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To conduct a comprehensive literature review of the area of neural stem cells and neuropsychiatry.
Methods:
‘Neural stem cells’ (NSCs) and ‘neurogenesis’ were used as keywords in Medline (1966 – November 2006) to identify relevant papers in the areas of Alzheimer’s disease (AD), depression, schizophrenia and Parkinson’s disease (PD). This list was supplemented with papers from reference lists of seminal reviews.
Results:
The concept of a ‘stem cell’ continues to evolve and is currently defined by operational criteria related to symmetrical renewal, multipotency and functional viability. In vivo adult mammalian neurogenesis occurs in discrete niches in the subventricular and subgranular zones – however, functional precursor cells can be generated in vitro from a wide variety of biological sources. Both artificial and physiological microenvironment is therefore critical to the characteristics and behaviour of neural precursors, and it is not straightforward how results from the laboratory can be extrapolated to the living organism. Transplant strategies in PD have shown that it is possible for primitive neural tissue to engraft into neuropathic brain areas, become biologically functional and lead to amelioration of clinical signs and symptoms. However, with long-term follow-up, significant problems related to intractable side-effects and potential neoplastic growth have been reported. These are therefore the potentials and pitfalls for NSC technology in neuropsychiatry. In AD, the physiology of amyloid precursor protein may directly interact with NSCs, and a role in memory function has been speculated. The role of endogenous neurogenesis has also been implicated in the etiology of depression. The significance of NSCs and neurogenesis for schizophrenia is still emerging.
Conclusions:
There are a number of technical and conceptual challenges ahead before the promise of NSCs can be harnessed for the understanding and treatment of neuropsychiatric disorders. Further research into fundamental NSC biology and how this interacts with the neuropsychiatric disease processes is required.
An area of recent interest in schizophrenia research is to investigate specific neural and cognitive abnormalities associated with symptoms of this disorder.
Objective:
To establish clinical, cognitive and neural correlates of self-monitoring deficits in schizophrenia, which according to various theoretical models can account for the first-rank symptoms of this disorder.
Methods:
Relevant data were identified from PubMed and PsycInfo searches up to July 2006 using combinations of keywords including ‘self-monitoring’, ‘symptoms’, ‘self-agency’, ‘neuropsychological’, ‘cognitive’, ‘brain activity’, ‘PET’ and ‘fMRI’.
Conclusions:
Self-monitoring deficit is most consistently observed in patients with schizophrenia with auditory hallucinations and passivity experiences. This deficit may not be schizophrenia specific. At present, there are insufficient direct data to reach meaningful conclusions about the cognitive correlates of this deficit. Functional neuroimaging studies in patients with schizophrenia with auditory hallucinations point to defective engagement of the neural regions known to be involved in self-monitoring in healthy people. Further multimodal studies using validated cognitive and clinical measures, self-monitoring paradigms and appropriate imaging tools to analyze patients with schizophrenia with and without self-monitoring deficits are required to increase our understanding of this topic.
There has been considerable debate about the diagnostic rules for bipolar II disorder, particularly the 4-day duration criteria for hypomanic episodes. This study examined whether highs lasting minutes or hours differed from longer highs in terms of clinical features and symptom severity. It also examined whether duration of highs predicted bipolar disorder being diagnosed.
Method:
A total of 518 subjects with significant episodes of depression and ‘highs’ completed a web-based self-report questionnaire. Those who reported their longest highs lasting minutes or hours were compared with those who reported longer durations of highs on a range of clinical variables and measures of symptom severity.
Results:
Subjects whose highs lasted minutes or hours reported clinical features and severity of symptoms similar to those whose highs lasted 3–7 days. However, the odds of being diagnosed with bipolar disorder for those with highs lasting 3–7 days were almost three times higher than for those whose highs lasted minutes or hours.
Conclusion:
The 4-day DSM-IV minimum-duration criteria for hypomania may lead to failure to diagnose subjects with brief highs who have true bipolar disorder and thus should be reconsidered.
The tryptophan metabolite kynurenic acid (KYNA) is an endogenous glutamate/nicotinic receptor antagonist. Previous studies have shown that the concentration of the compound is increased in cerebrospinal fluid (CSF) of patients with schizophrenia. Furthermore, it has been found that the CSF concentration of KYNA is positively correlated to CSF concentrations of the monoamine metabolites homovanillic acid (HVA) and 5-hydroxy indoleacetic acid (5-HIAA) in healthy control subjects.
Objectives:
To study the correlations between KYNA and the monoamine metabolites HVA, 5-HIAA and 4-hydroxy-3-methoxyphenylglycol (HMPG) in CSF of male patients (n= 53, ranging from 20 to 48 years of age) with verified schizophrenia.
Methods:
CSF was obtained by lumbar puncture, and KYNA analysis was performed with an isocratic reversed-phase high-performance liquid chromatography system connected to a fluorescence detector. HVA, 5-HIAA and HMPG concentrations were measured by mass fragmentography with deuterium-labelled internal standards.
Results:
Positive intercorrelations were found between CSF KYNA, HVA and 5-HIAA, while CSF content of HMPG did not correlate to KYNA or any of the monoamine metabolites in CSF.
Conclusion:
The results of this study suggest that increased KYNA formation is associated with an increased dopamine and serotonin turnover in male patients with schizophrenia.
The present trial was designed to investigate the influence of repetitive transcranial magnetic stimulation (rTMS) on negative schizophrenic symptoms using high-frequency stimulation of the left dorsolateral prefrontal cortex in a simple blind randomized design.
Methods:
The study was carried out on a 42-year-old patient with schizophrenia (paranoid subtype) with prominent negative symptoms who was first treated with sham rTMS during the first 3 weeks and then with real high frequency during the following 3 weeks. He was rated before and after the sham and after the real rTMS therapy for positive, negative and depressive symptoms.
Results:
rTMS was superior to sham treatment in reduction of negative and depressive symptoms.
Conclusion:
High-frequency rTMS applied over the left dorsolateral prefrontal cortex led to a reduction of severity of negative symptoms in a patient with chronic schizophrenia and may be beneficial as an augmentation option to antipsychotics in the treatment of negative symptoms of schizophrenia.
To observe spike activity in electroencephalograms (EEGs), patients with symptomatic partial epilepsy are rarely monitored during the hyperventilation stages.
Case:
A 38-year-old woman suffered from a ruptured arteriovenous malformation in the left temporal lobe. One and a half years later, the patient experienced her first generalized convulsion. EEG showed small spikes in the posterior of the left temporal lobe, which was observed during the hyperventilation and posthyperventilation stages. Because the location of the spikes correlated with the site of the lesion as observed from radiographic findings, she was diagnosed with lateral temporal lobe epilepsy. Drug treatment resulted in no further convulsive episodes and the patient has since returned to work.
Conclusion:
EEG recordings during hyperventilation should be regarded as an effective technique in analyzing epilepsy because of its ease and cost-effectiveness compared with other methods such as single-photon emission computed tomography.