The frames of the mind of a psychiatrist.

The structures of our mind may be understood as 'frames', which play a key role in our everyday goals, choices and decisions. Understanding these often unconscious processes may help us to understand the complex decisions we make in our clinical practice. Such frames may be many in number, being based, for example, on medical, psychological, social, trauma, or problem-solving models. The 'frames' we use in our clinical decisions should be tailored to the needs of our patients, and may need to be adapted at different phases of illness.

The association between subjective maternal stress during pregnancy and offspring clinically diagnosed psychiatric disorders.

OBJECTIVE: Exposure to prenatal stress is a ubiquitous and non-specific risk factor for adverse outcomes in adulthood. In this study, we examined associations between exposure to subjective maternal stress during pregnancy and subsequent diagnosis of psychiatric disorders in offspring. METHOD: This study used the Helsinki Longitudinal Temperament Cohort, a prospective birth cohort of individuals born between 1 July 1975 and 30 June 1976 in Helsinki, Finland. The sample for this study comprised 3626 infants whose mothers had completed health and well-being assessments during pregnancy which included a measure of self-reported stress. We ran logistic regressions to assess potential associations between prenatal stress and offspring psychiatric disorder in adulthood, identified through the Finnish Hospital Discharge Register. RESULTS: Individuals whose mothers reported stress during pregnancy had significantly greater odds of developing a psychiatric disorder (OR = 1.41, 95% CI = 1.10-1.81) particularly a mood disorder (OR = 1.67, 95% CI = 1.10-2.54). These associations remained after adjusting for parental psychiatric history, and other prenatal factors. CONCLUSIONS: Individuals exposed to prenatal stress had significantly increased risk of developing psychiatric disorders later in life. This finding highlights the importance of supporting the mental health and emotional well-being of women during pregnancy.

Polyvagal theory, neurodevelopment and psychiatric disorders.

Neurodevelopment is an area of psychiatry which has attracted huge interest in the last few decades. There is substantial evidence that perinatal events can contribute to later development of mental disorder. In the current perspective article we propose a novel polyvagal theory which attempts to link prenatal events with neurodevelopment and the later onset of psychiatric disorder.

Proton MRS in twin pairs discordant for schizophrenia.

Proton magnetic resonance spectroscopy ((1)H MRS) neurometabolite abnormalities have been detected widely in subjects with and at risk for schizophrenia. We hypothesized that such abnormalities would be present both in patients with schizophrenia and in their unaffected twin siblings. We acquired magnetic resonance spectra (TR/TE=3000/30 ms) at voxels in the mesial prefrontal gray matter, left prefrontal white matter and left hippocampus in 14 twin pairs discordant for schizophrenia (2 monozygotic, 12 dizygotic), 13 healthy twin pairs (4 monozygotic, 9 dizygotic) and 1 additional unaffected co-twin of a schizophrenia proband. In the mesial prefrontal gray matter voxel, N-acetylaspartate (NAA), creatine+phosphocreatine (Cr), glycerophosphocholine+phosphocholine (Cho) and myo-inositol (mI) did not differ significantly between patients with schizophrenia, their unaffected co-twins or healthy controls. However, glutamate (Glu) was significantly lower in patients with schizophrenia (31%, percent difference) and unaffected co-twins (21%) than in healthy controls (collapsed across twin pairs). In the left hippocampus voxel, levels of NAA (23%), Cr (22%) and Cho (36%) were higher in schizophrenia patients compared with controls. Hippocampal NAA (25%), Cr (22%) and Cho (37%) were also significantly higher in patients than in their unaffected co-twins. Region-to-region differences in metabolite levels were also notable within all three diagnosis groups. These findings suggest that (1)H MRS neurometabolite abnormalities are present not only in patients with schizophrenia, but also in their unaffected co-twins. Thus, reduced mesial prefrontal cortical Glu and elevated hippocampal NAA, Cr and Cho may represent trait markers of schizophrenia risk and, when exacerbated, state markers of schizophrenia itself.

Mitchell B. Balter Award. Human leukocyte antigen-A1 predicts a good therapeutic response to clozapine with a low risk of agranulocytosis in patients with schizophrenia.

Several studies indicate an association between human leukocyte antigens (HLA) and clozapine-induced agranulocytosis. The authors have previously reported a significantly increased frequency of HLA-A1 among patients with schizophrenia who do not respond to conventional drugs, but do respond to clozapine treatment. In this study, the authors addressed the question of whether the same association is found in patients developing granulocytopenia or agranulocytosis. The frequency of the HLA-A1 allele in patients with clozapine-induced agranulocytosis or granulocytopenia was low (11.5%), whereas HLA-A1 was associated with a good therapeutic response to clozapine at an allele frequency of 58%. The frequency of HLA-A1 is 20% in the Finnish population. These results suggest that HLA-A1 may predict a good therapeutic outcome and a low risk of agranulocytosis and, thus, enable defining a subgroup of patients with schizophrenia in whom clozapine treatment could be started early to stop the disease from progressing.

The inheritance of neuropsychological dysfunction in twins discordant for schizophrenia.

While genetic influences in schizophrenia are substantial, the disorder's molecular genetic basis remains elusive. Progress has been hindered by lack of means to detect nonpenetrant carriers of the predisposing genes and by uncertainties concerning the extent of locus heterogeneity. One approach to solving this complexity is to examine the inheritance of pathophysiological processes mediating between genotype and disease phenotype. Here we evaluate whether deficits in neurocognitive functioning covary with degree of genetic relationship with a proband in the unaffected MZ and DZ co-twins of patients with schizophrenia. Twin pairs discordant for schizophrenia were recruited from a total population cohort and were compared with a demographically balanced sample of control twin pairs, on a comprehensive neuropsychological test battery. The following four neuropsychological functions contributed uniquely to the discrimination of degree of genetic loading for schizophrenia and, when combined, were more highly correlated within MZ pairs than within DZ pairs, in both discordant and control twins: spatial working memory (i.e., remembering a sequence of spatial locations over a brief delay), divided attention (i.e., simultaneous performance of a counting and visual-search task), intrusions during recall of a word list (i.e., "remembering" nonlist items), and choice reaction time to visual targets. Together with evidence from human and animal studies of mediation of these functions by partially distinct brain systems, our findings suggest that there are multiple independently inherited dimensions of neural deficit in schizophrenia and encourage a search for genes contributing to quantitative variation in discrete aspects of disease liability. On tests of verbal and visual episodic memory, but not on the liability-related measures, patients were more impaired than their own MZ co-twins, suggesting a preferential impact of nongenetic influences on long-term memory systems.

Obstetric risk factors for early-onset schizophrenia in a Finnish birth cohort.

OBJECTIVE: Although case-control investigations have shown an association between obstetric complications and schizophrenia, particularly among patients with early onsets, cohort studies have mostly failed to confirm this effect. The authors examined whether a history of fetal hypoxia and other obstetric complications elevated risk for early-onset schizophrenia in a 1955 Helsinki birth cohort. METHOD: The subjects were 80 randomly selected patients with schizophrenia (36 with early and 44 with later onsets) representative of all available probands in the cohort, 61 of their nonschizophrenic siblings, and 56 demographically matched nonpsychiatric comparison subjects. Psychiatric diagnoses were obtained from structured clinical interviews, and obstetric data were taken from standardized, prospectively ascertained obstetric records. A score for hypoxia-associated obstetric complications was entered into logistic regression models, along with measures of prenatal infection and fetal growth retardation. RESULTS: Hypoxia-associated obstetric complications significantly increased the odds of early-onset schizophrenia but not of later-onset schizophrenia or unaffected sibling status, after prenatal infection and fetal growth retardation were taken into account. CONCLUSIONS: These findings support an association between obstetric complications and increased risk for early-onset schizophrenia. The authors advance a model whereby the neurotoxic effects of fetal hypoxia may lead to an early onset of schizophrenia due to premature cortical synaptic pruning.

Nausea during pregnancy: relation to early childhood temperament and behavior problems at twelve years.

Associations between maternal nausea during pregnancy and child behavioral outcomes were investigated in a large birth cohort. Generally, 2nd- and 3rd-trimester nausea were more predictive of child outcomes than 1st-trimester nausea. Children whose mothers reported nausea in middle or late pregnancy had lower sensory thresholds and higher levels of activity and emotional intensity in infancy and were reported to be lower in task persistence at age 5. At age 12, these children were viewed by teachers as more careless with their school work and as having more attentional and learning problems.