Executive functions

From Wikipedia, the free encyclopedia

Executive functions (collectively referred to as executive function and cognitive control) are a set of cognitive processes that are necessary for the cognitive control of behavior: selecting and successfully monitoring behaviors that facilitate the attainment of chosen goals. Executive functions include basic cognitive processes such as attentional control, cognitive inhibition, inhibitory control, working memory, and cognitive flexibility. Higher order executive functions require the simultaneous use of multiple basic executive functions and include planning and fluid intelligence (e.g., reasoning and problem solving).

Executive functions gradually develop and change across the lifespan of an individual and can be improved at any time over the course of a person's life. Similarly, these cognitive processes can be adversely affected by a variety of events which affect an individual. Both neuropsychological tests (e.g., the Stroop test) and rating scales are used to measure executive functions. They are usually performed as part of a more comprehensive assessment to diagnose neurological and psychiatric disorders.

Cognitive control and stimulus control, which is associated with operant and classical conditioning, represent opposite processes (internal vs external or environmental, respectively) that compete over the control of an individual's elicited behaviors; in particular, inhibitory control is necessary for overriding stimulus-driven behavioral responses (stimulus control of behavior). The prefrontal cortex is necessary but not solely sufficient for executive functions; for example, the caudate nucleus and subthalamic nucleus also have a role in mediating inhibitory control.

Cognitive control is impaired in addiction, attention deficit hyperactivity disorder, autism, and a number of other central nervous system disorders. Stimulus-driven behavioral responses that are associated with a particular rewarding stimulus tend to dominate one's behavior in an addiction.

Neuroanatomy

Historically, the executive functions have been seen as regulated by the prefrontal regions of the frontal lobes, but it is still a matter of ongoing debate if that really is the case. Even though articles on prefrontal lobe lesions commonly refer to disturbances of executive functions and vice versa, a review found indications for the sensitivity but not for the specificity of executive function measures to frontal lobe functioning. This means that both frontal and non-frontal brain regions are necessary for intact executive functions. Probably the frontal lobes need to participate in basically all of the executive functions, but it is not the only brain structure involved.

Neuroimaging and lesion studies have identified the functions which are most often associated with the particular regions of the prefrontal cortex.

• The dorsolateral prefrontal cortex (DLPFC) is involved with "on-line" processing of information such as integrating different dimensions of cognition and behavior. As such, this area has been found to be associated with verbal and design fluency, ability to maintain and shift set, planning, response inhibition, working memory, organisational skills, reasoning, problem solving and abstract thinking.

Side view of the brain, illustrating dorsolateral prefrontal and orbitofrontal cortex

• The anterior cingulate cortex (ACC) is involved in emotional drives, experience and integration. Associated cognitive functions include inhibition of inappropriate responses, decision making and motivated behaviors. Lesions in this area can lead to low drive states such as apathy, abulia or akinetic mutism and may also result in low drive states for such basic needs as food or drink and possibly decreased interest in social or vocational activities and sex;
• The orbitofrontal cortex (OFC) plays a key role in impulse control, maintenance of set, monitoring ongoing behavior and socially appropriate behaviors. The orbitofrontal cortex also has roles in representing the value of rewards based on sensory stimuli and evaluating subjective emotional experiences. Lesions can cause disinhibition, impulsivity, aggressive outbursts, sexual promiscuity and antisocial behavior.

Furthermore, in their review, Alvarez and Emory state that: "The frontal lobes have multiple connections to cortical, subcortical and brain stem sites. The basis of 'higher-level' cognitive functions such as inhibition, flexibility of thinking, problem solving, planning, impulse control, concept formation, abstract thinking, and creativity often arise from much simpler, 'lower-level' forms of cognition and behavior. Thus, the concept of executive function must be broad enough to include anatomical structures that represent a diverse and diffuse portion of the central nervous system."
The cerebellum also appears to be involved in mediating certain executive functions.

Hypothesized role

The executive system is thought to be heavily involved in handling novel situations outside the domain of some of our 'automatic' psychological processes that could be explained by the reproduction of learned schemas or set behaviors. Psychologists Don Norman and Tim Shallice have outlined five types of situations in which routine activation of behavior would not be sufficient for optimal performance:

1. Those that involve planning or decision making;
2. Those that involve error correction or troubleshooting;
3. Situations where responses are not well-rehearsed or contain novel sequences of actions;
4. Dangerous or technically difficult situations;
5. Situations that require the overcoming of a strong habitual response or resisting temptation.

A prepotent response is a response for which immediate reinforcement (positive or negative) is available or has been previously associated with that response. The executive functions are often invoked when it is necessary to override these prepotent responses that might otherwise be automatically elicited by stimuli in the external environment. For example, on being presented with a potentially rewarding stimulus, such as a tasty piece of chocolate cake, a person might have the automatic response to take a bite. However, where such behavior conflicts with internal plans (such as having decided not to eat chocolate cake while on a diet), the executive functions might be engaged to inhibit that response.

Although suppression of these prepotent responses is ordinarily considered adaptive, problems for the development of the individual and the culture arise when feelings of right and wrong are overridden by cultural expectations or when creative impulses are overridden by executive inhibitions.

Historical perspective

Although research into the executive functions and their neural basis has increased markedly over recent years, the theoretical framework in which it is situated is not new. In the 1940s, the British psychologist Donald Broadbent drew a distinction between "automatic" and "controlled" processes (a distinction characterized more fully by Shiffrin and Schneider in 1977), and introduced the notion of selective attention, to which executive functions are closely allied. In 1975, the US psychologist Michael Posner used the term "cognitive control" in his book chapter entitled "Attention and cognitive control".

The work of influential researchers such as Michael Posner, Joaquin Fuster, Tim Shallice, and their colleagues in the 1980s (and later Trevor Robbins, Bob Knight, Don Stuss, and others) laid much of the groundwork for recent research into executive functions. For example, Posner proposed that there is a separate "executive" branch of the attentional system, which is responsible for focusing attention on selected aspects of the environment. The British neuropsychologist Tim Shallice similarly suggested that attention is regulated by a "supervisory system", which can override automatic responses in favour of scheduling behaviour on the basis of plans or intentions. Throughout this period, a consensus emerged that this control system is housed in the most anterior portion of the brain, the prefrontal cortex (PFC).

Psychologist Alan Baddeley had proposed a similar system as part of his model of working memory and argued that there must be a component (which he named the "central executive") that allows information to be manipulated in short-term memory (for example, when doing mental arithmetic).

Development

The executive functions are among the last mental functions to reach maturity. This is due to the delayed maturation of the prefrontal cortex, which is not completely myelinated until well into a person's third decade of life. Development of executive functions tends to occur in spurts, when new skills, strategies, and forms of awareness emerge. These spurts are thought to reflect maturational events in the frontal areas of the brain. Attentional control appears to emerge in infancy and develop rapidly in early childhood. Cognitive flexibility, goal setting, and information processing usually develop rapidly during ages 7–9 and mature by age 12. Executive control typically emerges shortly after a transition period at the beginning of adolescence. It's not yet clear whether there is a single sequence of stages in which executive functions appear, or whether different environments and early life experiences can lead people to develop them in different sequences.

Early childhood

Inhibitory control and working memory act as basic executive functions that makes it possible for more complex executive functions like problem-solving to develop. Inhibitory control and working memory are among the earliest executive functions to appear, with initial signs observed in infants, 7 to 12-months old. Then in the preschool years, children display a spurt in performance on tasks of inhibition and working memory, usually between the ages of 3 to 5 years. Also during this time, cognitive flexibility, goal-directed behavior, and planning begin to develop. Nevertheless, preschool children do not have fully mature executive functions and continue to make errors related to these emerging abilities – often not due to the absence of the abilities, but rather because they lack the awareness to know when and how to use particular strategies in particular contexts.

Preadolescence

Preadolescent children continue to exhibit certain growth spurts in executive functions, suggesting that this development does not necessarily occur in a linear manner, along with the preliminary maturing of particular functions as well. During preadolescence, children display major increases in verbal working memory; goal-directed behavior (with a potential spurt around 12 years of age); response inhibition and selective attention; and strategic planning and organizational skills. Additionally, between the ages of 8 to 10, cognitive flexibility in particular begins to match adult levels. However, similar to patterns in childhood development, executive functioning in preadolescents is limited because they do not reliably apply these executive functions across multiple contexts as a result of ongoing development of inhibitory control.

Adolescence

Many executive functions may begin in childhood and preadolescence, such as inhibitory control. Yet, it is during adolescence when the different brain systems become better integrated. At this time, youth implement executive functions, such as inhibitory control, more efficiently and effectively and improve throughout this time period. Just as inhibitory control emerges in childhood and improves over time, planning and goal-directed behavior also demonstrate an extended time course with ongoing growth over adolescence. Likewise, functions such as attentional control, with a potential spurt at age 15, along with working memory, continue developing at this stage.

Adulthood

The major change that occurs in the brain in adulthood is the constant myelination of neurons in the prefrontal cortex. At age 20–29, executive functioning skills are at their peak, which allows people of this age to participate in some of the most challenging mental tasks. These skills begin to decline in later adulthood. Working memory and spatial span are areas where decline is most readily noted. Cognitive flexibility, however, has a late onset of impairment and does not usually start declining until around age 70 in normally functioning adults. Impaired executive functioning has been found to be the best predictor of functional decline in the elderly.

Models

Top-down inhibitory control

Aside from facilitatory or amplificatory mechanisms of control, many authors have argued for inhibitory mechanisms in the domain of response control, memory, selective attention, theory of mind, emotion regulation, as well as social emotions such as empathy. A recent review on this topic argues that active inhibition is a valid concept in some domains of psychology/cognitive control.

Working memory model

One influential model is Baddeley's multicomponent model of working memory, which is composed of a central executive system that regulates three other subsystems: the phonological loop, which maintains verbal information; the visuospatial sketchpad, which maintains visual and spatial information; and the more recently developed episodic buffer that integrates short-term and long-term memory, holding and manipulating a limited amount of information from multiple domains in temporal and spatially sequenced episodes.

Supervisory attentional system (SAS)

Another conceptual model is the supervisory attentional system (SAS). In this model, contention scheduling is the process where an individual's well-established schemas automatically respond to routine situations while executive functions are used when faced with novel situations. In these new situations, attentional control will be a crucial element to help generate new schema, implement these schema, and then assess their accuracy.

Self-regulatory model

Russell Barkley proposed a widely known model of executive functioning that is based on self-regulation. Primarily derived from work examining behavioral inhibition, it views executive functions as composed of four main abilities. One element is working memory that allows individuals to resist interfering information. A second component is the management of emotional responses in order to achieve goal-directed behaviors. Thirdly, internalization of self-directed speech is used to control and sustain rule-governed behavior and to generate plans for problem-solving. Lastly, information is analyzed and synthesized into new behavioral responses to meet one's goals. Changing one's behavioral response to meet a new goal or modify an objective is a higher level skill that requires a fusion of executive functions including self-regulation, and accessing prior knowledge and experiences.

According to this model, the executive system of the human brain provides for the cross-temporal organization of behavior towards goals and the future and coordinates actions and strategies for everyday goal-directed tasks. Essentially, this system permits humans to self-regulate their behavior so as to sustain action and problem solving toward goals specifically and the future more generally. Thus, executive function deficits pose serious problems for a person's ability to engage in self-regulation over time to attain their goals and anticipate and prepare for the future.

Problem-solving model

Yet another model of executive functions is a problem-solving framework where executive functions is considered a macroconstruct composed of subfunctions working in different phases to (a) represent a problem, (b) plan for a solution by selecting and ordering strategies, (c) maintain the strategies in short-term memory in order to perform them by certain rules, and then (d) evaluate the results with error detection and error correction.

Lezak's conceptual model

One of the most widespread conceptual models on executive functions is Lezak's model. This framework proposes four broad domains of volition, planning, purposive action, and effective performance as working together to accomplish global executive functioning needs. While this model may broadly appeal to clinicians and researchers to help identify and assess certain executive functioning components, it lacks a distinct theoretical basis and relatively few attempts at validation.

Miller & Cohen's model

In 2001, Earl Miller and Jonathan Cohen published their article "An integrative theory of prefrontal cortex function", in which they argue that cognitive control is the primary function of the prefrontal cortex (PFC), and that control is implemented by increasing the gain of sensory or motor neurons that are engaged by task- or goal-relevant elements of the external environment. In a key paragraph, they argue:

We assume that the PFC serves a specific function in cognitive control: the active maintenance of patterns of activity that represent goals and the means to achieve them. They provide bias signals throughout much of the rest of the brain, affecting not only visual processes but also other sensory modalities, as well as systems responsible for response execution, memory retrieval, emotional evaluation, etc. The aggregate effect of these bias signals is to guide the flow of neural activity along pathways that establish the proper mappings between inputs, internal states, and outputs needed to perform a given task.

Miller and Cohen draw explicitly upon an earlier theory of visual attention that conceptualises perception of visual scenes in terms of competition among multiple representations – such as colors, individuals, or objects. Selective visual attention acts to 'bias' this competition in favour of certain selected features or representations. For example, imagine that you are waiting at a busy train station for a friend who is wearing a red coat. You are able to selectively narrow the focus of your attention to search for red objects, in the hope of identifying your friend. Desimone and Duncan argue that the brain achieves this by selectively increasing the gain of neurons responsive to the color red, such that output from these neurons is more likely to reach a downstream processing stage, and, as a consequence, to guide behaviour. According to Miller and Cohen, this selective attention mechanism is in fact just a special case of cognitive control – one in which the biasing occurs in the sensory domain. According to Miller and Cohen's model, the PFC can exert control over input (sensory) or output (response) neurons, as well as over assemblies involved in memory, or emotion. Cognitive control is mediated by reciprocal PFC connectivity with the sensory and motor cortices, and with the limbic system. Within their approach, thus, the term 'cognitive control' is applied to any situation where a biasing signal is used to promote task-appropriate responding, and control thus becomes a crucial component of a wide range of psychological constructs such as selective attention, error monitoring, decision-making, memory inhibition, and response inhibition.

Miyake and Friedman's model

Miyake and Friedman's theory of executive functions proposes that there are three aspects of executive functions: updating, inhibition, and shifting. A cornerstone of this theoretical framework is the understanding that individual differences in executive functions reflect both unity (i.e., common EF skills) and diversity of each component (e.g., shifting-specific). In other words, aspects of updating, inhibition, and shifting are related, yet each remains a distinct entity. First, updating is defined as the continuous monitoring and quick addition or deletion of contents within one's working memory. Second, inhibition is one's capacity to supersede responses that are prepotent in a given situation. Third, shifting is one's cognitive flexibility to switch between different tasks or mental states.

Miyake and Friedman also suggest that the current body of research in executive functions suggest four general conclusions about these skills. The first conclusion is the unity and diversity aspects of executive functions. Second, recent studies suggest that much of one's EF skills are inherited genetically, as demonstrated in twin studies. Third, clean measures of executive functions can differentiate between normal and clinical or regulatory behaviors, such as ADHD. Last, longitudinal studies demonstrate that EF skills are relatively stable throughout development.

Banich's "Cascade of control" model

This model from 2009 integrates theories from other models, and involves a sequential cascade of brain regions involved in maintaining attentional sets in order to arrive at a goal. In sequence, the model assumes the involvement of the posterior dorsolateral prefrontal cortex (DLPFC), the mid-DLPFC, and the posterior and anterior dorsal ACC.

The cognitive task used in the article is selecting a response in the Stroop task, among conflicting color and word responses, specifically a stimulus where the word "green" is printed in red ink. The posterior DLPFC creates an appropriate attentional set, or rules for the brain to accomplish the current goal. For the Stroop task, this involves activating the areas of the brain involved in color perception, and not those involved in word comprehension. It counteracts biases and irrelevant information, like the fact that the semantic perception of the word is more salient to most people than the color in which it is printed.

Next, the mid-DLPFC selects the representation that will fulfill the goal. The task-relevant information must be separated from other sources of information in the task. In the example, this means focusing on the ink color and not the word.

The posterior dorsal anterior cingulate cortex (ACC) is next in the cascade, and it is responsible for response selection. This is where the decision is made whether you will say green (the written word and the incorrect answer) or red (the font color and correct answer).

Following the response, the anterior dorsal ACC is involved in response evaluation, deciding whether you were correct or incorrect. Activity in this region increases when the probability of an error is higher.

The activity of any of the areas involved in this model depends on the efficiency of the areas that came before it. If the DLPFC imposes a lot of control on the response, the ACC will require less activity.

Recent work using individual differences in cognitive style has shown exciting support for this model. Researchers had participants complete an auditory version of the Stroop task, in which either the location or semantic meaning of a directional word had to be attended to. Participants that either had a strong bias toward spatial or semantic information (different cognitive styles) were then recruited to participate in the task. As predicted, participants that has a strong bias toward spatial information had more difficulty paying attention to the semantic information and elicited increased electrophysiological activity from the ACC. A similar activity pattern was also found for participants that had a strong bias toward verbal information when they tried to attend to spatial information.

Assessment

Assessment of executive functions involves gathering data from several sources and synthesizing the information to look for trends and patterns across time and settings. Apart from standardized neuropsychological tests, other measures can and should be used, such as behaviour checklists, observations, interviews, and work samples. From these, conclusions may be drawn on the use of executive functions.

There are several different kinds of instruments (e.g., performance based, self-report) that measure executive functions across development. These assessments can serve a diagnostic purpose for a number of clinical populations.

• Behavioural Assessment of Dysexecutive Syndrome (BADS)
• Behavior Rating Inventory of Executive Function (BRIEF). Ages 2-90 covered by different versions of the scale.
• Barkley Deficits in Executive Functioning Scales (BDEFS)
• Behavioral Dyscontrol Scale (BDS)
• Comprehensive Executive Function Inventory (CEFI)
• CogScreen
• Continuous Performance Task (CPT)
• Controlled Oral Word Association Test (COWAT)
• d2 Test of Attention
• Delis-Kaplan Executive Function System (D-KEFS)
• Digit Vigilance Test
• Figural Fluency Test
• Halstead Category Test
• Hayling and Brixton tests
• Iowa gambling task
• Kaplan Baycrest Neurocognitive Assessment (KBNA)
• Kaufman Short Neuropsychological Assessment
• Paced Auditory Serial Addition Test (PASAT)
• Pediatric Attention Disorders Diagnostic Screener (PADDS)
• Rey-Osterrieth Complex Figure
• Ruff Figural Fluency Test
• Stroop task
• Tasks of Executive Control
• Test of Variables of Attention (T.O.V.A.)
• Tower of London Test
• Trail-Making Test (TMT) or Trails A & B
• Wisconsin Card Sorting Test (WCST)
• Symbol Digit Modalities Test

Experimental evidence

The executive system has been traditionally quite hard to define, mainly due to what psychologist Paul W. Burgess calls a lack of "process-behaviour correspondence". That is, there is no single behavior that can in itself be tied to executive function, or indeed executive dysfunction. For example, it is quite obvious what reading-impaired patients cannot do, but it is not so obvious what exactly executive-impaired patients might be incapable of.

This is largely due to the nature of the executive system itself. It is mainly concerned with the dynamic, "online" co-ordination of cognitive resources, and, hence, its effect can be observed only by measuring other cognitive processes. In similar manner, it does not always fully engage outside of real-world situations. As neurologist Antonio Damasio has reported, a patient with severe day-to-day executive problems may still pass paper-and-pencil or lab-based tests of executive function.

Theories of the executive system were largely driven by observations of patients having suffered frontal lobe damage. They exhibited disorganized actions and strategies for everyday tasks (a group of behaviors now known as dysexecutive syndrome) although they seemed to perform normally when clinical or lab-based tests were used to assess more fundamental cognitive functions such as memory, learning, language, and reasoning. It was hypothesized that, to explain this unusual behaviour, there must be an overarching system that co-ordinates other cognitive resources.

Much of the experimental evidence for the neural structures involved in executive functions comes from laboratory tasks such as the Stroop task or the Wisconsin Card Sorting Task (WCST). In the Stroop task, for example, human subjects are asked to name the color that color words are printed in when the ink color and word meaning often conflict (for example, the word "RED" in green ink). Executive functions are needed to perform this task, as the relatively overlearned and automatic behaviour (word reading) has to be inhibited in favour of a less practiced task – naming the ink color. Recent functional neuroimaging studies have shown that two parts of the PFC, the anterior cingulate cortex (ACC) and the dorsolateral prefrontal cortex (DLPFC), are thought to be particularly important for performing this task.

Context-sensitivity of PFC neurons

Other evidence for the involvement of the PFC in executive functions comes from single-cell electrophysiology studies in non-human primates, such as the macaque monkey, which have shown that (in contrast to cells in the posterior brain) many PFC neurons are sensitive to a conjunction of a stimulus and a context. For example, PFC cells might respond to a green cue in a condition where that cue signals that a leftwards fast movement of the eyes and the head should be made, but not to a green cue in another experimental context. This is important, because the optimal deployment of executive functions is invariably context-dependent.

One example from Miller & Cohen involves a pedestrian crossing the street. In the United States, where cars drive on the right side of the road, an American learns to look left when crossing the street. However, if that American visits a country where cars drive on the left, such as the United Kingdom, then the opposite behavior would be required (looking to the right). In this case, the automatic response needs to be suppressed and executive functions must make the American look to the right while in the UK.

Neurologically, this behavioural repertoire clearly requires a neural system that is able to integrate the stimulus (the road) with a context (US or UK) to cue a behaviour (look left or look right). Current evidence suggests that neurons in the PFC appear to represent precisely this sort of information. Other evidence from single-cell electrophysiology in monkeys implicates ventrolateral PFC (inferior prefrontal convexity) in the control of motor responses. For example, cells that increase their firing rate to NoGo signals as well as a signal that says "don't look there!" have been identified.

Attentional biasing in sensory regions

Electrophysiology and functional neuroimaging studies involving human subjects have been used to describe the neural mechanisms underlying attentional biasing. Most studies have looked for activation at the 'sites' of biasing, such as in the visual or auditory cortices. Early studies employed event-related potentials to reveal that electrical brain responses recorded over left and right visual cortex are enhanced when the subject is instructed to attend to the appropriate (contralateral) side of space.

The advent of bloodflow-based neuroimaging techniques such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) has more recently permitted the demonstration that neural activity in a number of sensory regions, including color-, motion-, and face-responsive regions of visual cortex, is enhanced when subjects are directed to attend to that dimension of a stimulus, suggestive of gain control in sensory neocortex. For example, in a typical study, Liu and coworkers presented subjects with arrays of dots moving to the left or right, presented in either red or green. Preceding each stimulus, an instruction cue indicated whether subjects should respond on the basis of the colour or the direction of the dots. Even though colour and motion were present in all stimulus arrays, fMRI activity in colour-sensitive regions (V4) was enhanced when subjects were instructed to attend to the colour, and activity in motion-sensitive regions was increased when subjects were cued to attend to the direction of motion. Several studies have also reported evidence for the biasing signal prior to stimulus onset, with the observation that regions of the frontal cortex tend to come active prior to the onset of an expected stimulus.

Connectivity between the PFC and sensory regions

Despite the growing currency of the 'biasing' model of executive functions, direct evidence for functional connectivity between the PFC and sensory regions when executive functions are used, is to date rather sparse. Indeed, the only direct evidence comes from studies in which a portion of frontal cortex is damaged, and a corresponding effect is observed far from the lesion site, in the responses of sensory neurons. However, few studies have explored whether this effect is specific to situations where executive functions are required. Other methods for measuring connectivity between distant brain regions, such as correlation in the fMRI response, have yielded indirect evidence that the frontal cortex and sensory regions communicate during a variety of processes thought to engage executive functions, such as working memory, but more research is required to establish how information flows between the PFC and the rest of the brain when executive functions are used. As an early step in this direction, an fMRI study on the flow of information processing during visuospatial reasoning has provided evidence for causal associations (inferred from the temporal order of activity) between sensory-related activity in occipital and parietal cortices and activity in posterior and anterior PFC. Such approaches can further elucidate the distribution of processing between executive functions in PFC and the rest of the brain.

Bilingualism and executive functions

A growing body of research demonstrates that bilinguals show advantages in executive functions, specifically inhibitory control and task switching. A possible explanation for this is that speaking two languages requires controlling one's attention and choosing the correct language to speak. Across development, bilingual infants, children, and elderly show a bilingual advantage when it comes to executive functioning. Bimodal bilinguals, or people who speak one oral language and one sign language, do not demonstrate this bilingual advantage in executive functioning tasks. This may be because one is not required to actively inhibit one language in order to speak the other. Bilingual individuals also seem to have an advantage in an area known as conflict processing, which occurs when there are multiple representations of one particular response (for example, a word in one language and its translation in the individual's other language). Specifically, the lateral prefrontal cortex has been shown to be involved with conflict processing. However, there are still some doubts. In a meta-analytic review, researchers concluded that bilingualism did not enhance executive functioning in adults.

In disease or disorder

The study of executive function in Parkinson's disease suggests subcortical areas such as the amygdala, hippocampus and basal ganglia are important in these processes. Dopamine modulation of the prefrontal cortex is responsible for the efficacy of dopaminergic drugs on executive function, and gives rise to the Yerkes Dodson Curve. The inverted U represents decreased executive functioning with excessive arousal (or increased catecholamine release during stress), and decreased executive functioning with insufficient arousal. The low activity polymorphism of Catechol-O-methyltransferase is associated with slight increase in performance on executive function tasks in healthy persons. Executive functions are impaired in multiple disorders include anxiety disorder, major depressive disorder, bipolar disorder, attention deficit hyperactivity disorder, schizophrenia and autism. Lesions to the prefrontal cortex, such as in the case of Phineas Gage, may also result in deficits of executive function. Damage to these areas may also manifest in deficits of other areas of function, such as motivation, and social functioning.

Future directions

Other important evidence for executive functions processes in the prefrontal cortex have been described. One widely cited review article emphasizes the role of the medial part of the PFC in situations where executive functions are likely to be engaged – for example, where it is important to detect errors, identify situations where stimulus conflict may arise, make decisions under uncertainty, or when a reduced probability of obtaining favourable performance outcomes is detected. This review, like many others, highlights interactions between medial and lateral PFC, whereby posterior medial frontal cortex signals the need for increased executive functions and sends this signal on to areas in dorsolateral prefrontal cortex that actually implement control. Yet there has been no compelling evidence at all that this view is correct, and, indeed, one article showed that patients with lateral PFC damage had reduced ERNs (a putative sign of dorsomedial monitoring/error-feedback) – suggesting, if anything, that the direction of flow of the control could be in the reverse direction. Another prominent theory emphasises that interactions along the perpendicular axis of the frontal cortex, arguing that a 'cascade' of interactions between anterior PFC, dorsolateral PFC, and premotor cortex guides behaviour in accordance with past context, present context, and current sensorimotor associations, respectively.

Advances in neuroimaging techniques have allowed studies of genetic links to executive functions, with the goal of using the imaging techniques as potential endophenotypes for discovering the genetic causes of executive function.

More research is required to develop interventions that can improve executive functions and help people generalize those skills to daily activities and settings.

Long-term effects of alcohol consumption

From Wikipedia, the free encyclopedia

Long-term effects of alcohol
Most significant of the possible long-term effects of ethanol. Consumption of alcohol by pregnant mothers may result in fetal alcohol spectrum disorders.

The best available current evidence suggests that consumption of alcohol (chemically known as ethanol) does not improve health. Previous assertions that low or moderate consumption of alcohol improved health have been deprecated by more careful and complete meta-analysis. Heavy consumption of ethanol (alcohol abuse) can cause severe detrimental effects. Health effects associated with alcohol intake in large amounts include an increased risk of alcoholism, malnutrition, chronic pancreatitis, alcoholic liver disease and cancer. In addition, damage to the central nervous system and peripheral nervous system can occur from chronic alcohol abuse. The long-term use of alcohol is capable of damaging nearly every organ and system in the body. The developing adolescent brain is particularly vulnerable to the toxic effects of alcohol. In addition, the developing fetal brain is also vulnerable, and fetal alcohol spectrum disorders (FASDs) may result if pregnant mothers consume alcohol.

The inverse relation in Western cultures between alcohol consumption and cardiovascular disease has been known for over 100 years. Many physicians do not promote alcohol consumption, however, given the many health concerns associated with it; some suggest that alcohol should be regarded as a recreational drug, and promote exercise and good nutrition to combat cardiovascular disease. The best available evidence indicates that the small beneficial effects of moderate ethanol use on cardiovascular health are outweighed by the increased risk of cancer, injuries, violence, fetal damage, liver disease. Alcohol liver disease (ALD) accounted for four fifths of all chronic diseases in Ireland in 2013.

Withdrawal effects and dependence are also almost identical. Alcohol at moderate levels has some positive and negative effects on health. The negative effects include increased risk of liver diseases, oropharyngeal cancer, esophageal cancer and pancreatitis. Conversely moderate intake of alcohol may have some beneficial effects on gastritis and cholelithiasis. Of the total number of deaths and diseases caused by alcohol, most happen to the majority of the population who are moderate drinkers, rather than the heavy drinker minority. Chronic alcohol misuse and abuse has serious effects on physical and mental health. Chronic excess alcohol intake, or alcohol dependence, can lead to a wide range of neuropsychiatric or neurological impairment, cardiovascular disease, liver disease, and malignant neoplasms. The psychiatric disorders which are associated with alcoholism include major depression, dysthymia, mania, hypomania, panic disorder, phobias, generalized anxiety disorder, personality disorders, schizophrenia, suicide, neurologic deficits (e.g. impairments of working memory, emotions, executive functions, visuospatial abilities and gait and balance) and brain damage. Alcohol dependence is associated with hypertension, coronary heart disease, and ischemic stroke, cancer of the respiratory system, and also cancers of the digestive system, liver, breast and ovaries. Heavy drinking is associated with liver disease, such as cirrhosis. Excessive alcohol consumption can have a negative impact on aging.

Mortality effects

A 2016 systematic review and meta-analysis found that moderate ethanol consumption does not prolong life compared with lifetime abstention from ethanol consumption. A systematic analysis of data from the Global Burden of Disease study found that consumption of ethanol increases the risk of cancer and increases the risk of all-cause mortality, and that the level of ethanol consumption that minimizes disease is zero consumption. Some studies have concluded that drinking small quantities of alcohol (less than one drink in women and two in men) is associated with a decreased risk of heart disease, stroke, diabetes mellitus, and early death. Some of these studies lumped former ethanol drinkers and life-long abstainers into a single group of nondrinkers, hiding the health benefits of life-long abstention from ethanol. Drinking more than this amount actually increases the risk of heart disease, high blood pressure, atrial fibrillation, and stroke. Risk is greater in younger people due to binge drinking which may result in violence or accidents. About 3.3 million deaths (5.9% of all deaths) are believed to be due to alcohol each year.

Maximum quantity recommended

Total recorded alcohol per capita consumption (15+), in litres of pure alcohol

Different countries recommend different maximum quantities. In the UK, the Chief Medical Officers' recommends men and women drink no more than 14 units per week. A single unit corresponds to 8 g of ethanol. For most countries, the maximum quantity for men is 140 g–210 g per week. For women, the range is 84 g–140 g per week. Most countries recommend total abstinence during pregnancy and lactation. A 2018 study on 599912 drinkers in 19 different countries recommends a "safe" drinking limit of seven "standard" drinks per week, or 100 grams of pure alcohol per week.

Alcohol-related death

Disability-adjusted life year for alcohol use disorders per 100,000 inhabitants in 2004.

 

  no data

  less than 50

  50–150

  150–250

  250–350

  350–450

  450–550

  550–650

  650–750

  750–850

  850–950

  950–1050

  more than 1050

Over-consumption of alcohol causes many deaths worldwide. The overall mortality from alcohol use was found to be similar to that of the effect of physical inactivity. A review in 2009 found that "the net effect of alcohol consumption on health is detrimental, with an estimated 3.8% of all global deaths and 4.6% of global disability-adjusted life-years attributable to alcohol."

Extensive research of Western cultures has consistently shown increased survival associated with light to moderate alcohol consumption. A 23-year prospective study of 12,000 male British physicians aged 48–78, found that overall mortality was significantly lower in current drinkers compared to non-drinkers even after correction for ex-drinkers. This benefit was strongest for ischemic heart disease, but was also noted for other vascular disease and respiratory disease. Death rate amongst current drinkers was higher for 'alcohol augmentable' disease such as liver disease and oral cancers, but these deaths were much less common than cardiovascular and respiratory deaths. The lowest mortality rate was found for consumption of 8 to 14 'units' per week. In the UK a unit is defined as 10ml or 8g of pure alcohol. Higher consumption increased overall mortality rate, but not above that of non-drinkers. Other studies have found age-dependent mortality risks of low-to-moderate alcohol use: an increased risk for individuals aged 16–34 (due to increased risk of cancers, accidents, liver disease, and other factors), but a decreased risk for individuals ages 55+ (due to lower incidence of ischemic heart disease).

This is consistent with other research that found a J-curve dependency between alcohol consumption and total mortality among middle aged and older men. While the mortality rates of ex-drinkers and heavy drinkers are significantly elevated, the all-cause mortality rates may be 15–18% lower among moderate drinkers. Although the definition of a drink varies between studies and countries, this meta-analysis found that low levels of alcohol intake, defined as 1–2 drinks per day for women and 2–4 drinks per day for men, was associated with lower mortality than abstainers. This claim was challenged by another study that found that in certain low quality studies occasional drinkers or ex-drinkers were included as abstainers, resulting in the increased mortality in that group. However, the J-curve for total and CHD mortality was reconfirmed by studies that took the mentioned confounders into account. There seems to be little discussion of what proportion of individuals classified as abstainers are those already at greater risk of mortality due to chronic conditions and do not or cannot consume alcohol for reasons of health or harmful interactions with medication.

The observed decrease in mortality of light-to-moderate drinkers compared to never drinkers might be partially explained by superior health and social status of the drinking group; however, the protective effect of alcohol in light to moderate drinkers remains significant even after adjusting for these confounders. Additionally, confounders such as underreporting of alcohol intake might lead to the underestimation of how much mortality is reduced in light-to-moderate drinkers.

A 2010 study confirmed the beneficial effect of moderate alcohol consumption on mortality. Subjects were grouped into abstainers, light, moderate, and heavy drinkers. The order of mortality rates from lowest to highest were moderate, light, heavy, and abstainers. The increased risk for abstainers was twice the mortality rate as for moderate drinkers. This study specifically sought to control for confounding factors including the problem of ex-drinkers considered as non-drinkers. According to another study, drinkers with heavy drinking occasions (six or more drinks at a time) have a 57% higher all-cause mortality than drinkers without heavy drinking occasions.

Mortality is lowest among young abstainers and highest among young heavy drinkers.

According to a 2018 study people who had more than seven and up to 14 standard drinks per week, were likely to have their life expectancy shortened by around 6 months. Those who consumed over 14 drinks and up to 25 per week were likely to have 1–2 years taken off their lifespan, and a consumption of over 25 standard drinks per week correlated with 4–5 fewer years.

In contrast to studies of Western cultures, research in other cultures has yielded some opposite findings. The landmark INTERHEART Study has revealed that alcohol consumption in South Asians was not protective against CAD in sharp contrast to other populations who benefit from it. In fact Asian Indians who consume alcohol had a 60% higher risk of heart attack which was greater with local spirits (80%) than branded spirits (50%). The harm was observed in alcohol users classified as occasional as well as regular light, moderate, and heavy consumers.

Another large study of 4465 subjects in India also confirmed the possible harm of alcohol consumption on coronary risk in men. Compared to lifetime abstainers, alcohol users had higher blood sugar (2 mg/dl), blood pressure (2 mm Hg) levels, and the HDL-C levels (2 mg/dl) and significantly higher tobacco use (63% vs. 21%).

Many countries collect statistics on alcohol-related deaths. While some categories relate to short-term effects, such as accidents, many relate to long-term effects of alcohol.

Russia

One study claims that "excessive alcohol consumption in Russia, particularly by men, has in recent years caused more than half of all the deaths at ages 15–54 years." However, there are some difficulties with this study. For instance the same study also found a protective effect of heavy drinking on breast cancer mortality. This contradicts the well established scientific view that alcohol increases breast cancer risk. On this account in further correspondence it was advised that "careful interpretation of mortality statistics in relation to alcohol use is needed, taking into account other relevant risk factors, incidence, and survival."

The authors replied that "whether or not the apparent shortfall in breast cancer mortality among heavy drinkers is real, it accounts for only about 0.1% of adult deaths in Russia. Careful interpretation of it is therefore of little relevance to the findings for alcohol and overall mortality".

United Kingdom

A governmental report from Britain has found that "There were 8,724 alcohol-related deaths in 2007, lower than 2006, but more than double the 4,144 recorded in 1991. The alcohol-related death rate was 13.3 per 100,000 population in 2007, compared with 6.9 per 100,000 population in 1991." In Scotland, the NHS estimate that in 2003 one in every 20 deaths could be attributed to alcohol. A 2009 report noted that the death rate from alcohol-related disease was 9,000, a number three times that of 25 years previously.

A UK report came to the result that the effects of low-to-moderate alcohol consumption on mortality are age-dependent. Low-to-moderate alcohol use increases the risk of death for individuals aged 16–34 (due to increased risk of cancers, accidents, liver disease, and other factors), but decreases the risk of death for individuals ages 55+ (due to decreased risk of ischemic heart disease).

A study in the United Kingdom found that alcohol causes about 4% of cancer cases in the UK (12,500 cases per year).

United States

The Centers for Disease Control and Prevention report, "From 2001–2005, there were approximately 79,000 deaths annually attributable to excessive alcohol use. In fact, excessive alcohol use is the 3rd leading lifestyle-related cause of death for people in the United States each year." A 1993 study estimated US deaths through alcohol at 100,000.

Another Centers for Disease Control report from 2001 estimated that medium and high consumption of alcohol led to 75,754 deaths in the United States in 2001. Low consumption of alcohol had some beneficial effects, so a net 59,180 deaths were attributed to alcohol.

Longevity

In 2016, a meta-analysis of 87 studies investigating alcohol use and mortality risk was conducted. The studies analyzed had shown the largest mortality risk reduction in moderate drinkers, but these studies did not correct for confounding variables common with certain abstainers, such as previous alcoholism, and chronic health issues. After adjusting these studies for abstainer biases, no reduction in mortality risk was found for low-volume drinkers. However, there have been individual studies that show abstainers and heavy drinkers have an increased mortality of about 50% over moderate drinkers after adjustment for confounding factors.

Some animal studies have found increased longevity with exposure to various alcohols. The roundworm Caenorhabditis elegans has been used as a model for aging and age-related diseases. The lifespan of these worms has been shown to double when fed 0.005% ethanol, but does not markedly increase at higher concentrations. Supplementing starved cultures with n-propanol and n-butanol also extended lifespan.

Cardiovascular system

A meta-analysis of 34 studies found a reduced risk of mortality from coronary heart disease in men who drank 2–4 drinks per day and women who drank 1–2 drinks per day. Alcohol has been found to have anticoagulant properties. Thrombosis is lower among moderate drinkers than abstainers. A meta-analysis of randomized trials found that alcohol consumption in moderation decreases serum levels of fibrinogen, a protein that promotes clot formation, while it increases levels of tissue type plasminogen activator, an enzyme that helps dissolve clots. These changes were estimated to reduce coronary heart disease risk by about 24%. Another meta-analysis in 2011 found favorable changes in HDL cholesterol, adiponectin, and fibrinogen associated with moderate alcohol consumption.

Also, serum levels of C-reactive protein (CRP), a marker of inflammation and predictor of CHD (coronary heart disease) risk, are lower in moderate drinkers than in those who abstain from alcohol, suggesting that alcohol consumption in moderation might have anti-inflammatory effects.

Despite epidemiological evidence, many have cautioned against recommendations for the use of alcohol for health benefits. A physician from the World Health Organization labeled such alcohol promotion as "ridiculous and dangerous". One reviewer has noted, "Despite the wealth of observational data, it is not absolutely clear that alcohol reduces cardiovascular risk, because no randomized controlled trials have been performed. Alcohol should never be recommended to patients to reduce cardiovascular risk as a substitute for the well-proven alternatives of appropriate diet, exercise, and drugs." It has been argued that the health benefits from alcohol are at best debatable and may have been exaggerated by the alcohol industry. Some investigators hold that alcohol should be regarded as a recreational drug with potentially serious adverse effects on health and should not be promoted for cardio-protection.

Nevertheless, a large prospective non-randomized study has shown that moderate alcohol intake in individuals already at low risk based on body mass index, physical activity, smoking, and diet, yields further improvement in cardiovascular risk. Furthermore, a multicenter randomized diet study published in 2013 found that a Mediterranean-diet, which included an encouragement to daily wine consumption in habitual drinkers, led to a dramatic reduction in cardiovascular events.

Peripheral arterial disease

A prospective study published in 1997 found "moderate alcohol consumption appears to decrease the risk of PAD in apparently healthy men." In a large population-based study, moderate alcohol consumption was inversely associated with peripheral arterial disease in women but not in men. But when confounding by smoking was considered, the benefit extended to men. The study concluded "an inverse association between alcohol consumption and peripheral arterial disease was found in nonsmoking men and women."

Intermittent claudication

A study found that moderate consumption of alcohol had a protective effect against intermittent claudication. The lowest risk was seen in men who drank 1 to 2 drinks per day and in women who drank half to 1 drink per day.

Heart attack and stroke

Drinking in moderation has been found to help those who have suffered a heart attack survive it. However, excessive alcohol consumption leads to an increased risk of heart failure. A review of the literature found that half a drink of alcohol offered the best level of protection. However, they noted that at present there have been no randomised trials to confirm the evidence which suggests a protective role of low doses of alcohol against heart attacks. However, moderate alcohol consumption is associated with hypertension. There is an increased risk of hypertriglyceridemia, cardiomyopathy, hypertension, and stroke if 3 or more standard drinks of alcohol are taken per day.

Cardiomyopathy

Large amount of alcohol over the long term can lead to alcoholic cardiomyopathy. Alcoholic cardiomyopathy presents in a manner clinically identical to idiopathic dilated cardiomyopathy, involving hypertrophy of the musculature of the heart that can lead to congestive heart failure.

Hematologic diseases

Alcoholics may have anemia from several causes; they may also develop thrombocytopenia from direct toxic effect on megakaryocytes, or from hypersplenism.

Atrial fibrillation

Alcohol consumption increases the risk of atrial fibrillation, a type of abnormal heart rhythm. This remains true even at moderate levels of consumption.

Nervous system

Results of the ISCD 2010 study ranking the levels of damage caused by drugs, in the opinion of drug-harm experts. When harm to self and others is summed, alcohol was the most harmful of all drugs considered, scoring 72%

Chronic heavy alcohol consumption impairs brain development, causes alcohol dementia, brain shrinkage, physical dependence, alcoholic polyneuropathy (also known as 'alcohol leg'), increases neuropsychiatric and cognitive disorders and causes distortion of the brain chemistry. At present, due to poor study design and methodology, the literature is inconclusive on whether moderate alcohol consumption increases the risk of dementia or decreases it. Evidence for a protective effect of low to moderate alcohol consumption on age-related cognitive decline and dementia has been suggested by some research; however, other research has not found a protective effect of low to moderate alcohol consumption. Some evidence suggests that low to moderate alcohol consumption may speed up brain volume loss. Chronic consumption of alcohol may result in increased plasma levels of the toxic amino acid homocysteine; which may explain alcohol withdrawal seizures, alcohol-induced brain atrophy and alcohol-related cognitive disturbances. Alcohol's impact on the nervous system can also include disruptions of memory and learning, such as resulting in a blackout phenomenon.

Strokes

Epidemiological studies of middle-aged populations generally find the relationship between alcohol intake and the risk of stroke to be either U- or J-shaped. There may be very different effects of alcohol based on the type of stroke studied. The predominant form of stroke in Western cultures is ischemic, whereas non-western cultures have more hemorrhagic stroke. In contrast to the beneficial effect of alcohol on ischemic stroke, consumption of more than 2 drinks per day increases the risk of hemorrhagic stroke. The National Stroke Association estimates this higher amount of alcohol increases stroke risk by 50%. "For stroke, the observed relationship between alcohol consumption and risk in a given population depends on the proportion of strokes that are hemorrhagic. Light-to-moderate alcohol intake is associated with a lower risk of ischemic stroke which is likely to be, in part, causal. Hemorrhagic stroke, on the other hand, displays a loglinear relationship with alcohol intake."

Brain

Alcohol abuse is associated with widespread and significant brain lesions. Alcohol related brain damage is not only due to the direct toxic effects of alcohol; alcohol withdrawal, nutritional deficiency, electrolyte disturbances, and liver damage are also believed to contribute to alcohol-related brain damage.

Cognition and dementia

Excessive alcohol intake is associated with impaired prospective memory. This impaired cognitive ability leads to increased failure to carry out an intended task at a later date, for example, forgetting to lock the door or to post a letter on time. The higher the volume of alcohol consumed and the longer consumed, the more severe the impairments. One of the organs most sensitive to the toxic effects of chronic alcohol consumption is the brain. In the United States approximately 20% of admissions to mental health facilities are related to alcohol-related cognitive impairment, most notably alcohol-related dementia. Chronic excessive alcohol intake is also associated with serious cognitive decline and a range of neuropsychiatric complications. The elderly are the most sensitive to the toxic effects of alcohol on the brain. There is some inconclusive evidence that small amounts of alcohol taken in earlier adult life is protective in later life against cognitive decline and dementia. However, a study concluded, "Our findings suggest that, despite previous suggestions, moderate alcohol consumption does not protect older people from cognitive decline."

There is tentative evidence that drinking a small amount of alcohol may decrease the risk of Alzheimer's disease latter in life.

Wernicke–Korsakoff syndrome is a manifestation of thiamine deficiency, usually as a secondary effect of alcohol abuse. The syndrome is a combined manifestation of two eponymous disorders, Korsakoff's Psychosis and Wernicke's encephalopathy, named after Drs. Sergei Korsakoff and Carl Wernicke. Wernicke's encephalopathy is the acute presentation of the syndrome and is characterised by a confusional state while Korsakoff's psychosis main symptoms are amnesia and executive dysfunction. Banana bags, a bag of intravenous fluids containing vitamins and minerals, can be used to mitigate these outcomes.

Essential tremor

Essential tremors—or, in the case of essential tremors on a background of family history of essential tremors, familial tremors—can be temporarily relieved in up to two-thirds of patients by drinking small amounts of alcohol.

Ethanol is known to activate aminobutyric acid type A (GABAA) and inhibit N-methyl-D-aspartate (NMDA) glutamate receptors, which are both implicated in essential tremor pathology and could underlie the ameliorative effects. Additionally, the effects of ethanol have been studied in different animal essential tremor models.

Sleep

Chronic use of alcohol used to induce sleep can lead to insomnia: frequent moving between sleep stages occurs, with awakenings due to headaches and diaphoresis. Stopping chronic alcohol abuse can also lead to profound disturbances of sleep with vivid dreams. Chronic alcohol abuse is associated with NREM stage 3 and 4 sleep as well as suppression of REM sleep and REM sleep fragmentation. During withdrawal REM sleep is typically exaggerated as part of a rebound effect.

Mental health effects

High rates of major depressive disorder occur in heavy drinkers and those who abuse alcohol. Whether it is more true that major depressive disorder causes self-medicating alcohol abuse, or the increased incidence of the disorder in alcohol abusers is caused by the drinking, is not known though some evidence suggests drinking causes the disorder. Alcohol misuse is associated with a number of mental health disorders and alcoholics have a very high suicide rate. A study of people hospitalised for suicide attempts found that those who were alcoholics were 75 times more likely to go on to successfully commit suicide than non-alcoholic suicide attempters. In the general alcoholic population the increased risk of suicide compared to the general public is 5-20 times greater. About 15 percent of alcoholics commit suicide. Abuse of other drugs is also associated with an increased risk of suicide. About 33 percent of suicides in the under 35s are correlated with alcohol or other substance misuse.

Social skills are significantly impaired in people suffering from alcoholism due to the neurotoxic effects of alcohol on the brain, especially the prefrontal cortex area of the brain. The social skills that are impaired by alcohol abuse include impairments in perceiving facial emotions, prosody perception problems and theory of mind deficits; the ability to understand humour is also impaired in alcohol abusers.

Studies have shown that alcohol dependence relates directly to cravings and irritability. Another study has shown that alcohol use is a significant predisposing factor towards antisocial behavior in children. Depression, anxiety and panic disorder are disorders commonly reported by alcohol dependent people. Alcoholism is associated with dampened activation in brain networks responsible for emotional processing (e.g. the amygdala and hippocampus). Evidence that the mental health disorders are often induced by alcohol misuse via distortion of brain neurochemistry is indicated by the improvement or disappearance of symptoms that occurs after prolonged abstinence, although problems may worsen in early withdrawal and recovery periods. Psychosis is secondary to several alcohol-related conditions including acute intoxication and withdrawal after significant exposure. Chronic alcohol misuse can cause psychotic type symptoms to develop, more so than with other drugs of abuse. Alcohol abuse has been shown to cause an 800% increased risk of psychotic disorders in men and a 300% increased risk of psychotic disorders in women which are not related to pre-existing psychiatric disorders. This is significantly higher than the increased risk of psychotic disorders seen from cannabis use making alcohol abuse a very significant cause of psychotic disorders. Approximately 3 percent of people who are alcohol dependent experience psychosis during acute intoxication or withdrawal. Alcohol-related psychosis may manifest itself through a kindling mechanism. The mechanism of alcohol-related psychosis is due to distortions to neuronal membranes, gene expression, as well as thiamin deficiency. It is possible in some cases that alcohol abuse via a kindling mechanism can cause the development of a chronic substance-induced psychotic disorder, i.e. schizophrenia. The effects of an alcohol-related psychosis include an increased risk of depression and suicide as well as psychosocial impairments. However, moderate wine drinking has been shown to lower the risk for depression.

While alcohol initially helps social phobia or panic symptoms, with longer term alcohol misuse can often worsen social phobia symptoms and can cause panic disorder to develop or worsen, during alcohol intoxication and especially during the alcohol withdrawal syndrome. This effect is not unique to alcohol but can also occur with long-term use of drugs which have a similar mechanism of action to alcohol such as the benzodiazepines, which are sometimes prescribed as tranquillizers to people with alcohol problems. Approximately half of patients attending mental health services for conditions including anxiety disorders such as panic disorder or social phobia suffer from alcohol or benzodiazepine dependence. It was noted that every individual has an individual sensitivity level to alcohol or sedative hypnotic drugs and what one person can tolerate without ill health another will suffer very ill health and that even moderate drinking can cause rebound anxiety syndromes and sleep disorders. A person who is suffering the toxic effects of alcohol will not benefit from other therapies or medications as they do not address the root cause of the symptoms.

Addiction to alcohol, as with any drug of abuse tested so far, has been correlated with an enduring reduction in the expression of GLT1 (EAAT2) in the nucleus accumbens and is implicated in the drug-seeking behavior expressed nearly universally across all documented addiction syndromes. This long-term dysregulation of glutamate transmission is associated with an increase in vulnerability to both relapse-events after re-exposure to drug-use triggers as well as an overall increase in the likelihood of developing addiction to other reinforcing drugs. Drugs which help to re-stabilize the glutamate system such as N-acetylcysteine have been proposed for the treatment of addiction to cocaine, nicotine, and alcohol.

Digestive system and weight gain

The impact of alcohol on weight-gain is contentious: some studies find no effect, others find decreased or increased effect on weight gain.

Alcohol use increases the risk of chronic gastritis (stomach inflammation); it is one cause of cirrhosis, hepatitis, and pancreatitis in both its chronic and acute forms.

Metabolic syndrome

A study concluded, "Mild to moderate alcohol consumption is associated with a lower prevalence of the metabolic syndrome, with a favorable influence on lipids, waist circumference, and fasting insulin. This association was strongest among whites and among beer and wine drinkers." This is also true for Asians. A J-curve association between alcohol intake and metabolic syndrome was found: "The results of the present study suggest that the metabolic syndrome is negatively associated with light alcohol consumption (1–15 g alcohol/d) in Korean adults". However, "odds ratios for the metabolic syndrome and its components tended to increase with increasing alcohol consumption."

Gallbladder effects

Research has found that drinking reduces the risk of developing gallstones. Compared with alcohol abstainers, the relative risk of gallstone disease, controlling for age, sex, education, smoking, and body mass index, is 0.83 for occasional and regular moderate drinkers (< 25 ml of ethanol per day), 0.67 for intermediate drinkers (25-50 ml per day), and 0.58 for heavy drinkers. This inverse association was consistent across strata of age, sex, and body mass index." Frequency of drinking also appears to be a factor. "An increase in frequency of alcohol consumption also was related to decreased risk. Combining the reports of quantity and frequency of alcohol intake, a consumption pattern that reflected frequent intake (5–7 days/week) of any given amount of alcohol was associated with a decreased risk, as compared with nondrinkers. In contrast, infrequent alcohol intake (1–2 days/week) showed no significant association with risk."

A large self-reported study published in 1998 found no correlation between gallbladder disease and multiple factors including smoking, alcohol consumption, hypertension, and coffee consumption. A retrospective study from 1997 found vitamin C (ascorbic acid) supplement use in drinkers was associated with a lower prevalence of gallbladder disease, but this association was not seen in non-drinkers.

Liver disease

Alcoholic liver disease is a major public health problem. For example, in the United States up to two million people have alcohol-related liver disorders. Chronic alcohol abuse can cause fatty liver, cirrhosis and alcoholic hepatitis. Treatment options are limited and consist of most importantly discontinuing alcohol consumption. In cases of severe liver disease, the only treatment option may be a liver transplant from alcohol abstinent donors. Research is being conducted into the effectiveness of anti-TNFs. Certain complementary medications, e.g., milk thistle and silymarin, appear to offer some benefit. Alcohol is a leading cause of liver cancer in the Western world, accounting for 32-45% of hepatic cancers. Up to half a million people in the United States [DJS:  per year?] develop alcohol-related liver cancer. Moderate alcohol consumption also increases the risk of liver disease.

Pancreatitis

Alcohol abuse is a leading cause of both acute pancreatitis and chronic pancreatitis. Alcoholic pancreatitis can result in severe abdominal pain and may progress to pancreatic cancer. Chronic pancreatitis often results in intestinal malabsorption, and can result in diabetes.

Other systems

Respiratory system

Chronic alcohol ingestion can impair multiple critical cellular functions in the lungs. These cellular impairments can lead to increased susceptibility to serious complications from lung disease. Recent research cites alcoholic lung disease as comparable to liver disease in alcohol-related mortality. Alcoholics have a higher risk of developing acute respiratory distress syndrome (ARDS) and experience higher rates of mortality from ARDS when compared to non-alcoholics. Despite these effects, a large prospective study has shown a protective effect of moderate alcohol consumption on respiratory mortality.

Kidney stones

Research indicates that drinking alcohol is associated with a lower risk of developing kidney stones. One study concludes, "Since beer seemed to be protective against kidney stones, the physiologic effects of other substances besides ethanol, especially those of hops, should also be examined." "...consumption of coffee, alcohol, and vitamin C supplements were negatively associated with stones." "After mutually adjusting for the intake of other beverages, the risk of stone formation decreased by the following amount for each 240-ml (8-oz) serving consumed daily: caffeinated coffee, 10%; decaffeinated coffee, 10%; tea, 14%; beer, 21%; and wine, 39%." "...stone formation decreased by the following amount for each 240-mL (8-oz) serving consumed daily: 10% for caffeinated coffee, 9% for decaffeinated coffee, 8% for tea, and 59% for wine." (CI data excised from last two quotes.).

Sexual dysfunction

Long term excessive intake of alcohol can lead to damage to the central nervous system and the peripheral nervous system resulting in loss of sexual desire and impotence in men. This is caused by reduction of testosterone from ethanol-induced testicular atrophy, resulting in increased feminisation of males and is a clinical feature of alcohol abusing males who have cirrhosis of the liver.

Hormonal Imbalance

Excessive alcohol intake can result in hyperoestrogenisation. It has been speculated that alcoholic beverages may contain estrogen-like compounds. In men, high levels of estrogen can lead to testicular failure and the development of feminine traits including development of male breasts, called gynecomastia. In women, increased levels of estrogen due to excessive alcohol intake have been related to an increased risk of breast cancer.

Diabetes mellitus

A meta-analysis found with data from 477,200 individuals determined the dose-response relationships by sex and end point using lifetime abstainers as the reference group. The search revealed 20 cohort studies that met the inclusion criteria. A U-shaped relationship was found for both sexes. Compared with lifetime abstainers, the relative risk (RR) for type 2 diabetes among men was most protective when consuming 22 g/day alcohol (RR 0.87 [95% CI 0.76–1.00]) and became deleterious at just over 60 g/day alcohol (1.01 [0.71–1.44]). Among women, consumption of 24 g/day alcohol was most protective (0.60 [0.52–0.69]) and became deleterious at about 50 g/day alcohol (1.02 [0.83–1.26]).

Because former drinkers may be inspired to abstain due to health concerns, they may actually be at increased risk of developing diabetes, known as the sick-quitter effect. Moreover, the balance of risk of alcohol consumption on other diseases and health outcomes, even at moderate levels of consumption, may outweigh the positive benefits with regard to diabetes.

Additionally, the way in which alcohol is consumed (i.e., with meals or bingeing on weekends) affects various health outcomes. Thus, it may be the case that the risk of diabetes associated with heavy alcohol consumption is due to consumption mainly on the weekend as opposed to the same amount spread over a week. In the United Kingdom "advice on weekly consumption is avoided".
Also, a twenty-year twin study from Finland has shown that moderate alcohol consumption may reduce the risk of type 2 diabetes in men and women. However, binge drinking and high alcohol consumption was found to increase the risk of type 2 diabetes in women.  A study in mice has suggested a beneficial effect of alcohol in promoting insulin sensitivity.

Rheumatoid arthritis

Regular consumption of alcohol is associated with an increased risk of gouty arthritis and a decreased risk of rheumatoid arthritis. Two recent studies report that the more alcohol consumed, the lower the risk of developing rheumatoid arthritis. Among those who drank regularly, the one-quarter who drank the most were up to 50% less likely to develop the disease compared to the half who drank the least.

The researchers noted that moderate alcohol consumption also reduces the risk of other inflammatory processes such as cardiovascualar disease. Some of the biological mechanisms by which ethanol reduces the risk of destructive arthritis and prevents the loss of bone mineral density (BMD), which is part of the disease process.

A study concluded, "Alcohol either protects from RA or, subjects with RA curtail their drinking after the manifestation of RA". Another study found, "Postmenopausal women who averaged more than 14 alcoholic drinks per week had a reduced risk of rheumatoid arthritis..."

Osteoporosis

Moderate alcohol consumption is associated with higher bone mineral density in postmenopausal women. "...Alcohol consumption significantly decreased the likelihood [of osteoporosis]." "Moderate alcohol intake was associated with higher BMD in postmenopausal elderly women." "Social drinking is associated with higher bone mineral density in men and women [over 45]." However, alcohol abuse is associated with bone loss.

Skin

Chronic excessive alcohol abuse is associated with a wide range of skin disorders including urticaria, porphyria cutanea tarda, flushing, cutaneous stigmata of cirrhosis, psoriasis, pruritus, seborrheic dermatitis and rosacea.

A 2010 study concluded, "Nonlight beer intake is associated with an increased risk of developing psoriasis among women. Other alcoholic beverages did not increase the risk of psoriasis in this study."

Immune system

Bacterial infection

There is a protective effect of alcohol consumption against active infection with H. pylori In contrast, alcohol intake (comparing those who drink > 30g of alcohol per day to non-drinkers) is not associated with higher risk of duodenal ulcer. Excessive alcohol consumption seen in alcoholics is a known risk factor for pneumonia.

Common cold

A study on the common cold found that "Greater numbers of alcoholic drinks (up to three or four per day) were associated with decreased risk for developing colds because drinking was associated with decreased illness following infection. However, the benefits of drinking occurred only among nonsmokers. [...] Although alcohol consumption did not influence risk of clinical illness for smokers, moderate alcohol consumption was associated with decreased risk for nonsmokers."

Another study concluded, "Findings suggest that wine intake, especially red wine, may have a protective effect against common cold. Beer, spirits, and total alcohol intakes do not seem to affect the incidence of common cold."

Cancer

In 1988 the International Agency for Research on Cancer (Centre International de Recherche sur le Cancer) of the World Health Organization classified alcohol as a Group 1 carcinogen, stating "There is sufficient evidence for the carcinogenicity of alcoholic beverages in humans.... Alcoholic beverages are carcinogenic to humans (Group 1)." The U.S. Department of Health & Human Services’ National Toxicology Program in 2000 listed alcohol as a known carcinogen.

It was estimated in 2006 that "3.6% of all cancer cases worldwide are related to alcohol drinking, resulting in 3.5% of all cancer deaths." A European study from 2011 found that one in 10 of all cancers in men and one in 33 in women were caused by past or current alcohol intake. The World Cancer Research Fund panel report Food, Nutrition, Physical Activity and the Prevention of Cancer: a Global Perspective finds the evidence "convincing" that alcoholic drinks increase the risk of the following cancers: mouth, pharynx and larynx, oesophagus, colorectum (men), breast (pre- and postmenopause).

Acetaldehyde, a metabolic product of alcohol, is suspected to promote cancer. Typically the liver eliminates 99% of acetaldehyde produced. However, liver disease and certain genetic enzyme deficiencies result in high acetaldehyde levels. Heavy drinkers who are exposed to high acetaldehyde levels due to a genetic defect in alcohol dehydrogenase have been found to be at greater risk of developing cancers of the upper gastrointestinal tract and liver. A review in 2007 found "convincing evidence that acetaldehyde... is responsible for the carcinogenic effect of ethanol... owing to its multiple mutagenic effects on DNA." Acetaldehyde can react with DNA to create DNA adducts including the Cr-Pdg adduct. This Cr-PdG adduct "is likely to play a central role in the mechanism of alcoholic beverage related carcinogenesis." Some have pointed out that even moderate levels of alcohol consumption are associated with an increased risk of certain forms of cancer.

Alcohol's effect on the fetus

Fetal alcohol syndrome or FAS is a birth defect that occurs in the offspring of women who drink alcohol during pregnancy. Drinking heavily or during the early stages of prenatal development has been conclusively linked to FAS; moderate consumption is associated with fetal damage. Alcohol crosses the placental barrier and can stunt fetal growth or weight, create distinctive facial stigmata, damaged neurons and brain structures, and cause other physical, mental, or behavioural problems. Fetal alcohol exposure is the leading known cause of intellectual disability in the Western world. Alcohol consumption during pregnancy is associated with brain insulin and insulin-like growth factor resistance.

Long-term effects of alcoholism on family and children

Children raised in alcoholic families have the potential to suffer emotional distress as they move into their own committed relationships. These children are at a higher risk for divorce and separation, unstable marital conditions and fractured families. Feelings of depression and antisocial behaviors experienced in early childhood frequently contribute to marital conflict and domestic violence. Women are more likely than men to be victims of alcohol-related domestic violence.

Children of alcoholics often incorporate behaviors learned as children into their marital relationships. These behaviors lead to poor parenting practices. For example, adult children of alcoholics may simultaneously express love and rejection toward a child or spouse. This is known as insecure attachment. Insecure attachment contributes to trust and bonding issues with intimate partners and offspring. In addition, prior parental emotional unavailability contributes to poor conflict resolution skills in adult relationships. Evidence shows a correlation between alcoholic fathers who display harsh and ineffective parenting practices with adolescent and adult alcohol dependence.

Children of alcoholics are often unable to trust other adults due to fear of abandonment. Further, because children learn their bonding behaviors from watching their parents’ interactions, daughters of alcoholic fathers may be unable to interact appropriately with men when they reach adulthood. Poor behavior modeling by alcoholic parents contributes to inadequate understanding of how to engage in opposite gender interactions.

Sons of alcoholics are at risk for poor self-regulation that is often displayed in the preschool years. This leads to blaming others for behavioral problems and difficulties with impulse control. Poor decision-making correlates to early alcohol use, especially in sons of alcoholics. Sons often demonstrate thrill-seeking behavior, harm avoidance, and exhibit a low level of frustration tolerance.”

Health risks and alcohol consumption

There are many short and long term health conditions that are attributed to alcohol consumption. These harmful conditions over prolonged use are well documented to be hard to treat and as some of these health conditions result in permanent damage to several vital organs. There remains a very real implication of death due to one or more of these conditions. Approximately 88,000 deaths have been reported between the years 2006 to 2010 due to excessive alcohol consumption in the United States.

Physicians often state alcohol consumption as a direct cause of several chronic conditions becoming harder to manage, thus recommending small quantities over a low frequency to limit further damaging impairments. Some physicians emphatically recommend giving up alcohol in order to prevent heart disease, brain impairment and liver disease.

Centers for Disease Control defines a drink as 0.6 ounces of pure alcohol and excessive drinking as 8 or more drinks per week for women and 15 or more drinks per week for men.

Major Health Risks
 
- Sexual functions
 
Prolonged use of alcohol has been known to impair the nervous system, heart, liver and the reproductive organs resulting in reduced sexual abilities in adult males. Furthermore, due to the mental impairment often related to prolonged use can also lead to tendencies of practicing unprotected sexual intercourse and intercourse with multiple partners. This can result in sexually transmitted diseases along with unintended pregnancies.

- Effects on the unborn

Women who continue to consume alcohol during pregnancy are highly likely to have offspring that have birth defects. As alcohol is able to get directly into the nutrition that the mother is passing on to the baby through her placenta, there is a direct effect to the development of the fetus resulting in damaged cells, birth defects, neurological disorders and miscarriage .

- Effects on the vital organs

Studies have shown a damaging relation between higher amounts of alcohol consumption and organ damage. Cardiovascular problems like high blood pressure, cardiomyopathy and heart attacks have been attributed to excessive alcohol consumption. Beyond the circulatory system, kidney and liver disease are also attributed to alcohol consumption. Effects on brain function have been found, for example memory loss reduced intellectual ability, reduced brain size and coordination.

- Social effects

Prolonged excessive use are known to induce many hard to treat conditions like depression, impulsive decision making, violent and abusive behavior, reduced cognitive abilities. All of these can limit the quality of interactions with family, friends and can lead to harmful behavior towards self and others.

Economic impact from long-term consumption of alcohol

There is currently no consistent approach to measuring the economic impact of alcohol consumption. The economic burden such as direct, indirect, and intangible cost of diseases can be estimated through cost-of-illness studies. Direct costs are estimated through prevalence and incidence studies, while indirect costs are estimated through the human capital method, the demographic method, and the friction cost method. However it is difficult to accurately measure the economic impact due to differences in methodologies, cost items related to alcohol consumption, and measurement techniques.

Alcohol dependence has a far reaching impact on health outcomes. A study conducted in Germany in 2016 found the economic burden for those dependent on alcohol was 50% higher than those who were not. In the study, over half of the economic cost was due to lost productivity, and only 6% was due to alcohol treatment programs. The economic cost was mostly borne by individuals between 30 – 49 years old. In another study conducted with data from eight European countries, 77% of alcohol dependent patients suffered from psychiatric and somatic co-morbidity, which in turn increased systematic healthcare and economic cost. Alcohol consumption can also affect the immune system and produce complications in people suffering from HIV, pneumonia, and tuberculosis.

Indirect costs due to alcohol dependence are significant. The biggest indirect cost comes from lost productivity, followed by premature mortality. Men with alcohol dependence in the U.S. have lower labor force participation by 2.5%, lower earnings by 5.0%, and higher absenteeism by 0.5–1.2 days. Female binge drinkers have higher absenteeism by 0.4–0.9 days. Premature mortality is another large contributor to indirect costs of alcohol dependence. In 2004, 3.8% of global deaths were attributable to alcohol (6.3% for men and 1.1 for women). Those under 60 years old have much higher prevalence in global deaths attributable to alcohol at 5.3%.

In general, indirect costs such as premature mortality due to alcohol dependence, loss of productivity due to absenteeism and presenteeism, and cost of property damage and enforcement, far exceed the direct health care and law enforcement costs. Aggregating the economic cost from all sources, the impact can range from 0.45%–5.44% of a country's gross domestic product (GDP). The wide range is due to inconsistency in measurement of economic burden, as researchers in some studies attributed possible positive effects from long term alcohol consumption.