The British Association for Psychopharmacology guidelines specify the scope and targets of treatment for bipolar disorder. The third version is based explicitly on the available evidence and ...presented, like previous Clinical Practice Guidelines, as recommendations to aid clinical decision making for practitioners: it may also serve as a source of information for patients and carers, and assist audit. The recommendations are presented together with a more detailed review of the corresponding evidence. A consensus meeting, involving experts in bipolar disorder and its treatment, reviewed key areas and considered the strength of evidence and clinical implications. The guidelines were drawn up after extensive feedback from these participants. The best evidence from randomized controlled trials and, where available, observational studies employing quasi-experimental designs was used to evaluate treatment options. The strength of recommendations has been described using the GRADE approach. The guidelines cover the diagnosis of bipolar disorder, clinical management, and strategies for the use of medicines in short-term treatment of episodes, relapse prevention and stopping treatment. The use of medication is integrated with a coherent approach to psychoeducation and behaviour change.
Why do we repeat choices that we know are bad for us? Decision making is characterized by the parallel engagement of two distinct systems, goal-directed and habitual, thought to arise from two ...computational learning mechanisms, model-based and model-free. The habitual system is a candidate source of pathological fixedness. Using a decision task that measures the contribution to learning of either mechanism, we show a bias towards model-free (habit) acquisition in disorders involving both natural (binge eating) and artificial (methamphetamine) rewards, and obsessive-compulsive disorder. This favoring of model-free learning may underlie the repetitive behaviors that ultimately dominate in these disorders. Further, we show that the habit formation bias is associated with lower gray matter volumes in caudate and medial orbitofrontal cortex. Our findings suggest that the dysfunction in a common neurocomputational mechanism may underlie diverse disorders involving compulsion.
Initially described as task-induced deactivations during goal-directed paradigms of high attentional load, the unresolved functionality of default mode regions has long been assumed to interfere with ...task performance. However, recent evidence suggests a potential default mode network involvement in fulfilling cognitive demands. We tested this hypothesis in a finger opposition paradigm with task and fixation periods which we compared with an independent resting state scan using functional magnetic resonance imaging and a comprehensive analysis pipeline including activation, functional connectivity, behavioural and graph theoretical assessments. The results indicate task specific changes in the default mode network topography. Behaviourally, we show that increased connectivity of the posterior cingulate cortex with the left superior frontal gyrus predicts faster reaction times. Moreover, interactive and dynamic reconfiguration of the default mode network regions' functional connections illustrates their involvement with the task at hand with higher-level global parallel processing power, yet preserved small-world architecture in comparison with rest. These findings demonstrate that the default mode network does not disengage during this paradigm, but instead may be involved in task relevant processing.
•Default mode network (DMN) processes do not disengage during task execution.•DMN actively contributes to mental processing in a finger opposition paradigm.•Task-induced changes in DMN connectivity correlate with faster reaction times.•DMN interactions show high efficiency and preserved small-world architecture.•Baseline fixation conditions in cognitive tasks cannot be regarded as true rest.
Cognitive functions dependent on the prefrontal cortex, such as the ability to suppress behavior (response inhibition) and to learn from complex feedback (probabilistic learning), play critical roles ...in activities of daily life. To what extent do different neurochemical systems modulate these two cognitive functions? Here, using stop-signal and probabilistic learning tasks, we show a double dissociation for the involvement of noradrenaline and serotonin in human cognition. In healthy volunteers, inhibition of central noradrenaline reuptake improved response inhibition but had no effect on probabilistic learning, whereas inhibition of central serotonin reuptake impaired probabilistic learning with no effect on response inhibition.
The precise localization of executive functions such as response inhibition within the prefrontal cortex (PFC), although theoretically crucial, has proven to be controversial and difficult. ...Functional neuroimaging has contributed importantly to this debate, but as human cortical lesions are seldom discrete, the literature still lacks definitive neuropsychological evidence that a specific region is necessary for task performance. We overcame this limitation by using a new observer-independent method to relate the degree of damage within a specific prefrontal region to performance on a stop-signal task that is sensitive to the neurodevelopmental aspects of stopping behavior and to attention-deficit/hyperactivity disorder (ADHD) as well as its amelioration by methylphenidate.
Selective serotonin reuptake inhibitors (SSRIs) are widely used for treating neuropsychiatric disorders. However, the exact mechanism of action and why effects can take several weeks to manifest is ...not clear. The hypothesis of neuroplasticity is supported by preclinical studies, but the evidence in humans is limited. Here, we investigate the effects of the SSRI escitalopram on presynaptic density as a proxy for synaptic plasticity. In a double-blind placebo-controlled study (NCT04239339), 32 healthy participants with no history of psychiatric or cognitive disorders were randomized to receive daily oral dosing of either 20 mg escitalopram (n = 17) or a placebo (n = 15). After an intervention period of 3-5 weeks, participants underwent a
CUCB-J PET scan (29 with full arterial input function) to quantify synaptic vesicle glycoprotein 2A (SV2A) density in the hippocampus and the neocortex. Whereas we find no statistically significant group difference in SV2A binding after an average of 29 (range: 24-38) days of intervention, our secondary analyses show a time-dependent effect of escitalopram on cerebral SV2A binding with positive associations between
CUCB-J binding and duration of escitalopram intervention. Our findings suggest that brain synaptic plasticity evolves over 3-5 weeks in healthy humans following daily intake of escitalopram. This is the first in vivo evidence to support the hypothesis of neuroplasticity as a mechanism of action for SSRIs in humans and it offers a plausible biological explanation for the delayed treatment response commonly observed in patients treated with SSRIs. While replication is warranted, these results have important implications for the design of future clinical studies investigating the neurobiological effects of SSRIs.
Cognitive function was assessed in chronic drug users on neurocognitive measures of executive and memory function. Current amphetamine users were contrasted with current opiate users, and these two ...groups were compared with former users of these substances (abstinent for at least one year). Four groups of participants were recruited: amphetamine-dependent individuals, opiate-dependent individuals, former users of amphetamines, and/or opiates and healthy non-drug taking controls. Participants were administered the Tower of London (TOL) planning task and the 3D-IDED attentional set-shifting task to assess executive function, and Paired Associates Learning and Delayed Pattern Recognition Memory tasks to assess visual memory function. The three groups of substance users showed significant impairments on TOL planning, Pattern Recognition Memory and Paired Associates Learning. Current amphetamine users displayed a greater degree of impairment than current opiate users. Consistent with previous research showing that healthy men are performing better on visuo-spatial tests than women, our male controls remembered significantly more paired associates than their female counterparts. This relationship was reversed in drug users. While performance of female drug users was normal, male drug users showed significant impairment compared to both their female counterparts and male controls. There was no difference in performance between current and former drug users. Neither years of drug abuse nor years of drug abstinence were associated with performance. Chronic drug users display pronounced neuropsychological impairment in the domains of executive and memory function. Impairment persists after several years of drug abstinence and may reflect neuropathology in frontal and temporal cortices.
Risk taking in a large cohort of adults (N = 177; ages 17-73) decreased with age, demonstrated by performance on a computer based gambling task, which has previously been shown to be sensitive to ...certain pharmacological manipulations including tryptophan depletion, lesions of the orbitofrontal cortex and neuropsychiatric disorders such as mania. Aging was also associated with longer deliberation times, poorer decision making, reduced risk taking, but no significant change in delay aversion. Subjects with a higher (NART-estimated) IQ were faster to make decisions and showed a greater modulation of risk-taking. Both sexes showed similar patterns of decision making, although male participants exhibited a greater modulation of risk-taking in response to the probability of winning. The Decision-Gamble task provides a variety of behavioral measures, corresponding to different aspects of impulsivity. Factor analysis of these measures suggested that two independent traits underlies performance on the task in normal individuals: one associated with risk tolerance, and a second associated with delay aversion. Age was related to decreases in the risk tolerance factor, but unrelated to the delay aversion; neither factor was significantly related to verbal IQ. This study thus provides support for the concept that impulsivity can be fractionated into 2 or more components.
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