1 00:00:00,530 --> 00:00:02,960 The following content is provided under a Creative 2 00:00:02,960 --> 00:00:04,370 Commons license. 3 00:00:04,370 --> 00:00:07,410 Your support will help MIT OpenCourseWare continue to 4 00:00:07,410 --> 00:00:11,070 offer high quality educational resources for free. 5 00:00:11,070 --> 00:00:13,960 To make a donation, or view additional materials from 6 00:00:13,960 --> 00:00:16,680 hundreds of MIT courses, visit MITOpenCourseWare@ocw.mit.edu. 7 00:00:30,500 --> 00:00:32,700 PROFESSOR JOHN GABRIELI: Good afternoon. 8 00:00:37,030 --> 00:00:40,490 So last time we talked about neuropsychiatric disorder. 9 00:00:40,490 --> 00:00:42,720 And I just want to remind you that we talked about it in a 10 00:00:42,720 --> 00:00:44,880 couple of context of challenges. 11 00:00:44,880 --> 00:00:48,500 That historically, different cultures at different times 12 00:00:48,500 --> 00:00:50,870 have interpreted unusual behavior in 13 00:00:50,870 --> 00:00:52,470 very different ways. 14 00:00:52,470 --> 00:00:56,310 From trephination, where you have to release evil spirits, 15 00:00:56,310 --> 00:01:02,370 to possession, to what we would now consider brutal 16 00:01:02,370 --> 00:01:05,430 patterns of taking people away from 17 00:01:05,430 --> 00:01:07,740 society who behave unusually. 18 00:01:07,740 --> 00:01:11,230 And that even in recent times, things like in the Soviet 19 00:01:11,230 --> 00:01:14,720 Union, the diagnosis of people who protest at utilitarian 20 00:01:14,720 --> 00:01:18,410 governments is a socially defined diagnosis. 21 00:01:18,410 --> 00:01:21,530 Obviously things like definition of homosexuality is 22 00:01:21,530 --> 00:01:24,200 a psychiatric disorder until about 20 years ago. 23 00:01:24,200 --> 00:01:26,160 It was a socially defined disorder. 24 00:01:26,160 --> 00:01:27,630 So there's a lot of challenges. 25 00:01:27,630 --> 00:01:30,150 On the other hand, there's a lot of people suffering with a 26 00:01:30,150 --> 00:01:33,430 huge range of neuropsychiatric disorders. 27 00:01:33,430 --> 00:01:36,110 So we're going to talk some more about that today. 28 00:01:36,110 --> 00:01:40,890 Think a little bit more about issues of treatment, talk a 29 00:01:40,890 --> 00:01:43,840 bit about depression, and ADHD. 30 00:01:43,840 --> 00:01:46,260 And I think of depression and ADHD, attention deficit 31 00:01:46,260 --> 00:01:51,360 hyperactivity disorder, as kind of different as 32 00:01:51,360 --> 00:01:52,110 schizophrenia. 33 00:01:52,110 --> 00:01:55,860 So most of us, except for the 1% approximately who have 34 00:01:55,860 --> 00:01:59,030 schizophrenia, don't hear voices, right. 35 00:01:59,030 --> 00:02:00,750 That's an unusual thing. 36 00:02:00,750 --> 00:02:03,920 But all of us can be sad. 37 00:02:03,920 --> 00:02:07,080 And many children are what we would consider to be a bit 38 00:02:07,080 --> 00:02:11,200 hyperactive, compared to a teenager or an adult, right. 39 00:02:11,200 --> 00:02:14,160 They won't sit still quietly in a large classroom like this 40 00:02:14,160 --> 00:02:15,370 for very long. 41 00:02:15,370 --> 00:02:17,580 And so when we talk about disorders like these. 42 00:02:17,580 --> 00:02:20,686 These are in some ways exaggerations, or extensions, 43 00:02:20,686 --> 00:02:23,460 of what we consider typical everyday behavior. 44 00:02:23,460 --> 00:02:26,580 But moving into a realm that makes life difficult for those 45 00:02:26,580 --> 00:02:28,620 who get the diagnosis. 46 00:02:28,620 --> 00:02:31,100 So when it comes to treatment, there's sort of two giant 47 00:02:31,100 --> 00:02:32,170 classes of them. 48 00:02:32,170 --> 00:02:33,700 One of them is behavioral treatment. 49 00:02:33,700 --> 00:02:36,550 Broadly speaking, you could call them talk therapies. 50 00:02:36,550 --> 00:02:40,240 And the other one is medical treatment with drugs. 51 00:02:40,240 --> 00:02:44,650 Within psychotherapy, which really covers all of the talk 52 00:02:44,650 --> 00:02:47,230 therapies, people sometimes make a distinction between 53 00:02:47,230 --> 00:02:50,935 psychoanalysis and cognitive behavioral therapy, or CBT. 54 00:02:53,470 --> 00:02:55,140 So what is psychological therapy? 55 00:02:55,140 --> 00:02:58,910 So you might have a sense that there's a lot of organization, 56 00:02:58,910 --> 00:03:01,030 and rules, and regulations about this. 57 00:03:01,030 --> 00:03:04,040 But the truth of the matter is that psychotherapy is a social 58 00:03:04,040 --> 00:03:05,960 interaction in which a trained professional tries to help 59 00:03:05,960 --> 00:03:07,890 another person behave and feel differently. 60 00:03:07,890 --> 00:03:09,920 There's really no boundaries on that. 61 00:03:09,920 --> 00:03:10,160 OK. 62 00:03:10,160 --> 00:03:11,530 There's no official rules. 63 00:03:11,530 --> 00:03:14,020 There's more and less official channels we're used to. 64 00:03:14,020 --> 00:03:16,000 But it can be a very wide sources of this. 65 00:03:16,000 --> 00:03:17,470 And if you flip open-- 66 00:03:17,470 --> 00:03:19,450 this is an archaic thing-- yellow pages. 67 00:03:19,450 --> 00:03:22,460 I realize a few years ago people, yellow pages. 68 00:03:22,460 --> 00:03:24,850 But they used to have things called phones and phone books 69 00:03:24,850 --> 00:03:26,420 that were tethered to the wall. 70 00:03:26,420 --> 00:03:29,300 And this is where you would look for information about 71 00:03:29,300 --> 00:03:31,870 people who list themselves as providing psychotherapy. 72 00:03:31,870 --> 00:03:33,980 All you have to do is put your name in that listing, even 73 00:03:33,980 --> 00:03:35,840 easier on the internet maybe. 74 00:03:35,840 --> 00:03:37,560 A psychiatrist, the big difference between 75 00:03:37,560 --> 00:03:41,110 psychiatrist in one practical sense and psychologist is 76 00:03:41,110 --> 00:03:43,440 psychiatrist of course, go to medical school. 77 00:03:43,440 --> 00:03:45,350 And they have prescription privileges. 78 00:03:45,350 --> 00:03:47,290 They can write prescriptions for drugs. 79 00:03:47,290 --> 00:03:52,260 That's rare to nonexistent currently among psychologists. 80 00:03:52,260 --> 00:03:55,800 Psychoanalyst, here's Sigmund Freud in the original 81 00:03:55,800 --> 00:03:58,120 psychotherapy couch. 82 00:03:58,120 --> 00:04:01,610 And I think we've barely mentioned Freud so far in this 83 00:04:01,610 --> 00:04:02,690 course, right? 84 00:04:02,690 --> 00:04:05,530 Which is kind of a big shock to many people. 85 00:04:05,530 --> 00:04:07,200 You might have thought coming into this course that there'd 86 00:04:07,200 --> 00:04:09,870 be Freud, Freud, Freud. 87 00:04:09,870 --> 00:04:11,880 And you know, that we would be sitting there and that we'd be 88 00:04:11,880 --> 00:04:13,670 discussing ideas about Freudian theory. 89 00:04:13,670 --> 00:04:15,630 I'll come back to that in a moment. 90 00:04:15,630 --> 00:04:18,560 Clinical psychologists can provide psychotherapy. 91 00:04:18,560 --> 00:04:21,269 Counseling psychologists in schools, clinical social 92 00:04:21,269 --> 00:04:26,970 workers, clergy, peer groups, self-help books. 93 00:04:26,970 --> 00:04:29,540 So let me just return to Freud just for a moment. 94 00:04:29,540 --> 00:04:32,070 Because intellectually, I think most people will agree 95 00:04:32,070 --> 00:04:35,100 that Freud was a giant mind. 96 00:04:35,100 --> 00:04:38,740 And that in many ways, the complexity of the modern human 97 00:04:38,740 --> 00:04:42,630 mind, the idea that we're made up of different parts, 98 00:04:42,630 --> 00:04:45,580 different feelings, that we're not just one simple operation 99 00:04:45,580 --> 00:04:49,050 machine, but that we have conflicts, different feelings, 100 00:04:49,050 --> 00:04:51,560 and thoughts, and patterns all within us. 101 00:04:51,560 --> 00:04:54,650 Freud probably articulated that thought more powerfully 102 00:04:54,650 --> 00:04:56,910 than anybody else in many ways, as a modern way in which 103 00:04:56,910 --> 00:04:58,020 we view people, right. 104 00:04:58,020 --> 00:04:59,330 People are not just simple things. 105 00:04:59,330 --> 00:05:01,840 They're complicated things, full of tensions and desires. 106 00:05:01,840 --> 00:05:03,420 They're all mixed together. 107 00:05:03,420 --> 00:05:07,720 At the same time, the specific ideas that Freud articulated 108 00:05:07,720 --> 00:05:10,480 using psychodynamic theories like free association, 109 00:05:10,480 --> 00:05:13,250 resistance, transference, interpretation, trying to have 110 00:05:13,250 --> 00:05:16,250 a corrective emotional experience, where you go back 111 00:05:16,250 --> 00:05:18,360 to your youth and you figure out 112 00:05:18,360 --> 00:05:19,360 something bad that happened. 113 00:05:19,360 --> 00:05:22,250 And if you can somehow grapple with that, that will let you 114 00:05:22,250 --> 00:05:28,030 be free of the consequences of that early experience. 115 00:05:28,030 --> 00:05:30,740 Almost none of that has withstood the scrutiny of 116 00:05:30,740 --> 00:05:31,550 practical science. 117 00:05:31,550 --> 00:05:33,180 A lot of it, you don't even know how you 118 00:05:33,180 --> 00:05:34,910 could begin to test. 119 00:05:34,910 --> 00:05:38,050 Now for those of you who become physicians, and the 120 00:05:38,050 --> 00:05:40,790 rest of you will be patients, it's amazing how much of 121 00:05:40,790 --> 00:05:42,690 medicine is not science-based. 122 00:05:42,690 --> 00:05:44,510 It's amazing. 123 00:05:44,510 --> 00:05:47,940 So you hear the cry all the time in medicine, we need to 124 00:05:47,940 --> 00:05:50,920 have science, or evidence-based medicine. 125 00:05:50,920 --> 00:05:52,090 And you might have thought, well, what 126 00:05:52,090 --> 00:05:53,000 else are they doing? 127 00:05:53,000 --> 00:05:53,380 OK. 128 00:05:53,380 --> 00:05:55,570 And the answer is they're treated as best they can and 129 00:05:55,570 --> 00:05:56,420 what works, works. 130 00:05:56,420 --> 00:05:58,150 A lot of stuff they don't understand exactly when and 131 00:05:58,150 --> 00:05:58,900 why it works. 132 00:05:58,900 --> 00:06:00,520 But they apply what they can. 133 00:06:00,520 --> 00:06:03,310 There's a patient in distress. 134 00:06:03,310 --> 00:06:08,170 Freudian ideas are everything that you know about ids, and 135 00:06:08,170 --> 00:06:10,530 electric complexes, and all that kinds of stuff. 136 00:06:10,530 --> 00:06:14,620 Hard to prove that they exist in any scientific sense. 137 00:06:14,620 --> 00:06:17,830 So weirdly, Freud is in many ways marginalized in the 138 00:06:17,830 --> 00:06:20,820 current scientific psychology. 139 00:06:20,820 --> 00:06:23,030 That doesn't mean he wasn't a creative mind that influenced 140 00:06:23,030 --> 00:06:26,200 the way people think about the human mind, and treating the 141 00:06:26,200 --> 00:06:27,380 human mind. 142 00:06:27,380 --> 00:06:31,060 But the specific ideas he has are in many ways at the edge 143 00:06:31,060 --> 00:06:33,350 of the field. 144 00:06:33,350 --> 00:06:38,060 So more central to the field is work called cognitive 145 00:06:38,060 --> 00:06:39,470 behavioral therapy, or CBT. 146 00:06:39,470 --> 00:06:41,330 This is Aaron Beck, who's maybe the 147 00:06:41,330 --> 00:06:42,960 foremost figure in that. 148 00:06:42,960 --> 00:06:46,450 And that CBT was developed to be exactly the opposite in 149 00:06:46,450 --> 00:06:48,420 many senses of psychoanalysis. 150 00:06:48,420 --> 00:06:51,170 So similar because it's about behavior, and about the 151 00:06:51,170 --> 00:06:54,310 interaction between a clinician and a person seeking 152 00:06:54,310 --> 00:06:57,380 a sort of happier, healthier approach to things. 153 00:06:57,380 --> 00:07:01,290 But the Woody Allen version of psychotherapy, where you go 154 00:07:01,290 --> 00:07:05,530 for 40 years weekly to your psychiatrist on the west side 155 00:07:05,530 --> 00:07:07,200 and talk through your problems, OK. 156 00:07:07,200 --> 00:07:10,880 That idea, people said, well, that's fine if you do that. 157 00:07:10,880 --> 00:07:12,780 But is that really what we mean by treating somebody? 158 00:07:12,780 --> 00:07:17,130 So Beck said, in things like anxiety or depression, people 159 00:07:17,130 --> 00:07:20,080 have dysfunctional beliefs that the world is threatening, 160 00:07:20,080 --> 00:07:22,720 that the world is hopeless. 161 00:07:22,720 --> 00:07:25,210 These are sort of logical thinking errors that you can 162 00:07:25,210 --> 00:07:27,710 work yourself out of to make yourself less depressed or 163 00:07:27,710 --> 00:07:29,010 less anxious. 164 00:07:29,010 --> 00:07:31,790 That you should focus not on childhood causes of what 165 00:07:31,790 --> 00:07:34,250 happened, but on current problems you face day-to-day 166 00:07:34,250 --> 00:07:35,610 and how to grapple with them. 167 00:07:35,610 --> 00:07:39,190 Develop strategies that don't make you get down and 168 00:07:39,190 --> 00:07:41,510 depressed, or fearful and anxious. 169 00:07:41,510 --> 00:07:43,220 And that it should be time limited. 170 00:07:43,220 --> 00:07:45,720 Eight weeks or something, from beginning to end period, not 171 00:07:45,720 --> 00:07:49,900 an endless review of your life and roots of your life. 172 00:07:49,900 --> 00:07:52,960 And so people are like that because of part, it's easy to 173 00:07:52,960 --> 00:07:54,630 test in research studies. 174 00:07:54,630 --> 00:07:56,980 It's been shown to be pretty effective, pretty much on a 175 00:07:56,980 --> 00:07:59,220 par with medications in most studies. 176 00:07:59,220 --> 00:08:01,910 And in some cases, better. 177 00:08:01,910 --> 00:08:04,350 And a psychoanalysis could go forever. 178 00:08:04,350 --> 00:08:07,490 It's hard to experimentally test that in many ways. 179 00:08:07,490 --> 00:08:10,170 So there was questions about whether psychotherapy works. 180 00:08:10,170 --> 00:08:12,480 And if you're kind of a scientist, you kind of like 181 00:08:12,480 --> 00:08:15,080 biological stuff like pills, not talking, right. 182 00:08:15,080 --> 00:08:18,040 Although talk is very powerful. 183 00:08:18,040 --> 00:08:20,230 And now, and early on, people say, well, 184 00:08:20,230 --> 00:08:22,190 maybe it's all baloney. 185 00:08:22,190 --> 00:08:25,350 And I would say that starting around 1980 from this review, 186 00:08:25,350 --> 00:08:27,130 people said, no, there's a lot to it. 187 00:08:27,130 --> 00:08:29,040 Although not everything we wish it did. 188 00:08:29,040 --> 00:08:30,610 So they performed a meta-analysis. 189 00:08:30,610 --> 00:08:32,130 You may have heard of these kinds of things. 190 00:08:32,130 --> 00:08:34,659 Where it was a quantitative method for averaging results 191 00:08:34,659 --> 00:08:36,159 of a large number of different studies. 192 00:08:36,159 --> 00:08:37,890 The ideas is that statistically, if you combined 193 00:08:37,890 --> 00:08:40,039 many different studies, you might have a sort of an 194 00:08:40,039 --> 00:08:40,890 overall picture. 195 00:08:40,890 --> 00:08:43,100 It's not just describing them, but taking their actual 196 00:08:43,100 --> 00:08:44,820 statistics and combining them. 197 00:08:44,820 --> 00:08:47,440 Looking for the effect size, something about the consistent 198 00:08:47,440 --> 00:08:51,040 size of, in this case, a psychotherapy treatment. 199 00:08:51,040 --> 00:08:53,000 And then asking what happens in the terms 200 00:08:53,000 --> 00:08:54,290 of the effect size. 201 00:08:54,290 --> 00:08:55,430 And you come out with a picture 202 00:08:55,430 --> 00:08:56,840 like this in the study. 203 00:08:56,840 --> 00:08:59,720 That you have an average effect side of a 0.7 that is 204 00:08:59,720 --> 00:09:00,310 treated people. 205 00:09:00,310 --> 00:09:01,870 This is getting better this way. 206 00:09:01,870 --> 00:09:04,610 We're on average better across many different studies. 207 00:09:04,610 --> 00:09:06,270 So the treatment seemed to move people 208 00:09:06,270 --> 00:09:08,310 in the right direction. 209 00:09:08,310 --> 00:09:13,730 And that furthermore, about half receiving psychotherapy, 210 00:09:13,730 --> 00:09:16,730 the average person was better off than 80% of the people who 211 00:09:16,730 --> 00:09:17,370 didn't get it. 212 00:09:17,370 --> 00:09:18,940 So not everybody benefits greatly. 213 00:09:18,940 --> 00:09:20,680 But many people benefit some. 214 00:09:20,680 --> 00:09:22,740 About 10% got worse. 215 00:09:22,740 --> 00:09:26,076 So this number says only a few get worse. 216 00:09:26,076 --> 00:09:29,120 A weirdly different thing, was that people have always want 217 00:09:29,120 --> 00:09:32,590 to develop very clear ideas about which forms, of many 218 00:09:32,590 --> 00:09:35,360 possible forms of behavioral therapy are really powerful 219 00:09:35,360 --> 00:09:37,630 for which difficulty, or which kind of person. 220 00:09:37,630 --> 00:09:38,790 It makes sense, right? 221 00:09:38,790 --> 00:09:40,580 That the different problem you're facing and the kind of 222 00:09:40,580 --> 00:09:43,760 person you are, a different kind of talk therapy, 223 00:09:43,760 --> 00:09:46,420 different kind of CBT would be powerful for you. 224 00:09:46,420 --> 00:09:48,020 And that's been incredibly hard to 225 00:09:48,020 --> 00:09:49,310 demonstrate in most cases. 226 00:09:49,310 --> 00:09:51,330 Shockingly hard to demonstrate. 227 00:09:51,330 --> 00:09:54,680 And part of that comes from these kinds of studies. 228 00:09:54,680 --> 00:09:57,610 So the best of these kinds of studies have random 229 00:09:57,610 --> 00:10:00,780 assignments and to different kinds of treatment. 230 00:10:00,780 --> 00:10:03,010 For psychotherapy, you might have a wait list. 231 00:10:03,010 --> 00:10:05,930 And you could be blinded as to getting a good or bad version. 232 00:10:05,930 --> 00:10:07,450 So again, here's another meta-analysis. 233 00:10:07,450 --> 00:10:09,900 And here's the kind of big surprise. 234 00:10:09,900 --> 00:10:12,450 Again in this next meta-analysis, about 2:1 235 00:10:12,450 --> 00:10:14,820 chance of improving, versus control, if you sit there and 236 00:10:14,820 --> 00:10:15,460 don't do anything. 237 00:10:15,460 --> 00:10:18,560 So that's again, a good way to go if you're in distress. 238 00:10:18,560 --> 00:10:21,610 Here's kind of a surprise, credentials don't matter, 239 00:10:21,610 --> 00:10:26,000 Ph.D., M.D., no degree. 240 00:10:26,000 --> 00:10:27,970 There might be something about the kind of person who's a 241 00:10:27,970 --> 00:10:30,610 more or less effective therapists. 242 00:10:30,610 --> 00:10:33,230 That's been hard to scientifically demonstrate. 243 00:10:33,230 --> 00:10:35,570 The degree you have has never correlated with the 244 00:10:35,570 --> 00:10:37,210 effectiveness of the treatment. 245 00:10:37,210 --> 00:10:39,110 Here's another big surprise, the experience of the 246 00:10:39,110 --> 00:10:40,450 therapist didn't matter. 247 00:10:40,450 --> 00:10:43,700 Beginning, middle, end of career, seen a lot of 248 00:10:43,700 --> 00:10:45,400 patients, not seen a lot of patients, that doesn't 249 00:10:45,400 --> 00:10:46,620 consistently matter. 250 00:10:46,620 --> 00:10:48,970 The type of therapy doesn't consistently matter. 251 00:10:48,970 --> 00:10:53,220 The length of therapy doesn't matter in any way that people 252 00:10:53,220 --> 00:10:54,910 have been able to show scientifically. 253 00:10:54,910 --> 00:10:58,660 What seems to matter is talking to somebody who 254 00:10:58,660 --> 00:11:01,560 listens to you on a consistent basis. 255 00:11:01,560 --> 00:11:01,870 Yeah? 256 00:11:01,870 --> 00:11:04,702 AUDIENCE: [INAUDIBLE] 257 00:11:04,702 --> 00:11:06,280 PROFESSOR JOHN GABRIELI: That's for all these kinds of 258 00:11:06,280 --> 00:11:06,940 things, right. 259 00:11:06,940 --> 00:11:09,810 So on the one hand, you wouldn't want to push it to an 260 00:11:09,810 --> 00:11:11,610 absurdest thing because there are humans involved. 261 00:11:11,610 --> 00:11:13,130 You wouldn't want to say, well, just for fun, let's take 262 00:11:13,130 --> 00:11:16,180 somebody's who like a three-year-old and send them 263 00:11:16,180 --> 00:11:17,480 out to see what they can do, right. 264 00:11:17,480 --> 00:11:19,400 So I mean, there's a real person involved 265 00:11:19,400 --> 00:11:20,650 here in real distress. 266 00:11:20,650 --> 00:11:22,010 But whenever they've done these kinds of 267 00:11:22,010 --> 00:11:22,950 things, they adjusted-- 268 00:11:22,950 --> 00:11:26,600 And CBT is the most consistently studied because 269 00:11:26,600 --> 00:11:27,960 it's very organized. 270 00:11:27,960 --> 00:11:30,080 Psychotherapy, so many people do so differently. 271 00:11:30,080 --> 00:11:33,120 It's very hard to study. 272 00:11:33,120 --> 00:11:34,760 And CBT is time-limited. 273 00:11:34,760 --> 00:11:38,560 So that approach seems more practical in some senses to 274 00:11:38,560 --> 00:11:39,140 people's minds. 275 00:11:39,140 --> 00:11:41,560 So most of the research on behavioral therapy is focused 276 00:11:41,560 --> 00:11:43,940 on CBT, but not exclusively. 277 00:11:43,940 --> 00:11:47,090 But people never been able to show that these things matter. 278 00:11:47,090 --> 00:11:49,910 Maybe there is something about the bedside manner so to 279 00:11:49,910 --> 00:11:52,750 speak, of the clinitioner or the person who talks with you. 280 00:11:52,750 --> 00:11:56,150 But that's never been extracted rigorously. 281 00:11:56,150 --> 00:11:58,190 And then the other approach of course is many different kinds 282 00:11:58,190 --> 00:12:01,280 of medications that you read about or hear about or 283 00:12:01,280 --> 00:12:03,920 experience all the time. 284 00:12:03,920 --> 00:12:07,560 It turned out, let me just say it were, to be extraordinarily 285 00:12:07,560 --> 00:12:10,560 hard to develop medications for psychiatric diseases. 286 00:12:10,560 --> 00:12:12,170 There's been a number that have mostly been 287 00:12:12,170 --> 00:12:13,880 discovered by accident. 288 00:12:13,880 --> 00:12:16,260 Most of these were medications developed for something else, 289 00:12:16,260 --> 00:12:17,920 they kind of stumbled on as useful 290 00:12:17,920 --> 00:12:19,810 for psychiatric disorders. 291 00:12:19,810 --> 00:12:21,990 In the last 20 years as people have developed drugs more 292 00:12:21,990 --> 00:12:25,510 systematically, it's been brutally hard to develop drugs 293 00:12:25,510 --> 00:12:26,640 for psychiatric disorders. 294 00:12:26,640 --> 00:12:30,330 There's hardly been any major new ones in the last 10 years. 295 00:12:30,330 --> 00:12:33,970 And many pharmaceutical companies are now abandoning 296 00:12:33,970 --> 00:12:36,580 their current research programs because they just 297 00:12:36,580 --> 00:12:38,380 don't feel they're making any traction on it. 298 00:12:38,380 --> 00:12:39,840 So it's been really, really hard. 299 00:12:39,840 --> 00:12:44,000 I mean the mind and brain is just so complicated. 300 00:12:44,000 --> 00:12:46,650 And so you get all kinds of partly political debates about 301 00:12:46,650 --> 00:12:48,810 people who are concerned about what's right for children. 302 00:12:48,810 --> 00:12:50,940 Are we giving kids too many drugs? 303 00:12:50,940 --> 00:12:53,140 Of course, you're never going to have a 304 00:12:53,140 --> 00:12:54,570 scientific answer to that. 305 00:12:54,570 --> 00:12:56,120 Some kids probably get too many drugs. 306 00:12:56,120 --> 00:12:59,230 Some kids probably don't get enough. 307 00:12:59,230 --> 00:13:02,530 We'll come back and talk about ADHD. 308 00:13:02,530 --> 00:13:06,800 So let's people let's pick for a moment one disorder. 309 00:13:06,800 --> 00:13:09,740 And then we'll pick OCD, obsessive compulsive disorder. 310 00:13:09,740 --> 00:13:14,060 So it's a kind of an anxiety disorder that features 311 00:13:14,060 --> 00:13:16,010 obsessions, recurrent unwanted thoughts. 312 00:13:16,010 --> 00:13:18,660 People are drawn to patterns of thought that they don't 313 00:13:18,660 --> 00:13:20,620 want to over and over again. 314 00:13:20,620 --> 00:13:23,290 So the obsessions are mental patterns of thought. 315 00:13:23,290 --> 00:13:25,780 The compulsions are physical repetitive behaviors, like 316 00:13:25,780 --> 00:13:27,530 endless hand-washing, counting, 317 00:13:27,530 --> 00:13:29,380 checking, and cleaning. 318 00:13:29,380 --> 00:13:32,190 Done with such intensity and ferocity that the person's 319 00:13:32,190 --> 00:13:33,730 really trapped by these. 320 00:13:33,730 --> 00:13:38,060 So let me show you one example of an individual patient 321 00:13:38,060 --> 00:13:41,070 describing her experience. 322 00:13:41,070 --> 00:13:44,620 So the thing with these disorders is we sometimes say 323 00:13:44,620 --> 00:13:49,610 somebody's a little OCD because they like to be extra 324 00:13:49,610 --> 00:13:53,060 careful to brush their teeth four times a day. 325 00:13:53,060 --> 00:13:54,590 But in these cases, these 326 00:13:54,590 --> 00:13:56,120 individuals are really trapped. 327 00:13:56,120 --> 00:13:58,150 I mean they have a hard time leaving their house, a hard 328 00:13:58,150 --> 00:14:01,900 time functioning socially, hard time getting jobs. 329 00:14:01,900 --> 00:14:05,960 So people wonder, what's the most helpful treatment? 330 00:14:05,960 --> 00:14:09,350 And here's a example of a study looking at how many 331 00:14:09,350 --> 00:14:11,170 symptoms you have with OCD. 332 00:14:11,170 --> 00:14:14,650 And these are individuals who get, in blue, placebo. 333 00:14:14,650 --> 00:14:15,920 So it's good to be low. 334 00:14:15,920 --> 00:14:19,350 In green, a medication that's used for the disorder. 335 00:14:19,350 --> 00:14:21,860 And then these colors are getting behavioral treatment, 336 00:14:21,860 --> 00:14:23,480 or behavioral treatment plus medication. 337 00:14:23,480 --> 00:14:25,760 So at least in this context for example, behavioral 338 00:14:25,760 --> 00:14:30,705 treatment is more effective by itself than the medication. 339 00:14:30,705 --> 00:14:33,970 It would be easy to tell you oh, there's a rule for 340 00:14:33,970 --> 00:14:36,200 different disorders, that it's behavioral treatment or 341 00:14:36,200 --> 00:14:36,810 medication. 342 00:14:36,810 --> 00:14:39,600 But it turns out on average, it just vary considerably 343 00:14:39,600 --> 00:14:42,250 depending on the medication, depending on the particular 344 00:14:42,250 --> 00:14:43,380 patients you see. 345 00:14:43,380 --> 00:14:46,055 There's no real understanding yet of which patient should 346 00:14:46,055 --> 00:14:49,430 get which treatment under what circumstances. 347 00:14:49,430 --> 00:14:51,530 And here is some evidence suggesting that if you get 348 00:14:51,530 --> 00:14:53,790 medication only, this is the percent who relapsed. 349 00:14:53,790 --> 00:14:56,050 So a concern is there's active treatment phase . 350 00:14:56,050 --> 00:14:58,240 And how many people slide back into the difficulty, 351 00:14:58,240 --> 00:14:59,450 medication-only. 352 00:14:59,450 --> 00:15:03,350 About half the people are relapsing about a year later. 353 00:15:03,350 --> 00:15:05,660 But if they get this sort of behavioral treatment, there 354 00:15:05,660 --> 00:15:08,000 sort of seems to be more sustained benefits. 355 00:15:08,000 --> 00:15:12,060 So people are thinking that might be important. 356 00:15:12,060 --> 00:15:15,850 And then people wonder, if we treat your mind by behavioral 357 00:15:15,850 --> 00:15:19,780 therapy, if we treat your brain by drugs, now we're 358 00:15:19,780 --> 00:15:21,210 going to reject that distinction. 359 00:15:21,210 --> 00:15:22,690 OK. 360 00:15:22,690 --> 00:15:24,970 When I talk to you, if you happen to remember anything I 361 00:15:24,970 --> 00:15:26,440 say, I'm changing your brain. 362 00:15:26,440 --> 00:15:27,220 OK. 363 00:15:27,220 --> 00:15:31,170 Talk, or experience, or thoughts, or imagination 364 00:15:31,170 --> 00:15:34,180 change your brain as much as any medical 365 00:15:34,180 --> 00:15:35,190 substance does, right. 366 00:15:35,190 --> 00:15:38,130 So it's a wrong way to think, like the drugs change the 367 00:15:38,130 --> 00:15:40,070 brain and the talk changes the mind. 368 00:15:40,070 --> 00:15:42,280 To change your mind is to change your brain. 369 00:15:42,280 --> 00:15:44,760 So but any case, you could ask whether these forms of 370 00:15:44,760 --> 00:15:47,090 treatment, in what ways are they similar or dissimilar? 371 00:15:47,090 --> 00:15:49,780 So here's PET scans of patients with OCD 372 00:15:49,780 --> 00:15:51,350 pre and post treatment. 373 00:15:51,350 --> 00:15:54,180 And you can see that there's sort of activation in the 374 00:15:54,180 --> 00:15:58,030 basal ganglia in the caudate that looks pretty similar 375 00:15:58,030 --> 00:16:01,580 across the treatments, as if both treatments were working 376 00:16:01,580 --> 00:16:05,470 on that over activation of the basal ganglia. 377 00:16:05,470 --> 00:16:08,770 On the other hand, here's looking at CBT and drug 378 00:16:08,770 --> 00:16:10,550 treatment for depression. 379 00:16:10,550 --> 00:16:12,830 And you can see these pictures with these blue areas, and 380 00:16:12,830 --> 00:16:16,000 these with these red areas, the brain changes in response 381 00:16:16,000 --> 00:16:18,420 to treatment, look very different. 382 00:16:18,420 --> 00:16:21,240 So there's no simple answer about whether behavioral 383 00:16:21,240 --> 00:16:25,060 therapy and drug therapy change the same or different 384 00:16:25,060 --> 00:16:26,150 things to help people. 385 00:16:26,150 --> 00:16:29,450 Depends on the disorder, depends on the drug. 386 00:16:29,450 --> 00:16:31,510 And we just have a lot more to learn about that. 387 00:16:31,510 --> 00:16:34,380 But both of those things affect the brain and can be 388 00:16:34,380 --> 00:16:36,250 effective to help people. 389 00:16:36,250 --> 00:16:38,720 So let's focus on depression a little bit. 390 00:16:38,720 --> 00:16:41,070 These are people with depression who feel fearful, 391 00:16:41,070 --> 00:16:43,510 gloomy, helpless, hopeless in an extreme way. 392 00:16:43,510 --> 00:16:46,450 So it's difficult to get out of bed, difficult to do work, 393 00:16:46,450 --> 00:16:48,800 relate to people. 394 00:16:48,800 --> 00:16:50,940 Literature, Hamlet's description of how weary, 395 00:16:50,940 --> 00:16:53,830 stale, flat, and unprofitable seem to me all the uses of 396 00:16:53,830 --> 00:16:56,390 this world, describes often what people with depression 397 00:16:56,390 --> 00:16:59,390 roughly describe their experiences like. 398 00:16:59,390 --> 00:17:01,780 A typical episode, it varies widely. 399 00:17:01,780 --> 00:17:04,599 It's about 4 to 12 months if untreated of intense 400 00:17:04,599 --> 00:17:05,680 depression. 401 00:17:05,680 --> 00:17:10,220 A pervasive dysphoria, just sort of inability to feel 402 00:17:10,220 --> 00:17:13,200 pleasure and intense mental pain, 403 00:17:13,200 --> 00:17:14,599 generalized loss of interest. 404 00:17:14,599 --> 00:17:18,089 It's estimated to sometimes affected some 5% of the 405 00:17:18,089 --> 00:17:19,020 world's population. 406 00:17:19,020 --> 00:17:21,300 That's a huge number of individuals. 407 00:17:21,300 --> 00:17:24,180 Average age of onset is 30. 408 00:17:24,180 --> 00:17:28,390 But it goes across wide ages, often unnoticed in children. 409 00:17:28,390 --> 00:17:30,750 People are picking this up more than they used to. 410 00:17:30,750 --> 00:17:32,740 They used to think there's a thought that children can't 411 00:17:32,740 --> 00:17:34,380 really be depressed. 412 00:17:34,380 --> 00:17:36,310 It's hard to know why that happened exactly. 413 00:17:36,310 --> 00:17:39,770 Psychiatric ideas are typically developed in adults. 414 00:17:39,770 --> 00:17:41,270 And it takes a while for the field to 415 00:17:41,270 --> 00:17:43,570 recognize them in children. 416 00:17:43,570 --> 00:17:46,200 But it's rare to have a first depressive episode after 60. 417 00:17:46,200 --> 00:17:48,815 It's rare to have gone your life and then get depression 418 00:17:48,815 --> 00:17:51,360 in older age. 419 00:17:51,360 --> 00:17:54,480 Kind of mysteriously at the moment, women have depression 420 00:17:54,480 --> 00:17:57,040 at two or three times the rate of men in the United States, 421 00:17:57,040 --> 00:17:58,730 and pretty much throughout the world at a two 422 00:17:58,730 --> 00:17:59,660 to threefold increase. 423 00:17:59,660 --> 00:18:01,470 That's a pretty big one. 424 00:18:01,470 --> 00:18:02,690 We'll talk later about ADHD. 425 00:18:02,690 --> 00:18:03,875 There the numbers kind of reverse. 426 00:18:03,875 --> 00:18:08,130 It's 2 to 3 times more frequent in boys than girls. 427 00:18:08,130 --> 00:18:11,270 And about 70% of people who will have one episode of 428 00:18:11,270 --> 00:18:13,110 depression will have another one later on. 429 00:18:15,990 --> 00:18:19,720 So the diagnosis in the DSM book requires at least three 430 00:18:19,720 --> 00:18:21,020 of the following for a period. 431 00:18:21,020 --> 00:18:23,170 Now what I wanted to give you a feeling if you think about 432 00:18:23,170 --> 00:18:26,230 this, you know you are the doctor talking to somebody. 433 00:18:26,230 --> 00:18:28,510 And you know, disturbed sleep, but how disturbed 434 00:18:28,510 --> 00:18:29,260 does it have to be? 435 00:18:29,260 --> 00:18:31,770 Diminished appetite, but how diminish, right? 436 00:18:31,770 --> 00:18:32,590 Loss of energy? 437 00:18:32,590 --> 00:18:34,850 Well, we all have periods where we're more sluggish or 438 00:18:34,850 --> 00:18:36,640 more focused, right? 439 00:18:36,640 --> 00:18:39,590 I mean so usually depression, these things are so extreme. 440 00:18:39,590 --> 00:18:40,540 It's very obvious. 441 00:18:40,540 --> 00:18:42,070 Sometimes it's at the edge. 442 00:18:42,070 --> 00:18:44,090 And there's a range of these things. 443 00:18:44,090 --> 00:18:45,830 We know there's a genetic predisposition. 444 00:18:45,830 --> 00:18:49,950 If you have identical twins 50%, dizygotic 10%. 445 00:18:49,950 --> 00:18:51,610 But we know there's environmental factors. 446 00:18:51,610 --> 00:18:55,820 So it's very hard to figure out whether diseases are 447 00:18:55,820 --> 00:18:58,700 getting more or less common over time. 448 00:18:58,700 --> 00:19:00,760 Because especially in psychiatric diseases, the 449 00:19:00,760 --> 00:19:04,350 criteria that defines those diseased change over time. 450 00:19:04,350 --> 00:19:06,725 So you don't know which it is, sensitivity to it. 451 00:19:06,725 --> 00:19:08,420 You know, 30 years ago teachers 452 00:19:08,420 --> 00:19:10,320 never heard of autism. 453 00:19:10,320 --> 00:19:13,850 Now every teacher in kindergarten is watching out 454 00:19:13,850 --> 00:19:14,900 for autism. 455 00:19:14,900 --> 00:19:17,470 So it's spotted much more quickly and consistently. 456 00:19:17,470 --> 00:19:19,250 So people say it's going up. 457 00:19:19,250 --> 00:19:20,280 Is it really going up? 458 00:19:20,280 --> 00:19:22,230 Is it being detected more often? 459 00:19:22,230 --> 00:19:24,680 It's very hard to tell those things apart. 460 00:19:24,680 --> 00:19:27,180 But where evidence is available, since 1940 there's 461 00:19:27,180 --> 00:19:29,980 nearly a 10-year drop in the average age of the first 462 00:19:29,980 --> 00:19:32,030 instance of depression. 463 00:19:32,030 --> 00:19:35,550 So is this 10-year drop that people are getting better at 464 00:19:35,550 --> 00:19:37,870 spotting it at adolescents, instead of seeing an 465 00:19:37,870 --> 00:19:41,130 adolescent or child as simply moody, they're recognizing 466 00:19:41,130 --> 00:19:42,220 depression? 467 00:19:42,220 --> 00:19:46,030 Or is the increased pressures in childhood driving 468 00:19:46,030 --> 00:19:47,860 depression up at an earlier age? 469 00:19:47,860 --> 00:19:49,330 Very hard to tell. 470 00:19:52,950 --> 00:19:55,320 So here's a video clip of some patients describing their 471 00:19:55,320 --> 00:20:01,470 experience in depression 472 00:20:01,470 --> 00:20:05,190 So people have been trying to understand by experiments, 473 00:20:05,190 --> 00:20:09,170 what are the thought patterns that are promoting depression? 474 00:20:09,170 --> 00:20:11,440 One approach has been this dot probe test. 475 00:20:11,440 --> 00:20:12,650 We've talked about that before. 476 00:20:12,650 --> 00:20:14,420 I'll remind you in a moment what that is. 477 00:20:14,420 --> 00:20:19,130 But basically, it's to experimentally test the idea 478 00:20:19,130 --> 00:20:23,100 that there's a sort of cycle of negative thought in 479 00:20:23,100 --> 00:20:25,580 depression that reinforces itself-- 480 00:20:25,580 --> 00:20:29,240 That you pay attention to sad or bad things. 481 00:20:29,240 --> 00:20:31,820 The more you think about bad things, the worse you feel. 482 00:20:31,820 --> 00:20:33,570 The worse you feel, the more you think about bad things. 483 00:20:33,570 --> 00:20:36,710 And this is sort of you know, a downward spiral of 484 00:20:36,710 --> 00:20:38,150 gloominess. 485 00:20:38,150 --> 00:20:40,210 And another question that people are very interested in 486 00:20:40,210 --> 00:20:43,270 is, when you see these kind of psychological mechanisms that 487 00:20:43,270 --> 00:20:46,790 may contribute to depression, are they there for somebody 488 00:20:46,790 --> 00:20:49,600 who has never yet been depressed, but it's a risk 489 00:20:49,600 --> 00:20:51,660 factor for becoming depressed? 490 00:20:51,660 --> 00:20:54,060 Or is it really a consequence of the depression, right? 491 00:20:54,060 --> 00:20:57,530 If you pay more attention to sad things is that a risk for 492 00:20:57,530 --> 00:21:00,220 becoming depressed first time ever? 493 00:21:00,220 --> 00:21:02,960 Or is that already part of the disease process 494 00:21:02,960 --> 00:21:05,020 itself once its hit? 495 00:21:05,020 --> 00:21:07,120 So here's a dot probe test. 496 00:21:07,120 --> 00:21:09,360 We talked about it before in regards to aging. 497 00:21:09,360 --> 00:21:10,480 You see two pictures. 498 00:21:10,480 --> 00:21:12,480 A neutral one and a happy one. 499 00:21:12,480 --> 00:21:13,730 They disappear. 500 00:21:13,730 --> 00:21:16,390 A dot appears behind one or the other. 501 00:21:16,390 --> 00:21:18,820 And you push a button to indicate which side it's on. 502 00:21:18,820 --> 00:21:22,720 All you're doing is indicating which side it's on. 503 00:21:22,720 --> 00:21:26,280 Or you might get another pair of faces with a negative 504 00:21:26,280 --> 00:21:28,470 expression and a neutral expression. 505 00:21:28,470 --> 00:21:30,860 Beneath one of them, sometimes it's a neutral, 506 00:21:30,860 --> 00:21:31,890 sometime it's negative. 507 00:21:31,890 --> 00:21:33,310 A dot appears. 508 00:21:33,310 --> 00:21:35,830 And then you can look at the response times, how quickly 509 00:21:35,830 --> 00:21:38,390 people responded to the dot depending on 510 00:21:38,390 --> 00:21:38,970 where the face was. 511 00:21:38,970 --> 00:21:43,260 And the idea is, the faster you respond to a dot, the more 512 00:21:43,260 --> 00:21:48,640 your attention was drawn to a positive, neutral, or a 513 00:21:48,640 --> 00:21:49,580 negative face, right. 514 00:21:49,580 --> 00:21:51,830 Because if your attention is sitting there already when the 515 00:21:51,830 --> 00:21:53,960 dot appears, boom, you're ready to go. 516 00:21:53,960 --> 00:21:55,840 If your attention is somewhere else, you'll 517 00:21:55,840 --> 00:21:57,340 have a slower response. 518 00:21:57,340 --> 00:21:59,440 And sure enough, in patients with depression, specifically 519 00:21:59,440 --> 00:22:03,010 for sad faces, they have this bias response. 520 00:22:03,010 --> 00:22:06,400 They tend to respond quickly when the dot appears where the 521 00:22:06,400 --> 00:22:08,880 negative face just has been. 522 00:22:08,880 --> 00:22:12,460 So it's a way that there was sort of the attention, even 523 00:22:12,460 --> 00:22:14,720 for such a trivial thing is drawn to the negative. 524 00:22:14,720 --> 00:22:16,290 It sits on the negative. 525 00:22:16,290 --> 00:22:19,680 And so now you can ask the question, what about girls who 526 00:22:19,680 --> 00:22:22,420 were born into families with a history of depression? 527 00:22:22,420 --> 00:22:27,090 So they're in a general way at genetic risk for depression. 528 00:22:27,090 --> 00:22:30,690 But they have never been depressed themselves. 529 00:22:30,690 --> 00:22:32,730 So now we can ask the question, does this mode of 530 00:22:32,730 --> 00:22:36,200 thinking, of dwelling on the negative is it apparent in 531 00:22:36,200 --> 00:22:39,190 these girls even before they ever have depression? 532 00:22:39,190 --> 00:22:40,600 And not all of them will. 533 00:22:40,600 --> 00:22:43,450 But you don't yet which ones will and which ones won't. 534 00:22:43,450 --> 00:22:47,060 And sure enough, if looking at sad or happy faces, and here 535 00:22:47,060 --> 00:22:50,600 it gets pretty opposite, for the young girls who have a low 536 00:22:50,600 --> 00:22:53,220 likelihood of having depression, no family history, 537 00:22:53,220 --> 00:22:55,850 they tend to dwell on the happy faces. 538 00:22:55,850 --> 00:22:57,480 And for the girls who were born in a family with 539 00:22:57,480 --> 00:23:00,680 depression, they tend to dwell on the negative faces. 540 00:23:00,680 --> 00:23:04,280 So you can see this mechanism of focusing on the negative, 541 00:23:04,280 --> 00:23:08,250 dwelling on the negative already even before the child 542 00:23:08,250 --> 00:23:12,040 has ever a episode of depression. 543 00:23:12,040 --> 00:23:14,730 So just for a moment let's discuss, does that mean it's 544 00:23:14,730 --> 00:23:15,980 genetic or environmental? 545 00:23:23,980 --> 00:23:26,280 Who are these girls who have a high risk for getting 546 00:23:26,280 --> 00:23:29,090 depression? 547 00:23:29,090 --> 00:23:30,450 What does high mean? 548 00:23:30,450 --> 00:23:32,820 Sorry to put you on the spot. 549 00:23:32,820 --> 00:23:34,150 What does high mean? 550 00:23:34,150 --> 00:23:36,370 They're in a family where they have a parent with depression. 551 00:23:36,370 --> 00:23:37,010 OK. 552 00:23:37,010 --> 00:23:39,890 So you can't tell that maybe having a parent with 553 00:23:39,890 --> 00:23:42,430 depression ups the child's focus on the negative. 554 00:23:42,430 --> 00:23:44,400 Because they've had some difficult things to deal with 555 00:23:44,400 --> 00:23:45,570 in their family. 556 00:23:45,570 --> 00:23:48,320 Maybe they have genes that draw them to negative things, 557 00:23:48,320 --> 00:23:49,210 or maybe both. 558 00:23:49,210 --> 00:23:50,930 You can't tell that apart from these kinds of studies. 559 00:23:54,440 --> 00:23:59,190 Every once in while there's sort of a success story in 560 00:23:59,190 --> 00:24:00,140 brain sciences. 561 00:24:00,140 --> 00:24:03,380 And why it's terribly important is this, to this 562 00:24:03,380 --> 00:24:06,300 day, as one of the speaker said, there's people who think 563 00:24:06,300 --> 00:24:08,455 psychiatric disorders are just for sissies. 564 00:24:08,455 --> 00:24:10,090 That you just stop being depressed. 565 00:24:10,090 --> 00:24:11,940 Just don't listen to those voices, right. 566 00:24:11,940 --> 00:24:13,730 Just stop washing your hands. 567 00:24:13,730 --> 00:24:17,570 And what's very confusing about this message is for 568 00:24:17,570 --> 00:24:20,760 people for example, who are addicted to substances or have 569 00:24:20,760 --> 00:24:24,420 alcoholism, we ask them to stop drinking and stop taking 570 00:24:24,420 --> 00:24:25,900 drugs, with support. 571 00:24:25,900 --> 00:24:27,905 But we say it's, we think it's somewhere in 572 00:24:27,905 --> 00:24:29,260 you to stop, right. 573 00:24:29,260 --> 00:24:31,810 So with the right support, we think it's 574 00:24:31,810 --> 00:24:33,280 somewhere in you to stop. 575 00:24:33,280 --> 00:24:34,095 So it's kind of hard. 576 00:24:34,095 --> 00:24:35,180 Where is that line, right? 577 00:24:35,180 --> 00:24:38,900 CBT is getting people to find ways to think so they're not 578 00:24:38,900 --> 00:24:40,080 anxious or not depressed. 579 00:24:40,080 --> 00:24:41,490 Again, we think it's in them with the 580 00:24:41,490 --> 00:24:42,460 right kind of support. 581 00:24:42,460 --> 00:24:44,810 So on the one hand we ask people to get themselves 582 00:24:44,810 --> 00:24:46,520 healthier with support, right. 583 00:24:46,520 --> 00:24:47,540 So it's kind of tricky. 584 00:24:47,540 --> 00:24:49,410 Where is the line of responsibility? 585 00:24:49,410 --> 00:24:51,710 But I think one of the triumphs of modern brain 586 00:24:51,710 --> 00:24:55,210 imaging is to make visible the brain basis of psychiatric 587 00:24:55,210 --> 00:24:57,520 disorders on average. 588 00:24:57,520 --> 00:25:00,675 So because there's no broken arm, no broken leg, no tumor 589 00:25:00,675 --> 00:25:02,730 or anything like that, right. 590 00:25:02,730 --> 00:25:05,110 That promotes discussion, or consideration, is our 591 00:25:05,110 --> 00:25:08,500 psychiatric disorders real brain differences? 592 00:25:08,500 --> 00:25:10,830 And I can also tell you that unfortunately, we're not 593 00:25:10,830 --> 00:25:14,860 anywhere near where a house can put up a picture of 594 00:25:14,860 --> 00:25:17,730 somebody's brain and say, oh, this person's certainly has 595 00:25:17,730 --> 00:25:21,870 depression, or schizophrenia, or ADHD, or dyslexia, or any 596 00:25:21,870 --> 00:25:23,480 difficulty that you know of. 597 00:25:23,480 --> 00:25:26,110 Nobody can say that on the basis of a single brain scan 598 00:25:26,110 --> 00:25:27,150 for a single person. 599 00:25:27,150 --> 00:25:27,750 We want to. 600 00:25:27,750 --> 00:25:29,120 We're not there yet. 601 00:25:29,120 --> 00:25:31,570 But we can see on average differences between people who 602 00:25:31,570 --> 00:25:34,010 have a diagnosis and people who don't. 603 00:25:34,010 --> 00:25:36,380 So here's a PET, positron emission tomography, top of 604 00:25:36,380 --> 00:25:37,960 the brain, bottom of the brain. 605 00:25:37,960 --> 00:25:41,790 They found less activation in this so called subgenual 606 00:25:41,790 --> 00:25:42,650 anterior cingulate. 607 00:25:42,650 --> 00:25:45,110 The anterior cingulate is this cortex that sits over the 608 00:25:45,110 --> 00:25:46,450 corpus callosum. 609 00:25:46,450 --> 00:25:49,540 And here in this bottom part of the anterior cingulate, 610 00:25:49,540 --> 00:25:53,180 less activation in patients with depression 611 00:25:53,180 --> 00:25:54,590 than control subjects. 612 00:25:54,590 --> 00:25:58,870 And then, looking at structure now, physical volume. 613 00:25:58,870 --> 00:26:03,100 Also reduced volume in these areas, in patients with both 614 00:26:03,100 --> 00:26:05,540 unipolar and bipolar, in this case, depression. 615 00:26:05,540 --> 00:26:07,050 So now we have both a structural 616 00:26:07,050 --> 00:26:08,340 difference on average. 617 00:26:08,340 --> 00:26:11,740 And a functional difference on average. 618 00:26:11,740 --> 00:26:14,160 Sometimes in psychiatry there'd be a brain banks. 619 00:26:14,160 --> 00:26:15,990 When patients passed away, they'd donate 620 00:26:15,990 --> 00:26:17,700 their brains to research. 621 00:26:17,700 --> 00:26:20,175 And people said, let's go look in this area in people who 622 00:26:20,175 --> 00:26:23,060 have passed away so we can look at the cellular level of 623 00:26:23,060 --> 00:26:23,800 what's going on there. 624 00:26:23,800 --> 00:26:25,160 We can't see with brain imaging 625 00:26:25,160 --> 00:26:27,440 anything close to cells. 626 00:26:27,440 --> 00:26:29,270 But with post-mortem analysis we can. 627 00:26:29,270 --> 00:26:30,440 And there was a big surprise. 628 00:26:30,440 --> 00:26:33,870 The big surprise was when they looked in this region, there 629 00:26:33,870 --> 00:26:37,720 was a reduced number of cells, which goes with the reduced 630 00:26:37,720 --> 00:26:40,050 the volume, and the reduced activation. 631 00:26:40,050 --> 00:26:42,310 But it was in the neurons, it was the glial. 632 00:26:42,310 --> 00:26:44,280 And you go glial? 633 00:26:44,280 --> 00:26:45,840 We haven't talked about glial for a long time. 634 00:26:45,840 --> 00:26:48,200 You know neurons are the stuff that compute the mind. 635 00:26:48,200 --> 00:26:49,260 We all agree with that. 636 00:26:49,260 --> 00:26:51,320 Glial are essential for brain function. 637 00:26:51,320 --> 00:26:53,050 So we don't understand what that means. 638 00:26:53,050 --> 00:26:55,350 That these patients would have an equal number of neurons but 639 00:26:55,350 --> 00:26:56,660 a reduced number of glial. 640 00:26:56,660 --> 00:26:58,240 We just don't know what that means. 641 00:26:58,240 --> 00:26:59,340 But it was a big surprise. 642 00:26:59,340 --> 00:27:03,710 And over time I think maybe we'll think about that. 643 00:27:03,710 --> 00:27:05,840 And furthermore, imaging studies looking at the 644 00:27:05,840 --> 00:27:08,300 anterior cingulate found that if you looked at the 645 00:27:08,300 --> 00:27:10,340 pre-treatment activity in this brain region-- 646 00:27:10,340 --> 00:27:12,440 I'll show another example in a moment-- 647 00:27:12,440 --> 00:27:16,410 you could see not only changes that occur with treatment, but 648 00:27:16,410 --> 00:27:19,540 that differences predicted which patients would benefit 649 00:27:19,540 --> 00:27:20,710 more or less for treatment. 650 00:27:20,710 --> 00:27:23,480 So all these conversion areas about the importance of the 651 00:27:23,480 --> 00:27:27,840 anterior cingulate cortex in depression although nobody 652 00:27:27,840 --> 00:27:29,730 thinks that's the whole story. 653 00:27:29,730 --> 00:27:32,230 That the anterior cingulate is part of a network of areas 654 00:27:32,230 --> 00:27:36,190 that are compromised in depression. 655 00:27:36,190 --> 00:27:38,720 And another thing that I think is sort of an exciting 656 00:27:38,720 --> 00:27:42,210 direction is each dot here is an individual person. 657 00:27:42,210 --> 00:27:44,380 Here's how much they improved. 658 00:27:44,380 --> 00:27:45,810 Better is down here. 659 00:27:45,810 --> 00:27:47,270 This is the patients who improved the most with 660 00:27:47,270 --> 00:27:50,270 treatment, the least with CBT treatment. 661 00:27:50,270 --> 00:27:51,850 And this is the initial activation. 662 00:27:51,850 --> 00:27:54,560 So it's telling you maybe that these are the patients who 663 00:27:54,560 --> 00:27:56,490 really should get CBT. 664 00:27:56,490 --> 00:27:57,910 And maybe these are the patients who 665 00:27:57,910 --> 00:27:59,390 didn't respond so much. 666 00:27:59,390 --> 00:28:01,910 And maybe they should get, by the initial brain measure, 667 00:28:01,910 --> 00:28:03,440 some other form of treatment. 668 00:28:03,440 --> 00:28:06,340 So that's I think an exciting areas where we could develop 669 00:28:06,340 --> 00:28:08,950 enough understanding of diversity among patients to 670 00:28:08,950 --> 00:28:11,370 understand which patient might benefit for which treatment. 671 00:28:11,370 --> 00:28:13,050 But we're just at the beginning of 672 00:28:13,050 --> 00:28:15,580 that kind of knowledge. 673 00:28:15,580 --> 00:28:19,180 So what about treatments for depression? 674 00:28:19,180 --> 00:28:21,230 In 2005, that's some years ago now, but there's an estimated 675 00:28:21,230 --> 00:28:23,110 27 million people in the US. 676 00:28:23,110 --> 00:28:26,270 There's $10billion now and more in sales. 677 00:28:26,270 --> 00:28:29,380 That's to drugs or CBT forms of treatment of depression, 678 00:28:29,380 --> 00:28:32,360 the most common forms of treatment. 679 00:28:32,360 --> 00:28:33,770 Even with these treatments-- 680 00:28:33,770 --> 00:28:34,770 so here's the message. 681 00:28:34,770 --> 00:28:37,220 Everybody agrees I think and reasonably, that if you know 682 00:28:37,220 --> 00:28:39,570 somebody with depression, or you're depressed yourself, or 683 00:28:39,570 --> 00:28:41,800 anxiety, but we're talking about depression, getting help 684 00:28:41,800 --> 00:28:42,540 is a good idea. 685 00:28:42,540 --> 00:28:44,380 Many people get helped. 686 00:28:44,380 --> 00:28:47,100 But the help is not nearly what we wish 687 00:28:47,100 --> 00:28:48,150 it were in the field. 688 00:28:48,150 --> 00:28:50,590 So in depression, about half of patients 689 00:28:50,590 --> 00:28:52,270 don't achieve remission. 690 00:28:52,270 --> 00:28:55,790 They still are depressed even after medicine 691 00:28:55,790 --> 00:28:57,490 or behavioral treatment. 692 00:28:57,490 --> 00:28:59,720 And even among those who improve a lot, there's still 693 00:28:59,720 --> 00:29:00,820 residual symptoms. 694 00:29:00,820 --> 00:29:03,770 It's not as if patients typically or often escape 695 00:29:03,770 --> 00:29:04,870 entirely that. 696 00:29:04,870 --> 00:29:06,970 But they can improve a lot. 697 00:29:06,970 --> 00:29:09,130 But the other thing is since nobody knows which approach to 698 00:29:09,130 --> 00:29:12,110 take with which patient by any scientific evidence, it's all 699 00:29:12,110 --> 00:29:12,900 trial and error. 700 00:29:12,900 --> 00:29:15,310 So finding a good treatment for a 701 00:29:15,310 --> 00:29:16,630 person could take months. 702 00:29:16,630 --> 00:29:18,810 And by then some people just give up and don't come back. 703 00:29:18,810 --> 00:29:20,810 Because in the throes of the diseases, or they just figure 704 00:29:20,810 --> 00:29:22,020 they're not going to be helped. 705 00:29:22,020 --> 00:29:23,400 It's all hit and miss. 706 00:29:23,400 --> 00:29:25,760 I have a colleague in CSAIL the computer science 707 00:29:25,760 --> 00:29:26,660 department. 708 00:29:26,660 --> 00:29:28,180 And we're doing research with her. 709 00:29:28,180 --> 00:29:31,230 And we say, you know, if you go to a doctor now with 710 00:29:31,230 --> 00:29:35,140 depression, or anxiety, or social anxiety disorder, it's 711 00:29:35,140 --> 00:29:37,600 almost completely random whether they assign you to one 712 00:29:37,600 --> 00:29:40,900 treatment or another within some broad constraints. 713 00:29:40,900 --> 00:29:43,830 There's no scientific basis for knowing what drug you 714 00:29:43,830 --> 00:29:46,920 should get, or a drug plus CBT, or CBT only. 715 00:29:46,920 --> 00:29:48,170 It's completely random. 716 00:29:48,170 --> 00:29:50,660 It's depending on the physician's background and 717 00:29:50,660 --> 00:29:51,660 intuitions. 718 00:29:51,660 --> 00:29:53,600 There's no scientific basis for knowing that. 719 00:29:53,600 --> 00:29:56,510 So there's a lot to be discovered. 720 00:29:56,510 --> 00:29:58,720 So sometimes people are trying to say, well, let's compare 721 00:29:58,720 --> 00:30:03,180 placebo treatments to a medicine treatment, to 722 00:30:03,180 --> 00:30:04,850 cognitive behavioral therapy. 723 00:30:04,850 --> 00:30:07,390 Here's responding to treatment, improving. 724 00:30:07,390 --> 00:30:09,850 So better than placebo or both drugs, about 725 00:30:09,850 --> 00:30:12,530 eight weeks, and CBT. 726 00:30:12,530 --> 00:30:14,810 And then at 16 weeks there's even more of a gain. 727 00:30:14,810 --> 00:30:19,140 And they look very similar on average across patients. 728 00:30:19,140 --> 00:30:21,860 And if you look over time now, after the treatment is over, 729 00:30:21,860 --> 00:30:24,750 at how many people sort of what the long-term picture is 730 00:30:24,750 --> 00:30:26,260 because you care about that. 731 00:30:26,260 --> 00:30:28,850 I mean there's two things, getting people out of crises 732 00:30:28,850 --> 00:30:31,090 and then keeping your head above water. 733 00:30:31,090 --> 00:30:33,770 It seems like the group that maintains the best response 734 00:30:33,770 --> 00:30:37,500 are the people who had the CBT over longer periods. 735 00:30:37,500 --> 00:30:38,560 So you might say, well why don't we just 736 00:30:38,560 --> 00:30:40,120 give everybody CBT? 737 00:30:40,120 --> 00:30:42,050 And part of it is not everybody responds to that. 738 00:30:42,050 --> 00:30:44,530 Some patients for example, with severe depression are 739 00:30:44,530 --> 00:30:45,830 talking about suicide. 740 00:30:45,830 --> 00:30:48,840 You don't feel like you can wait 8 weeks or 16 weeks to 741 00:30:48,840 --> 00:30:50,760 let a CBT process happen. 742 00:30:50,760 --> 00:30:54,340 Some patients just don't have the energy to go to sessions 743 00:30:54,340 --> 00:30:55,500 and work on things. 744 00:30:55,500 --> 00:30:57,460 And you need to rescue them from that. 745 00:30:57,460 --> 00:31:01,000 So there's all kinds of issues about what kinds of treatment 746 00:31:01,000 --> 00:31:03,215 ultimately are practical and effective for patients. 747 00:31:05,870 --> 00:31:10,120 So in clinical trials when they try a drug. 748 00:31:10,120 --> 00:31:12,090 And I'll focus on drugs for the moment. 749 00:31:12,090 --> 00:31:13,520 There's a random assignment. 750 00:31:13,520 --> 00:31:15,870 Patients with the diagnosis are assigned either to or a 751 00:31:15,870 --> 00:31:17,870 placebo or a drug. 752 00:31:17,870 --> 00:31:20,580 The physicians are not supposed to know what it is. 753 00:31:20,580 --> 00:31:23,580 Response means just getting better, which is valuable. 754 00:31:23,580 --> 00:31:26,800 Remission means, that you don't qualify for having the 755 00:31:26,800 --> 00:31:28,440 disease anymore. 756 00:31:28,440 --> 00:31:31,410 How people decide whether you have depression? 757 00:31:31,410 --> 00:31:32,400 They take a full history. 758 00:31:32,400 --> 00:31:35,220 But they'll often use some sort of rating scale. 759 00:31:35,220 --> 00:31:37,550 One of the most common is a Hamilton to say how severely 760 00:31:37,550 --> 00:31:38,680 depressed are you. 761 00:31:38,680 --> 00:31:40,750 So they can document it at beginning. 762 00:31:40,750 --> 00:31:42,120 Then give that to you at the end. 763 00:31:42,120 --> 00:31:44,470 And see how severely depressed at the end. 764 00:31:44,470 --> 00:31:46,880 So one thing to know that's really interesting, and really 765 00:31:46,880 --> 00:31:49,880 a problem from the field is there's incredibly strong 766 00:31:49,880 --> 00:31:51,060 placebo responses. 767 00:31:51,060 --> 00:31:56,920 In many studies the placebo responses rival the response 768 00:31:56,920 --> 00:31:58,850 of the drug itself. 769 00:31:58,850 --> 00:32:01,160 And people have had huge debates to this day about what 770 00:32:01,160 --> 00:32:01,630 that means. 771 00:32:01,630 --> 00:32:02,880 And it's not well understood. 772 00:32:05,600 --> 00:32:09,120 Some people say nobody is getting better, that the 773 00:32:09,120 --> 00:32:11,920 entire thing is regression to the mean from study entry. 774 00:32:11,920 --> 00:32:13,810 And what does that mean? 775 00:32:13,810 --> 00:32:16,570 Well when people have a drug trials for depression, they 776 00:32:16,570 --> 00:32:19,490 say we want to treat people with substantial depression. 777 00:32:19,490 --> 00:32:21,080 That makes sense, right? 778 00:32:21,080 --> 00:32:24,130 So you get people who are substantially depressed. 779 00:32:24,130 --> 00:32:27,640 Depression is inherently a fluctuating disorder. 780 00:32:27,640 --> 00:32:30,360 So from your understanding of regression to the mean, what 781 00:32:30,360 --> 00:32:33,280 happens to a patient when you get them with a really bad 782 00:32:33,280 --> 00:32:34,530 depression score? 783 00:32:34,530 --> 00:32:36,560 What's likely to be there score next 784 00:32:36,560 --> 00:32:39,010 week, better or worse? 785 00:32:39,010 --> 00:32:40,800 Better. 786 00:32:40,800 --> 00:32:43,260 So you get people with really low depression scores, you 787 00:32:43,260 --> 00:32:45,150 just sit back, you don't do anything. 788 00:32:45,150 --> 00:32:48,980 And because it's a fluctuating disorder, the chances are that 789 00:32:48,980 --> 00:32:51,340 because you're getting them at low points in, they're going 790 00:32:51,340 --> 00:32:52,320 to get better next week. 791 00:32:52,320 --> 00:32:52,750 OK. 792 00:32:52,750 --> 00:32:54,390 That's not a treatment effect. 793 00:32:54,390 --> 00:32:57,670 That's, you're getting at them at a low moment by definition. 794 00:32:57,670 --> 00:33:00,310 So some people say, wow, these studies could be full of that. 795 00:33:00,310 --> 00:33:01,900 We say, wow, look at this drug effect. 796 00:33:01,900 --> 00:33:02,900 Man, let's push it up. 797 00:33:02,900 --> 00:33:04,240 Yeah, That's because you're getting people 798 00:33:04,240 --> 00:33:05,420 at their worst moment. 799 00:33:05,420 --> 00:33:07,480 They're going to go back to their average, 800 00:33:07,480 --> 00:33:09,380 which will be better. 801 00:33:09,380 --> 00:33:12,670 Or another really interesting thing is could our brains have 802 00:33:12,670 --> 00:33:15,280 incredibly powerful responses to placebos? 803 00:33:15,280 --> 00:33:19,930 Do we have in us naturally occurring healing mechanisms? 804 00:33:19,930 --> 00:33:22,780 That if we just really believe in it, than 805 00:33:22,780 --> 00:33:23,810 those can take over. 806 00:33:23,810 --> 00:33:24,945 And could we harness that? 807 00:33:24,945 --> 00:33:27,330 Could we harness these naturally occurring 808 00:33:27,330 --> 00:33:30,110 self-healing capacities in people's minds and brains to 809 00:33:30,110 --> 00:33:32,960 make themselves better? 810 00:33:32,960 --> 00:33:36,000 So this is a kind of typical average results. 811 00:33:36,000 --> 00:33:37,440 Drug, psychotherapy, about the same. 812 00:33:37,440 --> 00:33:39,160 Placebo, pretty close. 813 00:33:39,160 --> 00:33:41,650 And here's the no treatment group. 814 00:33:41,650 --> 00:33:43,950 But even this, kind of the picture has 815 00:33:43,950 --> 00:33:45,120 been challenged recently. 816 00:33:45,120 --> 00:33:48,420 And let me tell you what the challenges have been and then 817 00:33:48,420 --> 00:33:50,730 let me tell you what I take as the takeaway message. 818 00:33:50,730 --> 00:33:53,540 But it's not scientifically certain. 819 00:33:53,540 --> 00:33:56,300 So one person did a meta-analysis and 820 00:33:56,300 --> 00:33:57,940 he's totally arguing-- 821 00:33:57,940 --> 00:33:59,700 and let me tell you, the argument's pretty clever. 822 00:33:59,700 --> 00:34:02,150 There's no effect of a drug at all. 823 00:34:02,150 --> 00:34:05,010 That typically, you get about 75% of a drug 824 00:34:05,010 --> 00:34:06,020 effect from the placebo. 825 00:34:06,020 --> 00:34:06,620 That's huge. 826 00:34:06,620 --> 00:34:10,250 75% from an inert substance, sugar or something like that. 827 00:34:10,250 --> 00:34:11,060 OK. 828 00:34:11,060 --> 00:34:14,610 75% in treating a severe psychiatric disorder. 829 00:34:14,610 --> 00:34:16,820 And he says that that small difference, that 830 00:34:16,820 --> 00:34:18,300 25% is due to this. 831 00:34:18,300 --> 00:34:20,760 And who even thinks of this until you read this, if you 832 00:34:20,760 --> 00:34:22,889 haven't been involved in a drug study, that apparent 833 00:34:22,889 --> 00:34:24,820 differences are due to patients realizing they have 834 00:34:24,820 --> 00:34:27,449 the active drug from the side effects. 835 00:34:27,449 --> 00:34:27,670 OK. 836 00:34:27,670 --> 00:34:30,020 So most studies give you the drug. 837 00:34:30,020 --> 00:34:35,380 Most drugs that treat things have unpleasant side effects. 838 00:34:35,380 --> 00:34:37,100 Because they're potent things, OK, that 839 00:34:37,100 --> 00:34:38,650 are perfectly targeted. 840 00:34:38,650 --> 00:34:40,340 So they're saying oh, it's double blind. 841 00:34:40,340 --> 00:34:41,900 You tell this patient, here's your pills. 842 00:34:41,900 --> 00:34:43,630 You don't know if they're placebo or drug. 843 00:34:43,630 --> 00:34:44,310 And here's your pills. 844 00:34:44,310 --> 00:34:45,929 You don't know if they're placebo or drugs. 845 00:34:45,929 --> 00:34:47,440 But patient's are reasonably smart. 846 00:34:47,440 --> 00:34:49,400 Many have been through treatment before. 847 00:34:49,400 --> 00:34:51,590 And they know if they're feeling nauseous, and yucky, 848 00:34:51,590 --> 00:34:54,570 and all kinds of other stuff, they got the drug. 849 00:34:54,570 --> 00:34:57,210 And if they take it and they don't feel anything funny, 850 00:34:57,210 --> 00:34:58,950 they got the sugar placebo. 851 00:34:58,950 --> 00:34:59,760 Does that make sense? 852 00:34:59,760 --> 00:35:02,520 Because they figure out-- 853 00:35:02,520 --> 00:35:05,250 and 80% of the time they're accurate, whether they got the 854 00:35:05,250 --> 00:35:07,420 inert placebo or the drug. 855 00:35:07,420 --> 00:35:10,050 Because this side effects tell them that, not the drug effect 856 00:35:10,050 --> 00:35:12,250 on the mind. 857 00:35:12,250 --> 00:35:14,670 And that in the few studies where they give you up a 858 00:35:14,670 --> 00:35:17,110 placebo that has peripheral effects, that make you 859 00:35:17,110 --> 00:35:20,020 nauseous like the drug, then in those couple of studies, 860 00:35:20,020 --> 00:35:22,130 there's just been a couple, there's no difference between 861 00:35:22,130 --> 00:35:23,370 placebo and drug. 862 00:35:23,370 --> 00:35:28,110 So here's a position that the entire thing is placebo. 863 00:35:28,110 --> 00:35:30,660 And an argument from this guy that we should tell patients, 864 00:35:30,660 --> 00:35:32,100 it's all placebo. 865 00:35:32,100 --> 00:35:34,470 Now why do you think that it's not necessarily a good idea to 866 00:35:34,470 --> 00:35:36,900 tell patients even if it were scientifically true? 867 00:35:36,900 --> 00:35:37,370 Yeah? 868 00:35:37,370 --> 00:35:39,568 AUDIENCE: Because if you tell them it's a 869 00:35:39,568 --> 00:35:40,196 placebo it could ruin-- 870 00:35:40,196 --> 00:35:41,140 PROFESSOR JOHN GABRIELI: Yeah. 871 00:35:41,140 --> 00:35:42,680 There's a pretty good chance you've ruined it. 872 00:35:42,680 --> 00:35:46,350 If you hand them the pills and you go, look, who know. 873 00:35:46,350 --> 00:35:47,100 It's all sugar. 874 00:35:47,100 --> 00:35:48,880 But you know give it a go for a person 875 00:35:48,880 --> 00:35:50,810 who's in misery, right. 876 00:35:50,810 --> 00:35:52,380 So they have to kind of believe. 877 00:35:52,380 --> 00:35:53,560 And it's kind of interesting. 878 00:35:53,560 --> 00:35:55,210 What is the biology of that belief? 879 00:35:55,210 --> 00:35:55,810 Right. 880 00:35:55,810 --> 00:35:58,070 So that's one side of the story. 881 00:35:58,070 --> 00:36:01,050 Another slightly less drastic interpretation, but also 882 00:36:01,050 --> 00:36:05,106 pretty strong, is that in recent meta-analysis is that 883 00:36:05,106 --> 00:36:08,930 the drug effect of a placebo only occurs for the most 884 00:36:08,930 --> 00:36:11,760 severe depressions, the most severe depressions. 885 00:36:11,760 --> 00:36:14,870 And the Depression Center even considered severe or moderate, 886 00:36:14,870 --> 00:36:16,780 where you do want to help people, there's no difference 887 00:36:16,780 --> 00:36:19,670 between the placebo and the drugs. 888 00:36:19,670 --> 00:36:23,150 So my only fear in telling you this is the last thing you 889 00:36:23,150 --> 00:36:25,320 want to do if in your life, or somebody you care about, 890 00:36:25,320 --> 00:36:27,830 there's depression or anything like that, get them help. 891 00:36:27,830 --> 00:36:28,700 Because there are helped. 892 00:36:28,700 --> 00:36:30,840 And if it's placebo, that's OK too. 893 00:36:30,840 --> 00:36:34,320 And if it's some unreputable person without a degree but 894 00:36:34,320 --> 00:36:36,350 they're really good at talking to people, that's good too. 895 00:36:36,350 --> 00:36:37,090 OK. 896 00:36:37,090 --> 00:36:38,230 The evidence is overwhelming. 897 00:36:38,230 --> 00:36:41,130 That getting help helps many people. 898 00:36:41,130 --> 00:36:42,640 And not getting help out people at 899 00:36:42,640 --> 00:36:43,690 greater and greater risks. 900 00:36:43,690 --> 00:36:44,490 It's overwhelming. 901 00:36:44,490 --> 00:36:46,800 Getting help is a really good thing. 902 00:36:46,800 --> 00:36:49,460 It's just that we don't understand how the help works. 903 00:36:49,460 --> 00:36:52,300 And we know it doesn't help nearly powerfully enough on a 904 00:36:52,300 --> 00:36:55,650 consistent basis. 905 00:36:55,650 --> 00:36:58,860 So now we're going to switch from depression to ADHD, a 906 00:36:58,860 --> 00:37:00,280 disease of childhood. 907 00:37:00,280 --> 00:37:03,980 These are children who have inattention, hyperactive in 908 00:37:03,980 --> 00:37:07,000 80% of cases, impulsive, moving around, and jumpy. 909 00:37:07,000 --> 00:37:09,500 The diagnosis, like everything, is by exclusion. 910 00:37:09,500 --> 00:37:11,430 They make sure that there's not some other problem in the 911 00:37:11,430 --> 00:37:13,320 child's life that's making them inattentive or 912 00:37:13,320 --> 00:37:13,930 impossible. 913 00:37:13,930 --> 00:37:16,370 For example, like abuse at home. 914 00:37:16,370 --> 00:37:19,570 Its prevalence is 2 million or more. 915 00:37:19,570 --> 00:37:22,700 It's tripled since 1981, increased 2.5 times since '90. 916 00:37:22,700 --> 00:37:25,010 So sort of like the discussions you hear now about 917 00:37:25,010 --> 00:37:29,660 autism, there was fantastic debates about ADHD. 918 00:37:29,660 --> 00:37:31,300 Does it exist at all? 919 00:37:31,300 --> 00:37:33,750 Are people just medicating kids to keep them lined up in 920 00:37:33,750 --> 00:37:37,890 classrooms, quietly listening to lectures like me? 921 00:37:37,890 --> 00:37:39,730 Is there a real problem? 922 00:37:39,730 --> 00:37:41,420 And there's incredibly polarized 923 00:37:41,420 --> 00:37:44,170 debates about these things. 924 00:37:44,170 --> 00:37:46,530 So how does the clinician make the diagnosis? 925 00:37:46,530 --> 00:37:48,140 They look at the child. 926 00:37:48,140 --> 00:37:50,340 They talk to parents, teachers. 927 00:37:50,340 --> 00:37:51,580 And they sort of fill out 928 00:37:51,580 --> 00:37:53,300 questionnaires and have a list. 929 00:37:53,300 --> 00:37:55,820 And I'll show you the kind of a list the clinician has to 930 00:37:55,820 --> 00:37:58,570 work against. 931 00:37:58,570 --> 00:38:00,520 Depending on studies, and this is kind of an interesting 932 00:38:00,520 --> 00:38:05,620 number, ranges from about 2% to about 15%. 933 00:38:05,620 --> 00:38:07,560 And you can say, well how could it possibly do that? 934 00:38:07,560 --> 00:38:09,330 Why can't researchers get it right? 935 00:38:09,330 --> 00:38:10,000 OK. 936 00:38:10,000 --> 00:38:13,180 You could take a 1/2 a percent off, or two or whatever it is. 937 00:38:13,180 --> 00:38:14,670 And again, it depends so much of your 938 00:38:14,670 --> 00:38:19,130 criteria for the diagnosis. 939 00:38:19,130 --> 00:38:21,220 Part of it too is over time these things change as you 940 00:38:21,220 --> 00:38:22,480 have different versions of DSM. 941 00:38:22,480 --> 00:38:26,410 And I mentioned also countries, professions, 942 00:38:26,410 --> 00:38:30,820 overnight in the same German population doubled as DSM book 943 00:38:30,820 --> 00:38:32,400 got revised and changed its criteria. 944 00:38:32,400 --> 00:38:33,592 OK. 945 00:38:33,592 --> 00:38:35,160 Is this the correct criteria? 946 00:38:35,160 --> 00:38:36,780 Are these the correct criteria? 947 00:38:36,780 --> 00:38:38,660 And how would you know if you had the correct criteria? 948 00:38:38,660 --> 00:38:40,440 How would you know if you've got it right? 949 00:38:40,440 --> 00:38:42,490 People just have to have consensus as 950 00:38:42,490 --> 00:38:43,550 best they can guess. 951 00:38:43,550 --> 00:38:46,050 Because there's no objective evidence beyond reasonable 952 00:38:46,050 --> 00:38:47,310 interpretation. 953 00:38:47,310 --> 00:38:50,300 So about 3-5% of school age children. 954 00:38:50,300 --> 00:38:53,360 And the reason that people take it seriously beyond these 955 00:38:53,360 --> 00:38:56,640 conceptual debates is that children with ADHD that is not 956 00:38:56,640 --> 00:38:59,970 treated struggle a lot. 957 00:38:59,970 --> 00:39:04,580 To a huge variation of course, but it predicts anti-social 958 00:39:04,580 --> 00:39:07,390 behavior, substance abuse, adverse occupational social 959 00:39:07,390 --> 00:39:07,780 adjustments. 960 00:39:07,780 --> 00:39:10,340 There are people with ADHD who are phenomenally successful. 961 00:39:10,340 --> 00:39:12,550 There's probably several of you in the class who have been 962 00:39:12,550 --> 00:39:15,020 diagnosed with that in any group like this. 963 00:39:15,020 --> 00:39:18,170 So it's not the certain thing, but on average if you don't 964 00:39:18,170 --> 00:39:21,330 have other talents, and situations, and support, it's 965 00:39:21,330 --> 00:39:24,460 a big risk factor for doing badly in life by the ways that 966 00:39:24,460 --> 00:39:26,390 most people want to do well. 967 00:39:26,390 --> 00:39:29,200 The most common, but not the only treatment, is a Ritalin 968 00:39:29,200 --> 00:39:30,140 or methylphenidate. 969 00:39:30,140 --> 00:39:32,160 The Ritalin is the commercial name, methylphedidate the 970 00:39:32,160 --> 00:39:33,510 generic name. 971 00:39:33,510 --> 00:39:35,080 We know there's a genetic piece about this. 972 00:39:35,080 --> 00:39:36,640 You've heard it so many times. 973 00:39:36,640 --> 00:39:40,340 7 times higher rate within families, about a 0.76 974 00:39:40,340 --> 00:39:43,100 heritability in twin studies. 975 00:39:43,100 --> 00:39:45,790 Some candidate genes have been identified and involved in the 976 00:39:45,790 --> 00:39:47,430 dopaminergic systems of the brain. 977 00:39:47,430 --> 00:39:49,890 But like with all neuropsychiatric diseases, in 978 00:39:49,890 --> 00:39:51,320 kind of a weak way. 979 00:39:51,320 --> 00:39:53,120 It's not like there's a gene, if you have it, 980 00:39:53,120 --> 00:39:54,000 you have the disorder. 981 00:39:54,000 --> 00:39:58,990 Is just a little higher on average in populations. 982 00:39:58,990 --> 00:39:59,310 OK. 983 00:39:59,310 --> 00:40:01,620 So here's the question, a kid comes in to you. 984 00:40:01,620 --> 00:40:02,520 You're the doctor. 985 00:40:02,520 --> 00:40:04,650 And it's quite interesting to talk to doctors about this. 986 00:40:04,650 --> 00:40:06,810 Because in many medical settings with the current 987 00:40:06,810 --> 00:40:10,550 economic environment, doctors are incredibly encouraged, and 988 00:40:10,550 --> 00:40:13,220 by for example, their salaries, to see patients 989 00:40:13,220 --> 00:40:14,800 really fast. 990 00:40:14,800 --> 00:40:17,110 The faster they see them, the more the health systems says, 991 00:40:17,110 --> 00:40:18,360 yeah, we're productive. 992 00:40:21,280 --> 00:40:24,160 So here's what they have to decide, do you had 993 00:40:24,160 --> 00:40:24,820 inattention? 994 00:40:24,820 --> 00:40:26,810 Because inattention was one of the big criteria. 995 00:40:26,810 --> 00:40:28,790 You have to have at least six for at least six months to 996 00:40:28,790 --> 00:40:32,200 agree that it's maladaptive and age inappropriate. 997 00:40:32,200 --> 00:40:35,350 Careless mistakes in school or productivity, I'm sure none of 998 00:40:35,350 --> 00:40:36,840 us ever make careless mistakes, right. 999 00:40:36,840 --> 00:40:39,060 Difficulty sustaining attention in tasks or play, 1000 00:40:39,060 --> 00:40:41,240 does not seem to listen when spoken to directly, not follow 1001 00:40:41,240 --> 00:40:44,180 instructions to finish tasks, difficult organizing tasks and 1002 00:40:44,180 --> 00:40:44,550 activities. 1003 00:40:44,550 --> 00:40:47,310 Avoids, listen to this one, avoids tasks engaging 1004 00:40:47,310 --> 00:40:50,090 sustained mental effort, OK. 1005 00:40:50,090 --> 00:40:52,290 Loses things, easily distracted by extraneous 1006 00:40:52,290 --> 00:40:54,080 stimuli, forgetful in daily activities. 1007 00:40:54,080 --> 00:40:56,710 What five-year-old is not describable 1008 00:40:56,710 --> 00:40:57,870 in these ways, right? 1009 00:40:57,870 --> 00:40:59,410 So you see how challenging it is? 1010 00:40:59,410 --> 00:41:01,070 And it's not to take it lightly. 1011 00:41:01,070 --> 00:41:03,380 Because the kids who really meet this, really 1012 00:41:03,380 --> 00:41:04,210 struggle over time. 1013 00:41:04,210 --> 00:41:06,320 There's been many longitudinal studies. 1014 00:41:06,320 --> 00:41:09,530 That on average, children who meet these criteria will 1015 00:41:09,530 --> 00:41:12,310 struggle in many ways. 1016 00:41:12,310 --> 00:41:13,260 But look at all of these. 1017 00:41:13,260 --> 00:41:15,810 There's nothing here like hearing a voice, right? 1018 00:41:15,810 --> 00:41:17,520 It's just like a kid. 1019 00:41:17,520 --> 00:41:20,970 But a little more of it for your age. 1020 00:41:20,970 --> 00:41:24,610 Hyperactivity, you fidget or squirm in your seat. 1021 00:41:24,610 --> 00:41:26,050 You leave your seat in the classroom. 1022 00:41:26,050 --> 00:41:28,290 You run about or climb excessively. 1023 00:41:28,290 --> 00:41:30,210 You have difficulty playing quietly. 1024 00:41:30,210 --> 00:41:31,370 You talk excessively. 1025 00:41:31,370 --> 00:41:33,350 Blurts out answers before questions are completed. 1026 00:41:33,350 --> 00:41:35,220 So these are kids who are tough on teachers in 1027 00:41:35,220 --> 00:41:36,470 classrooms. 1028 00:41:38,600 --> 00:41:41,020 The symptoms have to be present before the age of 1029 00:41:41,020 --> 00:41:44,650 seven, persistent in two or more settings, at home and 1030 00:41:44,650 --> 00:41:46,650 school for example, typically. 1031 00:41:46,650 --> 00:41:49,630 And then not because you don't hear well, or because you have 1032 00:41:49,630 --> 00:41:52,290 allergies, or you have other psychiatric disorders. 1033 00:41:52,290 --> 00:41:54,540 And sometimes people talk about both, inattention and 1034 00:41:54,540 --> 00:41:56,730 hyperactivity, or the combined type. 1035 00:41:56,730 --> 00:42:00,510 There is a thought that the more frequent finding in boys 1036 00:42:00,510 --> 00:42:03,000 is because boys are more frequently hyperactive. 1037 00:42:03,000 --> 00:42:04,410 So they're trouble making in a classroom. 1038 00:42:04,410 --> 00:42:05,290 They're jumping up and down. 1039 00:42:05,290 --> 00:42:06,610 They're not listening to the teacher. 1040 00:42:06,610 --> 00:42:10,400 And the girls might be more on average inattentive, quiet and 1041 00:42:10,400 --> 00:42:11,860 dreamy, not taking stuff in. 1042 00:42:11,860 --> 00:42:13,900 That's not a problem for classroom management. 1043 00:42:13,900 --> 00:42:16,540 So there's a thought the girls might be under diagnosed 1044 00:42:16,540 --> 00:42:21,120 because of the way it's expressed in boys and girls. 1045 00:42:21,120 --> 00:42:23,690 But there's a huge source of evidence that if left 1046 00:42:23,690 --> 00:42:26,720 completely untreated, rates of depression, anxiety, substance 1047 00:42:26,720 --> 00:42:28,820 abuse, academic failure, work problems, family problems, 1048 00:42:28,820 --> 00:42:31,265 emotional distress are much higher in children where 1049 00:42:31,265 --> 00:42:34,560 there's no attempt to treat or manage ADHD. 1050 00:42:34,560 --> 00:42:37,430 There's a huge amount of evidence for this. 1051 00:42:37,430 --> 00:42:40,790 So one of the sort of most famous studies in 1052 00:42:40,790 --> 00:42:46,000 developmental psychiatry of directly comparing individuals 1053 00:42:46,000 --> 00:42:48,570 on behavioral and drug treatments. 1054 00:42:48,570 --> 00:42:50,790 It was a study called the MTA study. 1055 00:42:50,790 --> 00:42:53,590 It was done in many different sites all put together with a 1056 00:42:53,590 --> 00:42:57,150 huge number of children, 14 months, they got medication 1057 00:42:57,150 --> 00:43:01,370 management alone, behavioral treatment alone, a combination 1058 00:43:01,370 --> 00:43:02,950 of both, or routine community care. 1059 00:43:02,950 --> 00:43:04,800 So they said, what happens when we give you better 1060 00:43:04,800 --> 00:43:07,360 behavioral treatment, or more careful medical management on 1061 00:43:07,360 --> 00:43:11,010 the drugs, or you go back to your standard community care? 1062 00:43:11,010 --> 00:43:13,610 And what people found was this, that medication 1063 00:43:13,610 --> 00:43:16,536 management alone-- 1064 00:43:16,536 --> 00:43:18,380 Here's what they did in those conditions. 1065 00:43:18,380 --> 00:43:20,890 They saw a doctor monthly for 30 minutes. 1066 00:43:20,890 --> 00:43:23,400 They would move the drugged amount up or down. 1067 00:43:23,400 --> 00:43:26,090 They would titrate it if it seemed to be sedating the 1068 00:43:26,090 --> 00:43:27,460 child too much, they'd make it less. 1069 00:43:27,460 --> 00:43:29,570 If it was not working enough, make it more. 1070 00:43:29,570 --> 00:43:31,390 And they will talk a lot with a child and the parent. 1071 00:43:31,390 --> 00:43:32,630 So that was the medication management. 1072 00:43:32,630 --> 00:43:34,820 More active than you typically get people get at medical 1073 00:43:34,820 --> 00:43:35,950 interactions. 1074 00:43:35,950 --> 00:43:39,110 Behavioral treatments involved an 8-week summer camp, or you 1075 00:43:39,110 --> 00:43:40,560 got the two of them together. 1076 00:43:40,560 --> 00:43:43,610 Or you were sent back to your community and got the regular 1077 00:43:43,610 --> 00:43:47,010 care from a regular doctor that people typically get. 1078 00:43:47,010 --> 00:43:50,450 So and the big outcomes were that the best thing was to 1079 00:43:50,450 --> 00:43:52,350 have the medical management alone, or a 1080 00:43:52,350 --> 00:43:55,050 combination of the two. 1081 00:43:55,050 --> 00:43:57,850 And in some cases, you would get lower doses of medications 1082 00:43:57,850 --> 00:44:00,280 if you got the behavioral treatment. 1083 00:44:00,280 --> 00:44:03,160 So you could say, and for many years I heard lecturers who 1084 00:44:03,160 --> 00:44:05,530 were expert in this field saying, the definitive thing 1085 00:44:05,530 --> 00:44:08,410 is the medication pretty much does it all. 1086 00:44:08,410 --> 00:44:11,120 Maybe the behavioral treatment had something, the behavioral 1087 00:44:11,120 --> 00:44:12,790 treatment by itself didn't add much. 1088 00:44:12,790 --> 00:44:14,750 This was what everybody was taught. 1089 00:44:14,750 --> 00:44:18,080 But they kept following these people and 1090 00:44:18,080 --> 00:44:18,760 here's what they found. 1091 00:44:18,760 --> 00:44:21,180 Eight years later after the study was over, no difference 1092 00:44:21,180 --> 00:44:23,020 in which group you were in. 1093 00:44:23,020 --> 00:44:27,380 About 60% of kids stopped taking medication, the family 1094 00:44:27,380 --> 00:44:29,640 decided to stop, or the doctor decided to stop. 1095 00:44:29,640 --> 00:44:31,890 And there's no difference between those who did or did 1096 00:44:31,890 --> 00:44:36,240 not stop taking medication, in terms of difficulties in life. 1097 00:44:36,240 --> 00:44:38,320 So now this is very complicated. 1098 00:44:38,320 --> 00:44:40,450 Because people always say like, what is the long-term 1099 00:44:40,450 --> 00:44:42,020 effects of taking Ritalin in children? 1100 00:44:42,020 --> 00:44:43,790 What is the long-term effects? 1101 00:44:43,790 --> 00:44:47,750 And you go well, you could say the first 1102 00:44:47,750 --> 00:44:48,760 interpretation is this. 1103 00:44:48,760 --> 00:44:51,740 Well, since it didn't make any difference, the drug has no 1104 00:44:51,740 --> 00:44:53,420 effect at all, right. 1105 00:44:53,420 --> 00:44:54,890 You take the drug, you don't take the drug, you have the 1106 00:44:54,890 --> 00:44:56,280 same outcome. 1107 00:44:56,280 --> 00:44:57,660 14-months was something. 1108 00:44:57,660 --> 00:44:59,780 But eight years, it doesn't matter. 1109 00:44:59,780 --> 00:45:02,480 But of course, who's more likely to stop taking the 1110 00:45:02,480 --> 00:45:03,000 medication? 1111 00:45:03,000 --> 00:45:06,100 Kids who are doing better or kids who are doing worse? 1112 00:45:06,100 --> 00:45:09,030 Who's more likely to stop probably? 1113 00:45:09,030 --> 00:45:10,880 On average, kids who are doing better, right. 1114 00:45:10,880 --> 00:45:13,590 So maybe what you're really-- maybe no difference is some 1115 00:45:13,590 --> 00:45:14,960 kids were improving for other reasons. 1116 00:45:14,960 --> 00:45:18,370 And so really, the kids who got the medications caught up 1117 00:45:18,370 --> 00:45:19,690 with them because of the medications. 1118 00:45:19,690 --> 00:45:21,080 And you can't tell those two things apart. 1119 00:45:21,080 --> 00:45:24,030 So it's just incredibly hard to know with certainty what 1120 00:45:24,030 --> 00:45:26,690 the right thing to do is in any long-term view. 1121 00:45:26,690 --> 00:45:29,300 Because you can control for 14-months what people do, if 1122 00:45:29,300 --> 00:45:30,810 they're willing to let you do that. 1123 00:45:30,810 --> 00:45:32,090 But you can't control it over years. 1124 00:45:32,090 --> 00:45:34,260 They go back to their own complicated lives. 1125 00:45:34,260 --> 00:45:36,430 And sorting out what the treatment did, versus the rest 1126 00:45:36,430 --> 00:45:37,990 of their life is really hard. 1127 00:45:37,990 --> 00:45:40,060 So Charlie, if we could do the VCR movie. 1128 00:45:40,060 --> 00:45:44,110 Here's a example of a kid with ADHD and some 1129 00:45:44,110 --> 00:45:45,360 discussion about that. 1130 00:45:48,082 --> 00:45:50,300 You know, amazingly I can tell you that even though they're 1131 00:45:50,300 --> 00:45:54,190 as good as it can do, there is no behavioral test you can 1132 00:45:54,190 --> 00:45:57,830 give like this that's better than 50/50 at separating an 1133 00:45:57,830 --> 00:46:00,310 ADHD child from other children. 1134 00:46:00,310 --> 00:46:02,390 So you could be part of the story. 1135 00:46:02,390 --> 00:46:04,960 But many, many, many children will not be identified this 1136 00:46:04,960 --> 00:46:06,540 way even though they're having real problems at 1137 00:46:06,540 --> 00:46:07,400 school and at home. 1138 00:46:07,400 --> 00:46:09,020 I want to say two things about the video game. 1139 00:46:09,020 --> 00:46:11,880 People, as they noted here, sometimes ADHD 1140 00:46:11,880 --> 00:46:13,180 diagnoses are tough. 1141 00:46:13,180 --> 00:46:16,570 Because when kids come into a new situation, a doctor's 1142 00:46:16,570 --> 00:46:18,490 office, a new doctor, an evaluation, 1143 00:46:18,490 --> 00:46:19,690 it gets their attention. 1144 00:46:19,690 --> 00:46:23,090 And they look more focused, OK. 1145 00:46:23,090 --> 00:46:25,430 And people have noticed that kids with ADHD seem to do 1146 00:46:25,430 --> 00:46:28,750 quite well when they have an entertaining video game, which 1147 00:46:28,750 --> 00:46:31,400 is easier to enjoy, right, than most things. 1148 00:46:31,400 --> 00:46:34,540 So they actually did the study to ask how long does an ADHD 1149 00:46:34,540 --> 00:46:37,400 kid play a video game versus a kid without ADHD. 1150 00:46:37,400 --> 00:46:40,420 And when they're both playing video games, still the ADHD 1151 00:46:40,420 --> 00:46:42,740 kid plays for less long. 1152 00:46:42,740 --> 00:46:44,330 So it's not that it takes it away. 1153 00:46:44,330 --> 00:46:46,545 But it in many ways, obfuscates the difference. 1154 00:46:50,750 --> 00:46:55,670 So one interesting question is what is the right dose? 1155 00:46:55,670 --> 00:46:58,580 Because we said the treatments where they titrated the dose, 1156 00:46:58,580 --> 00:47:00,980 where you went to a doctor frequently and they said let's 1157 00:47:00,980 --> 00:47:03,220 push it up, let's push it down, let's get the dose 1158 00:47:03,220 --> 00:47:05,700 that's right for the child. 1159 00:47:05,700 --> 00:47:07,010 What is that number? 1160 00:47:07,010 --> 00:47:09,660 So here's a paper all the way back from 1977. 1161 00:47:09,660 --> 00:47:13,030 Here's placebo, here's a small dose, here's a large dose. 1162 00:47:13,030 --> 00:47:14,690 And they measured three different things. 1163 00:47:14,690 --> 00:47:17,670 They measured how well you did in terms 1164 00:47:17,670 --> 00:47:19,330 of the teacher ratings. 1165 00:47:19,330 --> 00:47:21,130 So a teacher say, how's the kid doing? 1166 00:47:21,130 --> 00:47:23,160 That's the open bars, OK. 1167 00:47:23,160 --> 00:47:25,320 So the teacher said, here's how the kid's doing. 1168 00:47:25,320 --> 00:47:27,690 They go, well, this is even better. 1169 00:47:27,690 --> 00:47:29,880 And they go this is even the best, OK. 1170 00:47:29,880 --> 00:47:32,280 So the teachers are saying, the more drug the better. 1171 00:47:32,280 --> 00:47:35,460 Here's an objective measure of learning performance by those 1172 00:47:35,460 --> 00:47:37,130 children, the same children. 1173 00:47:37,130 --> 00:47:39,320 Better, worse. 1174 00:47:39,320 --> 00:47:42,820 So you see, we go back to the ideas that came out of the 1175 00:47:42,820 --> 00:47:46,160 prefrontal lobotomies, completely different topic. 1176 00:47:46,160 --> 00:47:48,550 Everybody pretty much in the field agrees that these drugs 1177 00:47:48,550 --> 00:47:50,550 help these kids on average, OK. 1178 00:47:50,550 --> 00:47:52,980 But think about the complications of what the 1179 00:47:52,980 --> 00:47:54,290 right dose is. 1180 00:47:54,290 --> 00:47:56,890 For the teacher, the biggest dose is best. 1181 00:47:56,890 --> 00:47:59,090 And why do you think that's likely to be? 1182 00:47:59,090 --> 00:48:00,640 For the teacher doing classroom 1183 00:48:00,640 --> 00:48:02,610 management with the 30 kids? 1184 00:48:02,610 --> 00:48:04,275 Why does a big dose seem best? 1185 00:48:07,070 --> 00:48:07,370 Yeah? 1186 00:48:07,370 --> 00:48:09,438 AUDIENCE: Because they want the kids to be really 1187 00:48:09,438 --> 00:48:09,880 manageable. 1188 00:48:09,880 --> 00:48:10,840 PROFESSOR JOHN GABRIELI: Yes Yeah, yeah. 1189 00:48:10,840 --> 00:48:11,810 You were going to say the same thing. 1190 00:48:11,810 --> 00:48:12,070 Yeah. 1191 00:48:12,070 --> 00:48:14,600 For them it's the kid is not fidgeting, not jumping around, 1192 00:48:14,600 --> 00:48:16,250 distracting the other kids. 1193 00:48:16,250 --> 00:48:19,690 So a slightly over-sedated kid seems like a triumph. 1194 00:48:19,690 --> 00:48:23,530 And it can be to a parent also, like listening to me. 1195 00:48:23,530 --> 00:48:26,060 But objective learning measures, this is optimal. 1196 00:48:26,060 --> 00:48:28,310 And this is overdosing. 1197 00:48:28,310 --> 00:48:29,580 So I think we'd all agree. 1198 00:48:29,580 --> 00:48:31,220 This is the one that matters most of all. 1199 00:48:31,220 --> 00:48:34,830 But you can see, you don't often have this kind of 1200 00:48:34,830 --> 00:48:35,220 measurement. 1201 00:48:35,220 --> 00:48:37,470 Often the doctor says, what does a teacher think? 1202 00:48:37,470 --> 00:48:38,580 What does the parent think? 1203 00:48:38,580 --> 00:48:41,160 And the kid will end up over here because that's what seems 1204 00:48:41,160 --> 00:48:45,690 most correct to the eyes of the teacher or the parent, the 1205 00:48:45,690 --> 00:48:48,170 biggest change in the child's behavior. 1206 00:48:48,170 --> 00:48:49,360 So for the last couple of minutes I want to talk about 1207 00:48:49,360 --> 00:48:51,470 brain imaging in regards to ADHD. 1208 00:48:51,470 --> 00:48:54,150 So we talked about the idea that the cerebral cortex, you 1209 00:48:54,150 --> 00:48:57,330 have too much of it, too many neurons and over connected. 1210 00:48:57,330 --> 00:49:00,500 And that what it is to grow the adult brain you have is to 1211 00:49:00,500 --> 00:49:03,340 eliminate neurons and synapses that are not 1212 00:49:03,340 --> 00:49:04,670 functionally valuable. 1213 00:49:04,670 --> 00:49:06,290 You're picking out the most valuable 1214 00:49:06,290 --> 00:49:09,040 players of your neurons. 1215 00:49:09,040 --> 00:49:11,750 And so you can say there's a peak age at which you go up 1216 00:49:11,750 --> 00:49:12,420 and then you go down. 1217 00:49:12,420 --> 00:49:14,640 And you consider that peak to be a sort of milestone of 1218 00:49:14,640 --> 00:49:15,840 development. 1219 00:49:15,840 --> 00:49:18,383 And you can see here in the dorsal lateral prefrontal of 1220 00:49:18,383 --> 00:49:20,410 the cortex, here's the front of the brain. 1221 00:49:20,410 --> 00:49:23,170 Here's the delay in ADH children. 1222 00:49:23,170 --> 00:49:28,120 They take an average two years longer to reach that peak than 1223 00:49:28,120 --> 00:49:30,290 do typically developing kids. 1224 00:49:30,290 --> 00:49:33,120 But there's no difference at all in primary 1225 00:49:33,120 --> 00:49:34,890 somatosensory cortex. 1226 00:49:34,890 --> 00:49:39,530 So you might imagine it on systems that are the inputs of 1227 00:49:39,530 --> 00:49:41,320 sensory stimulation from the world, an 1228 00:49:41,320 --> 00:49:43,580 ADHD child is typical. 1229 00:49:43,580 --> 00:49:46,500 For parts of the brain that regulate, like I'm not going 1230 00:49:46,500 --> 00:49:48,870 to pay attention to that or I'm going to focus on this. 1231 00:49:48,870 --> 00:49:50,430 That's slower developing. 1232 00:49:50,430 --> 00:49:53,060 And you could see how that might lead to inattention or 1233 00:49:53,060 --> 00:49:54,790 easy distractability. 1234 00:49:54,790 --> 00:49:58,790 So a two-year delay in the development on average of 1235 00:49:58,790 --> 00:50:03,290 prefrontal cortex structure. 1236 00:50:03,290 --> 00:50:04,600 I talked with you before, and I'm just going to 1237 00:50:04,600 --> 00:50:05,290 remind you of this. 1238 00:50:05,290 --> 00:50:09,390 That if we look at reward systems, anticipation of a 1239 00:50:09,390 --> 00:50:12,580 reward coming up in a few moments activates the nucleus 1240 00:50:12,580 --> 00:50:14,170 accumbens in animals and humans. 1241 00:50:14,170 --> 00:50:16,880 This is in humans, anticipation of a reward. 1242 00:50:19,490 --> 00:50:22,830 And the same system that's measured here goes on to the 1243 00:50:22,830 --> 00:50:25,220 medial prefrontal cortex. 1244 00:50:25,220 --> 00:50:28,590 And that system turns on when you get the reward. 1245 00:50:28,590 --> 00:50:30,000 So one thing anticipates. 1246 00:50:30,000 --> 00:50:32,740 And one thing responds when you get the reward. 1247 00:50:32,740 --> 00:50:35,120 And there's been some slightly divergent studies in ADHD. 1248 00:50:35,120 --> 00:50:37,570 But one suggestion one is this. 1249 00:50:37,570 --> 00:50:40,920 So here's the control subjects anticipating the reward. 1250 00:50:40,920 --> 00:50:44,800 Here's the ADHD individuals also anticipating the reward 1251 00:50:44,800 --> 00:50:47,390 but not showing any activation. 1252 00:50:47,390 --> 00:50:50,900 It's as if, now remember the reward is this, you get a 1253 00:50:50,900 --> 00:50:53,520 signal that tells you in a few moments if you push a button, 1254 00:50:53,520 --> 00:50:54,940 you're going to get $1. 1255 00:50:54,940 --> 00:50:58,460 This is not like study now, and if you complete college, 1256 00:50:58,460 --> 00:50:59,650 you get to go to medical school. 1257 00:50:59,650 --> 00:51:01,280 It's not delayed gratification. 1258 00:51:01,280 --> 00:51:05,776 It's anticipating reward coming up in about 10 seconds. 1259 00:51:05,776 --> 00:51:07,860 And at least in these patients, it 1260 00:51:07,860 --> 00:51:09,290 doesn't drive the system. 1261 00:51:09,290 --> 00:51:13,800 It's as if delayed gratification were not having 1262 00:51:13,800 --> 00:51:16,760 any attraction with these brains. 1263 00:51:16,760 --> 00:51:19,570 On the other hand, then you find out if you got it or not, 1264 00:51:19,570 --> 00:51:22,650 because sometimes they trick you don't get it, orbital 1265 00:51:22,650 --> 00:51:24,630 frontal response and controls, and much 1266 00:51:24,630 --> 00:51:25,890 more in ADHD patients. 1267 00:51:25,890 --> 00:51:29,320 If this picture is true, or at least true for some patients, 1268 00:51:29,320 --> 00:51:34,840 imagine the consequences of anticipating reward, but being 1269 00:51:34,840 --> 00:51:36,800 overly responsive to whether you got it or not. 1270 00:51:36,800 --> 00:51:38,650 You'd be stimulus bound, right. 1271 00:51:38,650 --> 00:51:40,620 You couldn't hold yourself back. 1272 00:51:40,620 --> 00:51:44,640 It's not helping you develop delayed gratification. 1273 00:51:44,640 --> 00:51:46,600 And here's one more thing that people ask, 1274 00:51:46,600 --> 00:51:48,970 which is if you have-- 1275 00:51:48,970 --> 00:51:50,660 because now there's some evidence about this-- if you 1276 00:51:50,660 --> 00:51:54,730 give Ritalin for a while, does it's slow the development of 1277 00:51:54,730 --> 00:51:55,750 the cerebral cortex? 1278 00:51:55,750 --> 00:51:57,180 And I won't go into the details here. 1279 00:51:57,180 --> 00:51:59,100 But he answers is it does not. 1280 00:51:59,100 --> 00:52:01,700 So people are worried, like if we keep giving Ritalin for 1281 00:52:01,700 --> 00:52:04,130 some more years are we affecting brain structure? 1282 00:52:04,130 --> 00:52:05,560 And the evidence is clear. 1283 00:52:05,560 --> 00:52:07,810 Objectives of it is that it is not. 1284 00:52:07,810 --> 00:52:10,220 So I think a lot of people feel like if the medication's 1285 00:52:10,220 --> 00:52:12,470 helpful, there's very little evidence there's 1286 00:52:12,470 --> 00:52:14,070 harmful side effects. 1287 00:52:14,070 --> 00:52:15,680 Weirdly enough, Ritalin-- 1288 00:52:15,680 --> 00:52:17,220 and we'll come back to this just in a -- 1289 00:52:17,220 --> 00:52:19,890 is one of the least problematic medications in 1290 00:52:19,890 --> 00:52:24,300 psychiatry, and frequently helpful. 1291 00:52:24,300 --> 00:52:28,520 So the last FMRI study I want to show you is this. 1292 00:52:28,520 --> 00:52:31,285 Let's say you gave Ritalin not only to children with ADHD who 1293 00:52:31,285 --> 00:52:32,170 are taking it. 1294 00:52:32,170 --> 00:52:35,410 But also typically developing children who've never taken 1295 00:52:35,410 --> 00:52:38,790 Ritalin because they're typically developing. 1296 00:52:38,790 --> 00:52:41,260 And how do their brains respond to that? 1297 00:52:41,260 --> 00:52:45,480 So here's some ADHD children, and children without ADHD. 1298 00:52:45,480 --> 00:52:47,750 And here's the tasks they perform. 1299 00:52:47,750 --> 00:52:51,680 Sometimes they push a button every time a letter appears-- 1300 00:52:51,680 --> 00:52:54,670 they're having a whole bunch of letters here, push, push, 1301 00:52:54,670 --> 00:52:55,980 push, push. 1302 00:52:55,980 --> 00:52:59,520 But they're told when an X appears, don't push. 1303 00:52:59,520 --> 00:53:00,880 So you're tricking the subjects. 1304 00:53:00,880 --> 00:53:02,860 Because you're getting a habit going. 1305 00:53:02,860 --> 00:53:03,910 What people call . prepotent response. 1306 00:53:03,910 --> 00:53:05,730 So it's push, push, push, push. 1307 00:53:05,730 --> 00:53:08,840 Oops, hold yourself back, OK. 1308 00:53:08,840 --> 00:53:11,410 What people call no go, don't go. 1309 00:53:11,410 --> 00:53:13,170 And that's hard to do for a kid. 1310 00:53:13,170 --> 00:53:15,770 It's harder to do for somebody to do with ADHD, to control 1311 00:53:15,770 --> 00:53:18,740 the impulse to push. 1312 00:53:18,740 --> 00:53:20,110 And so you measure brain. 1313 00:53:20,110 --> 00:53:21,540 And here's the behavior. 1314 00:53:21,540 --> 00:53:22,860 And then let me tell you the issue. 1315 00:53:22,860 --> 00:53:25,240 So here's the percent of false alarms. 1316 00:53:25,240 --> 00:53:27,640 This is when you pushed for the X, you should have held 1317 00:53:27,640 --> 00:53:29,230 yourself back. 1318 00:53:29,230 --> 00:53:32,840 Here's the control, here's the ADHD children, making more 1319 00:53:32,840 --> 00:53:35,400 impulsive errors overall, harder to control themselves 1320 00:53:35,400 --> 00:53:38,590 and stop themselves from pushing for that X. When 1321 00:53:38,590 --> 00:53:42,480 they're off Ritalin they make more mistakes when they're on. 1322 00:53:42,480 --> 00:53:47,090 But look at these kids who have no ADHD and never took it 1323 00:53:47,090 --> 00:53:49,300 because they have no reason to take it. 1324 00:53:49,300 --> 00:53:50,060 They perform better. 1325 00:53:50,060 --> 00:53:52,090 But look at the drug effect. 1326 00:53:52,090 --> 00:53:54,090 Just the same size. 1327 00:53:54,090 --> 00:53:56,600 And this is not the only study that has found that giving 1328 00:53:56,600 --> 00:54:00,400 typical children Ritalin, will make them perform better on 1329 00:54:00,400 --> 00:54:02,590 cognitively demanding tasks. 1330 00:54:02,590 --> 00:54:06,160 They are typically not done so well by children as by adults. 1331 00:54:06,160 --> 00:54:09,910 So the psychiatrist we worked with on the study said, wow, 1332 00:54:09,910 --> 00:54:12,110 we used to think that if we gave somebody Ritalin and they 1333 00:54:12,110 --> 00:54:15,080 behaved better, we knew we gave the right treatment. 1334 00:54:15,080 --> 00:54:17,390 But it's not clear that these kids aren't behaving better. 1335 00:54:17,390 --> 00:54:18,540 OK. 1336 00:54:18,540 --> 00:54:19,470 They have no problem. 1337 00:54:19,470 --> 00:54:23,150 And there's no reason to give them the medication. 1338 00:54:23,150 --> 00:54:25,700 And let me step through this. 1339 00:54:25,700 --> 00:54:28,230 If you look in the brains at where the Ritalin's affecting 1340 00:54:28,230 --> 00:54:31,490 things, and lots of the brain, the control subjects, and ADHD 1341 00:54:31,490 --> 00:54:33,240 children look alike. 1342 00:54:33,240 --> 00:54:35,260 The only part of their brain that looks really different is 1343 00:54:35,260 --> 00:54:37,240 in the basal ganglia, part of their brain that's involving 1344 00:54:37,240 --> 00:54:40,320 in habits and impulse controls. 1345 00:54:40,320 --> 00:54:44,640 Also implicated in OCD that we talked about before. 1346 00:54:44,640 --> 00:54:47,280 It's an area that's full of dopaminergic systems. 1347 00:54:47,280 --> 00:54:50,090 It's an area that Ritalin binds to. 1348 00:54:50,090 --> 00:54:53,220 When you look inside the brain in animals, and here what was 1349 00:54:53,220 --> 00:54:53,860 found was this. 1350 00:54:53,860 --> 00:54:56,010 So this is a behavioral difference you saw before. 1351 00:54:56,010 --> 00:54:58,690 So if you look in the basal ganglia, here's the controlled 1352 00:54:58,690 --> 00:55:02,930 children off the medication, and then on the medication. 1353 00:55:02,930 --> 00:55:05,470 Here's the ADHD showing this opposite response. 1354 00:55:05,470 --> 00:55:08,360 So here's the only place where the responses are different 1355 00:55:08,360 --> 00:55:09,560 between the controlled children 1356 00:55:09,560 --> 00:55:11,050 and the ADHD children. 1357 00:55:11,050 --> 00:55:13,470 And you can see in a way the medication is so-called 1358 00:55:13,470 --> 00:55:14,680 normalizing the activation. 1359 00:55:14,680 --> 00:55:19,540 So here's typical kids just being themselves, no Ritalin. 1360 00:55:19,540 --> 00:55:22,270 Here's children with ADHD not treated. 1361 00:55:22,270 --> 00:55:23,000 And now you can see. 1362 00:55:23,000 --> 00:55:25,350 Now look how similar they get with the treatment. 1363 00:55:25,350 --> 00:55:26,010 OK. 1364 00:55:26,010 --> 00:55:28,730 So in this part of the brain, and its opposite effect when 1365 00:55:28,730 --> 00:55:31,420 the typical children get the drug, the activation go down, 1366 00:55:31,420 --> 00:55:32,550 the ADHD children, it goes up. 1367 00:55:32,550 --> 00:55:34,820 So this part of the brain seems like it's an important 1368 00:55:34,820 --> 00:55:35,850 part of the story. 1369 00:55:35,850 --> 00:55:38,600 And also of how the medication influences somebody. 1370 00:55:38,600 --> 00:55:41,280 So last thing I want to talk about for two minutes 1371 00:55:41,280 --> 00:55:46,050 including the chapter in this, or three minutes is the 1372 00:55:46,050 --> 00:55:49,040 struggle that people have of, what's the boundary between 1373 00:55:49,040 --> 00:55:52,220 treating an outright disease and 1374 00:55:52,220 --> 00:55:53,810 manipulating normal variation? 1375 00:55:53,810 --> 00:55:57,310 So for example, here's the average height in the US of 1376 00:55:57,310 --> 00:55:58,850 men and women. 1377 00:55:58,850 --> 00:56:03,560 Huge debate about whether people who are on a very sort 1378 00:56:03,560 --> 00:56:06,910 of, are projected to have a very short stature in 1379 00:56:06,910 --> 00:56:10,380 adulthood, should they get growth hormone or not? 1380 00:56:10,380 --> 00:56:12,330 One argument is no, why even think about it? 1381 00:56:12,330 --> 00:56:15,280 Some parents will feel like, my kid might struggle. 1382 00:56:15,280 --> 00:56:16,460 Give the kid a break. 1383 00:56:16,460 --> 00:56:17,570 You can do something about it. 1384 00:56:17,570 --> 00:56:20,680 You don't have to do that. 1385 00:56:20,680 --> 00:56:22,130 How about sadness and depression? 1386 00:56:22,130 --> 00:56:25,965 If you're somewhat sad, should they get CBT? 1387 00:56:25,965 --> 00:56:28,270 Or do they have to be and dark depression? 1388 00:56:28,270 --> 00:56:31,530 Where's the boundary between shyness and social anxiety? 1389 00:56:31,530 --> 00:56:34,110 Or a kid doesn't follow directions, when do you say 1390 00:56:34,110 --> 00:56:37,060 that's a kid not paying attention to ADHD? 1391 00:56:37,060 --> 00:56:41,300 So one of the big surprises has been that when people 1392 00:56:41,300 --> 00:56:43,710 have--and you guys can tell me in a moment. 1393 00:56:43,710 --> 00:56:45,260 When people pole things, you never know how 1394 00:56:45,260 --> 00:56:47,070 accurate these are. 1395 00:56:47,070 --> 00:56:50,460 In some polls 7% of university students without ADHD say they 1396 00:56:50,460 --> 00:56:52,890 take methylphenidate to help them focus and concentrate on 1397 00:56:52,890 --> 00:56:54,020 their studies. 1398 00:56:54,020 --> 00:56:57,360 And even more disturbing to scientists, in one study in 1399 00:56:57,360 --> 00:57:01,340 nature, 20% percent of scientists said they do it. 1400 00:57:01,340 --> 00:57:05,140 So I'm not asking you to turn yourself in. 1401 00:57:05,140 --> 00:57:07,690 But this is my little poll of undergraduates in the world 1402 00:57:07,690 --> 00:57:10,460 out there, because that's what I read in the magazines. 1403 00:57:10,460 --> 00:57:15,260 So is there moderately widespread use of it by people 1404 00:57:15,260 --> 00:57:19,445 who are not prescribed directly themselves? 1405 00:57:19,445 --> 00:57:20,695 Or is it pretty rare? 1406 00:57:28,480 --> 00:57:29,870 Rare? 1407 00:57:29,870 --> 00:57:33,660 It could be rare, you know. 1408 00:57:33,660 --> 00:57:34,910 OK. 1409 00:57:36,550 --> 00:57:37,680 And then what is the right thing? 1410 00:57:37,680 --> 00:57:41,440 Where in all this will people debate about this? 1411 00:57:41,440 --> 00:57:43,180 I think there's no debate that for people who are really 1412 00:57:43,180 --> 00:57:44,670 suffering, you want to help them. 1413 00:57:44,670 --> 00:57:47,790 But where should the line be drawn between you know, 1414 00:57:47,790 --> 00:57:52,250 helping those in despair and boosting those in the middle. 1415 00:57:52,250 --> 00:57:54,230 So last example I want to give you just for a minute is this 1416 00:57:54,230 --> 00:57:58,960 chapter from a man who mistook his wife for a hat. 1417 00:57:58,960 --> 00:58:01,630 Because of this question about boosting experience. 1418 00:58:01,630 --> 00:58:04,150 So this is a woman of 90, Natasha Kay. 1419 00:58:04,150 --> 00:58:05,180 She comes to the clinic. 1420 00:58:05,180 --> 00:58:08,220 And after her 88th birthday she began to change. 1421 00:58:08,220 --> 00:58:09,045 She felt thrilled. 1422 00:58:09,045 --> 00:58:11,110 She was extremely well. 1423 00:58:11,110 --> 00:58:14,030 People said see had changed from being shy to flirtatious, 1424 00:58:14,030 --> 00:58:16,720 giggling, telling jokes at age 88. 1425 00:58:16,720 --> 00:58:18,730 She had this huge transformation. 1426 00:58:18,730 --> 00:58:21,240 It turns out she has syphilis, what she 1427 00:58:21,240 --> 00:58:23,340 calls cupid's disease. 1428 00:58:23,340 --> 00:58:26,160 But she's quite enjoying the change in personality. 1429 00:58:26,160 --> 00:58:28,760 She's disinhibited and having a good time, OK. 1430 00:58:28,760 --> 00:58:32,410 It's like the small bit of alcohol that loosens you up 1431 00:58:32,410 --> 00:58:35,340 but all the time without any of the downside, right. 1432 00:58:35,340 --> 00:58:36,820 And then they said well, should we treat it? 1433 00:58:36,820 --> 00:58:39,750 Because she got the disease at an age when penicillin was not 1434 00:58:39,750 --> 00:58:40,870 widely given. 1435 00:58:40,870 --> 00:58:44,100 And they discover happily that if they treat the penicillin 1436 00:58:44,100 --> 00:58:45,610 it protects her medically. 1437 00:58:45,610 --> 00:58:48,250 But because the brain changed from the neurosyphilis has 1438 00:58:48,250 --> 00:58:52,080 occurred, she remains very happy all the time. 1439 00:58:52,080 --> 00:58:55,790 So you know, if somebody could give you a drug that could 1440 00:58:55,790 --> 00:59:01,760 make you very happy all the time, bad idea, good idea? 1441 00:59:01,760 --> 00:59:03,030 Anyway, so you could think about it. 1442 00:59:03,030 --> 00:59:04,280 Thanks very much.