[Structural and functional brain changes in schizophrenic disorders. Indications of early neuronal developmental disturbances?]. / Strukturelle und funktionelle Hirnveränderungen bei schizophrenen Psychosen. Hinweis auf eine frühe neuronale Entwicklungsstörung?

The neurodevelopmental hypothesis of schizophrenia, which was established 30 years ago and discussed controversially for a long time, postulates that pre- and perinatally acting cerebral noxae cause disturbances of corticogenesis in the developing neuronal fibre systems which are essential for later onset of the disease. During recent years the cerebral alterations of schizophrenic patients could be further characterized as area-, layer-, and cell type-specific changes in temporolimbic and frontal regions leading to specific abnormalities of intrinsic and extrinsic connectivity. Animal models allowed for realistic imitations of these structural lesions and for elucidating their functional consequences concerning transmitter systems and behaviour. With modern neuroimaging techniques microstructural changes and alterations in cerebral activation can be exactly demonstrated and related to the specific psychopathologic features of schizophrenia.

Serotonergic effects of smoking are independent from the human serotonin transporter gene promoter polymorphism: evidence from auditory cortical stimulus processing.

BACKGROUND: Cigarette smoking has been associated with mood enhancing properties and modulating effects on serotonin activity. The loudness dependence (LD) of the auditory-evoked N1/P2-component has been related to serotonergic neurotransmission, i. e. the allelic variants in the promoter of the 5-hydroxytryptamine-transporter (5-HTT) gene (SCL6A4). Moreover, smoking behavior has been associated to the 5-HTT-genotype. It was hypothesized that cigarette smoking modulates the LD and this effect was expected to interact with the 5-HTT-genotype. METHODS: 5-HTT-genotype and LD were determined in 63 healthy smokers and 114 nonsmokers. RESULTS: LD was significantly affected by smoking status (p = 0.008) and 5-HTT-genotype (p = 0.045) but not by smoking*genotype-interaction or daily cigarette consumption. Current smokers exhibited a significantly weaker LD compared to nonsmokers. 5-HTT-genotype showed no significant effect on smoking behavior. DISCUSSION: The results indicate a higher serotonergic activity in smokers as compared to nonsmokers independent of 5-HTT-genotype. Since former smokers and never smokers showed similar LDs, the serotonin enhancing effect of smoking seems to be a characteristic state, which may contribute to the maintenance of smoking behavior.

Subsecond changes of global brain state in illusory multistable motion perception.

This study explored transient changes in EEG microstates and spatial Omega complexity associated with changes in multistable perception. 21-channel EEG was recorded from 13 healthy subjects viewing an alternating dot pattern that induced illusory motion with ambiguous direction. Baseline epochs with stable motion direction were compared to epochs immediately preceding stimuli that were perceived with changed motion direction ('reference stimuli'). About 750 ms before reference stimuli, Omega complexity decreased as compared to baseline, and two of four classes of EEG microstates changed their probability of occurrence. About 300 ms before reference stimuli, Omega complexity increased and the previous deviations of EEG microstates were reversed. Given earlier results on Omega complexity and microstates, these sub-second EEG changes might parallel longer-lasting fluctuations in vigilance. Assumedly, the discontinuities of illusory motion thus occur during sub-second dips in arousal, and the following reconstruction of the illusion coincides with a state of relative over-arousal.

[Phytotherapeutic drugs in psychiatry]. / Phytotherapeutika in der Psychiatrie.

During recent years, the use of phytotherapeutics in psychiatry has gained enormous significance. The present paper reviews current scientific data on the most important herbal substances including St. John's wort, kava, valerian, and gingko. Although psychotropic phytotherapeutics have been shown to be partly effective in some psychiatric disorders, they cannot generally be recommended as an alternative to conventional medicaments because sufficient data concerning their efficacy, differentiated indication, and safety profile are still missing. Psychiatric patients treated with herbal drugs need intensive medical advice and supervision.

The neurophysiological meaning of auditory P300 in subtypes of schizophrenia.

Event-related potentials are a powerful tool to investigate the real-time course of brain electrical mass activation during cognitive processing. In several psychiatric disorders, differences compared to healthy subjects have been reliably described. The specificity and the pathophysiological meaning of the findings were unclear in most studies, however. This review summarizes methodological aspects and findings, in healthy subjects and psychiatric patients, of investigations based on the auditory oddball paradigm, which evokes the P300 component of event-related potentials. Recent convergent results from P300 and brain imaging studies allowed the interpretation of P300 findings in psychotic disorders in terms of different specific and meaningful neurophysiological disturbances. Namely, core schizophrenia is characterized by a left-temporal dysfunction associated with deficits in verbal processing. Acute remitting schizophrenia-like psychoses (cycloid psychosis, ICD-10 F23), on the other hand, show normal hemispheric balance but consistent signs of cerebral hyperarousal. Recent studies further indicate that the drive for action of manic patients does not rely on over-excitation but rather on frontal disinhibition. The findings may help to further advance the understandings and sub-grouping of functional psychoses based on pathophysiological mechanisms.

The dendritic architecture of prefrontal pyramidal neurons in schizophrenic patients.

Despite a considerable number of investigations revealing the prefrontal cortex (PFC) to be a major site of pathological changes in schizophrenia, the neuronal basis of these alterations is still unknown. We used a 3-D image analysis technique to investigate the dendritic arborization of Golgi-impregnated prefrontal pyramidal neurons in schizophrenic patients and controls. While the apical dendrites were found to be unchanged in schizophrenics, the basilar dendritic systems were markedly reduced in the patient group. A segment analysis showed that the observed alterations were mainly confined to distal dendritic segments. The dendritic changes are likely to be associated with specific dysfunctions of prefrontal circuitry and point to the pathogenetical relevance of pre- and perinatal disturbances of PFC maturation in schizophrenic patients.

Disturbances of corticogenesis in schizophrenia: morphological findings provide new evidence for the maldevelopmental hypothesis.

A comprehensive neuropathology of schizophrenic psychoses has not yet been established. According to the findings of clinical investigations, neurohistological studies mainly focused on limbic structures, the prefrontal cortex and the anterior cingulate cortex. The results of morphometric and stereological studies based on the classical neuropathological techniques are controversial and point to the necessity for a differentiated characterization of the morphological features of neurons. Therefore, methods of neurobiological fundamental research are employed for the detailed demonstration of the different neuron types that constitute cortical circuits. Using these techniques, the schizophrenic cortex is shown to contain a variety of characteristic alterations which are discussed in the light of hypotheses favoring a maldevelopmental pathogenesis of schizophrenic psychoses which can be looked upon as neuronal system disorders.

Inhibitory cartridge synapses in the anterior cingulate cortex of schizophrenics.

Axon cartridges are the specific terminal structures of GABAergic inhibitory chandelier interneurons. Cartridges form axo-axonal synapses with local projection neurons, thus modulating the neuronal output of diverse brain areas. In order to examine the distribution of cartridges, the anterior cingulate cortices from the brains of schizophrenic patients and control persons were examined with an antibody against parvalbumin. Axon cartridges were mainly located in layers V and VI. In our study, schizophrenic patients showed a significantly higher density of axon cartridges than controls. These findings add new evidence for disturbances of the circuitry of the anterior cingulate cortex in schizophrenia implicating that there may be an elevated inhibitory influence on the cortical output of this brain region.

Altered distribution of parvalbumin-immunoreactive local circuit neurons in the anterior cingulate cortex of schizophrenic patients.

Several lines of evidence support an involvement of the anterior cingulate cortex in the pathophysiology of schizophrenia. Immunocytochemical techniques using antibodies against calcium-binding proteins permit a selective demonstration of certain subgroups of cortical GABAergic interneurons. The anterior cingulate cortex from the brains of schizophrenic patients and control subjects was studied with an antibody against parvalbumin. The immunoreactive structures were assessed qualitatively and quantitatively. Parvalbumin immunoreactivity was detected in a subpopulation of GABAergic local circuit neurons, in axonal structures (including axon cartridges) and in diffuse, band-like neuropil material. Schizophrenic anterior cingulate cortex was found to contain the same interneuron types as controls, but displayed a significant increase of parvalbumin-immunoreactive neuronal soma profiles in layers Va and Vb, whereas the total neuronal density determined in Nissl preparations showed no difference in the two groups. A higher density of parvalbumin-positive local circuit neurons may indicate an increased inhibition of projection neurons, thus altering the neuronal output pattern of the anterior cingulate cortex in schizophrenia.

Cortical layer I changes in schizophrenia: a marker for impaired brain development?

The prefrontal cortices of healthy control subjects and schizophrenic patients were examined with an antibody mixture against non-phosphorylated neurofilaments (SMI 311). SMI 311 immunoreactivity was observed in numerous pyramidal neurons of layers II to VI and in Cajal-Retzius cells (CRC) of layer I. On the basis of their Golgi-like immunostaining, CRC could be classified into three morphologically heterogeneous groups, which showed different distributions in the two proband groups. The overall density of CRC in layer I did not differ significantly between controls and schizophrenics. However, CRC were more numerous in the lower third of layer I in schizophrenics and in the upper and middle third of layer I in controls. CRC play a key role in neuronal migration, thus, our results support the neurodevelopmental hypotheses of schizophrenic pathophysiology.

[Sexual dimorphism of the human brain--a review of the literature]. / Sexueller Dimorphismus des menschlichen Gehirns--eine Literaturübersicht.

Some findings of neurobiological brain research regarding structural sex differences of the human brain are reviewed and discussed. Besides the well known difference in brain size, especially some cell groups of the hypothalamus display differences between the sexes. The results obtained for other regions, such as the corpus callosum and other commissural systems, are inconclusive. Further dimorphisms involve the temporal lobes and sex-specific brain asymmetry. These differences seem to be subtle and are superimposed by high interindividual variability. Finally, little morphological support is found for behavioural differences between the sexes.

Parvalbumin in the human anterior cingulate cortex: morphological heterogeneity of inhibitory interneurons.

The calcium-binding protein parvalbumin (PV) is a marker for a certain subset of GABAergic cortical interneurons. In the present study, indirect immunocytochemistry with an antibody against PV was performed on serial sections of human anterior cingulate cortex (Brodmann's area 24), an important relay centre of the limbic system. PV-positive structures are distributed in a layer- and cell type-specific manner. Based on morphological features and laminar distribution pattern, PV-immunoreactive interneurons are subdivided into eight different classes. PV immunoreactivity within the neuropil comprises dendritic and axonal processes. Area 24 contains two densely immunolabelled neuropil bands in layers III and Vb. Axon cartridges are preferably located in layers V and VI. The results provide a "PV immunoarchitecture' as a basis for further studies of PV immunoreactivity under pathological conditions. PV is assumed to play a role in maintaining calcium homeostasis in nerve cells, and to modulate neuronal excitability and resistance to biochemical damage. On the other hand, PV immunoreactivity has recently been shown to undergo characteristic changes during different stages of brain maturation. Therefore, examination of PV-positive structures will provide new insights into cortical circuitry in neurodegenerative as well as neurodevelopmental disorders.

The presubicular region in Alzheimer's disease: topography of amyloid deposits and neurofibrillary changes.

Specific silver impregnation techniques for extracellular amyloid and intraneuronal neurofibrillary changes were used to examine the presubiculum in Alzheimer victims. Extended amyloid clouds in the absence of neurofibrillary changes were noted in the parvopyramidal layer of the presubiculum proper. The corresponding layer in the parasubiculum, in contrast, showed many neurofibrillary tangles and neuropil threads in the absence of amyloid. The transsubicular parvopyramidal layer contained both amyloid deposits and neurofibrillary changes. This severe involvement of all subdivisions of the presubicular region in Alzheimer's disease is considered to impair functions of the Papez circuit.

Alzheimer's disease: areal and laminar pathology in the occipital isocortex.

Sensitive and specific silver methods for demonstration of (1) amyloid and/or precursors of amyloid and (2) neurofibrillary changes were applied to examine the pathology revealed by the occipital isocortex in cases of Alzheimer's disease and age-matched controls. In general, amyloid and/or precursors of amyloid are encountered in plaque-like formations. Large numbers of amyloid plaques occur in layers that only occasionally harbor neuritic plaques. Amyloid deposits can be found in abundance in the occipital cortex of demented individuals exhibiting an only sparse number of neuritic plaques. In demented individuals the striate area contains almost as much amyloid as the parastriate area or the peristriate region. Neurofibrillary changes are encountered in neuritic plaques, neurofibrillary tangles, and neuropil threads. Neuritic plaques are predominantly found in layers II and III. Their density changes even within the boundaries of architectonic units. Large numbers of plaques are found in the cortex covering the depth of the sulci. The number of neurofibrillary tangles increases abruptly when passing the striate/parastriate and the parastriate/peristriate boundaries. The neuropil threads may densely fill a layer without the presence of neurofibrillary tangles (layer V of the striate area). Neuropil threads contribute a substantial part to the total amount of the intraneuronally deposited pathological material.