The importance of early detection and intervention in the treatment of bipolar affective disorder has led to attempts to identify prodromal features of the disorder in highrisk subjects.For example, an analysis of sleep microstructure has identified increased REM density as a Mofezolac vulnerability marker for affective disorders.Biological markers allow early detection of disorders in highrisk subjects and provide cues for useful endophenotypes in genetic association studies.During periods of heavy drinking and up to two years after the discontinuation of alcohol intake, patients sleep phases show reduced slow wave sleep states, suppressed REM sleep, fragmented sleep during the second half of a normal hour bedtime and shortened overall sleep durations.Rates of insomnia in this group of people with alcohol problems are reported to be between. Interestingly, patients with alcohol addictions who have a good prognosis for recovery are those individuals who tend to return to normal ratios of nREM:REM sleep and who sleep well in general.Altered sleep patterns, such as short REM latencies and high REM densities, are thought to predispose individuals to a relapse as they may be more prone to use ethanol to induce sleep.Excessive alcohol consumption in addicted and nonaddicted individuals can cause depressivelike states.Indeed, ethanol is classified as a depressant drug as it has sedative effects due to its facilitation of the response at gABA ergic Mofezolac synapses and inhibition of glutamatergic nMDAR signalling. Comorbid addiction to alcohol in patients with bipolar disorder is common and seems to influence circadian preference; patients who are addicted to alcohol show a predominance of morning chronotypes, whereas patients who are not addicted to alcohol show a predominance of evening chronotypes.EAA is primarily expressed in astroglia and acts to clear excess glutamate from the synaptic cleft and to transport glutamate back into the neuron.Additional links between alcohol preference and both clock genes and sleep genes have been identified.Elevated cortisol levels are also reported in patients with schizophrenia.However, many treatment paradigms focus exclusively on the modulation of dopamine and serotoninmediated synaptic signalling, often with only limited success.In view of such widespread alterations in brain architecture and physiology it is hardly surprising that abnormal sleep has been described in patients with schizophrenia since the s and, more recently, has been documented as a common feature in previously unmedicated patients who are now undergoing treatment and also in patients who are undergoing longterm antipsychotic treatment. Abnormal sleep patterns in schizophrenia include reductions in REM latency, REM density, sleep efficiency, total sleep time and the duration of nREM stage, and an increase in sleep latency. Multiple circadian abnormalities have also been recorded and these include delayed phase, advanced phase, freerunning andor irregular sleep timing patterns. At the core of all neurological disease is an abnormality of some level in one or more of the neurotransmitter systems.Such an abnormality probably impinges upon the circadian and sleep timing as this system is itself regulated across different brain regions and by a range of neurotransmitters.Many of these abnormalities will activate the stress axis which will distort physiological responses even further.Patients with poor sleep also score badly on many quality of life clinical subscales.