Robert R. Rawlings

Seasonality of births in schizophrenia and bipolar disorder: a review of the literature

More than 250 studies, covering 29 Northern and five Southern Hemisphere countries, have been published on the birth seasonality of individuals who develop schizophrenia and/or bipolar disorder. Despite methodological problems, the studies are remarkably consistent in showing a 5-8% winter-spring excess of births for both schizophrenia and mania/bipolar disorder. This seasonal birth excess is also found in schizoaffective disorder (December-March), major depression (March-May), and autism (March) but not in other psychiatric conditions with the possible exceptions of eating disorders and antisocial personality disorder. The seasonal birth pattern also may shift over time. Attempts to correlate the seasonal birth excess with specific features of schizophrenia suggest that winter-spring births are probably related to urban births and to a negative family history. Possible correlations include lesser severity of illness and neurophysiological measures. There appears to be no correlation with gender, social class, race, measurable pregnancy and birth complications, clinical subtypes, or neurological, neuropsychological, or neuroimaging measures. Virtually no correlation studies have been done for bipolar disorder. Regarding the cause of the birth seasonality, statistical artifact and parental procreational habits are unlikely explanations. Seasonal effects of genes, subtle pregnancy and birth complications, light and internal chemistry, toxins, nutrition, temperature/weather, and infectious agents or a combination of these are all viable possibilities.

Changes in consumption of omega-3 and omega-6 fatty acids in the United States during the 20th century

BACKGROUND The consumption of omega-3 (n-3) and omega-6 (n-6) essential fatty acids in Western diets is thought to have changed markedly during the 20th century. OBJECTIVE We sought to quantify changes in the apparent consumption of essential fatty acids in the United States from 1909 to 1999. DESIGN We calculated the estimated per capita consumption of food commodities and availability of essential fatty acids from 373 food commodities by using economic disappearance data for each year from 1909 to 1999. Nutrient compositions for 1909 were modeled by using current foods (1909-C) and foods produced by traditional early 20th century practices (1909-T). RESULTS The estimated per capita consumption of soybean oil increased >1000-fold from 1909 to 1999. The availability of linoleic acid (LA) increased from 2.79% to 7.21% of energy (P < 0.000001), whereas the availability of α-linolenic acid (ALA) increased from 0.39% to 0.72% of energy by using 1909-C modeling. By using 1909-T modeling, LA was 2.23% of energy, and ALA was 0.35% of energy. The ratio of LA to ALA increased from 6.4 in 1909 to 10.0 in 1999. The 1909-T but not the 1909-C data showed substantial declines in dietary availability (percentage of energy) of n-6 arachidonic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Predicted net effects of these dietary changes included declines in tissue n--3 highly unsaturated fatty acid status (36.81%, 1909-T; 31.28%, 1909-C; 22.95%, 1999) and declines in the estimated omega-3 index (8.28, 1909-T; 6.51, 1909-C; 3.84, 1999). CONCLUSION The apparent increased consumption of LA, which was primarily from soybean oil, has likely decreased tissue concentrations of EPA and DHA during the 20th century.

Relative risk for cognitive impairments in siblings of patients with schizophrenia

BACKGROUND Patients with schizophrenia have impairments in several domains of cognition, including working memory/executive function, verbal memory, language, oculomotor scanning/psychomotor speed, and general intelligence. Impairments have also been found in unaffected siblings, suggesting they could be heritable. To assess the suitability of cognitive dysfunction for use in genetic studies, we estimated relative risk (lambda) in a large cohort of siblings. METHODS One hundred forty-seven patients with schizophrenia, 193 of their siblings, and 47 control subjects were studied using a neuropsychological test battery, which included intelligence quotient (IQ), Wide Range Achievement Test, Wisconsin Card Sort, Wechsler Memory Scale (revised), California Verbal List Test, Trails A and B, and Letter and Category Fluency. Relative risk was estimated using a cutoff score of 1 SD below the control mean. RESULTS As expected, patients performed markedly worse than control subjects on all tests except the Wide Range Achievement Test. Siblings had impaired performance on the Wisconsin Card Sort and Trails B, with trends for reduction (p = .01-.05) on the California Verbal List Test and Letter Fluency. Relative risk to siblings was elevated on the Trails B (lambda = 4.0) and California Verbal List Test (lambda = 2.8). Trends (p = .01-.05) for increased lambda were also seen for Wisconsin Card Sort, Letter Fluency, Wechsler Memory Scale and decline in IQ (lambda = 1.74-2.4). Correlations between tests of different cognitive functions were weak, indicating they measure relatively independent processes. CONCLUSION Unselected siblings of patients with schizophrenia have impairments in several cognitive domains. Relative risk scores were in the moderate range, suggesting a significant genetic component. Impairments on one test only weakly predicted impairments on other tests. Thus, cognitive phenotypes identify distinct, familial traits associated with schizophrenia. Using this dimensional approach to subdividing schizophrenia may reduce the clinical and genetic heterogeneity of schizophrenia and improve the power of genetic studies.

Effects of acute tryptophan depletion on plasma and cerebrospinal fluid tryptophan and 5-hydroxyindoleacetic acid in normal volunteers.

Abstract: Brain serotonin synthesis and metabolism (turnover), as indicated by CSF concentrations of 5‐hydroxyindoleacetic acid (5‐HIAA), may depend on plasma concentrations of the essential amino acid L‐tryptophan (TRP). We investigated the biochemical effects of acute plasma TRP depletion (ATD) in normal volunteers undergoing a 36‐h CSF collection via lumbar drain. Six subjects who were in good health were put on a low‐TRP diet (160 mg/day) 24 h before lumbar puncture; this diet was continued for the first 22 h of the CSF collection. At hour 22, subjects ingested a TRP‐deficient 15‐amino acid drink shown previously to deplete plasma TRP. Total plasma TRP, free plasma TRP, and CSF TRP subsequently decreased 86.3, 86.5, and 92.3%, respectively. CSF 5‐HIAA decreased by 32.8%. Plasma total and free TRP concentrations were both decreased at ∼2 h following ingestion of the TRP‐free amino acid drink and were lowest ∼6 h after ATD; CSF TRP and 5‐HIAA were decreased at 2.5 h and ∼4 h after ATD, respectively. CSF TRP was lowest 8.0 h later. CSF 5‐HIAA continued to decrease 14 h after the TRP‐deficient amino acid drink was given.

Schizophrenic births and viral diseases in two states.

In order to investigate a possible relationship between schizophrenic births and viral diseases, the birth month and year of all state hospital admissions for schizophrenia in Connecticut and Massachusetts from 1973-1974 were compared with the occurrence of reportable viral diseases for 1920-1955. Data was statistically examined by time series using spectral analysis. Statistically significant coherences were found between schizophrenic births and measles (both states), varicella-zoster (Connecticut) and polio (Connecticut). Influenza just missed statistical significance. No temporal relationship between schizophrenic births and rubella or mumps was found. The results are compared with similar studies in Minnesota and Finland. Definitive explanations for the observed relationships are precluded by the emerging complexity of virus-CNS interactions. A triggering of immune dysfunction by the infectious agents is proposed as the most reasonable explanation.

Statistical analysis of functional MRI data in the wavelet domain

The use of the wavelet transform is explored for the detection of differences between brain functional magnetic resonance images (fMRIs) acquired under two different experimental conditions. The method benefits from the fact that a smooth and spatially localized signal can be represented by a small set of localized wavelet coefficients, while the power of white noise is uniformly spread throughout the wavelet space. Hence, a statistical procedure is developed that uses the imposed decomposition orthogonality to locate wavelet-space partitions with large signal-to-noise ratio (SNR), and subsequently restricts the testing for significant wavelet coefficients to these partitions. This results in a higher SNR and a smaller number of statistical tests, yielding a lower detection threshold compared to spatial-domain testing and, thus, a higher detection sensitivity without increasing type I errors. The multiresolution approach of the wavelet method is particularly suited to applications where the signal bandwidth and/or the characteristics of an imaging modality cannot be well specified. The proposed method was applied to compare two different fMRI acquisition modalities, Differences of the respective useful signal bandwidths could be clearly demonstrated; the estimated signal, due to the smoothness of the wavelet representation, yielded more compact regions of neuroactivity than standard spatial-domain testing.

A replication study of violent and nonviolent subjects: cerebrospinal fluid metabolites of serotonin and dopamine are predicted by plasma essential fatty acids

BACKGROUND Among an independent group of subjects selected for their history of violent, impulsive behaviors and nonviolent control subjects, we attempted to replicate the finding that plasma docosahexaenoic acid concentrations were negatively correlated with cerebrospinal fluid 5-hydroxyindoleacetic acid (CSF 5-HIAA) concentrations. METHODS CSF 5-HIAA and homovanillic acid (HVA), fasting total cholesterol, and plasma fatty acid concentrations were examined in violent and nonviolent subjects matched for their severity of alcohol dependence. RESULTS Violent subjects had significantly higher lifetime violence and hostility ratings and lower concentrations of CSF 5-HIAA than nonviolent subjects. Plasma docosahexaenoic acid was negatively correlated with CSF 5-HIAA only among violent subjects. CONCLUSIONS This observational study suggests that dietary essential fatty acids may change neurotransmitter concentrations. Prospective dietary intervention trials will be required to determine if increasing dietary intake of docosahexaenoic acid will increase or decrease either CSF 5-HIAA concentrations or impulsive and violent behaviors.

Seasonal Birth Patterns of Neurological Disorders

Existing seasonal birth studies were reviewed for multiple sclerosis (MS), Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis (ALS), epilepsy, cerebral palsy, congenital malformations of the central nervous system and mental retardation. Epilepsy appears to have the most consistent pattern, with an excess of births in winter and a deficit in September. MS, ALS and possibly Parkinson’s disease appear to have an excess of spring births. Studies of cerebral palsy are not conclusive, although there are suggestions that there may be an excess of summer births. The findings for Alzheimer’s disease, congenital malformations of the central nervous system, and mental retardation are contradictory and insufficient to draw any conclusions.

Negative association of neuroticism with brain volume ratio in healthy humans

BACKGROUND Brain volume decreases with normal aging. We sought to determine whether, in addition to age, individual differences in stress reactivity (i.e., neuroticism) would also predict reductions in brain volume. METHODS Brain volume ratios were calculated for a sample of 86 healthy volunteers, based on segmented brain volumes taken from T(1)-weighted magnetic resonance imaging and corrected for intracranial volume. Standardized self-reported measures of dispositional neuroticism were concurrently obtained by administering the Revised NEO Personality Inventory. RESULTS After statistically controlling for age and sex, neuroticism showed a significant negative association with the ratio of brain to the remainder of the intracranial volume, but was not related to intracranial volume itself. In particular, subfactors of neuroticism related to the chronic experience of arousing negative emotions were associated with reduced brain ratio. CONCLUSIONS These results suggest that individual differences in stress reactivity contribute to reductions in brain volume observed during adulthood.

Birth seasonality in bipolar disorder, schizophrenia, schizoaffective disorder and stillbirths

Abstract Background: More than 40 studies have been done on seasonal birth patterns for schizophrenia, but only two small studies have been done for DSM-III-R bipolar disorder and none for schizoaffective disorder. Two studies have also reported a significant relationship between schizophrenia births and stillbirths. Methods: In the largest study to date, birth data from four states was obtained on 126 987 state psychiatric hospitals inpatients divided into ‘process’ schizophrenia (disorganized, catatonic, undifferentiated), paranoid schizophrenia, schizoaffective disorder, bipolar disorder and major depression. Time series analysis compared these births to all general births and to stillbirths. Results: ‘Process’ schizophrenia, paranoid schizophrenia, schizoaffective disorder and bipolar disorder all had statistically significant seasonal excess births from December through March ( p = 0.0000). The largest excess was 5.8% for bipolar disorder. Major depression had significant excess births from March through May. Time series analysis showed statistically significant coherences between major depression and bipolar disorder (0.995) and between schizoaffective disorder and both ‘process’ schizophrenia (0.977) and bipolar disorder (0.977). Unexpectedly, a significant coherence was also found between paranoid schizophrenia and bipolar disorder (0.972). Excess stillbirths were found for each month from January through June and a significant coherence was found between stillbirths and paranoid schizophrenia (0.998). Conclusions: This study demonstrates that DSM-III-R bipolar disorder and schizoaffective disorder both have an excess of winter births, similar to that found in schizophrenia. Time series analysis, however, suggests that the causes may not be identical. Major depression, by contrast, has an excess of spring births.