Introduction. Patients with unipolar depression show impaired performance on the Tower of London planning task. Positron emission tomography, which has previously identified resting state blood flow abnormalities in depression, was used to investigate neural activity associated with performance of this task in depressed patients and normal controls.

Methods. Six patients with unipolar depression and six matched controls were scanned while performing easy and hard Tower of London problems in a one-touch computerized paradigm and while performing a perceptuomotor control task.

Results. The patients in this study showed an expected task-related performance deficit compared with normal subjects. In normal subjects, the task engaged a network of prefrontal cortex, anterior cingulate, posterior cortical areas and subcortical structures including the striatum, thalamus and cerebellum. Depressed patients failed to show significant activation in the cingulate and striatum; activation in the other prefrontal and posterior cortical regions was significantly attenuated relative to controls. Crucially, patients also failed to show the normal augmentation of activation in the caudate nucleus, anterior cingulate and right prefrontal cortex associated with increasing task difficulty.

Conclusions. These findings provide evidence for cingulate, prefrontal and striatal dysfunction associated with impaired task performance in depression. The present results are consistent with a central role of cingulate dysfunction in depression as well as suggesting impaired frontostriatal function.

Background. The idea that superior cognitive function acts as a protective factor against dementia and the consequences of head injury is well established. Here we suggest the hypothesis that cognitive reserve is also important in neuropsychiatric disorders including schizophrenia, bipolar disorder and depression.

Method. We review the history of passive and active models of reserve, and apply the concept to neuropsychiatric disorders. Schizophrenia is used as an exemplar because the effects of premorbid IQ and cognitive function in this disorder have been extensively studied.

Results. Cognitive reserve may impact on neuropsychiatric disorders in three ways: by affecting the risk for developing the disorder, in the expression of symptoms within disorders, and in patients' functional outcome. Cognitive failure below a certain threshold may alone, or in combination with common psychiatric symptoms, produce neuropsychiatric syndromes.

Conclusions. Consideration of cognitive reserve may considerably improve our understanding of individual differences in the causes and consequences of neuropsychiatric disorders. For these reasons, the concept of cognitive reserve should be incorporated in future studies of neuropsychiatric disorder. It may be possible to enhance cognitive reserve through pharmacological or non-pharmacological means, such as education, neurocognitive activation or other treatment programmes.

Background. This study examined the patterns of familial aggregation and co-morbidity of alcoholism and anxiety disorders in the relatives of 165 probands selected for alcoholism and/or anxiety disorders compared to those of 61 unaffected controls.

Methods. Probands were either selected from treatment settings or at random from the community. DSM-III-R diagnoses were obtained for all probands and their 1053 first-degree relatives, based on direct interview or family history information.

Results. The findings indicate that: (1) alcoholism was associated with anxiety disorders in the relatives, particularly among females; (2) both alcoholism and anxiety disorders were highly familial; (3) the familial aggregation of alcoholism was attributable to alcohol dependence rather than to alcohol abuse, particularly among male relatives; and (4) the pattern of co-aggregation of alcohol dependence and anxiety disorders in families differed according to the subtype of anxiety disorder; there was evidence of a partly shared diathesis underlying panic and alcoholism, whereas social phobia and alcoholism tended to aggregate independently.

Conclusions. The finding that the onset of social phobia tended to precede that of alcoholism, when taken together with the independence of familial aggregation of social phobia and alcoholism support a self-medication hypothesis as the explanation for the co-occurrence of social phobia and alcoholism. In contrast, the lack of a systematic pattern in the order of onset of panic and alcoholism among subjects with both disorders as well as evidence for shared underlying familial risk factors suggests that co-morbidity between panic disorder and alcoholism is not a consequence of self-medication of panic symptoms. The results of this study emphasize the importance of examining co-morbid disorders and subtypes thereof in identifying sources of heterogeneity in the pathogenesis of alcoholism.

To date, the precise prevalence of co-morbidity of anxiety and depression in the perinatal period is not well known. We aimed to estimate the prevalence of co-morbid anxiety and depression in the antenatal and postnatal periods. Systematic searches of multiple electronic databases were conducted for studies published between January 1950 and January 2016. We included 66 (24 published and 42 unpublished) studies incorporating 162 120 women from 30 countries. Prevalence of self-reported antenatal anxiety symptoms and mild to severe depressive symptoms was 9.5% [95% confidence interval (CI) 7.8–11.2, 17 studies, n = 25 592] and of co-morbid anxiety symptoms and moderate/severe depressive symptoms was 6.3% (95% CI 4.8–7.7, 17 studies, n = 27 270). Prevalence of a clinical diagnosis of any antenatal anxiety disorder and depression was 9.3% (95% CI 4.0–14.7, 10 studies, n = 3918) and of co-morbid generalized anxiety disorder and depression was 1.7% (95% CI 0.2–3.1, three studies, n = 3085). Postnatally between 1 and 24 weeks postpartum, the prevalence of co-morbid anxiety symptoms and mild to severe depressive symptoms was 8.2% (95% CI 6.5–9.9, 15 studies, n = 14 731), while co-morbid anxiety symptoms and moderate/severe depressive symptoms was 5.7% (95% CI 4.3–7.1, 13 studies, n = 20 849). The prevalence of a clinical diagnosis of co-morbid anxiety and depression was 4.2% (95% CI 1.9–6.6, eight studies, n = 3251). Prevalence rates did not differ with regard to year of publication, country income, selection bias and attrition bias. The results suggest that co-morbid perinatal anxiety and depression are prevalent and warrant clinical attention given the potential negative child developmental consequences if left untreated. Further research is warranted to develop evidence-based interventions for prevention, identification and treatment of this co-morbidity.

Various types of reliability measures were conducted on the Disability Assessment Schedule, a structured interview devised to elicit from parents or care staff details of impairments, skills and behaviour problems in mentally retarded children and adults. The results indicated high overall agreement when the schedule was repeated over time, and also when used by several trained interviewers to rate the same interview. Problems arising from the use of such interview schedules are discussed, and suggestions are made for improving the design and method of administration.

Background. Women are consistently reported to have a greater prevalence of depressive disorders than men. The reason for this is unclear, and is as likely to be social as biological. There is some evidence that the excess of depression is greater during women's reproductive lives. Data from the National Survey of Psychiatric Morbidity were used to test the hypothesis that the excess disappeared in the post-menopausal years and that obvious social explanations for this were inadequate.

Method. Subjects (N=9792) from a random sample of the British population provided data for the analysis. Psychiatric assessment was carried out by lay interviewers using the CIS-R. Subjects with ICD-10 depressive episode or mixed anxiety/depression were compared with the remainder. Social variables that were likely to contribute to a post-menopausal decline in depressive disorders were controlled in logistic regression analyses.

Results. There was a clear reversal of the sex difference in prevalence of depression in those over age 55. This could not be explained in terms of differential effects of marital status, child care, or employment status.

Conclusions. This large and representative survey adds considerably to the increasingly held view that the sex difference in prevalence of depression is less apparent in later middle age. This may be linked to the menopause, and our attempts to explain it in terms of obvious conditions among social variables were not successful. More specific studies are required to clarify the finding.

Background. Intellectual impairments are a recognized feature of tuberous sclerosis complex (TSC), but the frequency and degree of intellectual impairments has not been systematically studied in large epidemiological samples using standardized measures. As such, the form of the IQ distribution (uni- or bi-modal) has not been established and the relationship between IQ and other features (e.g. epilepsy history) is poorly delineated. To address these shortcomings, we assessed the intellectual abilities of a large epidemiological sample of individuals with TSC, drawn from the ‘Wessex’ area of SW England and compared them with the abilities of their unaffected siblings.

Method. Standardized tests were used to estimate the abilities of 108 (56 males, 52 females, median age=25, range=4–75) individuals with TSC and 29 unaffected siblings (14 males, 15 females, median age=18, range=6–55). Seizure history was obtained from informants and medical records.

Results. Estimated IQ was bi-modally distributed: 55·5% had an IQ in the normal range; 14% had mild to severe impairments; and 30·5% had profound disability (IQ<21). Forty-four per cent of the individuals with TSC had an IQ<70. In the subset of normally intelligent individuals with TSC, IQ was normally distributed with a mean of 93·6. This mean was significantly lower than the mean IQ of unaffected siblings (IQ=105·6). All individuals with learning disability had a history of seizures that usually commenced before 12 months of age and that often presented as infantile spasms. Multivariate analyses indicated that a history of seizures as well as a history of infantile spasms was predictive of the degree of intellectual impairment.

Conclusions. Intellectual abilities were bi-modally distributed in a representative sample of individuals with TSC. The likelihood of impairment was associated with a history of seizures, particularly infantile spasms. The genetic and brain basis of these findings requires further investigation.

Background. Despite markedly different clinical presentations, few studies have reported differences in neuropsychological functioning between mania and depression. Recent work has suggested that differences may emerge on cognitive tasks requiring affective processing, such as decision-making. The present study sought to compare decision-making cognition in mania and depression in order to clarify the current profiles of impairment for these disorders and to contribute to our more general understanding of the relationship between mood and cognition.

Methods. Medicated manic patients, depressed patients, and normal healthy controls completed a computerized decision-making task. All subjects were asked to win as many points as possible by choosing outcomes based on variably-weighted probabilities and by placing ‘bets’ on each decision.

Results. Both patient groups were impaired on this task, as evidenced by slower deliberation times, a failure to accumulate as many points as controls and suboptimal betting strategies. Manic, but not depressed, patients made suboptimal decisions – an impairment that correlated with the severity of their illness.

Conclusions. These findings are consistent with a growing consensus that manic and depressed patients are characterized by significant impairments in cognitive and particularly executive, functioning. Furthermore, the distinct patterns of observed impairment in manic and depressed patients suggests that the nature and extent of cognitive impairment differ between these two groups. Viewed in the context of other recent studies, these findings are consistent with a role for the ventromedial prefrontal cortex in mediating mood–cognition relationships.

Background. Although overwhelming evidence suggests that genetic and environmental risk factors both contribute to the aetiology of major depression (MD), we know little of how these two risk factor domains inter-relate. In particular, can the genetic liability to MD increase the risk of experiencing stressful life events (SLEs)?

Methods. Using discrete time survival analysis in a population-based sample of 2164 female twins, we examined whether the risks for nine personal and three aggregate network SLEs were predicted by the level of genetic liability to MD, indexed by the lifetime history of MD in monozygotic and dizygotic co-twins.

Results. Genetic liability to MD was associated with a significantly increased risk for six personal SLEs (assault, serious marital problems, divorce/breakup, job loss, serious illness and major financial problems) and one network SLE (trouble getting along with relatives/friends). This effect was not due to SLEs occurring during depressive episodes. Similar results were found using structural equation twin modelling. In contrast to the pattern observed with MD, the genetic liability to alcoholism impacted on the risk for being robbed and having trouble with the law.

Conclusion. In women, genetic risk factors for MD increase the probability of experiencing SLEs in the interpersonal and occupational/financial domains. Genes can probably impact on the risk for psychiatric illness by causing individuals to select themselves into high risk environments.

Background. Although women are at consistently greater risk for major depression (MD) than men, it is unclear whether sex modifies the aetiological impact of genetic factors on MD. Is the heritability of MD different in men and women? Do the same genetic risk factors predispose to MD in the two sexes?

Methods. We obtained a lifetime history of MD by personal interview on two occasions from 6672 individual twins and 2974 complete twin pairs. Three diagnostic criteria of increasing narrowness were employed: DSM-III-R, DSM-III-R plus impairment and Washington University. To increase power by controlling for unreliability of assessment, we evaluated sex differences on genetic risk for MD using a structural equation measurement model.

Results. Using DSM-III-R criteria, but not the two narrower definitions, heritability of MD was significantly greater in women than in men. In the three diagnostic systems, the genetic correlation in liability to MD in men and women was estimated at between +0·50 and +0·65. These estimates differed significantly from unity for the two broader definitions.

Conclusion. Using broad but not narrower definitions of illness, genetic factors play a greater role in the aetiology of MD in women than in men. The genes that influence risk for MD in the two sexes are correlated but are probably not entirely the same. These results raise the possibility that, in linkage and association studies, the impact of some loci on risk for MD will differ in men and women.