Nonpsychiatric Control Subjects Research Articles

Circumscribed numerical deficit of dorsal raphe neurons in mood disorders

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. 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 microm axial serial sections of the brainstem. 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. 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.

Recollection memory deficits in patients with major depressive disorder predicted by past depressions but not current mood state or treatment status.

Neuropsychological studies have suggested that memory systems reliant on medial temporal lobe structures are impaired in patients with depression. There is less data regarding whether this impairment is specific to recollection memory systems, and whether clinical features predict impairment. This study sought to address these issues. A computerized process-dissociation memory task was utilized to dissociate recollection and habit memory in 40 patients with past or current major depression and 40 age, sex and IQ matched non-psychiatric control subjects. The Cognitive Failures Questionnaire was used to assess patients' perceptions of day-to-day memory failures. Patients had impaired recollection memory (t = 4.7, P < 0.001), but no impairment in habit memory when compared to controls. Recollection memory performance was not predicted by indices of current mood state, but was predicted by self-assessments of impairment (beta = -0.33; P = 0.008) and past number of depressions (beta = -0.41; P = 0.001). There was no evidence that standard therapy with antidepressant medication either improved or worsened memory performance. The results confirm that patients with multiple past depressions have reduced function on recollection memory tasks, but not on habit memory performance. The memory deficits were independent of current mood state but related to past course of illness and significant enough that patients detected impairment in day-to-day memory function.

Temperament and Character Inventory (TCI) personality profile and sub-typing in alcoholic patients: a controlled study.

Cloninger's Temperament and Character Inventory (TCI) personality profile was used to compare alcohol-dependent patients with non-psychiatric control subjects, and a search made for sub-types of alcoholics with different TCI profiles, using the criteria age of onset of alcohol-related problems, paternal dependence on alcohol and familial antecedents of alcohol dependence. Alcohol-dependent patients (n = 38) were characterized by higher Novelty-Seeking [corresponding to Diagnostic and Statistical Manual of Mental Disorders (4th edition) group B personality type] and lower Self-Directedness than non-psychiatric control subjects (n = 47). Lower Self-Directedness indicates a higher probability of personality disorder in the alcohol-dependent population. Only age of onset of alcohol-related problems delineated the two sub-populations with different TCI profiles: early-onset alcoholics (< or =25 years of age, n = 19), but not late-onset ones (n = 16), in comparison with control subjects, were associated with higher Novelty-Seeking. Both early and late-onset patients scored lower on Self-Directedness than control subjects. Self-Directedness and Cooperation scores were lower in early-onset than in late-onset patients. These results in part support Cloninger's typology, and the TCI data add to evidence concerning a higher probability of personality disorder in alcohol-dependent patients, particularly those with early-onset.

Backward masking task performance in stable, euthymic out-patients with bipolar disorder.

Several studies have suggested that visual backward masking (VBM) impairment is present in patients with bipolar disorder, but the clinical features, such as current symptoms, treatment status and past burden of illness that may contribute to the impairment have not been well described. This study examined well-characterized euthymic patients on two VBM tasks to ascertain the extent of VBM impairment in this group and the clinical correlates of this impairment. Twenty-eight euthymic patients with a DSM-IV diagnosis of bipolar disorder were matched by age, sex and IQ with 28 non-psychiatric control subjects. Both groups completed two VBM tasks; one required subjects to locate the target stimulus, one required identification of the target stimulus. Reaction times and error rates across a range of target-mask inter-stimulus intervals were assessed. Patients were significantly slower and had more errors on both VBM tasks. There was a significant relation between reaction times on the identification task and past burden of illness, particularly past number of depressions. There was no discernible impact of treatment status on reaction time or performance, including no difference in lithium-treated versus not treated subjects. These results are consistent with previous reports of neuropsychological deficits in euthymic bipolar disorder patients. The potential benefit to employing tasks such as VBM is that it may provide a method for relating clinical variables such as illness burden with known neural pathways in order to elucidate better the pathophysiology leading to impaired cognitive performance in patients with bipolar disorder.

Oxytocin and autistic disorder: alterations in peptide forms

Background: Oxytocin (OT) is synthesized as a prohormone that is sequentially processed to peptides. These peptides are the bioactive amidated form (OT) and the C-terminal extended peptides, OT-Gly, OT-Gly-Lys and OT-Gly-Lys-Arg, which are designated together as OT-X. As an extension of our previous study finding decreased plasma OT in autism, studies were conducted to determine whether there were changes in OT peptide forms in autistic children.Methods: Twenty eight male subjects (97 ± 20 months; range, 70–139 months), diagnosed with DSM-IV autistic disorder through observation and semi-structured interview, were compared with 31 age-matched nonpsychiatric control subjects (106 ± 22 months; range, 74–140 months). Using OT antisera with different specificity for the peptide forms, we measured plasma OT and OT-X in each group.Results: T tests showed that there was a decrease in plasma OT (t = 4.4, p < .0001), an increase in OT-X (t = 2.3, p < .03) and an increase in the ratio of OT-X/OT (t = 4.5, p < .0001) in the autistic sample, compared with control subjects.Conclusions: The results suggest that children with autistic disorder show alterations in the endocrine OT system. Deficits in OT peptide processing in children with autism may be important in the development of this syndrome.

Dysregulation of olfactory receptor neuron lineage in schizophrenia.

Growing evidence implicates abnormal neurodevelopment in schizophrenia. While neuron birth and differentiation is largely completed by the end of gestation, the olfactory epithelium (OE) is a unique part of the central nervous system that undergoes regeneration throughout life, thus offering an opportunity to investigate cellular and molecular events of neurogenesis and development postmortem. We hypothesized that OE neurons exhibit deviant progress through neurodevelopment in schizophrenia characterized by an increase in immature neurons. Olfactory epithelium was removed at autopsy from 13 prospectively assessed elderly subjects who had schizophrenia and 10 nonpsychiatric control subjects. Sections were immunolabeled with antibodies that distinguish OE neurons in different stages of development, including basal cells (low-affinity nerve growth factor receptor, p75NGFR), postmitotic immature neurons (growth-associated protein 43 [GAP43]), and mature olfactory receptor neurons (olfactory marker protein). Absolute and relative densities of each cell type were determined. We observed a significantly lower density of p75NGFR basal cells (37%) in schizophrenia and increases in GAP43 + postmitotic immature neurons (316%) and ratios of GAP43 + postmitotic immature neurons to p75NGFR + cells (665%) and olfactory marker protein + mature neurons to p75NGFR + basal cells (328%). Neuroleptic-free schizophrenia subjects exhibited the highest GAP43 + postmitotic immature neuron values. Abnormal densities and ratios of OE neurons at different stages of development indicate dysregulation of OE neuronal lineage in schizophrenia. This could be because of intrinsic factors controlling differentiation or an inability to gain trophic support from axonal targets in the olfactory bulb. While caution is necessary in extrapolating developmental findings in mature OE to early brain development, similarities in molecular events suggest that such studies may be instructive.

Increased hippocampal bdnf immunoreactivity in subjects treated with antidepressant medication

Background: The cAMP signaling pathway, and its downstream neurotrophic factor BDNF, are major targets of antidepressant medications. Abnormalities in this pathway have previously been reported in postmortem brain of subjects with mood disorders. This study was designed to test whether the diagnosis of a mood disorder, or treatment with an antidepressant or mood stabilizer was associated with changes in hippocampal BDNF in postmortem brain Methods: Frozen postmortem anterior hippocampus sections were obtained from the Stanley Foundation Neuropathology Consortium. Tissue from subjects with major depression, bipolar disorder, schizophrenia and nonpsychiatric control subjects were stained for BDNF using immunohistochemistry Results: Increased BDNF expression was found in dentate gyrus, hilus and supragranular regions in subjects treated with antidepressant medications at the time of death, compared with antidepressant-untreated subjects. Furthermore, there was a trend toward increased BDNF expression in hilar and supragranular regions in depressed subjects treated with antidepressants, compared with the subjects not on these medications at the time of death Conclusions: These findings are consistent with recent studies measuring CREB levels in this same subject sample, and support current animal and cellular models of antidepressant function.

A quantitative immunohistochemical study of astrocytes in the entorhinal cortex in schizophrenia, bipolar disorder and major depression: absence of significant astrocytosis

A number of macroscopic changes have been reported in the temporal lobe in schizophrenia. We have evaluated the density of glial fibrillary acidic protein (GFAP)-positive astrocytes in cortical layers 2 through 6 in the intermediate subarea of entorhinal cortex in two cohorts: the first, 15 cases, made up of schizophrenic ( n = 7) and normal nonpsychiatric control subjects ( n = 8), and the second, 56 cases, composed of schizophrenic ( n = 14), bipolar disorder ( n = 13), major depressive ( n = 14) and normal control subjects ( n = 15). No significant difference in density of GFAP-positive astrocytes was detected between the psychiatric diagnostic groups and the normal controls in either of the two cohorts. In both cohorts there was a positive correlation between increasing age and astrocytic density which reached statistical significance in only the larger cohort ( r = 0.38, p = 0.004). Our results find no evidence for astrocytosis in the entorhinal cortex in several mental illnesses. Although other studies have reported macroscopic and other structural abnormalities in this region, we have not detected astrocytic proliferation, which is a typical hallmark of atrophy and/or progressive neuronal loss.

Reduced activation and expression of ERK1/2 MAP kinase in the post-mortem brain of depressed suicide subjects.

The extracellular regulated kinases (ERK) 1 and ERK2 are members of mitogen-activated protein (MAP) kinase family that play an important role in transducing extracellular signals to the nucleus and have been implicated in a broad spectrum of biological responses. To test the hypothesis that MAP kinases may be involved in depression, we examined the activation of p44/42 MAP kinase and expression of ERK1 and ERK2 in the post-mortem brain tissue obtained from non-psychiatric control subjects (n = 11) and age- and the post-mortem interval-matched depressed suicide subjects (n = 11). We observed that p44/42 MAP kinase activity was significantly decreased in the prefrontal cortical areas (Brodmann's areas 8, 9 and 10) and the hippocampus of depressed suicide subjects without any change in the cerebellum. This decrease was associated with a decrease in mRNA and protein levels of ERK1 and ERK2. In addition, the expression of MAP kinase phosphatase (MKP)2, a 'dual function' ERK1/2 phosphatase, was increased in the prefrontal cortex and hippocampus. These studies suggest that p44/42 MAP kinases are less activated in the post-mortem brain of depressed suicide subjects and this may be because of reduced expression of ERK1/2 and increased expression of MKP2. Given the role of MAP kinases in various physiological functions and gene expression, alterations in p44/42 MAP kinase activation and expression of ERK1/2 may contribute significantly to the pathophysiology of depressive disorders.

Verbal self-monitoring and auditory verbal hallucinations in patients with schizophrenia.

Contemporary cognitive models of auditory verbal hallucinations propose that they arise through defective self-monitoring. We used a paradigm that engages verbal self-monitoring to investigate this theory in patients with schizophrenia. Ten patients with auditory verbal hallucinations and delusions (hallucinators), eight patients with delusions but no hallucinations (non-hallucinators), and 20 non-psychiatric control subjects were tested. Participants read single adjectives aloud, under the following randomized conditions: reading aloud; reading aloud with acoustic distortion of their own voice; reading aloud with alien feedback (someone else's voice); and reading aloud with distorted alien feedback. Immediately after articulating each word, participants identified the source of the speech they heard ('self'/'other'/'unsure'), via a button press. Response choice and reaction time were recorded. When reading aloud with distorted feedback of their own voice, patients in both groups made more errors than controls; they either misidentified its source or were unsure. Hallucinators were particularly prone to misattributing their distorted voice to someone else, and were more likely to make errors when the words presented were derogatory. Both patient groups made faster decisions than controls about the source of distorted or alien speech, but faster responses were only associated with errors in the former condition. Impaired verbal self-monitoring was evident in both hallucinators and non-hallucinators. As both groups had delusions, the results suggest an association between delusions and impaired judgements about ambiguous sensory stimuli. The specific tendency of hallucinators to misattribute their distorted voice to someone else may reflect impaired awareness of internally generated verbal material.

Reductions in neuronal and glial density characterize the dorsolateral prefrontal cortex in bipolar disorder

Background: Bipolar disorder (BPD) is a mental illness in which depression and mania typically alternate, and both phases can present with psychotic features. The symptomatology of BPD, therefore, resembles major depressive disorder (MDD) and schizophrenia (SCHZ), posing diagnostic dilemmas. Distinct alterations in cellular architecture of the dorsolateral prefrontal cortex distinguish SCHZ and MDD, whereas the cellular neuropathology of BPD has not been studied. Methods: Dorsolateral prefrontal area 9 was analyzed using a three-dimensional morphometric method in postmortem brains from 10 BPD patients and 11 matched nonpsychiatric control subjects. Results: Area 9 in BPD was characterized by reduced neuronal density in layer III (16%–22%) and reduced pyramidal cell density in layers III and V (17%–30%). A 19% reduction in glial density was found in sublayer IIIc coupled with enlargement and changes in shape of glial nuclei spanning multiple layers. Conclusions: The morphologic signature of BPD, i.e., decreased neuronal and glial density in association with glial hypertrophy, is distinct from previously described elevations in neuronal density in SCHZ, instead resembling the reductions in cell density found in MDD. Thus, the neuropathologic distinctions between BPD and SCHZ are indicative of separate mental illnesses, each with a unique morphologic disturbance of specific neural circuits.

Clinical and biological concomitants of resting state EEG power abnormalities in schizophrenia

Background: This study investigated the clinical and biological concomitants of electroencephalogram power abnormalities in schizophrenia. Methods: We examined the power characteristics of resting electroencephalograms in 112 schizophrenic patients. Also collected were measures of psychotic symptomatology, brain morphology, ocular motor functioning, electrodermal activity, and nailfold plexus visibility. Seventy-eight nonschizophrenic psychosis patients (e.g., mood disorder patients with psychosis) and 107 nonpsychiatric control subjects were included for comparison. Results: Schizophrenic patients whose electroencephalograms were characterized by augmented low-frequency power and diminished alpha-band power had more negative symptoms, larger third ventricles, larger frontal horns of the lateral ventricles, increased cortical sulci widths, and greater ocular motor dysfunction compared with schizophrenic patients without these electroencephalogram characteristics. In nonschizophrenic psychosis patients, augmented low-frequency and diminished alpha-band powers failed to be associated with any clinical or biological indices. Conclusions: Results suggest that clinical and biological concomitants of low-frequency and alpha-band power abnormalities in schizophrenia are unique, perhaps indicating the presence of thalamic and frontal lobe dysfunction.

G Protein-coupled cyclic AMP signaling in postmortem brain of subjects with mood disorders: effects of diagnosis, suicide, and treatment at the time of death.

Components of cyclic AMP (cAMP) signaling were examined in postmortem cerebral cortex of a well characterized group of patients with mood disorders and nonpsychiatric control subjects. We measured G protein levels, adenylyl cyclase (AC) activity, and CREB levels in cerebral cortex of the subjects with respect to diagnosis, treatment, and suicide. There was no effect of diagnosis on any measure, except for a trend toward decreased stimulated AC activity in subjects with mood disorders relative to control subjects. We also detected a significant effect of suicide on temporal cortex CREB levels in subjects that died as a result of suicide relative to those that did not, which was more evident in patients with major depressive disorder. Bipolar disorder (BD) subjects treated with anticonvulsants at the time of death had decreased temporal cortex CREB levels relative to those not receiving anticonvulsants. Furthermore, we found a trend toward decreased occipital cortex G alpha(s) (short) levels in BD subjects treated with lithium. These results support the hypothesis of altered cAMP signaling in mood disorders and raise the possibility that factors other than diagnosis, such as treatment and suicide, may be relevant to cell-signaling abnormalities reported in the literature.

An electroencephalographic study comparing maximum blink rates in schizophrenic and nonschizophrenic psychiatric patients and nonpsychiatric control subjects

We did a retrospective electroencephalographic (EEG) analysis of blink rates in patients with psychiatric disorders and control subjects to determine whether maximum blink rates under different conditions were higher in patients with psychiatric disorders. Maximum blink rates in those with schizophrenia (n = 23), those with nonschizophrenic psychiatric illnesses (n = 21), and nonpsychiatric control subjects (n = 35) were obtained from patients' EEGs and compared with one-way analysis of variance and post hoc tests. In addition, correlation analysis was performed to determine if patients' medications affected maximum blink rates. Patients with schizophrenic and nonschizophrenic psychiatric disorders had twofold higher maximum resting blink rates compared to controls (p < .05 respectively). No difference was found between those with schizophrenic and nonschizophrenic psychiatric disorders. The maximum blink rate during cognitive testing was also twofold higher in those with nonschizophrenic psychiatric disorders (n = 11) compared to controls (n = 16; p < .05). Within each group, maximum blink rates during quiet rest and cognitive testing did not differ, nor were there differences between groups in the duration of high-frequency blinking (greater than 40 blinks per minute) during quiet rest. In psychiatric patients, none of the medications taken at the time of EEG recording correlated with maximum blink rates. High maximum blink rates recorded by EEG may suggest the presence of a psychiatric disorder.

Cognitive functioning and GABA A/benzodiazepine receptor binding in schizophrenia: A 1231-iomazenil SPET study

The role of the inhibitory neurotransmitter gamma aminobutyric acid (GABA) in schizophrenia has previously been investigated using postmortem material. Recently, using single photon emission tomography (SPET) with the selective benzodiazepine antagonist 123I-Iomazenil as the radioligand, we have demonstrated an in vivo relationship between reduced GABAA/benzodiazepine receptor binding and the severity of positive symptomatology in schizophrenia. The present study aimed to build on this using the same in vivo scanning techniques, and relating findings to cognitive functioning. Ten nonpsychiatric control subjects and 15 schizophrenic patients, matched for age and handedness, were scanned. A battery of neuropsychologic tests was also administered. Correlational analysis revealed a pattern of increased correlations between GABAA/benzodiazepine receptor binding and task performance, in the schizophrenic group compared to the control group. Findings are preliminary but suggest a relationship between reduced GABAA/benzodiazepine receptor binding and poorer cognitive functioning, involving memory and visual attention processes, in the schizophrenic group but not in the control group. A role for GABA in the pathophysiology of schizophrenia is suggested. Limitations of the present study and suggestions for future research are discussed.

The structure of DSM-III-R schizotypal personality disorder diagnosed by direct interviews.

Confirmatory factor analysis techniques were applied to test how competing models (unifactorial, bifactorial, and trifactorial) could be used to explain the structure of schizotypal disorder as defined in DSM-III-R and DSM-IV. Subjects were 538 nonpsychotic psychiatric outpatients and a replication sample of 225 nonpsychiatric patients and control subjects, interviewed by clinicians using the Structured Interview for DSM-III-R Personality Disorders. The study found that the best-fit solution encompassed three factors: cognitive-perceptual, interpersonal, and oddness. Future studies may benefit from considering schizotypal personality disorder as composed of three factors that may indicate the existence of three underlying (dys)functional systems.

Global self-esteem as contingent on body satisfaction among patients with bulimia nervosa: Lack of diagnostic specificity?

To examine whether the self-esteem of patients with bulimia nervosa was more contingent on body satisfaction than that of nonpsychiatric control and of depressed participants. Patients with bulimia nervosa (selected according to DSM-III-based structured clinical interviews), those with depression (selected based on chart diagnoses), and nonpsychiatric control samples completed measures of body dissatisfaction and of global self-esteem. Consistent with past work, we found that body dissatisfaction accounted for a greater amount of global self-esteem among bulimia nervosa patients, as compared to nonpsychiatric control subjects. However, the relation between global self-esteem and body dissatisfaction was similar in patients with bulimia nervosa as in those with depression. Although our depressed group possessed bulimic characteristics, this did not appear to account for our findings, in that the correlation between body dissatisfaction and self-esteem was highest among the nonbulimic depressed participants. Our results raise questions about the specific pathognomonic quality of body satisfaction-dependent self-esteem in bulimia nervosa.

Specific comorbidity between bulimia nervosa and personality disorders.

The present study investigates the comorbidity between bulimia nervosa (BN) and the entire range of American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, 3rd rev. ed. (DSM-III-R) personality disorders and controls for the presence of coexisting depression. The Personality Disorders Examination (PDE), a structured interview that encompasses all 13 (provisional) DSM-III-R personality disorders, was administered to three groups of subjects: depressed BN patients (n = 15), nondepressed BN patients (n = 15), and nonpsychiatric controls (n = 15). The BN patients were referrals to a dieting disorder unit affiliated with the University of Sydney. They all met DSM-III-R criteria and all had body mass indexes (BMIs) greater than 19. The nonpsychiatric control group were recruited from an undergraduate psychology course. All subjects were given the Bulimic Investigatory Test, Edinburgh (BITE), the Eating Disorders Inventory-2 (EDI-2), the Hamilton Depression Rating Scale (HDRS), and the PDE. 46.7% of depressed BN patients met the criteria for at least one Axis II diagnosis, as assessed by the PDE, and 33.3% of nondepressed BN patients received such a diagnosis, whereas only 6.7% of nonpsychiatric control subjects met this criterion (p < .05). The results of the present study provide support for an increased comorbidity between personality disorders and BN that cannot be attributed to the confounding influence of coexisting depression. This finding enables the identification of subgroups of individuals with BN, enabling them to be compared and contrasted. The identification of differences between subgroups may provide information regarding prognosis and differential response to treatment, which could enable more appropriate treatment decisions to be made.

MRI changes in schizophrenia in late life: a preliminary controlled study

The aim of this pilot study was to compare cerebral changes on magnetic resonance imaging (MRI) scans in elderly schizophrenic subjects with those in psychiatric and normal control subjects. We compared the MRIs of 19 subjects with schizophrenia, 19 age- and gender-matched subjects with recurrent major depression, and 19 age- and gender-matched nonpsychiatric control subjects. Deep white matter hyperintensities (DWMH) in right posterior regions were significantly more prominent in the schizophrenic group than in the two comparison groups. Total ratings of MRI abnormalities were significantly related to age in both the normal control and schizophrenic groups, but not in the depressive group. Age of onset was positively associated with total ratings in the depressive group, but not in the schizophrenic group. Thus, a subset of elderly patients with schizophrenia appear to have cerebral white matter abnormalities; such abnormalities may not be confined to lage-onset schizophrenia. Systematic MRI studies of early- and late-onset schizophrenia in late life are needed to resolve this question.

Brain morphology assessed by computed tomography in patients with geriatric depression, patients with degenerative dementia, and normal control subjects

To determine whether patients with geriatric depression have specific alterations in brain morphology, internal (ventricles) and external (frontal, temporal, and parieto-occipital) components of the cerebrospinal fluid (CSF) spaces were examined Planimetric measurements of computed tomographic (CT) scans from patients with geriatric depression were compared with measurements from two age- and sex-matched control groups normal control subjects and patients with primary degenerative dementia. Scans of 34 patients (6 men, 28 women; mean age = 70.7 years) who met DSM-III-R diagnostic criteria for major depression, 29 patients with DSM-III-R primary degenerative dementia (8 men, 21 women; mean age = 71.2 years), and 43 nonpsychiatric control subjects (10 men, 33 women; mean age = 70.8 years) were evaluated. The areas of the frontal and parieto-occipital sulci, the Sylvian fissures, and the lateral and third ventricles were measured separately for the right and left hemispheres. Compared with the control subjects, patients with geriatric depression revealed a remarkable enlargement (up to 125%) of the left Sylvian fissure on several levels and a more subtle enlargement of the ventricles, cortical sulci, and right Sylvian fissure (20–50%). The laterality index differed significantly between depressed patients and normal control subjects (but not between the demented patients and the normal control group) only for the Sylvian fissure. Demented patients showed a considerable brain atrophy that affected all CSF components (enlargment of 30–160%), but the left temporal region was less affected than in the depressed patients. Compared with the findings in geriatric depression, ventricular enlargement was significant in dementia. In the group with geriatric depression, there was no correlation between CT parameters and disease duration. The findings provide further evidence of alterations in brain morphology of patients with geriatric depression. The pattern of pathomorphology differs from that of demented patients.