In schizophrenia, sex differences related to age of onset, course of illness and response to antipsychotic treatment may be mirrored by differences in the underlying molecular pathways. We attempted to increase our understanding of these phenomena by carrying out multiplex immunoassay profiling of 95 serum molecules using samples from 4 independent cohorts of male and female first episode antipsychotic naive schizophrenia patients (n=133) and matched controls (n=133). The concentrations of 16 molecules associated with hormonal, inflammation and growth factor pathways showed significant sex differences in schizophrenia patients compared with controls. In line with the numerous sex differences reported in schizophrenia, our findings included alterations in the levels of several hormones, including elevated free and total testosterone in female patients and concomitant sex differences in sex hormone binding globulin and prolactin concentrations. We also found higher levels of thyroxine binding globulin and seven inflammatory markers in male schizophrenia patients only, raising the possibility that some aspects of the widely-reported immunological abnormalities in schizophrenia may be specific for males. Several of these markers showed sexspecific associations with positive and negative syndrome scale (PANSS) scores and changes in concentration after 6 weeks of treatment with antipsychotics. Finally, we also evaluated overlapping and distinct sex-specific biomarkers for schizophrenia, Asperger syndrome, major depressive disorder and bipolar disorder. We propose that future studies should investigate the common and sex-specific aetiologies of schizophrenia, as the current findings suggest that different therapeutic strategies may be required for male and female patients.

Based on the neuroinflammatory hypothesis of schizophrenia, we have quantified the numerical density of immunostained CD3+ T-lymphocytes, CD20+ B-lymphocytes, and HLA-DR+ microglial cells in the posterior hippocampus of 17 schizophrenia patients and 11 matched controls. Disease course-related immune alterations were considered by a separate analysis of residual (prevailing negative symptoms, n=7) and paranoid (prominent positive symptoms, n=10) schizophrenia cases. Higher lymphocyte densities were observed in residual schizophrenia. In contrast, HLA-DR+ microglia were increased in paranoid schizophrenia. BBB impairment and infiltration of T cells and B cells may contribute to the pathophysiology of residual schizophrenia, while microglial activation seems to play a role in paranoid schizophrenia. The identification of diverse immune endophenotypes may facilitate the development of distinct anti-inflammatory schizophrenia therapies to normalize BBB function, (auto)antibody production or microglial activity.

Background. Neurocircuits comprising limbic, striato–pallidal and thalamo–cortical brain areas are assumed to be involved in the pathophysiology of mood disorders. All these brain regions receive serotonergic afferents arising from the rostral raphe, mainly the dorsal raphe. Although serotonergic systems appear to be involved in the pathology of mood disorders, there is uncertainty as to whether structural alterations in raphe nuclei exist alongside a functional dysregulation of the serotonergic system.

Methods. In the brains of 12 patients with mood disorders (major depressive disorder N = 6, bipolar disorder N = 6) and 12 normal subjects we performed a morphometric post-mortem study on neuronal morphology in all subnuclei of the dorsal raphe nucleus using Nissl stained 20 μm axial serial sections of the brainstem.

Results. The number of neurones of the ventrolateral subnucleus of the dorsal raphe was reduced by 31% in patients with mood disorders compared with non-psychiatric control subjects. Ventrally located subnuclei of the rostral dorsal raphe (ventrolateral, ventral, interfascicular) taken together also showed a smaller number of neurones. Neurone numbers of the dorsal and the caudal subnucleus and volumes of all single subnuclei appeared to be unchanged. Analysis of morphological neuronal types revealed a smaller number of triangular neurones in the ventrolateral subnucleus. Numbers of ovoid and round neurones in the ventrolateral subnucleus also showed a trend to reduction. No correlation was found between neurone numbers in any subnucleus of the dorsal raphe and duration of illness. Neurone numbers did not differ in any subnucleus between patients with unipolar and those with bipolar affective disorder.

Conclusions. Results indicate that patients with primary mood disorders have a circumscribed numerical neuronal deficiency in the dorsal raphe. This structural deviation may contribute to impaired serotonergic innervation of brain regions which are involved in the pathology of mood disorders.

Background. Catatonia is a psychomotor syndrome that can be characterized by behavioural, affective and motor abnormalities. In order to reveal further underlying pathophysiological mechanisms of psychomotor disturbances in catatonia we investigated neuropsychological function and regional cerebral perfusion (r-CBF) in a combined study.

Methods. Ten catatonic patients were investigated with Tc-99mECD brain SPECT and compared with 10 psychiatric (similar age, sex, medication and underlying psychiatric diagnosis but without catatonic syndrome) and 20 healthy controls. Neuropsychological measures included tests for general intelligence, attention, executive functions and right parietal visual–spatial abilities. Correlational analyses were performed between neuropsychological measures, catatonic symptoms and r-CBF.

Results. Catatonic patients showed a significant decrease of r-CBF in right lower and middle prefrontal and parietal cortex compared with psychiatric and healthy controls as well as significantly poorer performance in visual–spatial abilities associated with right parietal function. Correlational analysis revealed significant correlations between visual–spatial abilities and right parietal r-CBF only in psychiatric and healthy controls but not in catatonic patients. In contrast, attentional measures correlated significantly with motor symptoms, visual–spatial abilities and right parietal r-CBF in catatonia only but not in psychiatric or in healthy controls.

Conclusion. Findings are preliminary but suggest right lower prefronto-parietal cortical dysfunction in catatonia, which may be closely related to psychomotor disturbances.

Background. Catatonia, a symptom complex with motor, affective and cognitive symptoms seen in a variety of psychotic conditions and with organic disease, was examined using a motor task using functional magnetic resonance imaging (fMRI).

Methods. Two acute catatonic patients and two age- and sex-matched healthy controls performed sequential finger opposition (SFO) after being medicated with 2 mg of lorazepam (i.v.). Functional magnetic resonance images were collected using a gradient echo pulse sequence (EPI).

Results. Patients with catatonia showed reduced motor activation of the contralateral motor cortex during SFO of the right hand, ipsilateral activation was similar for patients and controls. There were no differences in the activation of the SMA. During left hand activation the right-handed catatonic patients showed more activation in the ipsilateral cortex, a reversal from the normal pattern of activation in which the contralateral side shows four to five times more activation than the ipsilateral side.

Conclusions. In catatonic patients there is a decreased activation in motor cortex during a motor task compared to matched medicated healthy controls. In addition activation of the non-dominant side, left-handed activity in right-handed patients, results in a total reversal of the normal pattern of lateral activation suggesting a disturbance in hemispheric localization of activity during a catatonic state.

Background. Several clinical and neuroimaging investigations support the notion that underlying brain changes may relate to depression in older patients, especially those with a later-age initial episode. However uncertainty still exists about diagnostic and pathogenic significance of structural brain abnormalities in aged depressives, in part because many studies lack all-elderly and age-similar normal comparison populations.

Methods. Brain morphology of elderly depressives (N = 30) and normal controls (N = 36) was compared by assessing magnetic resonance imaging (MRI) brain scans with qualitative criteria-based scales. Ratings included lateral and third ventricle enlargement, and cortical, medial temporal, and caudate atrophy.

Results. Significant differences between depressed and control groups were not demonstrated. Later-onset depressives had significantly more left medial temporal and left caudate atrophy than early-onset counterparts of similar age. Medial temporal atrophy significantly correlated with cognitive impairment and was not related to physical illness. Depressives with medial temporal atrophy (N = 7) were older and had later age at onset of depression than those without such changes. Cerebrovascular disease risk factors did not predict MRI abnormalities.

Conclusions. Results indicate non-specificity and lack of homogeneity of qualitatively measured structural brain changes in geriatric depression, but suggest that pathology of specific, lateralized brain regions may be implicated in some later-onset patients. The relationship between medial temporal atrophy and late-onset depression raises the possibility that such patients may suffer from as-yet undeclared Alzheimer's disease. Lack of association between cerebrovascular disease risk factors and brain changes suggests other pathophysiological contributions.