Cognitive behavioural therapy for depression: systematic review of imaging studies.

OBJECTIVE: Although cognitive behavioural therapy (CBT) has been shown to be an effective treatment for depression, the biological mechanisms underpinning it are less clear. This review examines if it is associated with changes identifiable with current brain imaging technologies. METHODS: To better understand the mechanisms by which CBT exerts its effects, we undertook a systematic review of studies examining brain imaging changes associated with CBT treatment of depression. RESULTS: Ten studies were identified, five applying functional magnetic resonance imaging, three positron emission tomography, one single photon emission computer tomography, and one magnetic resonance spectroscopy. No studies used structural MRI. Eight studies included a comparator group; in only one of these studies was there randomised allocation to another treatment. CBT-associated changes were most commonly observed in the anterior cingulate cortex (ACC), posterior cingulate, ventromedial prefrontal cortex/orbitofrontal cortex (VMPFC/OFC) and amygdala/hippocampus. DISCUSSION: The evidence, such as it is, suggests resting state activity in the dorsal ACC is decreased by CBT. It has previously been suggested that treatment with CBT may result in increased efficiency of a putative 'dorsal cognitive circuit', important in cognitive control and effortful regulation of emotion. It is speculated this results in an increased capacity for 'top-down' emotion regulation, which is employed when skills taught in CBT are engaged. Though changes in activity of the dorsal ACC could be seen as in-keeping with this model, the data are currently insufficient to make definitive statements about how CBT exerts its effects. Data do support the contention that CBT is associated with biological brain changes detectable with current imaging technologies.

Brain structure in adolescents and young adults with alcohol problems: systematic review of imaging studies.

AIMS: Alcohol-dependent people who are middle-aged or older have a widespread loss of cortical grey and white matter, particularly in the prefrontal cortex (PFC). We examine if brain abnormalities are detectable in alcohol use disorders before the fifth decade (i.e., <40), and the brain structural differences associated with alcohol abuse/dependence in adolescence. METHODS: Case-control studies comparing brain structure in alcohol-abusing/-dependent individuals with normal controls in which the mean age of participants was <40 were identified using Medline, EMBASE and PsychInfo. Studies in which mean age was over and under 21 were considered separately. RESULTS: Twelve papers fulfilled inclusion criteria, five in the adolescent (14-21) and seven in the young adult age range. Two independent groups reported hippocampal and prefrontal volume reductions in adolescents, although this was consistently observed only in females. In young adults (aged 21-40), there were grey matter deficits in the PFC in both sexes. Adult women appeared to, particularly, exhibit white matter differences, evident as reduced area of the corpus callosum. Hippocampal volume reduction was observed in one study of young adults study but not another. CONCLUSION: The available data suggest that quantitative structural abnormalities of the brain are detectable in young alcohol abusers. There is overlap between the abnormalities seen in adolescents and young adults, although hippocampal volume loss is most consistently seen in the former group. The adolescent hippocampus may be particularly susceptible to alcohol, potentially because of an interaction between adolescent brain development and alcohol exposure.

Impact of cannabis use on thalamic volume in people at familial high risk of schizophrenia.

BACKGROUND: No longitudinal study has yet examined the association between substance use and brain volume changes in a population at high risk of schizophrenia. AIMS: To examine the effects of cannabis on longitudinal thalamus and amygdala-hippocampal complex volumes within a population at high risk of schizophrenia. METHOD: Magnetic resonance imaging scans were obtained from individuals at high genetic risk of schizophrenia at the point of entry to the Edinburgh High-Risk Study (EHRS) and approximately 2 years later. Differential thalamic and amygdala-hippocampal complex volume change in high-risk individuals exposed (n = 25) and not exposed (n = 32) to cannabis in the intervening period was investigated using repeated-measures analysis of variance. RESULTS: Cannabis exposure was associated with bilateral thalamic volume loss. This effect was significant on the left (F = 4.47, P = 0.04) and highly significant on the right (F= 7.66, P= 0.008). These results remained significant when individuals using other illicit drugs were removed from the analysis. CONCLUSIONS: These are the first longitudinal data to demonstrate an association between thalamic volume loss and exposure to cannabis in currently unaffected people at familial high risk of developing schizophrenia. This observation may be important in understanding the link between cannabis exposure and the subsequent development of schizophrenia.

The effects of DISC1 risk variants on brain activation in controls, patients with bipolar disorder and patients with schizophrenia.

Three risk variants (rs1538979, rs821577, and rs821633) in the Disrupted-in-Schizophrenia-1 (DISC1) gene have previously been associated with both schizophrenia and bipolar disorder in a recent collaborative analysis of European cohorts. In this study we examined the effects of these risk variants on brain activation during functional magnetic resonance imaging (fMRI) of the Hayling Sentence Completion Task (HSCT) in healthy volunteers (n=33), patients with schizophrenia (n=20) and patients with bipolar disorder (n=36). In the healthy controls the risk associated allele carriers of SNPs rs1538979 and rs821633 demonstrated decreased activation of the cuneus. Moreover, there was an effect of SNP rs1538979 in the pre/postcentral gyrus with decreased activation in healthy controls and increased activation in patients with schizophrenia. In the bipolar group there was decreased activation in the risk carriers of SNP rs821633 in the inferior parietal lobule and left cingulate cortex. Clusters in the precentral gyrus, left middle temporal gyrus and left cerebellum were found to be significant on examining the group × genotype interactions. These findings may provide a better understanding of the neural effects of DISC1 variants and on the pathophysiology of schizophrenia and bipolar disorder.

Neurological complications of alcohol and misuse of drugs.

The nature of many of the symptoms associated with substance and alcohol use means that patients often present to neurologists. The frequently catastrophic consequences of overlooking these patients makes this an important cause to identify. Here I will discuss various acute and non-acute substance misuse associated presentations, with particular emphasis on the neurology. As neurological sequelae are particularly common in alcohol use, there will be an emphasis on this drug while other substances are included when relevant, extending to the recently notorious 'legal highs'. I hope this review will increase vigilance to the possibility of substance use disorder, and persuade neurologists that they have a role in the detection and treatment of these conditions.

When psychiatric symptoms reflect medical conditions.

The brain dysfunction associated with certain medical and neurological conditions can produce essentially any psychiatric symptom. This means there is always a chance that presentations thought to be 'psychiatric' are actually explained by unidentified medical pathology. This paper aims to outline an approach to minimise these missed diagnoses.

The impact of substance use on brain structure in people at high risk of developing schizophrenia.

Ventricular enlargement and reduced prefrontal volume are consistent findings in schizophrenia. Both are present in first episode subjects and may be detectable before the onset of clinical disorder. Substance misuse is more common in people with schizophrenia and is associated with similar brain abnormalities. We employ a prospective cohort study with nested case control comparison design to investigate the association between substance misuse, brain abnormality, and subsequent schizophrenia. Substance misuse history, imaging data, and clinical information were collected on 147 subjects at high risk of schizophrenia and 36 controls. Regions exhibiting a significant relationship between level of use of alcohol, cannabis or tobacco, and structure volume were identified. Multivariate regression then elucidated the relationship between level of substance use and structure volumes while accounting for correlations between these variables and correcting for potential confounders. Finally, we established whether substance misuse was associated with later risk of schizophrenia. Increased ventricular volume was associated with alcohol and cannabis use in a dose-dependent manner. Alcohol consumption was associated with reduced frontal lobe volume. Multiple regression analyses found both alcohol and cannabis were significant predictors of these abnormalities when simultaneously entered into the statistical model. Alcohol and cannabis misuse were associated with an increased subsequent risk of schizophrenia. We provide prospective evidence that use of cannabis or alcohol by people at high genetic risk of schizophrenia is associated with brain abnormalities and later risk of psychosis. A family history of schizophrenia may render the brain particularly sensitive to the risk-modifying effects of these substances.