (mean +/- SD=8.0 +/- 1.0, range=6-9 mg/day) was determined as approximately half of the haloperidol-equivalent dose of previous neuroleptics. Before risperidone treatment, the mean (+/- SD) BPRS score was 23.5 +/- 7.1; no significant improvement was observed after risperidone (22.0 +/- 7.5). The subjects showed relatively high serum prolactin before risperidone treatment (mean +/- SD=16.5 +/- 9.7 ng/mL), that was not significantly decreased by risperidone (14.2 +/- 7.9 ng/mL). The monthly means (+/- SD) of NDWG and USG before risperidone were 5.5 +/- 1.5 (%) and 1.002 +/- 0.001, respectively. These and other indices did not significantly improve throughout the study period. Although the sample size is relatively small, our preliminary data showed that risperidone might not be effective on polydipsia-hyponatremia of schizophrenic patients.     

Atrial natriuretic peptide and arginine vasopressin secretion in schizophrenic patients

Plasma levels of arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) were measured in 15 patients with schizophrenic or schizoaffective disorders and 15 healthy volunteers during oral water loading at 20 ml/kg. In the patient group, plasma AVP was secreted even when plasma osmolality was below 270 mosmol kg, although the sensitivity of AVP secretion response to osmolality was lower than in the controls. The ANP level was higher in the group of patients than in the controls. There was a negative correlation between plasma ANP and osmolality in the patients. We speculate that the volume expansion caused by inappropriate AVP secretion stimulated plasma ANP release and that the natriuresis resulting from the elevated plasma ANP level might contribute to hyponatremia.     

Reduced planum temporale volume and delusional behaviour in patients with schizophrenia

The structural abnormality of planum temporale (PT), a part of the superior temporal heteromodal association cortex involved in auditory and language processing, has been implicated in the pathophysiology of schizophrenia. However, its relationship to clinical manifestations remains unclear. Magnetic resonance images were obtained from 17 right-handed Japanese men with schizophrenia and from 22 age-, handedness-, and parental socioeconomic-status-matched healthy Japanese men in order to manually evaluate grey matter volumes of Heschl’s gyrus (HG) and PT. Psychiatric symptoms were assessed using positive and negative syndrome scale among the patients. Compared with healthy participants, patients with schizophrenia were associated with a statistically significant PT grey matter volume reduction without left or right lateralization, whereas HG volume was preserved. Smaller right PT volume was significantly correlated with more severe delusional behaviour in the patients. Previous investigations have focused on smaller-than-normal left PT in the pathophysiology of schizophrenia; however, the present results suggest a possible role of the right PT, which is involved in social cognition such as understanding the intentions of others, in the production of psychotic experiences in patients with schizophrenia.     

Increased urine volume in chronic schizophrenic patients

Polydipsia and polyuria have a long association with schizophrenia. To assess the prevalence of polydipsia and polyuria in schizophrenia, urine volume was examined in medication-free chronic schizophrenic patients, normal controls, and nonschizophrenic patients. Mean urine volume was significantly higher in the schizophrenic patients (2319 +/- SD 2052 ml/24 hours) than in the other two groups (1054 +/- SD 471 ml/24 hours for nonschizophrenic patients and 1265 +/- SD 613 ml/24 hours for normals). Seven of 35 patients with schizophrenia but 0/7 nonschizophrenics had urine volumes greater than any normal control. Polyuria was associated with a good premorbid history and a positive neuroleptic response. Among polyuric patients, those with hyponatremia may represent a different, distinct subgroup. Neuroleptic treatment was associated with a further, significant increase in urine volume. Hence, polydipsia and polyuria appear to be relatively common in schizophrenia.     

Smaller anterior hippocampal formation volume in antipsychotic-naive patients with first-episode schizophrenia

OBJECTIVE: The authors investigated volumetric alterations of the anterior hippocampal formation in patients experiencing a first episode of schizophrenia relative to healthy comparison subjects. METHOD: From contiguous 1.5-mm coronal magnetic resonance images, the hippocampal formation was divided into posterior and anterior segments, and the anterior hippocampal formation was separated from the amygdala. Volumes of the posterior and anterior hippocampal formation and amygdala were computed in 46 (31 male and 15 female) patients experiencing a first episode of schizophrenia and in 34 (21 male and 13 female) healthy comparison subjects. Twenty-four patients were antipsychotic naive at the time of the scan. RESULTS: Patients had significantly reduced total (right plus left) anterior hippocampal formation volume relative to healthy comparison subjects but did not differ in volumes of either the posterior hippocampal formation or amygdala. Similar findings were obtained when analyses were restricted to the antipsychotic-naive subgroup of patients. CONCLUSIONS: These findings suggest that volumetric abnormalities of the hippocampus-amygdala complex may be specific to the anterior hippocampal formation in patients experiencing a first episode of schizophrenia and are consistent with hypotheses regarding abnormal frontolimbic connectivity playing a role in the pathophysiology of the disorder.     

Reduced hippocampal volume in unmedicated, remitted patients with major depression versus control subjects.

BACKGROUND: Hippocampal volumes obtained from a group of medication-free, remitted subjects with recurrent major depressive disorder (MDD) were compared against corresponding measures from healthy controls. METHODS: Thirty-one subjects with recurrent MDD in full remission, and 57 healthy controls underwent high resolution magnetic resonance imaging (MRI) on a GE 3T scanner. Eight patients with MDD were medication-naive, and twenty-three MDD patients were off antidepressant medications for a mean of 30 months at the time of the MRI study. RESULTS: Patients showed smaller total and posterior hippocampal volume relative to controls. Anterior hippocampal volume did not differ between patients and controls. CONCLUSIONS: Recurrent depression is associated with smaller hippocampal volume which is most prominent in the posterior hippocampus. Smaller hippocampal volume appears to be a trait characteristic for MDD.     

Reduced growth hormone response to apomorphine in schizophrenic patients with poor premorbid social functioning

Summary The apomorphine-induced growth hormone (GH) response of 16 drug-free schizophrenic patients and nine control subjects were studied. The sub-group of nine patients with poor premorbid psychosocial functioning had a significantly lower GH response than the controls. Additional evidence for state dependent effects is provided.     

Differences in the subregional and cellular distribution of GABAA receptor binding in the hippocampal formation of schizophrenic brain

Recent postmortem studies have reported a marked upregulation of GABA_A receptor binding activity in the anterior cingulate and prefrontal cortices of schizophrenic subjects. Because the hippocampal formation is a key corticolimbic region that has also been implicated by both postmortem and brain imaging studies in the pathophysiology of this disorder, the current report has sought to determine whether alterations of GABA_A receptor binding might also be detected in this region from 15 normal controls and 8 schizophrenic subjects. Using a low resolution autoradiographic approach, the results show a significant increase of specific GABA_A receptor binding activity in the area dentata (granule cell layer), CA4, CA3 (str. oriens, str. pyramidale), subiculum, and presubiculum of the schizophrenic group. The magnitude of the increase was greatest in CA3 and lowest in the CA1 sector. When high resolution analyses were performed on emulsion-coverslip preparations, a modest increase of binding (43%, P = 0.05) was observed on pyramidal, but not non-pyramidal neurons in sector CA1. Rather unexpectedly, GABA_A binding in sector CA3 was not significantly different on pyramidal cells, but was almost three-fold higher (P = 0.015) on non-pyramidal neurons of the schizophrenic group. There was no relationship of age or the postmortem interval to the parameters showing significant changes in the schizophrenic group. Moreover, patients both with and without neuroleptic exposure showed upregulation of GABA_A receptor binding activity. Taking together the rather modest increase of binding activity in CA1 and the more marked upregulation in CA3, as well as the differential changes on pyramidal neurons of CA1 vs. non-pyramidal neurons in CA3, the findings reported here are consistent with the possibility that a disturbance of brain development could have occurred either perinatally or perhaps even well into the postnatal period, and have given rise to discreet subregional and cellular alterations of disinhibitory GABAergic modulation in sector CA3 of schizophrenics. Overall, the data reported here provide further evidence that alterations of GABAergic activity may occur in the hippocampal formation of schizophrenic patients. © 1996 Wiley-Liss, Inc.     

Suicidal behaviour in schizophrenic day patients

A survey of non-hospitalised schizophrenics was conducted to test the hypothesis that schizophrenics who had attempted suicide are phenomenologically and demographically different from the ones that do not. On comparison, it emerged that the former had significantly higher incidence of psychiatric morbidity in the family, were on the whole younger and had a much larger number of Present State Examination (PSE) depressive symptoms.     

Smaller hippocampal volume in patients with recent-onset posttraumatic stress disorder.

BACKGROUND: Previous structural magnetic resonance (MR) research in patients with posttraumatic stress disorder (PTSD) has found smaller hippocampal volumes in patients compared with control subjects. These studies have mostly involved subjects who have had PTSD for a number of years, such as war veterans or adult survivors of childhood abuse. Patients with recent-onset PTSD have rarely been investigated. To our knowledge only one other study has investigated such a group. The aim of this study was to compare hippocampal volumes of patients with recent onset PTSD and nontrauma-exposed control subjects. METHODS: Fifteen patients with PTSD, recruited from an accident and emergency department, were compared with 11, non-trauma-exposed, healthy control subjects. Patients underwent a structural MR scan soon after trauma (mean time = 158 +/- 41 days). Entire brain volumes, voxel size 1 x 1 x 1 mm, were acquired for each subject. Point counting and stereology were used to measure the hippocampal and amygdala volume of each subject. RESULTS: Right-sided hippocampal volume was significantly smaller in PTSD patients than control subjects after controlling for effects of whole brain volume and age. Neither left nor total hippocampal volume were significantly smaller in the PTSD group after correction. Whole brain volume was also found to be significantly smaller in patients. There were no differences in amygdala or white matter volumes between patients and control subjects. CONCLUSIONS: This result replicates previous findings of smaller hippocampal volumes in PTSD patients, but in an underinvestigated population, suggesting that either smaller hippocampal volume is a predisposing factor in the development of PTSD or that damage occurs within months of trauma, rather than a number of years. Either of these two hypotheses have significant implications for the treatment of PTSD. For instance, if it could be shown that screening for hippocampal volume may, in some cases, predict those likely to develop clinical PTSD.     

Reduced left anterior cingulate volumes in untreated bipolar patients.

BACKGROUND: Functional and morphologic abnormalities of the cingulate cortex have been reported in mood disorder patients. To examine the involvement of anatomic abnormalities of the cingulate in bipolar disorder, we measured the volumes of this structure in untreated and lithium-treated bipolar patients and healthy control subjects, using magnetic resonance imaging (MRI). METHODS: The volumes of gray matter at the right and left anterior and posterior cingulate cortices were measured in 11 bipolar patients not taking any psychotropic medications (aged 38 +/- 11 years, 5 women), 16 bipolar patients treated with lithium monotherapy (aged 33 +/- 11 years, 7 women), and 39 healthy control subjects (aged 37 +/- 10 years, 14 women). Volumetric measurements were made with T1-weighted coronal MRI images, with 1.5-mm-thick slices, at 1.5T, and were done blindly. RESULTS: Using analysis of covariance with age and intracranial volume as covariates, we found that untreated bipolar patients had decreased left anterior cingulate volumes compared with healthy control subjects [2.4 +/-.3 cm3 and 2.9 +/-.6 cm3, respectively; F(1,58) = 6.4, p =.042] and compared with lithium-treated patients [3.3 +/-.5 cm3; F(1,58) = 11.7, p =.003]. The cingulate volumes in lithium-treated patients were not significantly different from those of healthy control subjects. CONCLUSIONS: Our findings indicate that anatomic abnormalities in left anterior cingulate are present in bipolar patients. Furthermore, our results suggest that lithium treatment might influence cingulate volumes in bipolar patients, which could possibly reflect postulated neuroprotective effects of lithium.     

Hallucinations in Kenyan schizophrenic patients

ABSTRACT - Eighty Kenyan‘psychotic’patients were screened using the New Haven Schizophrenic Index (NHSI) and were all studied for hallucinations using standardised definitions. Fifty-one of the patients were NHSI positive and the rest NHSI negative. Sixty-one percent of the NHSI positive had hallucinations in one or more modalities as compared with 31 % of the NHSI negative group. Of the NHSI positive 51 % had auditory hallucinations directly to the patient, 43 % had visual hallucinations and 25 % had olfactory hallucinations. These results are compared and contrasted with the very few similar observations made elsewhere.     

Dorsolateral prefrontal cortex volume in patients with deficit or nondeficit schizophrenia

Deficit schizophrenia (DS) represents a promising putative clinical subtype of schizophrenia and is characterized by the presence of primary and enduring negative symptoms. Previous studies have often reported a reduced amount of gray matter within prefrontal and temporal cortices in schizophrenia subjects with prevailing negative symptoms; however, the evidence concerning brain structural abnormalities in patients with DS remains controversial. The aim of the present study was to investigate whether patients with DS differed from those with nondeficit schizophrenia (NDS) with respect to the volume of the dorsolateral prefrontal cortex (DLPFC) and hippocampus, two brain areas considered as key regions in the pathogenesis of schizophrenia. In the present study a 3D-T1w MR imaging procedure and an extensive clinical assessment was carried out in 18 patients with schizophrenia, (10 DS and 8 NDS). 3D MPRAGE images were preprocessed with SPM software and two regions of interest (hippocampus and DLPFC) were manually traced to obtain their gray matter volumes. We found a significant reduction of DLPFC in the entire schizophrenia group, with respect to healthy subjects. Although the subgroup of patients with DS had a more severe clinical picture and more impaired social functioning, the DLPFC volume reduction was greater in NDS than in DS patients. In conclusion, according to our structural neuroimaging findings, DS patients, although characterized by a more severe clinical picture and a worse outcome, show less neurobiological abnormalities.     

Obsessive-compulsive symptoms in clozapine-treated schizophrenic patients

The aim of the present study was to assess the occurrence of obsessive-compulsive symptoms (OCS) in schizophrenic patients treated with clozapine, and to examine the relationship between OCS and other clinical variables. The results support earlier findings which suggest that clozapine produces or unmasks OCS. In addition, the severity of OCS was not related to other dimensions of psychopathology, severity of illness, clinical improvement or dose and duration of clozapine treatment.     

Dermatoglyphic patterns in schizophrenic patients

Schizophrenics (n= 250) and normal controls (n= 90) were studied to investigate and compare their dermatoglyphic patterns. Their fingerprint patterns were studied. The frequency of arches in the patient and control groups was similar. The frequency of loops in the control group was higher than in the patient group, and the trend was consistent in all the digits. The whorls in the patient group showed an increase over the control group in all the digits, although this finding was not statistically significant.     

Serine and glycine metabolism in schizophrenic patients

Adelio Lucca, Sebastiano Cortinovis, and Valentina Lucini: Serine and Glycine Metabolism in Schizophrenic Patients. Progr. Neuro-Psychopharmacol. & Biol. Psychiatry 1993, 17(6): 947–953.

1. 1. The brain glycine is almost exclusively derived from serine via serine-hydroxymethyltransferase. 17 males schizophrenic inpatients and 10 males healthy volounteers were submitted to the serine tolerance test.

2. 2. Plasma serine and glycine concentration were evaluated before and after 1, 2, 3, 4 hours of an oral load with L-serine to test the interconversion between the two aminoacids.

3. 3. The authors did not find any significant difference between schizophrenic patients and control group and concluded that the enzyme serine-hydroximethyltransferase is not deficient in the conversion of serine to glycine in schizophrenic patients as suggested by other authors.

Insight and recovery in schizophrenic patients

Objective: To investigate the correlation between insight and recovery in schizophrenic patients according to criteria for both symptomatic and functional remission. Methods: Seventy patients affected by paranoid schizophrenia were recruited and treated with olanzapine, risperidone, aripiprazole, haloperidol and ziprasidone; visits were scheduled at baseline, 12 and 36 months. We administered PANSS (Positive and Negative Syndrome Scale), GAF (Global Assessment of Functioning), SF-36 (Short Form 36 Health Survey), PGWBI (Psychological General Well-Being index) and SAI (Schedule for the Assessment of Insight). Results: After 1 year, 50% of the subjects obtained symptom remission and 25.5% had adequate social functioning for 2 years or more. Only 12% of subjects met full recovery criteria for 2 years or longer. The recovery group also showed an improvement in insight levels, especially patients treated with second-generation antipsychotics (SGA). Recovery was predicted by female sex, higher age, SGA treatment, pre-morbid social adaptation and low level of negative symptoms at baseline. Conclusions: Only a small proportion of schizophrenic patients achieved recovery, therefore greater patient’s insight could have prognostic validity in terms of treatment outcome. More sensitive instruments and a larger sample are necessary to confirm these results.