Part two of this three-part series commences with anomalous dominance and special talents. Part one appears in a previous issue of theArchives. 1 ANOMALOUS DOMINANCE AND SPECIAL TALENTS According to our hypothesis, slowed growth within certain zones of the left hemisphere is likely to result in enlargement of other cortical regions, in particular, the homologous contralateral area, but also adjacent unfaffected regions. The influences that favor anomalous dominance may thus favor talents associated with superior development of certain regions either in the right hemisphere or in adjacent parts of the left hemisphere. Even with excessive retardation of growth and the resultant migration abnormalities and learning disorders (LD), high talents may exist as a result of compensatory enlargement of other cortical regions. Several types of data are in concordance with these conclusions. Several studies have claimed that the average level of spatial talents is higher in male subiects. 2 Hier

https://jamanetwork.com/journals/jamaneurology/articlepdf/584161/archneur_42_5_008.pdf

Cerebral lateralization. Biological mechanisms, associations, and pathology: II. A hypothesis and a program for research.

Despite a hundred years' research, the neuropathology of schizophrenia remains obscure. However, neither can the null hypothesis be sustained--that it is a 'functional' psychosis, a disorder with no structural basis. A number of abnormalities have been identified and confirmed by meta-analysis, including ventricular enlargement and decreased cerebral (cortical and hippocampal) volume. These are characteristic of schizophrenia as a whole, rather than being restricted to a subtype, and are present in first-episode, unmedicated patients. There is considerable evidence for preferential involvement of the temporal lobe and moderate evidence for an alteration in normal cerebral asymmetries. There are several candidates for the histological and molecular correlates of the macroscopic features. The probable proximal explanation for decreased cortical volume is reduced neuropil and neuronal size, rather than a loss of neurons. These morphometric changes are in turn suggestive of alterations in synaptic, dendritic and axonal organization, a view supported by immunocytochemical and ultrastructural findings. Pathology in subcortical structures is not well established, apart from dorsal thalamic nuclei, which are smaller and contain fewer neurons. Other cytoarchitectural features of schizophrenia which are often discussed, notably entorhinal cortex heterotopias and hippocampal neuronal disarray, remain to be confirmed. The phenotype of the affected neuronal and synaptic populations is uncertain. A case can be made for impairment of hippocampal and corticocortical excitatory pathways, but in general the relationship between neurochemical findings (which centre upon dopamine, 5-hydroxytryptamine, glutamate and GABA systems) and the neuropathology of schizophrenia is unclear. Gliosis is not an intrinsic feature; its absence supports, but does not prove, the prevailing hypothesis that schizophrenia is a disorder of prenatal neurodevelopment. The cognitive impairment which frequently accompanies schizophrenia is not due to Alzheimer's disease or any other recognized neurodegenerative disorder. Its basis is unknown. Functional imaging data indicate that the pathophysiology of schizophrenia reflects aberrant activity in, and integration of, the components of distributed circuits involving the prefrontal cortex, hippocampus and certain subcortical structures. It is hypothesized that the neuropathological features represent the anatomical substrate of these functional abnormalities in neural connectivity. Investigation of this proposal is a goal of current neuropathological studies, which must also seek (i) to establish which of the recent histological findings are robust and cardinal, and (ii) to define the relationship of the pathological phenotype with the clinical syndrome, its neurochemistry and its pathogenesis.

/pdf/the-neuropathology-of-schizophrenia-a-critical-review-of-the-1zxk39qd1v.pdf

The neuropathology of schizophrenia. A critical review of the data and their interpretation.

Background and Methods. The cause of childhood hyperactivity (attention deficit–hyperactivity disorder) is unknown. We investigated the hypothesis that cerebral glucose metabolism might di...

https://www.nejm.org/doi/pdf/10.1056/NEJM199011153232001

Cerebral glucose metabolism in adults with hyperactivity of childhood onset

Recent neuroradiologic and neuropathological studies indicate that at least some patients with schizophrenia have slightly enlarged cerebral ventricles and subtle anatomical abnormalities in the region of the anterior hippocampus. Using magnetic resonance imaging (MRI), we studied 15 sets of monozygotic twins who were discordant for schizophrenia (age range, 25 to 44 years; 8 male and 7 female pairs). For each pair of twins, T1-weighted contiguous coronal sections (5 mm thick) were compared blindly, and quantitative measurements of brain structures were made with a computerized image-analysis system. In 12 of the 15 discordant pairs, the twin with schizophrenia was identified by visual inspection of cerebrospinal fluid spaces. In two pairs no difference could be discerned visually, and in one the twin with schizophrenia was misidentified. Quantitative analysis of sections through the level of the pes hippocampi showed the hippocampus to be smaller on the left in 14 of the 15 affected twins, as compared with their normal twins, and smaller on the right in 13 affected twins (both P less than 0.001). In the twins with schizophrenia, as compared with their normal twins, the lateral ventricles were larger on the left in 14 (P less than 0.003) and on the right in 13 (P less than 0.001). The third ventricle also was larger in 13 of the twins with schizophrenia (P less than 0.001). None of these differences were found in seven sets of monozygotic twins without schizophrenia who were studied similarly as controls. We conclude that subtle abnormalities of cerebral anatomy (namely, small anterior hippocampi and enlarged lateral and third ventricles) are consistent neuropathologic features of schizophrenia and that their cause is at least in part not genetic. Further study is required to determine whether these changes are primary or secondary to the disease.

https://www.nejm.org/doi/pdf/10.1056/NEJM199003223221201

Anatomical abnormalities in the brains of monozygotic twins discordant for schizophrenia.

Sixty-four autopsied brains of schizophrenic patients were neuropathologically examined and compared with 10 brains of non-schizophrenic controls. Clinical diagnoses were established retrospectively according to the Research Diagnostic Criteria and the International Classification of Diseases. We found:
 Generally, these anatomical abnormalities were asymmetric. The histological findings in the two limbic regions consisted mainly of poorly developed structure in the upper layers, with a heterotopic displacement of single groups of nerve cells in the entorhinal region. Particularly, the disturbed structure of the second layer Pre-α in medial and central fields of the entorhinal region, situated in the parahippocampal gyrus (group 2 a), suggests a disturbance of neuronal migration in a later phase of cortical development.

Prenatal developmental disturbances in the limbic allocortex in schizophrenics.

• Lateral cerebral ventricular enlargement is now known to occur in some schizophrenic patients. To determine whether ventriculomegaly in schizophrenia is a static vs progressive process, we conducted a follow-up computed tomographic brain scan study on 11 young male patients, three years after initial scans were obtained. No significant change was found in the mean ventricles-brain ratio of this small schizophrenic sample after three years. Four of 11 patients showed noticeable increases (>50%) in individual ratio. Methodologic problems are discussed and the need for follow-up studies as a research strategy is emphasized.

Cerebral Ventricular Enlargement in Schizophrenia: A Preliminary Follow-up Study

• A computed tomographic study of the brain in 55 young men with chronic schizophrenia and 27 age- and sex-matched control subjects showed a significantly higher ventricle-brain ratio (VBR) in the patients with chronic schizophrenia. Using the Tsuang-Winokur criteria, the sample was classified into paranoid and nonparanoid-hebephrenic subtypes. Nonparanoid patients who did not fulfill the criteria for hebephrenia were grouped as a nonparanoid-undifferentiated subtype. All three groups of subtypes had a significantly higher mean VBR than control subjects. Among the schizophrenia subtypes, the paranoid and nonparanoid-hebephrenic groups were not different, and both had a significantly larger mean VBR than the nonparanoid-undifferentiated group. The results suggest that although the extent of ventricular enlargement varies among schizophrenia subtypes, they all show a significant enlargement compared with the control group. Also, in contrast with previous reports linking a high VBR with negative symptoms, poor prognosis, and impaired cognition, the data in this study show the largest mean VBR in the paranoid patients who generally have a good premorbid history, positive symptoms, less impaired cognition, and relatively better prognosis.

https://jamanetwork.com/journals/PSYCH/articlepdf/492829/archpsyc_39_7_003.pdf

Cerebral Ventricular Enlargement in Subtypes of Chronic Schizophrenia

Fifty-five schizophrenic, 24 manic and 27 control subjects, all males between 20-45 years of age, were examined for structural brain abnormalities with computerized tomography (CT) scans. Both manic and schizophrenic samples had significantly larger ventricles than the control group. Cerebral atrophy was more frequent in schizophrenia, while cerebellar atrophy was more frequent in mania. An association between increased ventricular size and cerebellar atrophy was found in mania but not in schizophrenia. Cerebral atrophy was not associated with ventricular enlargement in either disorder. Implications of these findings are discussed.

Cortical atrophy in schizophrenia and mania: a comparative CT study.

In a group of 55 chronic schizophrenic men aged 20-45 years, the mean ventricle to brain ratio (VBR) on computerized tomographic brain scan was significantly greater than in 27 matched control subjects. A clinical comparison was then conducted between the schizophrenic patients with VBRs above (N = 19) or below (N = 36) 2 SD from the control mean. No differences were found in age of onset, premorbid history, duration of illness, severity of illness, response to neuroleptic drug treatment, presence of positive or negative symptoms, substance abuse, or cognitive testing. However patients with VBRs greater than 2 SD above the mean were significantly older and had a significantly higher frequency of history of schizophrenia in a first-degree relative.

Mona McCalley-Whitters

Papers

Cerebral Ventricular Enlargement in Schizophrenia: A Preliminary Follow-up Study

Cerebral Ventricular Enlargement in Subtypes of Chronic Schizophrenia

Cortical atrophy in schizophrenia and mania: a comparative CT study.

Clinical differences between schizophrenic patients with and without large cerebral ventricles

Cerebral venticular enlargement in young manic males